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Biomedical subjects

D J Fink

Publications and source records attributed to D J Fink.

At least 19 recordsLinked to original sources
PubMed1992

Innovative materials processing strategies: a biomimetic approach.

Many organisms construct structural ceramic (biomineral) composites from seemingly mundane materials; cell-mediated processes control both the nucleation and growth of mineral and the development of composite microarchitecture. Living systems fabricate biocomposites by: (i) confining biomineralization within specific subunit compartments; (ii) producing a specific mineral with defined crystal size and orientation; and (iii) packaging many incremental units together in a moving front process to form fully densified, macroscopic structures. By adapting biological principles, materials scientists are attempting to produce novel materials. To date, neither the elegance of the biomineral assembly mechanisms nor the intricate composite microarchitectures have been duplicated by nonbiological processing. However, substantial progress has been made in the understanding of how biomineralization occurs, and the first steps are now being taken to exploit the basic principles involved.

Animals↗
PubMed1992

Phosphorylation-dependent neurofilament epitopes are reduced at the node of Ranvier.

Neurofilaments in axons are highly phosphorylated at multiple sites on the 200 kDa neurofilament (neurofilament-H) and 160 kDa (neurofilament-M) subunit peptides. We used a panel of monoclonal and polyclonal antibodies against distinct neurofilament epitopes to study the distribution of these epitopes along the axons of large myelinated fibres in rat sciatic nerve using quantitative electron microscopic immunocytochemistry with colloidal gold. Antibodies specific for phosphorylated epitopes on neurofilament-H showed a 60% reduction in density of immunoreactivity at the node of Ranvier, compared to the internodal axon. Antibodies directed against neurofilament-M, which recognized phosphorylated epitopes preferentially, showed a 40% reduction in density of immunoreactivity at the node. Following dephosphorylation of the neurofilaments in tissue sections by alkaline phosphatase treatment, antibodies which recognized dephosphorylated forms of neurofilament-H showed no reduction in density of immunoreactivity at the node. Similarly, an antibody directed against the 70 kDa subunit (neurofilament-L), showed no reduction in density of immunoreactivity at the node. An antibody against tubulin also showed no decrease in the density of immunoreactivity at the node of Ranvier. Tubulin immunoreactivity was similar in myelinated and unmyelinated fibres. In contrast to phosphorylated neurofilament epitopes, immunoreactivity was much greater in myelinated than unmyelinated fibres. These results suggest that the degree of phosphorylation of neurofilament-H and neurofilament-M subunits is reduced at the node of Ranvier, in comparison to internodal neurofilaments, and imply that a post-translational modification of neurofilaments must occur along the length of the axon at the node.

Alkaline Phosphatase↗
PubMed1992

In vivo expression of beta-galactosidase in hippocampal neurons by HSV-mediated gene transfer.

Stereotactic inoculation of a herpes simplex virus (HSV) gene transfer vector into the hippocampus and caudate of rat brain resulted in limited and transient viral replication and the establishment of latency. Virus attenuation was achieved by insertional inactivation of a viral gene, Us3. Insertion of a lacZ reporter gene, under the control of the HSV glycoprotein C (gC) late gene promoter, allowed viral replication to be monitored in vivo. Unlike unattenuated virus, the Us3::pgC-lacZ recombinant caused little apparent damage to normal hippocampal morphology. Transient lacZ expression was detected in a considerable population of neurons of the dentate gyrus following hippocampal injection, whereas few positively staining neurons were present within the caudate after injection at that site. Latency-associated transcripts, the hallmark of latent infection, were detected in the brain 10 months after injection. This recombinant virus may be useful as a gene transfer vector for long-term expression of foreign genes in the central nervous system.

Animals↗
PubMed1992

Activity-dependent regulation of Na+, K(+)-ATPase alpha isoform mRNA expression in vivo.

To investigate the functional role of the different Na+, K(+)-ATPase alpha (catalytic) subunit isoforms in neuronal cells, we used quantitative in situ hybridization with riboprobes specific for alpha 1, alpha 2, and alpha 3 isoforms to measure the level of alpha isoform-specific expression in the neuroendocrine cells of the supraoptic (SON) and paraventricular (PVN) nuclei of rat hypothalamus. A prolonged increase in electrical activity of these cells, achieved by 5 days of salt treatment, increased the amount of alpha 1 isoform mRNA in the SON and PVN by 50%. Levels of alpha 1 mRNA in other brain regions and levels of alpha 2 and alpha 3 mRNAs were not affected by salt treatment. We conclude that the alpha 1 isoform Na+, K(+)-ATPase may be specifically adapted to pump out Na+, which enters the cells through voltage-gated channels during neuronal depolarization.

Animals↗
PubMed1991

Calpain II in rat peripheral nerve.

We used a polyclonal antiserum directed against calpain II to study the distribution of that enzyme in rat sciatic nerve. Western blot of nerve homogenate showed that the antibody reacted with a single protein band of 80 kDa, corresponding to the catalytic subunit of calpain II. By light microscopy, immunoreactivity appeared predominantly in Schwann cell cytoplasm. By electron microscopy, calpain II was especially dense along the plasmalemma of Schwann cells, and was also seen in axoplasm.

Animals↗
PubMed1991

Differential distribution of (Na,K)-ATPase alpha isoform mRNAs in the peripheral nervous system.

mRNA transcripts for 3 isoforms of the alpha subunit of (Na,K)-ATPase have been previously identified in the nervous system (designated alpha 1, alpha 2, and alpha 3). In order to study the localization and expression of the different alpha isoforms in the peripheral nervous system, we prepared probes from the unique 3' untranslated region of alpha 1 cDNA, and from the translated region of alpha 3 cDNA. These probes were used in dot blot and in situ hybridization assays of rat spinal cord, dorsal root ganglia (DRG), and sciatic nerve. Within the ventral horn of lumbar spinal cord, alpha 1 mRNA was found in a discrete set of laterally placed motor neurons, while alpha 3 was found in all the identified neurons of the spinal cord, including those motor neurons containing alpha 1. In the lumbar DRG, alpha 3 was uniformly distributed in DRG neurons, while alpha 1 was abundant in some neurons but little or none was found in other neurons. Satellite cells contained neither isoform. Schwann cells in sciatic nerve were labeled with the alpha 1 probe in a perinuclear distribution, but contained no detectable alpha 3. Dot blot analysis showed alpha 1 and alpha 3 in spinal cord and DRG, but only alpha 1 in peripheral nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Differential distribution of (Na, K)-ATPase alpha isoforms in the central nervous system.

1. mRNA transcripts for three isoforms of the alpha subunit of (Na,K)-ATPase have been previously identified in the rat nervous system and designated alpha 1, alpha 2 and alpha 3. 2. In order to study the localization and expression of the different alpha isoform mRNAs on a regional and cellular level in the brain, we prepared probes from the unique 3' untranslated region of rat alpha 1 cDNA and from a segment containing a portion of the translated region of rat alpha 3 cDNA. These probes were used in dot blot and in situ hybridization assays of rat brain. 3. alpha 1 mRNA was found predominantly in cerebral cortex, dentate gyrus of hippocampus, and specific isolated brain-stem nuclei such as locus ceruleus and motor nuclei V and VII. In contrast alpha 3 mRNA was found predominantly in pyramidal neurons in the deep layers of cerebral cortex, in both pyramidal and dentate gyrus neurons of the hippocampus, and in neurons of most subcortical structures of the thalamus, basal ganglia, and brain-stem nuclei. 4. In the cerebellum, Purkinje cells showed predominantly alpha 3, as did stellate and basket cells. The granule cells contained predominantly alpha 1. 5. These experiments show that mRNAs for both alpha 1 and alpha 3 isoforms of (Na,K)-ATPase are found in neurons of the CNS. The isoforms have unique cellular and regional distributions, which in some cases overlap.

Animals↗
PubMed1991

Immunocytochemical demonstration of Na+,K(+)-ATPase in internodal axolemma of myelinated fibers of rat sciatic and optic nerves.

We used postembedding electron microscopic immunocytochemistry with colloidal gold to determine the ultrastructural distribution of Na+,K(+)-ATPase in the sciatic and optic nerves of the rat. Using a polyclonal antiserum raised against the denatured catalytic subunit of brain Na+,K(+)-ATPase, we found immunoreactivity along the internodal axolemma of myelinated fibers in both nerves. This antiserum did not produce labeling of nodal axolemma. These results suggest that an important site of energy-dependent sodium-potassium exchange is along the internodal axolemma of myelinated fibers in the mammalian CNS and PNS and that there may be differences between the internodal and nodal forms of the enzyme.

Animals↗
PubMed1990

Transfer of technology. Cancer education.

Advances in research are transmitted to practicing physicians through a variety of continuing medical education approaches. Physicians are sophisticated managers of their learning and use group and self-instruction methods. Local hospitals and professional societies along with reading are major sources of continuing education. Cancer education to transmit the latest advances draws on all methods of continuing medical education. A study of practicing physicians' interests and preferences in cancer education provides guidance about tailoring continuing medical education to physician needs. The use of personal computers may be important in bringing information directly to the physician in the practice setting. The challenge is to provide educational opportunities in a variety of ways to meet the diverse needs of the practicing medical community.

American Cancer Society↗
PubMed1990

S100 is preferentially distributed in myelin-forming Schwann cells.

In order to elucidate the role of S100 protein in vivo we used postembedding electron microscopical immunocytochemistry with commercially available antibodies to S100, and secondary antibodies conjugated to colloidal gold to determine the distribution of S100 protein in the sciatic nerve and the cervical sympathetic trunk of the rat. We found that S100 immunoreactivity in Schwann cells was differentially distributed. The amount of S100 immunoreactivity in myelinated fibres appeared to correlate directly with the thickness of the myelin sheath formed by the Schwann cell. Unmyelinated fibres were identical to the small myelinated fibres in S100 immunoreactivity. Within the Schwann cells, the immunoreactivity was seen in the nucleus and in the perikaryal cytoplasm, as well as in the Schmidt-Lanterman clefts and in the paranodal loops at the node of Ranvier, but not in the myelin itself. Using these antibodies we did not see reproducible or convincing intra-axonal immunoreactivity in normal nerve. These results suggest that in Schwann cells S100 expression may be related to axon diameter and degree of myelination. Future studies of S100 expression in development or in response to injury may clarify the role of S100 in Schwann cell biology.

Animals↗
PubMed1990

Prevalence of use of cocaine and other substances in an obstetric population.

Increasing use of cocaine among pregnant women has been reported. This study was conducted to determine the prevalence of positive urine toxicologic screens for cocaine and other substances of patients admitted to the Sloane Hospital for Women. Urine samples were obtained from 509 women admitted to the delivery suite. The overall prevalence of cocaine was 10% (n = 51). Cocaine use was 10 times more prevalent in the clinic population (14%) than in the private population, (1.4%). In addition, women whose urine samples were positive for cocaine were more likely to have no prenatal care, previous induced abortions, to be human immunodeficiency virus-positive, and admitted previous use of cigarettes, alcohol, cocaine, and other drugs. Amphetamines were detected in 13% (n = 65) of patients. However, the screens did not distinguish between metabolites of amphetamines and other drugs such as cold medications. The medical history alone predicted only 37% (n = 19) of the cocaine-positive screens and none of the amphetamine-positive screens.

Adolescent↗
PubMed1989

Community programs. Breast cancer detection awareness.

The American Cancer Society initiated a major nationwide program to raise public and health professional awareness about the benefits of breast cancer detection, particularly screening mammography. Activities were carried out at the community level and attempted to develop local collaboration and participation. Barriers to use of screening, including cost, quality assurance, physician attitudes and practices, and women's knowledge, were addressed in communities across the United States. Early indications are that the program has made a major impact, contributing to the recent increase in the number of women who have had mammograms, the number of mammograms done in hospitals, the number of physicians who follow Society Guidelines for Mammography 0 (in Illinois, this rose from 15% in 1985 to 46% in 1987), and in the number of early breast cancers being diagnosed. The challenge remains to more broadly integrate breast cancer detection into health practice. The BCDA provides a valuable example to make this goal a reality.

Adult↗
PubMed1989

Serum cholesterol and primary brain tumours: a case-control study.

The association between serum cholesterol level and primary brain tumours in adults was studied in a case-control study. Some 150 cases were compared with 649 hospital-based controls. An association between elevated serum cholesterol level and primary brain tumours was found. This relationship was concentrated in meningioma cases and may represent a marker for an elevated socioeconomic status.

Aged↗
PubMed1989

Ca++-ATPase in the central nervous system: an EM cytochemical study.

Ca++-ATPase plays an important role in regulation of the intracellular Ca++ concentration. Biochemical studies of brain have demonstrated that Ca++-ATPase co-purifies with synaptosomes, with synaptic plasma membrane and synaptic vesicle fractions. To better understand the role of this enzyme in normal brain function, we used an electron microscopic (EM) cytochemical method to determine the localization of Ca++-ATPase in rat brain. Reaction product occurred along cytoplasmic membranes. Specific areas of increased reaction product were seen at many but not all post-synaptic densities. Intracellular Ca++-ATPase reaction product was associated with all synaptic vesicles examined and with the Golgi and smooth endoplasmic reticulum (SER). Unlike the situation in peripheral nerve, Ca++-ATPase at the node of Ranvier in the CNS localized preferentially to the nodal axolemma. The localization of Ca++-ATPase at synaptic vesicles agrees with the biochemical evidence for its localization and with the cytochemical evidence for Ca++-ATPase sequestration in those vesicles. The restricted localization at postsynaptic densities suggests that it may be involved in extrusion of Ca++ at synapses where neurotransmitter release causes Ca++ influx.

Animals↗
PubMed1988

Cytochemical localization of Ca2+-ATPase activity in peripheral nerve.

We used an electron microscopic cytochemical method to determine the localization of Ca2+-ATPase in rat peripheral nerve. We found that reaction product occurred along most cytoplasmic membranes in the dorsal root ganglia (DRG). Unmyelinated axons demonstrated reaction product on the axolemma diffusely along their length. Myelinated fibers, in contrast, had reaction product limited to the axolemma in the paranodal region. Internodal axolemma never showed reaction product and nodal axolemma was only occasionally stained, usually in sections reacted for the maximum times. Schwann cell plasma membranes uniformly showed reaction product. The restricted localization of Ca2+-ATPase to the paranodal region of myelinated fibers suggests that calcium efflux may occur principally at those sites.

Animals↗
PubMed1987

Retrograde axonal transport in rat sciatic nerve after nerve crush injury.

We investigated the quantitative alterations in retrograde transport of proteins following a nerve crush injury using the 3H N-succinimidyl propionate (3H NSP) method in rat sciatic nerve. After subepineurial injection of 3H NSP into the nerve the amount of radioactively labeled proteins accumulating in the cell bodies of the motor and sensory neurons was determined 1 day or 7 days later in nerves which had been crushed distal to the injection site 1, 3, 5, 7, or 33 days prior to 3H NSP labeling. One day accumulation in the DRG and spinal cord was not altered by nerve crush. Seven day accumulation in the DRG was initially slightly increased, then fell to 73% of control by 7 days, remaining reduced 33 days after crush. Seven day accumulation in the spinal cord was reduced to 25% of control 1 day after crush and remained at that low level except for 5 days post-crush when a normal amount of labeled protein was transported to the spinal cord. The time course of these changes suggests that quantitative alterations in retrograde transport may be involved in the long-term trophic interactions between the cell body and periphery, but are too slow to account for the earliest perikaryal responses to injury. In addition, the difference between the alterations of retrograde transport in motor and sensory neurons may reflect fundamental differences in the composition of retrograde transport in those different systems.

Animals↗
PubMed1987

Alterations in retrograde axonal transport in streptozocin-induced diabetic rats.

Retrograde axonal transport in the sciatic nerve of rats with streptozocin-induced diabetes was studied by the [3H]N-succinimidyl propionate [( 3H]NSP) method. The accumulation of retrogradely transported labeled proteins in the dorsal root ganglia and the ventral horn of spinal cord 1 day after [3H]NSP injection was not statistically significantly different from controls in rats diabetic for 1 or 14 days at the time of [3H]NSP injection. However, accumulation of labeled proteins in the dorsal root ganglia 7 days after [3H]NSP injection was reduced by 35% and transport to the ventral horn of spinal cord 7 days after [3H]NSP injection was reduced by 70% at the same time points. Partial control of the diabetes with insulin resulted in a partial reversal of these deficits. The early occurrence of defects in retrograde transport suggests that such defects may play a role in the pathogenesis of the neuropathy.

Animals↗