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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 415 records · Page 23Linked to original sources

A new method for expressing axonal size: rat optic nerve analysis.

Analysis of the shape of the cross sections of adult rat optic nerve axons reveals that the majority of axons do not have a true circular shape. Therefore, determination of axonal size has to utilize methods of approximation. The method presented here utilizes three calculated parameters for expression of axonal size: (i) axonal diameter, as calculated from its area, or (ii) axonal diameter, as calculated from its perimeter, both assuming axonal shape to be a perfect circle and (iii) axonal shape factor, which represents the divergence of the axon from a perfect circular shape. The use of the calculated axonal diameter, with a correction for its shape factor, provides a normalized way of expressing axonal size.

Animals↗

Genetic heterogeneity among blue-cone monochromats.

Thirty-three unrelated subjects with blue-cone monochromacy or closely related variants of blue-cone monochromacy were examined for rearrangements in the tandem array of genes encoding the red- and green-cone pigments. In 24 subjects, eight genotypes were found that would be predicted to eliminate the function of all of the genes within the array. As observed in an earlier study, the rearrangements involve either deletion of a locus control region adjacent to the gene array or loss of function via homologous recombination and point mutation. One inactivating mutation, Cys203-to-Arg, was found in 15 probands who carry single genes and in both visual pigment genes in one subject whose array has two genes. This mutation was also found in at least one of the visual pigment genes in 1 subject whose array has multiple genes and in 2 of 321 control subjects, suggesting that preexisting Cys203-to-Arg mutations constitute a reservoir of chromosomes that are predisposed to generate blue-cone-monochromat genotypes by unequal homologous recombination and/or gene conversion. Two other point mutations were identified: (a) Arg247-to-Ter in one subject with a single red-pigment gene and (b) Pro307-to-Leu in one subject with a single 5' red-3' green hybrid gene. The observed heterogeneity of genotypes points to the existence of multiple one- and two-step mutational pathways to blue-cone monochromacy.

Base Sequence↗

Hepatitis C in liver allografts.

Recurrent or intercurrent hepatitis C represents significant problems in patients with liver transplants and must be differentiated from hepatic allograft rejection and other conditions affecting allografts. Often, the currently available anti-hepatitis C virus (HCV) tests are not helpful in the differential diagnosis, because preexisting anti-HCV may persist after transplantation or its development may be delayed. We determined the presence of HCV RNA by the reverse double polymerase chain reaction in biopsy specimens of liver allografts from nine patients with acute or chronic hepatitis of uncertain origin and from three patients with cellular allograft rejection. The NS3 region sequences of HCV were detected in seven of nine liver allograft biopsy specimens 6 weeks to 20 months after transplantation. Hepatitis C virus RNA was not detected in two patients. One of these patients was anti-HCV positive, showing mild acute hepatitis 5 weeks after transplantation. Anti-HCV was present in three patients with detectable HCV RNA in the liver but was absent from four other patients with HCV RNA. These findings suggest that HCV is a major cause of acute and chronic hepatitis following liver transplantation, that detection of HCV RNA by polymerase chain reaction in the liver biopsy specimen represents a reliable method for the diagnosis of hepatitis C in liver allografts, and that in some patients HCV may be acquired during transplantation while in others it may represent a recurrent infection.

Hepacivirus↗

Liver fat-storing cell clones obtained from a CCl4-cirrhotic rat are heterogeneous with regard to proliferation, expression of extracellular matrix components, interleukin-6, and connexin 43.

BACKGROUND: Immunocytochemical analysis of liver has revealed that fat-storing cells (FSC) are heterogeneous with regard to vitamin A content, staining for cytokeratins, desmin, and vimentin and the cytoskeletal protein alpha-smooth muscle actin. Since fat-storing cells play an important role in collagen deposition in normal and cirrhotic liver, we considered it important to study whether fat-storing cells were heterogeneous with regard to cell proliferation, expression of mRNAs coding for cytokines interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta), and extracellular matrix components alpha 1(I), alpha 1(III), alpha 1(IV) procollagens, laminin B1 chain and fibronectin. EXPERIMENTAL DESIGN: We used a FSC line (CFSC) that was developed in our laboratory after spontaneous immortalization of a primary culture of fat-storing cells that were obtained from the liver of a CCl4-cirrhotic rat (Lab. Invest. 65:644-653, 1991). The cells were cloned by limiting dilution and have been maintained in culture for over 3 years without appreciable changes in the parameters investigated. RESULTS: In this communication we report the characterization of 4 of the clones obtained. We show that they are heterogeneous with regard to proliferation index, expression of alpha 1(I), alpha 1(III) and alpha 1(IV) procollagen, IL-6 and TGF-beta mRNAs. The clones also differ in their response to IL-6. We also showed that clones are coupled through functional gap junctions but that they are heterogeneous with regard to the expression of the gap junction protein connexin 43. CONCLUSIONS: We suggest that clonal heterogeneity of FSC may occur in vivo. Since each of the clones expresses a unique phenotype, these FSC clones could be excellent models to study the role of defined extracellular matrices on the expression of liver specific genes by cultured hepatocytes.

Animals↗

Prospective evaluation of the course of disc herniations in patients with proven radiculopathy.

Although surgery is often recommended as the definitive treatment for radiculopathy when definite disc herniation is demonstrated with imaging techniques, complete improvement can occur with nonoperative treatment. However, what happens to the disc in the latter circumstance is not well defined. We report the first prospective study in subjects with proven radiculopathy and definite disc herniation who improve with nonoperative management to determine what occurs to the herniated disc material. Eighteen subjects with lower extremity pain or paresthesia, positive straight leg raising, weakness in a myotomal distribution, reflex asymmetry, or electromyogram evidence of radiculopathy were studied. Subjects were admitted to the study if computed tomography (CT) scanning demonstrated definite disc herniation corresponding to the side and level of the radiculopathy. After complete clinical improvement, repeat CT scan was performed at six to 18 months after the initial study. The CT scans were interpreted separately by two neuroradiologists. Disc herniations were characterized by size (large, moderate, or minimal); the presence of absence of free fragments; and location. Follow-up scans were compared with the original study and characterized as resolved, improved, or unchanged. Fourteen subjects completed the study, an additional three had operative treatment, and one refused repeat scanning. Subjects were followed an average of 30.4 months with no recurrence of radicular symptoms during this follow-up period in 13 patients. One had recurrence of symptoms at 21 months and surgery at 26 months. Six follow-up scans (43%) were interpreted as completely resolved, five (36%) as improved, and three (21%) as unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biliary cystadenocarcinoma arising in a liver with fibropolycystic disease.

Intrahepatic cholangiocarcinoma associated with fibropolycystic disease of the liver and biliary cystadenocarcinoma are rare tumors that are considered distinct entities. We present a case of a malignant tumor with features of hepatic cystadenocarcinoma arising in a background of fibropolycystic disease.

Bile Duct Neoplasms↗

Benign schwannoma of the liver.

We report a case of benign schwannoma presenting as a rapidly enlarging liver mass in a 67-year-old man and review the literature on nerve sheath tumors of the hepatobiliary system. Such tumors, which may occur in patients with and without neurofibromatosis, are very uncommon in the liver. The case reported herein, to our knowledge, is the first well-documented benign schwannoma of the liver occurring in a patient without neurofibromatosis.

Aged↗

Rehabilitation of patients with Hallervorden-Spatz syndrome.

Hallervorden-Spatz Syndrome is an infrequently occurring disorder involving pigmentary degeneration of the globus pallidus, red nucleus, and substantia nigra. Resultant corticospinal and extrapyramidal signs and symptoms predominate early in the course of the disease, with concomitant intellectual deterioration paralleling the developing muscular disorder. To date, there have been no reports in the literature of rehabilitative intervention in patients with this disabling pathology. We report the case of a 43-year-old man whose illness spanned 20 years. He was referred for rehabilitation after a precipitous decline in function over the course of six months. An interdisciplinary team approach was implemented and various medical strategies were used, including the initiation of carbidopa-levodopa. An improvement in functional skills, communication, and the ability to use cognitive strategies was observed. We conclude that a multidisciplinary team approach and in selected cases, the use of carbidopa-levodopa are valid methods for the rehabilitation of patients with Hallervorden-Spatz Syndrome.

Activities of Daily Living↗

The utility of color flow Doppler examination in penetrating extremity arterial trauma.

Recent reports from our institution have demonstrated the safety of nonoperative management of minimal arterial injuries. The purpose of this pilot study was to evaluate whether color flow Doppler (CFD) examination could detect minimal arterial injuries caused by penetrating extremity trauma. Twelve patients with minimal arterial injuries identified by arteriography were treated nonoperatively. Each also underwent color flow examination. Seven of 12 arteriographic abnormalities were detected by color flow examination. Two intimal injuries (brachial artery, superficial femoral artery (SFA)), one small (1 mm) pseudoaneurysm (popliteal artery), and two minor vessel occlusions (interosseous artery, branch off SFA) were not detected. These preliminary data suggest that color flow scans may be less sensitive than arteriography in the detection of clinically insignificant lesions such as small intimal defects or small vessel occlusions. Despite this, CFD examination was successful in detecting more significant lesions such as pseudoaneurysms, arteriovenous fistulae, and major vessel occlusions. This is relevant since these lesions may require immediate intervention. These findings suggest the possibility that color Doppler sonography may be able to sequentially monitor these lesions to determine if they resolve or progress. If progression is documented they may require surgical correction. Further prospective studies must be performed to assess whether color flow Doppler examination can supplant arteriography in patients at low or intermediate risk for arterial injury following penetrating arterial trauma.

Adolescent↗

Identification of an interleukin 2-like substance as a factor cytotoxic to oligodendrocytes and associated with central nervous system regeneration.

Axons of the central nervous system in adult mammals do not regenerate spontaneously after injury, partly because of the presence of oligodendrocytes that inhibit axonal growth. This is not the case in lower vertebrates (e.g., in fish), where regeneration of the optic nerve does occur spontaneously and has been correlated with the presence of factors cytotoxic to oligodendrocytes. The present study provides evidence that the substance originating from the fish optic nerves, which is cytotoxic to oligodendrocytes, is an interleukin 2-like substance.

Animals↗

Horseradish peroxidase labeling of growth cones and axons beyond the site of injury in injured rabbit optic nerve axons growing in their own environment.

Spontaneous growth of injured axons in the mammalian central nervous system is limited. We have previously shown an apparently regenerative growth of injured optic axons in the adult rabbit, achieved by supplying them with soluble substances originating from growing axons, followed by low energy helium-neon laser irradiation. The growing unmyelinated and thinly myelinated axons were embedded in astrocytes, and some were in the process of remyelination by oligodendrocytes. They were shown to have originated from the retinal ganglion cells. The present study further supports evidence relating to the origin and nature of these axons. Light microscopic analysis of these axons labeled with anterogradely transported horseradish peroxidase revealed that many of these axons have varicosities and bear growth cone-like swellings in their tips. These axons traverse the lesion site and extend into the distal stump in a disorganized pattern.

Animals↗

L1 immunoreactivity in the developing fish visual system.

Previous studies have suggested that L1, the cell adhesion molecule, is present in the regenerating fish optic nerve. The present study was undertaken in order to determine whether L1 is expressed by fish neurons and specifically by non-myelinated axons, using fish retinal explants in vitro and the developing fish visual system in vivo. In vitro, the nonmyelinated axons emerging from retinal explants showed L1 immunoreactivity and in vivo, L1 immunoreactive sites were found to be associated with areas rich in non-myelinated axons. At embryonic stage 23, as the eye developed and optic nerve axons began to elongate towards the tectum, L1-like immunoreactivity was seen both in optic nerve and in plexiform layers of the retina. At this stage and until hatching, the cellular layers within the retina showed little or no staining relative to the layers containing axons or dendrites. After hatching, L1 immunoreactivity was also observed in the ganglion cell layer, but upon maturation both the retina and the optic nerve lost most of their L1 immunoreactivity. We therefore suggest that non-myelinated axons of the fish visual system express L1 during development, which is lost after myelination and presumably reappears during regeneration.

Animals↗

Characteristics of fish glial cells in culture: possible implications as to their lineage.

Regeneration of injured central nervous system axons is largely dependent on the response of the associated nonneuronal glial cells to injury. Glial cells of the mammalian central nervous system, unlike those of fish, are apparently not conducive to axonal regeneration. While the lineage of rat glial cells is well characterized and its role in the support or inhibition of regenerative growth is beginning to be understood, little is known about fish glial cells. Accordingly, glial cells in cultures of adult goldfish brain and of newly hatched goldfish larvae were studied in an attempt to establish their lineage. The cells were identified by means of indirect immunofluorescence, using antibodies against fish astrocytes and oligodendrocytes. The cell count in the cultures increased from a small number of cells at 24 h after plating to a large number of both astrocytes and oligodendrocytes after 1 week in culture. Both of these cell types had originated from proliferating cells, as shown by their uptake of tritiated thymidine and by the inhibition of cell proliferation by 5-fluoro-2'-deoxyuridine. Both astrocytes, i.e., glial fibrillary acidic protein-positive cells, and oligodendrocytes, i.e., 6D2-positive cells, were positively labeled also by A2B5 antibodies, which are known to label progenitors of type-2 astrocytes and oligodendrocytes in the rat optic nerve. The results suggest that A2B5 positive progenitor cells in the goldfish central nervous system, as in the rat optic nerve, might be a common progenitor of astrocytes and oligodendrocytes.

Animals↗