It would not be much of an exaggeration to say that the notion of ecological and social embeddedn... more It would not be much of an exaggeration to say that the notion of ecological and social embeddedness is one of the most exploited philosophical ideas these days, both in the academia and beyond. The most troublesome about the overall trend is that many proponents of the idea of social embeddedness simplistically consider selfhood as a form of aberration which merely provides vindication for inequality and violence. In this paper, instead of attacking the problem of the individual versus the collective head-on, I approach it by way of a critique of Stephen Turner’s repudiation of transcendental collectivism (Turner, 1994; Turner, 2010). According to Turner, transcendental entities, such as tacit knowledge, presuppositions, or traditions, should be altogether removed from explanatory schemata in the social sciences. I believe that Turner’s razor cuts too deep and the rejection of implicit framing is at best premature. Against the background of the identified shortcomings of Turner’s m...
Summary In the methodology of science, intersubjectivity is usually associated with replicability... more Summary In the methodology of science, intersubjectivity is usually associated with replicability of experimental results. A related, judicial conception of objectivity as impartiality has it that a theory or judgment is objective if it covers all the relevant angles of the object or phenomenon in question, ensuring that the latter is not ephemeral and the concepts referring to them are valid. Based on the assumption that in the social sciences, the researcher is also a participant, an alternative view was conceived, according to the notion that intersubjectivity rests on either sharing of a lifeworld and its associated practices or on empathy, or on some form of direct social cognition. My aim in this paper is to bring some elements of the Gestalt theory – and more specifically, Rudolf Arnheim’s (1988) adapted model of field dynamics – to bear on the problematic of intersubjectivity. The proposed model suggests that intersubjectivity is a dynamic phenomenon, best described as a pro...
The heritage of transcendental philosophy, and more specifically its viability when it comes to t... more The heritage of transcendental philosophy, and more specifically its viability when it comes to the problematic of the philosophy of social sciences, has been a key point of dissensus between Jürgen Habermas and Karl-Otto Apel. Whereas Apel has explicitly aimed at a transcendental-pragmatic transformation of philosophy, Habermas has consequently insisted that his formal pragmatics, and the theory of communicative action which is erected upon it, radically de-transcendentalizes the subject. In a word, the disagreement concerns whether transcendental entities have any substantial role to play in philosophical discourse and social-scientific explanations. My aim is to reconstruct how Apel establishes a connection between transcendentals, qua the ideal communicative community and the possibility of non-objectifying self-reflection. As I shall demonstrate, the principles that transcendental pragmatics sees as underlying social actions are not to be understood in a strictly judicial way, ...
Cadmium (Cd) is known to have a long biological half-life in the body, possibly due to its bindin... more Cadmium (Cd) is known to have a long biological half-life in the body, possibly due to its binding to metallothionein (MT). This study was designed to determine the role of MT in the tissue distribution and retention of Cd using MT-I and -II null (MT-null) mice. Mice were given 109CdCl(2) (15 mumol/kg, 25 microCi/kg, i.p.), and radioactivity was quantified in 14 major organs at 2 hr, 1, 2, 3, 7 and 15 days thereafter. The lack of MT in MT-null mice 2 hr after Cd administration (74% vs 72% of the dose, respectively). However, the elimination of Cd was much faster in MT-null mice than in control mice. In control mice, approximately 40% of Cd administered was found in liver 24 hr after administration, and the majority was bound to MT. In contrast, only 20% of Cd was found in liver of MT-null mice, which was not bound to MT. Cd concentrations in kidney, pancreas, and spleen were also lower in MT-null than in control mice 1 week after administration. No apparent difference in Cd retentio...
Overexpression of metallothioneins (MTs) protects some cells against heavy metals, mutagens, anti... more Overexpression of metallothioneins (MTs) protects some cells against heavy metals, mutagens, anticancer agents, and reactive oxygen species. We have examined the effect of the loss of MT expression on the cytotoxicity of anticancer agents and mutagens using embryonic fibroblast cells from transgenic mice with targeted disruptions of MT I and II genes (MT -/-). MT -/- cells expressed no detectable MT. Compared to wild type cells, MT -/- cells showed enhanced sensitivity to a 2-h exposure to cisplatin, melphalan, bleomycin, cytarabine, or N-methyl-N'-nitro-N-nitrosoguanidine but were equally sensitive to doxorubicin and neocarzinostatin. Basal expression of the DNA damage-response genes, gadd 45 and gadd 153, were elevated in MT -/- cells compared to MT +/+ cells. Anticancer drug treatment, however, did not produce a greater increase in gadd 45 or gadd 153 expression in MT null cells compared to MT +/+ cells. These results support the hypothesis that endogenous MT levels affect th...
Six transgenic pigs have been produced by microinjecting a human metallothionein promoter/porcine... more Six transgenic pigs have been produced by microinjecting a human metallothionein promoter/porcine growth hormone gene construct into the pronuclei of fertilized eggs which were transferred to synchronized recipient sows. The resulting transgenic animals contained between 0.5 and 15 copies of the gene construct per cell, and at least one of the animals expressed the introduced gene and grew at an increased rate compared to both transgenic and non-transgenic littermates. Some of the transgenic animals that did not appear to grow at increased rates were found to contain rearranged gene sequences. Two of the transgenic pigs have been shown to pass on the introduced genes to their offspring.
Confirmation of nuclear contribution is essential to all nuclear transfer experiments. Contributi... more Confirmation of nuclear contribution is essential to all nuclear transfer experiments. Contribution is easily demonstrated in nuclear transfer progeny but more difficult to confirm in nuclear transfer embryos. The use of donor nuclei isolated from lacZ transgenic mice offers a clear and simple method to demonstrate contribution in nuclear transfer embryos and offspring. The unique line of transgenic mice (Zin40) used in this study displays nuclear localised lacZ expression in all cells, including embryonic blastomeres, and demonstrates distinctive blue nuclei when treated with X-gal substrate. This characteristic staining pattern provided an ideal marker for demonstrating nuclear contribution. Nuclear transfer embryos were generated following serial nuclear transfer of metaphase-arrested nuclei from transgenic and non-transgenic 4-cell embryos. Totipotency of nuclear transfer blastocysts was confirmed by the generation of live born offspring. Transgenic blastocysts and all tissue samples from fetuses and pups generated by nuclear transfer displayed distinctive blue nuclei when stained with X-gal. This staining pattern was characteristic of the transgenic mice from which the donor nuclei were isolated and clearly confirmed nuclear origin. The use of this marker will also allow the opportunity to investigate the developmental potential of nuclear transfer embryos by examining the contribution of nuclear transfer embryonic cells in chimaeric embryos.
Proceedings of the National Academy of Sciences, 1993
We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes... more We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.
The actin cytoskeleton plays a crucial role in pollen tube growth. In elongating pollen tubes the... more The actin cytoskeleton plays a crucial role in pollen tube growth. In elongating pollen tubes the organization and arrangement of actin filaments (AFs) differs between the shank and apical region. However, the orientation of AFs in pollen tubes has not yet been successfully demonstrated. In the present work we have used myosin II subfragment 1 (S1) decoration to determine the polarity of AFs in pollen tubes. Electron microscopy studies revealed that in the shank of the tube bundles of AFs exhibit uniform polarity with those close to the cell cortex having their barbed ends oriented towards the tip of the pollen tube while those in the cell center have their barbed ends oriented toward the base of the tube. At the subapex, some AFs are organized in closely packed and longitudinally oriented bundles and some form curved bundles adjacent to the cell membrane. In contrast, few AFs are dispersed with random orientation in the extreme apex of the pollen tube. Our results confirm that the direction of cytoplasmic streaming within pollen tubes is determined by the polarity of AFs in the bundles.
Journal of Trace Elements in Medicine and Biology, 1997
In order to clarify a possible protective role of metallothionein (MT) in the development of stre... more In order to clarify a possible protective role of metallothionein (MT) in the development of streptozotocin (STZ) -caused insulin-dependent diabetes mellitus (lDDM) and its mechanisms, we studied whether MT is effective for protection against STZ-caused IDDM by utilizing MT-null (isoforms MT-I and II) transgenic mice. It was found that Zn pretreatment (l mg/kg body weight as ZnS0 4 ) has a unique inhibitory effect on IDDM development in MT-null mice in contrast to no marked effect in control (C57BL/6J) mice, suggesting that Zn ions free from MT molecules exerted this protective effect. The highest Zn dose (10 mg/kg body weight) fully suppressed development of hyperglycaemia in both types of mice. Pretreatment with Zn partially led to recovery of superoxide dismutase activities in the liver and pancreas in which STZ administration suppressed superoxide dismutase activity in both types of mice. The present study suggests that Zn plays an important role in the pathogenesis of IDDM, although a possible involvement of MT in the protection of STZ-caused IDDM cannot be completely negated.
The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immu... more The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immunosuppressive action of ultraviolet B (UVB; 280±320 nm) radiation has been examined. Mice were exposed to a series of increasing daily UVB doses, each dose administered to the dorsum on 3 consecutive days. Erythema was assessed, and measured as its oedema component by the postirradiation dorsal skinfold thickness, but there was no effect of the null mutation (MT ±/± ) observed after 3r3 . 4 kJ/m 2 of UVB radiation. Immune function was assessed by the contact hypersensitivity (CHS) response, which was initiated by sensitization on unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal treatments. In comparison with the wild-type MT +/+ mouse, the MT ±/± mouse was signi®cantly more immunosuppressed by moderate daily UVB doses (1 . 75±5 . 9 kJ/m 2 ). When topically applied cis-urocanic acid (cis-UCA) replaced UVB radiation as the immunosuppressive agent, contact hypersensitivity in MT ±/± mice was again markedly more suppressed than in MT +/+ mice, in a dose-responsive manner. The results infer that MT, which was shown immunohistochemically to be strongly induced in the epidermis of MT +/+ mice, but to be absent in MT ±/± epidermis, has the potential to protect from photoimmunosuppression, and that the mechanism of action may be via the inactivation of the epidermal UVB-photoproduct, cis-UCA.
Using transeenic mice in which metallothionein (MT)-1 and MT-II penes. we havpe studied a putativ... more Using transeenic mice in which metallothionein (MT)-1 and MT-II penes. we havpe studied a putative role of MT as a free radical scavenger against paraquat. a free radical generator. Male mice were injected S.C. with paraquat (PQ) at a single dose of 40 or 60 mg/kg of body weight (b.w.1. Two of the six MT-null mice died within 16 h at the dose of 60 mg PQ/kg. b. w. PQ administration increased hepatic MT concentration in the normal mice (C57BL/hJl, but not in the MT-null mice. The lipid peroxidation (LPI determined by thiobarbituric acid-reactive substance formation was increased by PQ in the liver of normal and MT-null mice, and the enhanced level was greater in the MT-null mice than in the C57BL/hJ mice. Administration of PQ significantly increased blood urea nitrogen only in the MT-null mice. indicating renal damage. Without paraquat administration. the hepatic concentration of non-protein sulphydryl compounds was less in the MT-null mice than in the CS7BL/hJ mice. and the basal level of LP wtas higher in the MT-null mice than in the C57BL/6J mice. The present results support the notion that MT plays an antioxidativje role against paraquat insult under physiolo@cal conditions.
The distribution of cadmium (Cd) in the organs of mice was studied using metallothionein (MT)-nul... more The distribution of cadmium (Cd) in the organs of mice was studied using metallothionein (MT)-null transgenic mice. When mice were administered with Cd chloride at a single subcutaneous dose of 1.0 mg Cd/kg body weight, Cd accumulated mainly in the liver and kidney by 6 h after injection without any significant difference between the MT-null mice and control (C57BL/6J) mice. MT was not detected in these organs of MT-null mice both before and after Cd administration whereas MT was induced mainly in these organs of the control mice. There was a marked elimination of Cd from the liver of MT-null mice by 21 days after administration, compared with a relatively slow Cd elimination in the C57BL/6J mice. Under the condition that no significant liver or kidney damage was observed, MT was considered to play a significant role in the retention of Cd in the liver but not in the uptake of this metal.
Pluripotent human stem cells isolated from early embryos represent a potentially unlimited source... more Pluripotent human stem cells isolated from early embryos represent a potentially unlimited source of many different cell types for cell-based gene and tissue therapies [1-3]. Nevertheless, if the full potential of cell lines derived from donor embryos is to be realised, the problem of donor-recipient tissue matching needs to be overcome. One approach, which avoids the problem of transplant rejection, would be to establish stem cell lines from the patient's
The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 l... more The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue-nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allelespecific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
It would not be much of an exaggeration to say that the notion of ecological and social embeddedn... more It would not be much of an exaggeration to say that the notion of ecological and social embeddedness is one of the most exploited philosophical ideas these days, both in the academia and beyond. The most troublesome about the overall trend is that many proponents of the idea of social embeddedness simplistically consider selfhood as a form of aberration which merely provides vindication for inequality and violence. In this paper, instead of attacking the problem of the individual versus the collective head-on, I approach it by way of a critique of Stephen Turner’s repudiation of transcendental collectivism (Turner, 1994; Turner, 2010). According to Turner, transcendental entities, such as tacit knowledge, presuppositions, or traditions, should be altogether removed from explanatory schemata in the social sciences. I believe that Turner’s razor cuts too deep and the rejection of implicit framing is at best premature. Against the background of the identified shortcomings of Turner’s m...
Summary In the methodology of science, intersubjectivity is usually associated with replicability... more Summary In the methodology of science, intersubjectivity is usually associated with replicability of experimental results. A related, judicial conception of objectivity as impartiality has it that a theory or judgment is objective if it covers all the relevant angles of the object or phenomenon in question, ensuring that the latter is not ephemeral and the concepts referring to them are valid. Based on the assumption that in the social sciences, the researcher is also a participant, an alternative view was conceived, according to the notion that intersubjectivity rests on either sharing of a lifeworld and its associated practices or on empathy, or on some form of direct social cognition. My aim in this paper is to bring some elements of the Gestalt theory – and more specifically, Rudolf Arnheim’s (1988) adapted model of field dynamics – to bear on the problematic of intersubjectivity. The proposed model suggests that intersubjectivity is a dynamic phenomenon, best described as a pro...
The heritage of transcendental philosophy, and more specifically its viability when it comes to t... more The heritage of transcendental philosophy, and more specifically its viability when it comes to the problematic of the philosophy of social sciences, has been a key point of dissensus between Jürgen Habermas and Karl-Otto Apel. Whereas Apel has explicitly aimed at a transcendental-pragmatic transformation of philosophy, Habermas has consequently insisted that his formal pragmatics, and the theory of communicative action which is erected upon it, radically de-transcendentalizes the subject. In a word, the disagreement concerns whether transcendental entities have any substantial role to play in philosophical discourse and social-scientific explanations. My aim is to reconstruct how Apel establishes a connection between transcendentals, qua the ideal communicative community and the possibility of non-objectifying self-reflection. As I shall demonstrate, the principles that transcendental pragmatics sees as underlying social actions are not to be understood in a strictly judicial way, ...
Cadmium (Cd) is known to have a long biological half-life in the body, possibly due to its bindin... more Cadmium (Cd) is known to have a long biological half-life in the body, possibly due to its binding to metallothionein (MT). This study was designed to determine the role of MT in the tissue distribution and retention of Cd using MT-I and -II null (MT-null) mice. Mice were given 109CdCl(2) (15 mumol/kg, 25 microCi/kg, i.p.), and radioactivity was quantified in 14 major organs at 2 hr, 1, 2, 3, 7 and 15 days thereafter. The lack of MT in MT-null mice 2 hr after Cd administration (74% vs 72% of the dose, respectively). However, the elimination of Cd was much faster in MT-null mice than in control mice. In control mice, approximately 40% of Cd administered was found in liver 24 hr after administration, and the majority was bound to MT. In contrast, only 20% of Cd was found in liver of MT-null mice, which was not bound to MT. Cd concentrations in kidney, pancreas, and spleen were also lower in MT-null than in control mice 1 week after administration. No apparent difference in Cd retentio...
Overexpression of metallothioneins (MTs) protects some cells against heavy metals, mutagens, anti... more Overexpression of metallothioneins (MTs) protects some cells against heavy metals, mutagens, anticancer agents, and reactive oxygen species. We have examined the effect of the loss of MT expression on the cytotoxicity of anticancer agents and mutagens using embryonic fibroblast cells from transgenic mice with targeted disruptions of MT I and II genes (MT -/-). MT -/- cells expressed no detectable MT. Compared to wild type cells, MT -/- cells showed enhanced sensitivity to a 2-h exposure to cisplatin, melphalan, bleomycin, cytarabine, or N-methyl-N'-nitro-N-nitrosoguanidine but were equally sensitive to doxorubicin and neocarzinostatin. Basal expression of the DNA damage-response genes, gadd 45 and gadd 153, were elevated in MT -/- cells compared to MT +/+ cells. Anticancer drug treatment, however, did not produce a greater increase in gadd 45 or gadd 153 expression in MT null cells compared to MT +/+ cells. These results support the hypothesis that endogenous MT levels affect th...
Six transgenic pigs have been produced by microinjecting a human metallothionein promoter/porcine... more Six transgenic pigs have been produced by microinjecting a human metallothionein promoter/porcine growth hormone gene construct into the pronuclei of fertilized eggs which were transferred to synchronized recipient sows. The resulting transgenic animals contained between 0.5 and 15 copies of the gene construct per cell, and at least one of the animals expressed the introduced gene and grew at an increased rate compared to both transgenic and non-transgenic littermates. Some of the transgenic animals that did not appear to grow at increased rates were found to contain rearranged gene sequences. Two of the transgenic pigs have been shown to pass on the introduced genes to their offspring.
Confirmation of nuclear contribution is essential to all nuclear transfer experiments. Contributi... more Confirmation of nuclear contribution is essential to all nuclear transfer experiments. Contribution is easily demonstrated in nuclear transfer progeny but more difficult to confirm in nuclear transfer embryos. The use of donor nuclei isolated from lacZ transgenic mice offers a clear and simple method to demonstrate contribution in nuclear transfer embryos and offspring. The unique line of transgenic mice (Zin40) used in this study displays nuclear localised lacZ expression in all cells, including embryonic blastomeres, and demonstrates distinctive blue nuclei when treated with X-gal substrate. This characteristic staining pattern provided an ideal marker for demonstrating nuclear contribution. Nuclear transfer embryos were generated following serial nuclear transfer of metaphase-arrested nuclei from transgenic and non-transgenic 4-cell embryos. Totipotency of nuclear transfer blastocysts was confirmed by the generation of live born offspring. Transgenic blastocysts and all tissue samples from fetuses and pups generated by nuclear transfer displayed distinctive blue nuclei when stained with X-gal. This staining pattern was characteristic of the transgenic mice from which the donor nuclei were isolated and clearly confirmed nuclear origin. The use of this marker will also allow the opportunity to investigate the developmental potential of nuclear transfer embryos by examining the contribution of nuclear transfer embryonic cells in chimaeric embryos.
Proceedings of the National Academy of Sciences, 1993
We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes... more We report the generation of transgenic mice deficient in the metallothionein MT-I and MT-II genes. The mutations were introduced into embryonic stem cells by homologous recombination. Chimeric mice resulting from the targeted embryonic stem cells transmitted the disrupted alleles through their germ line. Homozygous animals were born alive and appeared phenotypically normal and fertile. Absence of MT proteins was confirmed by direct measurement in liver extracts. Challenging the mutant animals with moderate levels of CdSO4 indicated their greater susceptibility to cadmium toxicity than wild-type animals. These mice should provide a useful model to allow detailed study of the physiological roles of MT-I and MT-II.
The actin cytoskeleton plays a crucial role in pollen tube growth. In elongating pollen tubes the... more The actin cytoskeleton plays a crucial role in pollen tube growth. In elongating pollen tubes the organization and arrangement of actin filaments (AFs) differs between the shank and apical region. However, the orientation of AFs in pollen tubes has not yet been successfully demonstrated. In the present work we have used myosin II subfragment 1 (S1) decoration to determine the polarity of AFs in pollen tubes. Electron microscopy studies revealed that in the shank of the tube bundles of AFs exhibit uniform polarity with those close to the cell cortex having their barbed ends oriented towards the tip of the pollen tube while those in the cell center have their barbed ends oriented toward the base of the tube. At the subapex, some AFs are organized in closely packed and longitudinally oriented bundles and some form curved bundles adjacent to the cell membrane. In contrast, few AFs are dispersed with random orientation in the extreme apex of the pollen tube. Our results confirm that the direction of cytoplasmic streaming within pollen tubes is determined by the polarity of AFs in the bundles.
Journal of Trace Elements in Medicine and Biology, 1997
In order to clarify a possible protective role of metallothionein (MT) in the development of stre... more In order to clarify a possible protective role of metallothionein (MT) in the development of streptozotocin (STZ) -caused insulin-dependent diabetes mellitus (lDDM) and its mechanisms, we studied whether MT is effective for protection against STZ-caused IDDM by utilizing MT-null (isoforms MT-I and II) transgenic mice. It was found that Zn pretreatment (l mg/kg body weight as ZnS0 4 ) has a unique inhibitory effect on IDDM development in MT-null mice in contrast to no marked effect in control (C57BL/6J) mice, suggesting that Zn ions free from MT molecules exerted this protective effect. The highest Zn dose (10 mg/kg body weight) fully suppressed development of hyperglycaemia in both types of mice. Pretreatment with Zn partially led to recovery of superoxide dismutase activities in the liver and pancreas in which STZ administration suppressed superoxide dismutase activity in both types of mice. The present study suggests that Zn plays an important role in the pathogenesis of IDDM, although a possible involvement of MT in the protection of STZ-caused IDDM cannot be completely negated.
The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immu... more The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immunosuppressive action of ultraviolet B (UVB; 280±320 nm) radiation has been examined. Mice were exposed to a series of increasing daily UVB doses, each dose administered to the dorsum on 3 consecutive days. Erythema was assessed, and measured as its oedema component by the postirradiation dorsal skinfold thickness, but there was no effect of the null mutation (MT ±/± ) observed after 3r3 . 4 kJ/m 2 of UVB radiation. Immune function was assessed by the contact hypersensitivity (CHS) response, which was initiated by sensitization on unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal treatments. In comparison with the wild-type MT +/+ mouse, the MT ±/± mouse was signi®cantly more immunosuppressed by moderate daily UVB doses (1 . 75±5 . 9 kJ/m 2 ). When topically applied cis-urocanic acid (cis-UCA) replaced UVB radiation as the immunosuppressive agent, contact hypersensitivity in MT ±/± mice was again markedly more suppressed than in MT +/+ mice, in a dose-responsive manner. The results infer that MT, which was shown immunohistochemically to be strongly induced in the epidermis of MT +/+ mice, but to be absent in MT ±/± epidermis, has the potential to protect from photoimmunosuppression, and that the mechanism of action may be via the inactivation of the epidermal UVB-photoproduct, cis-UCA.
Using transeenic mice in which metallothionein (MT)-1 and MT-II penes. we havpe studied a putativ... more Using transeenic mice in which metallothionein (MT)-1 and MT-II penes. we havpe studied a putative role of MT as a free radical scavenger against paraquat. a free radical generator. Male mice were injected S.C. with paraquat (PQ) at a single dose of 40 or 60 mg/kg of body weight (b.w.1. Two of the six MT-null mice died within 16 h at the dose of 60 mg PQ/kg. b. w. PQ administration increased hepatic MT concentration in the normal mice (C57BL/hJl, but not in the MT-null mice. The lipid peroxidation (LPI determined by thiobarbituric acid-reactive substance formation was increased by PQ in the liver of normal and MT-null mice, and the enhanced level was greater in the MT-null mice than in the C57BL/hJ mice. Administration of PQ significantly increased blood urea nitrogen only in the MT-null mice. indicating renal damage. Without paraquat administration. the hepatic concentration of non-protein sulphydryl compounds was less in the MT-null mice than in the CS7BL/hJ mice. and the basal level of LP wtas higher in the MT-null mice than in the C57BL/6J mice. The present results support the notion that MT plays an antioxidativje role against paraquat insult under physiolo@cal conditions.
The distribution of cadmium (Cd) in the organs of mice was studied using metallothionein (MT)-nul... more The distribution of cadmium (Cd) in the organs of mice was studied using metallothionein (MT)-null transgenic mice. When mice were administered with Cd chloride at a single subcutaneous dose of 1.0 mg Cd/kg body weight, Cd accumulated mainly in the liver and kidney by 6 h after injection without any significant difference between the MT-null mice and control (C57BL/6J) mice. MT was not detected in these organs of MT-null mice both before and after Cd administration whereas MT was induced mainly in these organs of the control mice. There was a marked elimination of Cd from the liver of MT-null mice by 21 days after administration, compared with a relatively slow Cd elimination in the C57BL/6J mice. Under the condition that no significant liver or kidney damage was observed, MT was considered to play a significant role in the retention of Cd in the liver but not in the uptake of this metal.
Pluripotent human stem cells isolated from early embryos represent a potentially unlimited source... more Pluripotent human stem cells isolated from early embryos represent a potentially unlimited source of many different cell types for cell-based gene and tissue therapies [1-3]. Nevertheless, if the full potential of cell lines derived from donor embryos is to be realised, the problem of donor-recipient tissue matching needs to be overcome. One approach, which avoids the problem of transplant rejection, would be to establish stem cell lines from the patient's
The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 l... more The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue-nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allelespecific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
The amnion is the inner of two membranes surrounding the fetus. That it arises from embryonic epi... more The amnion is the inner of two membranes surrounding the fetus. That it arises from embryonic epiblast cells prior to gastrulation suggests that it may retain a reservoir of stem cells throughout pregnancy. We found that human amniotic epithelial cells (hAECs) harvested from term-delivered fetal membranes express mRNA and proteins present in human embryonic stem cells (hESCs), including POU domain, class 5, transcription factor 1; Nanog homeobox; SRY-box 2; and stage-specific embryonic antigen-4. In keeping with possible stem cell-like activity, hAECs were also clonogenic, and primary hAEC cultures could be induced to differentiate into cardiomyocytic, myocytic, osteocytic, adipocytic (mesodermal), pancreatic, hepatic (endodermal), neural, and astrocytic (neuroectodermal) cells in vitro, as defined by phenotypic, mRNA expression, immunocytochemical, and/or ultrastructural characteristics. However, unlike hESCs, hAECs did not form teratomas upon transplantation into severe combined immunodeficiency mice testes. Last, using flow cytometry we have shown that only a very small proportion of primary hAECs contain class IA and class II human leukocyte antigens (HLAs), consistent with a low risk of tissue rejection. However, following differentiation into hepatic and pancreatic lineages, significant proportions of cells contained class IA, but not class II, HLAs. These observations suggest that the term amnion, an abundant and easily accessible tissue, may be a useful source of multipotent stem cells that possess a degree of immune privilege.
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