Biliary complications in 400 cases of liver transplantation.
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Adolescent↗
Biomedical subjects
M Schwartz
Publications and source records attributed to M Schwartz.
Case report: fatal lymphoproliferative disease seven weeks after liver transplantation.
A 42-year-old man developed a lymphoproliferative disorder and died seven weeks after undergoing liver transplantation for primary biliary cirrhosis. At autopsy, diffuse large cell lymphoma was noted to involve almost every organ. Molecular analyses of DNA isolated from an enlarged periportal lymph node indicated the presence of Epstein-Barr virus sequences and several JH immunoglobulin gene rearrangements (consistent with the presence of more than one greatly expanded clone of lymphoid cells of B-cell lineage). This case underscores the possibility of the rapid emergence of lymphoproliferative disorder related to Epstein-Barr virus early after liver transplantation, masked by a concurrent episode of acute rejection.
Adult↗
Astrocytes play a major role in the control of neuronal proliferation in vitro.
The elements that control neuronal proliferation are largely unknown. Proliferating neurons in cultures of goldfish brain were studied in an attempt to identify the cell types involved. Neuronal proliferation was found to occur only when the neuronal stem cells were in direct contact with astrocytes, and never directly on the substrate. The regulation of neuronal proliferation thus appears to be mediated, at least in part, by contact with astrocytes. In addition, neurite extension was inhibited by medium conditioned by fish astrocytes. Since neurite extension and neuronal proliferation are mutually exclusive processes, inhibition of neurite extension by soluble substances derived from the astrocytes is probably one of the mechanisms controlling neuronal proliferation. The complex reciprocal relationship between neurons and astrocytes is also demonstrated by an observed inhibition of astrocytic proliferation by medium conditioned by differentiating fish neurons. This inhibition of astrocytic proliferation might be part of a mechanism through which interference with neuronal differentiation by astrocytes is avoided. The results of this study thus suggest that astrocytes, in addition to their known roles in controlling neuronal migration, neuronal differentiation and neurite elongation, may also play a role in the control of neuronal proliferation.
Animals↗
Splice site mutation in the human protein C gene associated with venous thrombosis: demonstration of exon skipping by ectopic transcript analysis.
Heterozygosity for a G-->C mutation converting the highly conserved Gln184 (CAG) to His (CAC) was identified at the last nucleotide of exon 7 of the protein C gene in two family members with deep vein thrombosis. As the nucleotide is a part of the 5 splice site of intron G, it was examined how the mutation affected splicing of protein C pre-mRNA. Relevant protein C cDNA fragments were amplified with polymerase chain reaction after reverse transcription of ectopic mRNA from peripheral blood lymphocytes. Southern blot analysis and nucleotide sequencing of these fragments showed a fragment (A) corresponding to correctly spliced mRNA originating from the normal allele and a fragment (B) corresponding to a truncated mRNA lacking exon 7, originating from the mutant allele. A third fragment (C) lacking exons 7 and 8 was identified in both affected and unaffected family members, as well as in normal controls. Analysis of human liver protein C mRNA indicated that the ectopic lymphocyte mRNA was qualitatively representative for the tissue-specific mRNA. In conclusion, evidence is provided showing that the mutation abolishes formation of correctly spliced mRNA. This agrees with the observation that the mutation results in a type 1 protein C deficiency.
Adult↗
Linkage of Wiskott-Aldrich syndrome with three marker loci, DXS426, SYP and TFE3, which map to the Xp11.3-p11.22 region.
Linkage analysis was performed in 19 families segregating for the Wiskott-Aldrich syndrome (WAS) and in 1 family with X-linked thrombocytopenia using nine polymorphic DNA markers spanning the interval DXS7-DXS14. The results confirm close linkage of WAS to the DXS7, TIMP, OATL1, DXS255, DXS146, and DXS14 loci and reveal three additional marker loci, DXS426, SYP, and TFE3, to be closely linked to WAS. The linkage data are also consistent with the localization of X-linked thrombocytopenia to the same chromosomal region as WAS and support localization of the WAS gene between the TIMP and DXS146 loci. However, the data were insufficient for positioning these disease genes with respect to the four marker loci that map within this latter interval. Analysis of recombination events between the marker loci place the TFE3 gene distal to DXS255 and favor the marker loci order Xpter-DXS7-(DXS426, TIMP)-(OATL1, SYP, TFE3)-DXS255-DXS146-DXS14.
Base Sequence↗
Evidence for two exponent scaling in the random field Ising model.
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Journal Article↗
Familial Pallister-Hall syndrome: case report and hormonal evaluation.
Pallister-Hall syndrome is a usually lethal dysplasia/malformation syndrome characterized by hypothalamic hamartoblastoma, hypopituitarism, postaxial polydactyly, craniofacial malformations, imperforate anus, and other malformations. We report a familial case in a male infant and his female sib fetus, suggesting autosomal recessive inheritance, or germinal mosaicism for an autosomal dominant mutation, or a segregating submicroscopic chromosome abnormality. Detailed endocrine evaluation on the surviving infant revealed documented pituitary function, pituitary deficit, and hypothalamic deficiency. We suggest that hypothalamic dysfunction contributes to the hypopituitarism seen in Pallister-Hall syndrome.
Abnormalities, Multiple↗
Cloning and characteristics of fish glial fibrillary acidic protein: implications for optic nerve regeneration.
Mammalian central nervous system neurons do not regenerate after axonal injury, unlike their counterparts in fish and amphibians. After axonal injury, glial cells in mammals do not support regrowth of axons, while in fish they support the regeneration process. Controversy exists as to whether or not the intact fish optic nerve expresses glial fibrillary acidic protein, a well-known marker for mature astrocytes, and thus whether its astrocytes differ in this respect from those of the brain and spinal cord, as well as from optic nerve astrocytes of other species. In an attempt to resolve this question we cloned fish glial fibrillary acidic protein. Two different complementary DNA clones were isolated from a carp brain complementary DNA library, each encoding a different form of glial fibrillary acidic protein apparently originating from different genes. Monospecific polyclonal antibodies were raised against a peptide synthesized according to the predicted amino acid sequence, and used to identify and localize the fish glial fibrillary acidic protein. Two glial fibrillary acidic proteins (of 49 kDa and 51 kDa) were identified by the antibodies in all tested fish central nervous system tissues. The antibodies were then used to examine glial fibrillary acidic protein immunoreactivity in sections taken from uninjured and injured optic nerves of goldfish. Injury was followed by an elevation in glial fibrillary acidic protein immunoreactivity along the whole length of the nerve, except at the site of the injury, where--as in the case of vimentin--no immunoreactivity was detectable. However, in contrast to vimentin-positive glial cells, which repopulate the site of the injury soon after the optic nerve is injured, glial fibrillary acidic protein-positive glial cells remained outside the injury site for as long as 6 weeks after the injury. Despite the injury-induced changes in glial fibrillary acidic protein immunoreactivity, no change was observed in the level of transcript encoding glial fibrillary acidic protein after injury, while there was an increase in the amount of glial fibrillary acidic protein associated with the cytoskeleton and a reduction in the soluble form. These results suggest that the injury-induced changes in immunoreactivity on sections involve changes not in transcription or translation of glial fibrillary acidic protein, but in glial fibrillary acidic protein compartmentalization.
Animals↗
Binary fluids in Vycor: Anticorrelated random fields.
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Journal Article↗
Electrogenicity of the frog gastric mucosa proton pump based on polarization responses in the presence of H(+)-secretion inhibitors.
Recently, we have shown that polarization of an electrogenic H+/K(+)-ATPase pump located in the secretory (luminal) membrane of the frog gastric mucosa is the major factor contributing to the increase in open circuit potential difference (OCPD) induced by voltage clamping. While this transmucosal polarization was not affected by removal of Cl- and Na+ and minimally affected by increasing the K+ concentration to 79 mM in both nutrient and secretory solutions, it was markedly reduced by 10(-3) M famotidine (beta blocker) or 10(-4) M omeprazole (H+/K(+)-ATPase inhibitor) in the nutrient solution. In present experiments, the effects of three other inhibitors of H+ secretion were examined, namely, cimetidine (beta blocker), SCH 28,080 (H+/K(+)-ATPase inhibitor) and SCN- (non-specific inhibitor). While cimetidine and SCH 28,080 markedly reduced the polarization induced by voltage clamp, SCN- affected the polarization to a lesser extent. These data further support the electrogenicity of the frog gastric mucosa proton pump and the lack of a direct effect of SCN- on the pump.
Animals↗
A transglutaminase that converts interleukin-2 into a factor cytotoxic to oligodendrocytes.
Regenerating optic nerves from fish produce a factor that is cytotoxic to oligodendrocytes. The cytotoxic factor is recognized by antibodies to interleukin-2 (IL-2) and has the apparent molecular size of a dimer of IL-2. An enzyme, identified as a nerve transglutaminase, was purified from regenerating optic nerves of fish and was found to catalyze dimerization of human IL-2. The dimerized IL-2, unlike monomeric IL-2, is cytotoxic to oligodendrocytes from rat brain in culture. The results suggest that posttranslational modification of a cytokine can alter its activity. Under conditions in which oligodendrocytes inhibit neuronal regeneration, dimerization of IL-2 might provide a mechanism to permit nerve growth.
Amino Acid Sequence↗
Axonal regeneration is associated with glial migration: comparison between the injured optic nerves of fish and rats.
The central nervous systems of mammals and fish differ significantly in their ability to regenerate. Central nervous system axons in the fish readily regenerate after injury, while in mammals they begin to elongate but their growth is aborted at the site of injury, an area previously shown to contain no glial cells. In the present study we compared the ability of glial cells to migrate and thus to repopulate the injured area in fish and rats, and used light and electron microscopy in an attempt to correlate such migration with the ability of axons to traverse this area. One week after the optic nerve was crushed, both axonal and glial responses to injury were similar in fish and rat. In both species glial cells were absent in the injured area (indicated by the disappearance of glial fibrillary acidic protein and vimentin immunoreactive cells from the site of injury in rat and fish, respectively), while at the same time axonal growth, indicated by expression of the growth-associated protein GAP-43, was restricted to the proximal part of the nerve. In fish, 2 weeks after the crush, GAP-43 staining (i.e., growing axons) was seen at the site of injury, in association with migrating vimentin-positive glial cells. One week later the site of injury in the fish optic nerve was repopulated by vimentin-positive glial cells, and GAP-43-positive axons had already traversed the site of injury and reached the distal part of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Immune-mediated thrombocytopenia secondary to suramin.
The authors report a case of suramin-induced immune-mediated thrombocytopenia occurring in a patient on a Phase II protocol for treatment of metastatic renal cell carcinoma. On withdrawal of suramin, the acute and severe thrombocytopenia did not respond initially to plasmapheresis; subsequently, it resolved promptly and dramatically during the administration of intravenous gamma globulin, also coinciding with a decline in suramin blood levels. Results of immunologic and coagulation studies are reported and clinical implications discussed.
Humans↗
Morphological and functional properties of TM preneoplastic mammary outgrowths.
The TM series of preneoplastic mammary outgrowth lines was derived from the transplantation of the FSK mammary cell lines into the cleared mammary fat pads of syngeneic female BALB/c mice. The tumor-producing capabilities of the 6 TM outgrowth lines varied from high (TM2, -4, -6) to low (TM9, -10) to nil (TM3). Outgrowth lines 2, 4, and 6 each segregated into sublines of high and low tumor potential. The majority of the outgrowth lines exhibited a moderate to dense alveolar hyperplasia typical of mouse mammary hyperplasias. The exceptions to this picture were lines TM2H and TM10 which exhibited a unique ductular morphology. The ductular morphology was not correlated with tumor potential of the outgrowth lines but was correlated with the expression of K6 and K14 keratins in luminal epithelial cells. In an examination of the growth and hormonal responsiveness properties of the TM outgrowth lines, the TM3 line stands as distinct from the other lines and from any other lines previously characterized in BALB/c mice. The TM3 line grew very slowly and failed to fill the fat pad by 12 months of age. At 12 months of age, the alveolar hyperplasia had regressed so that only bare ducts were present. The TM3 outgrowth was ovarian hormone dependent for growth and alveolar differentiation. TM3 outgrowth represents a minimally deviated mammary hyperplasia which has acquired the immortal phenotype but not the other phenotypic characteristics of mammary preneoplasias. This outgrowth line will be useful for examining the essential molecular changes important for the preneoplastic state, some of which are reported in an accompanying paper (D. Medina et al., Cancer Res., 53: 668-674, 1993).
Animals↗
Growth factor dependency and gene expression in preneoplastic mouse mammary epithelial cells.
The TM preneoplastic mammary outgrowth lines were established in vivo from mammary epithelial cell lines and have been characterized with respect to their tumorigenic, morphological, and functional properties. The TM outgrowth lines were then established as in vitro cell lines. A comparison of the growth factor dependencies of the TM preneoplastic lines and their progenitor cell lines grown in monolayer cell culture indicated that the TM preneoplastic cell lines exhibited a decreased dependence on epidermal growth factor for growth in vitro. The exception to this result was the TM3 cell line which still exhibited a marked dependence on epidermal growth factor for growth. An examination of several genes for mRNA levels indicated that the expression of c-neu, c-H-ras, c-myc, and retinoblastoma was not elevated in those TM preneoplasias which exhibited a decreased dependence on epidermal growth factor. Additionally, there was no evidence that c-H-ras was activated in the preneoplastic outgrowths or tumors. In contrast, mouse mammary tumor virus long terminal repeat mRNA was increased in preneoplasias and tumors, whereas gelsolin mRNA was decreased in tumors but not in preneoplasias. The down-regulation of gelsolin mRNA is consistent with recent reports in human breast cancers. These results together with those reported in another paper (D. Medina et al., Cancer Res., 53: 663-667, 1993) indicate that the TM3 outgrowth line is a minimally deviated preneoplasia which does not share many of the molecular alterations exhibited in tumorigenic TM preneoplastic outgrowth lines. These data, along with other recent data, are interpreted in a hypothesis which views the three essential characteristics of the mammary preneoplastic state as independent and dissociable genetic alterations. Importantly, each of the three characteristics is independently isolated in one or more of the in vivo outgrowth populations. These outgrowth lines should allow identification of the nature and function of the molecular alterations associated with each stage of mammary preneoplasia.
Animals↗
[Cystic fibrosis. From clinical diagnosis to a mutation specific test].
By use of classical linkage analysis and modern DNA technology the gene for cystic fibrosis (CF) was mapped to the long arm of chromosome 7 in 1985. Cloning of the entire gene (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator) was published in 1989. The most common mutation (delta F508) is a three base pair deletion in exon 10, which results in a protein without the amino acid phenylalanine at position 508. The frequency of this mutation varies among different populations, ranging from 45% in the Mediterranean countries to a height in Denmark of 88% of the disease genes. More than 150 different mutations have been identified so far, most of which are very rare. CF is one of the most common severe inherited diseases, but the cloning of the gene and identification of the mutations give great possibilities for prevention permitting both carrier and prenatal diagnosis. The function of the CFTR protein is still not fully known. However, the amino acid sequence of the protein is highly homologous to those of several membrane proteins. In vitro transfection experiments indicate that it constitutes a chloride channel. Recently in vivo experiments involving somatic gene therapy on rats have been successful.
Chromosome Mapping↗
[Psychiatric manifestations in Wilson's disease].
Wilson's disease is an inherited, autosomal recessive disease characterized by progressive hepatic and neurological symptoms. Clinical features usually start between the ages of 10 and 40. Psychiatric disturbances are present in almost all patients. In about a third of them psychiatric symptoms are present early in the disease and in almost 20% they precede hepatic and neurological dysfunction. In these cases the diagnosis of Wilson's disease is often difficult, as a result of which treatment is begun when the illness is already advanced. We report 3 patients with Wilson's disease in whom the psychiatric manifestations preceded neurological symptoms and necessitated admission for psychiatric treatment.
Adult↗
Identification of mutations in Danish choroideremia families.
We have searched for mutations in the choroideremia gene (CHM) in patients from 12 Danish families in which CHM is segregating. Employing polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing, different mutations have been identified in 6 patients. All the mutations will interfere with the correct translation of the mRNA predicting a truncated protein or no gene product at all.
Amino Acid Sequence↗