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Biomedical subjects

S C Zhang

Publications and source records attributed to S C Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Enhanced proliferation and directed migration of oligodendroglial progenitors co-grafted with growth factor-secreting cells.

Transplantation repair of demyelinating lesions is restricted because relatively few cells can be introduced at only a limited number of sites. Repair could be enhanced by stimulating division of transplanted cells and by directing migration to multiple or distant lesions. This article demonstrates that transplanted oligodendroglial progenitors proliferate more when co-grafted with growth factor-secreting cells, yet retain the capacity to form myelin. Transplanted glial cells also migrate preferentially toward the growth factor-secreting cells when the two are implanted at separate sites. This opens avenues to examine growth factor actions on glia in vivo and improves the prospects for human remyelination therapies.

Animals↗
PubMed2000

Early and late long-term effects of vasectomy on Zn, Cd, and Cu levels in prostatic fluid and serum.

AIM: To evaluate the early and late long-term effects of vasectomy on the serum and prostatic fluid trace elements. METHODS: In 37 vasectomized and 25 non-vasectomized (control) men, the Zn, Cd and Cu levels in the serum and prostatic fluid were measured by means of inductively coupled plasma-atomic emission spectroscopy (ICP-AES). RESULTS: No significant difference was found in the prostatic Zn, Cd and Cu levels between the vasectomized and control group. The Zn level in the serum were significantly lower in the vasectomized men than in the controls (11.04 and 13.54 umol/L, respectively; P < 0.05), while the serum Cd and Cu levels were not significantly different between the two groups. CONCLUSION: Vasectomy may decrease the serum, but not the prostatic Zn levels. Its pathophysiological significance is worthy of further investigation.

Body Fluids↗
PubMed1999

Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity.

Remyelination of focal areas of the central nervous system (CNS) in animals can be achieved by transplantation of glial cells, yet the source of these cells in humans to similarly treat myelin disorders is limited at present to fetal tissue. Multipotent precursor cells are present in the CNS of adult as well as embryonic and neonatal animals and can differentiate into lineage-restricted progenitors such as oligodendroglial progenitors (OPs). The OPs present in adults have a different phenotype from those seen in earlier life, and their potential role in CNS repair remains unknown. To gain insights into the potential to manipulate the myelinating capacity of these precursor and/or progenitor cells, we generated a homogenous culture of OPs from neural precursor cells isolated from adult rat subependymal tissues. Phenotypic characterization indicated that these OPs resembled neonatal rather than adult OPs and produced robust myelin after transplantation. The ability to generate such cells from the adult brain therefore opens an avenue to explore the potential of these cells for repairing myelin disorders in adulthood.

Aging↗
PubMed1999

Expression of stem cell factor and c-kit receptor in neural cells after brain injury.

Previously it has been shown that c-kit receptor (c-kitR) and its ligand, stem cell factor (SCF), are expressed in the central nervous system. We have reported that SCF in cultures regulates mouse microglial function. Here we demonstrate that SCF/c-kitR signaling also takes place in situ. We used a penetrating stab wound injury as a model and analyzed the SCF and c-kitR expression in neural cells by immunohistochemistry and in situ hybridization. We found that microglia activated by injury up-regulated c-kitR expression, whereas some astrocytes in the vicinity of the wound expressed SCF mRNA in addition to neurons. This observation suggests that SCF/c-kitR signaling between neurons, astrocytes and microglia also occurs in situ.

Animals↗
PubMed1999

Intraventricular transplantation of oligodendrocyte progenitors into a fetal myelin mutant results in widespread formation of myelin.

Transplantation of myelin-forming cells is a promising strategy for the treatment of myelin disorders. In this study, transplantation of glial cell progenitors into the cerebral ventricles of the embryonic myelin-deficient rat, a model of Pelizaeus-Merzbacher disease, was performed to assess the ability of these cells to incorporate into the developing brain and produce myelin. The donor cells migrated into the white and gray matter and produced myelin at widespread sites ranging from the corpus callosum and optic nerve to the cerebellum. These data suggest that myelin repair might be achieved by intraventricular delivery and transependymal incorporation of myelin-producing cells. Because these cells were genetically transduced to express a reporter gene, similar ex vivo manipulation with genes known to promote survival, migration, or proliferation of the transplanted cells could be used to enhance repair. Such a therapeutic strategy may be feasible in patients with inherited myelin disorders or in multiple sclerosis, particularly where the lesions are periventricular.

Animals↗
PubMed1998

Self-renewing canine oligodendroglial progenitor expanded as oligospheres.

We have previously shown that oligodendroglial progenitors (OP) can be generated from multipotent rat neural precursor cells. We now report the generation of a homogeneous culture of canine OP from neural precursor cells. In non-adherent cultures, homogeneous OP cultures were obtained in 6-8 weeks of treatment with B104 cell conditioned medium (B104CM). In adherent cultures where astrocytes grew as a layer of substrate, colonies of OP invariably appeared at 10-14 days in vitro (DIV) and the colonies were expanded as free-floating spheres (oligospheres), in the presence of B104CM, suggesting that astrocytes facilitate the generation of canine OP. The oligosphere cells were characterized by self-renewal in the presence of B104CM and by terminal differentiation into oligodendrocytes after withdrawal of B104CM. Transplantation studies indicated that the extensively expanded oligosphere cells retained myelination capacity. The oligospheres thus provide a valuable source for experimental cell therapy studies.

Animals↗
PubMed1998

Modulation of microglia by stem cell factor.

We reported previously that stem cell factor (SCF) is produced mainly by neurons and that its receptor (c-kitR), encoded by the protooncogene c-kit, is expressed in microglia, suggesting that SCF/c-kitR signaling may be involved in neuron-microglia interactions. We now report that SCF supports microglial survival in cultures, maintains them in process-bearing morphology, and inhibits microglial proliferation induced by colony stimulating factor-1. SCF potentiates microglial expression of the mRNAs of nerve growth factor, brain-derived neurotrophic factor and ciliary neurotrophic factor, and downregulates microglial expression of the inflammation-associated cytokines, tumor necrosis factor-a (TNF-alpha), and interleukin-1beta (IL-1beta). SCF potentiates lipopolysaccharide-stimulated, but attenuates interferon-gamma TFNalpha mediated expression of the mRNAs of IL-1beta and TNF-alpha. The SCF-induced expression of neurotrophin mRNAs is enhanced by the addition of lipopolysaccharide (LPS) but is reduced by IFNgamma. The interactions between SCF and LPS or IFNgamma in the regulation of inflammation-associated cytokine gene expression are accompanied by the differential regulation of c-kitR in microglia. These observations suggest that SCF/c-kitR signaling modulates microglial activity.

Animals↗
PubMed1998

Early development of the peripheral nervous system in a lancelet species.

The developmental pattern of the lancelet (amphioxus) peripheral nervous system from embryos to larvae has been studied by using wholemount immunostaining and transmission electron microscopy. The peripheral nerves first appeared on the anterior dorsal surface of the medulla at the middle neurula stage, when the anterior nerve cord was just closing. A single axon with a large growth cone was the progenitor of each nerve. The nerve roots adopted an asymmetric arrangement soon after. The first nerve, likely a pair of pure sensory nerves, sprouted from the anterior tip of the nerve cord. This nerve may be comparable topographically to the preoptic nerve (the posterior branch of the terminal nerve) in lungfishes. However, the neuron that first extends its axon was located in the medulla, as in the other posterior nerves. One of the extramedullary primary sensory neurons, the corpuscles of de Quatrefages, appeared in larvae with the mouth and two anterior gill pores. Their axons were seemingly fasciculated with the efferent axon of the first nerve. The second nerve, the most complex one to appear during embryonic and early larval development, innervated the preoral pit and the buccal region. The third and fourth nerves on the left side also innervated the buccal region. The larval innervation patterns in the anterior region differed from the adult organization, suggesting a segmental rearrangement of the nerve supply during development. There was no evidence to dichotomize the peripheral nerves into cranial and spinal nerves, as exist in vertebrates. These characteristics of the peripheral nervous system in the lancelet indicate that this animal has a rather derived or primitive developmental system of peripheral nerves, making the analysis of homology with vertebrates difficult.

Animals↗
PubMed1998

Expression of a twist-related gene, Bbtwist, during the development of a lancelet species and its relation to cephalochordate anterior structures.

Mesoderm formation plays a crucial role in the establishment of the chordate body plan. In this regard, lancelet embryos develop structures such as the anteriorly extended notochord and the lateral divertecula in their anterior body. To elucidate the developmental basis of these structures, we examined the expression pattern of a lancelet twist-related gene, Bbtwist, from the late gastrula to larval stages. In late-gastrula embryos, the transcripts of Bbtwist were detected in the presumptive first pair of somites and the middorsal wall of the primitive gut. The expression of Bbtwist was then upregulated in the lateral wall of somites and the notochord. At the late-neurula stage, it was also expressed in the anterior wall of the primitive gut, as well as in the evaginating lateral diverticula. No signal was detected in the left lateral diverticulum when it was separated from the gut, while in the right one, the gene was expressed later during the formation of the head coelom in knife-shaped larvae, and in the anterior part of the notochord in the same larvae. In 36-h larvae, only faint expression was detected in the differentiating notochordal and paraxial mesoderm in the caudal region. These expression patterns suggest that Bbtwist is involved in early differentiation of mesodermal subsets as seen in Drosophila and vertebrates. The expression in the anterior notochord may be related to its anterior expansion. The expression in the anterior wall of the primitive gut and its derivative, the lateral diverticula, suggests that lancelets share the capability to produce a mesodermal population from the tip of the primitive gut with nonchordate deuterostome embryos.

Amino Acid Sequence↗
PubMed1998

Generation of oligodendroglial progenitors from neural stem cells.

To understand how the differentiation of stem cells to oligodendroglial progenitors is regulated, we established cultures of neural stem cells from neonatal rat striatum in the presence of epidermal growth factor (EGF) as free-floating neurospheres that were then exposed to an increasing amount of B104 cell-conditioned medium (B104CM). The resultant cells proliferated in response to B104CM but no longer to EGF. In vitro analysis and transplantation studies indicated that these cells were committed to the oligodendroglial lineage, and they were thus referred to as oligospheres. Further characterization of their expression of early markers, cell cycle, migration, and self-renewal suggests that they were pre-O2A progenitors. RT-PCR analysis indicated that the oligosphere cells expressed mRNAs of platelet-derived growth factor alpha receptor in addition to fibroblast growth factor receptor but not EGF receptor; the latter two receptor mRNAs were expressed by neurosphere cells. Thus, the progression of stem cells to oligodendroglial progenitors is likely induced by factors in B104CM.

Animals↗
PubMed1997

Cellular localization of stem cell factor and c-kit receptor in the mouse nervous system.

We have characterized the cellular localization of stem cell factor (SCF) and c-kit receptor (c-kitR) in the adult mouse nervous system in situ and in culture by using immunocytochemistry. We found that SCF is largely confined to the neuronal population in normal brain, whereas c-kitR is expressed by glial cells as well as some neurons. We also found that astroglia at an early stage of culture (7 days in vitro) are strongly SCF positive and weakly c-kitR positive. Microglia in cultures express both SCF and c-kitR, but the immunostaining of SCF is weak and diffuse when microglia are cultured in the presence of colony stimulating factor-1. Northern blot analysis confirmed the expression of mRNAs of c-kit and SCF in cultured neurons, astroglia, and microglia. The addition of recombinant SCF to astroglia in culture upregulates the expression of mRNAs of nerve growth factor, brain derived neurotrophic factor, and ciliary neurotrophic factor. These observations suggest that SCF/c-kitR signaling is involved in neuron-neuron as well as neuron-glia interactions.

Animals↗
PubMed1997

Sequence and developmental expression of AmphiTob, an amphioxus homolog of vertebrate Tob in the PC3/BTG1/Tob family of tumor suppressor genes.

Tob is a member of the PC3/ BTG1/Tob family of vertebrate tumor suppressor genes; its expression is known to inhibit proliferation of cells in vitro, but its possible roles during normal development have not been investigated previously. The present study concerns the structure and developmental expression of AmphiTob in an invertebrate chordate, amphioxus. This is the first investigation of any Tob gene during embryological development. The 311 amino acid AmphiTob protein is similar to vertebrate Tob but lacks the C-terminal PQ-rich domain of the latter. In early embryos of amphioxus, in situ hybridization first reveals AmphiTob expression in the hypoblast at the gastrula stage on the likely dorsal side of the embryo. During subsequent development, expression is seen in several tissues of the ectoderm, mesoderm, and endoderm. The most striking expression domains are in the developing somitic musculature and dorsal nerve cord. In the medial wall of each somite, AmphiTob is expressed strongly by cells destined to differentiate into the axial trunk muscles; this pattern persists until late in the larval stage, evidently because undifferentiated cells are continually becoming myogenic as the muscles grow. Nerve cord cells conspicuously transcribe AmphiTob from the late neurula until the early larval stage: Expression occurs in a few cells scattered along the nerve cord and in a group of cells located in the cerebral vesicle (in a region presumably homologous to the vertebrate diencephalic forebrain). During development, an intense and transitory transcription of AmphiTob may be an early event in cells exiting the cell cycle in preparation for differentiation.

Amino Acid Sequence↗
PubMed1997

Repair of myelin disease: strategies and progress in animal models.

Myelin disorders form an important group of human neurological diseases that are as yet incurable. Recent studies on experimental remyelination have suggested that it might be feasible to repair the CNS, either by transplanting normal myelinating cells or by enhancing endogenous repair. Progress in animal models, particularly in transplanting cells of the oligodendrocyte lineage, has resulted in significant focal remyelination and physiological evidence of restoration of function. These data suggest that focal lesions in multiple sclerosis could be repaired by the transplantation of myelin-forming cells. Future therapies could involve both transplantation and promotion of endogenous repair, and the two approaches could be combined with ex vivo manipulation of the donor tissue.

Adult↗
PubMed1996

Neuron-microglia interactions in vitro.

We observed that soluble factor(s) in microglia-conditioned medium supported the survival of cerebral cortical neurons from E15 mouse in a dose-dependent manner. In mixed neuron-microglia cultures, neurons possessed long neurites with extensive arborization and could survive for up to 4 weeks. In such cultures, neurons had an up-regulated level of phosphotyrosine immunoreactivity as compared to those in pure neuron cultures. In mixed cultures, microglia extended cytoplasmic processes toward the growing neurites, and when they contacted neurites, the microglia changed morphology by flattening and rounding up by extending thin cytoplasmic processes. Microglia survived longer in mixed cultures than in pure microglia cultures, with or without neuron-conditioned medium. Under all these culture conditions, microglia were phagocytic as evaluated by Fc receptor-mediated phagocytosis of opsinized sheep erythrocytes, suggesting that the phagocytic activity of microglia does not impair their capacity to support neuronal survival. However, lipopolysaccharide treated microglia did impede neuronal survival in mixed cultures. These observations indicate that, in vitro, microglia can be either neurotrophic or neurotoxic depending upon the microenvironment. The mixed neuron-microglia cultures described provide a valuable in vitro model systems for studying the direct interactions between neurons and microglia.

Animals↗
PubMed1996

Relationship between hepatocellular carcinoma and subtypes of hepatitis C virus: a nationwide analysis.

Although hepatitis C virus (HCV) has now been classified into several subtypes, the clinical significance of HCV subtypes is not well known. Typing of HCV is now routinely performed in Japan. In the present study, HCV subtypes in hepatocellular carcinoma (HCC) patients were analysed from nationwide data collected in Japan using a standard questionnaire. Answers to the questionnaire concerning HCV subtypes in patients with chronic hepatitis (CH), liver cirrhosis (LC) and HCC were obtained from 14 hospitals. The prevalence of the 1b-related subtype, which includes the mixed subtype of 1b and 2a or 2b, in patients with LC and HCC in each hospital was higher than in patients with CH, with few exceptions. However, the differences were not statistically significant because of the small number of patients in each hospital. In summarized data from all 14 hospitals, the 1b-related subtype was found in 1370 of 1922 patients with CH (71.2%). In 356 LC and 426 HCC patients, the prevalence of the 1b-related subtype was 79.8 and 80.5%, respectively. The prevalence of the 1b-related subtype in patients with LC and HCC was significantly higher than in patients with CH. There was no significant difference between the prevalence of the 1b-related subtype in patients with HCC and LC. These results indicate that the oncogenic activity of subtype 1b, although not yet clearly characterized, may be stronger than subtypes 2a and 2b.

Carcinoma, Hepatocellular↗
PubMed1995

Early and late long-term effects of vasectomy on serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels.

PURPOSE: We investigated whether the association between vasectomy and prostate cancer has a hormonal basis. MATERIALS AND METHODS: We examined serum testosterone, dihydrotestosterone, luteinizing hormone and follicle-stimulating hormone levels by radioimmunoassay on 91 pairs of men who did and did not undergo vasectomy. RESULTS: Men who underwent vasectomy 10 to 19 years previously had higher dihydrotestosterone levels than age matched controls. In men who underwent vasectomy 20 years or more ago testosterone was higher than in corresponding controls. No statistically significant difference in luteinizing hormone and follicle-stimulating hormone levels was noted between the men who had had vasectomy and controls. CONCLUSIONS: Our results indirectly support the hypothesis that there is an elevated risk of prostate cancer among men who underwent vasectomy 20 or more years previously.

Dihydrotestosterone↗