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Biomedical subjects

M D Weiss

Publications and source records attributed to M D Weiss.

At least 19 recordsLinked to original sources

Oligodendrocytes in aging mice lacking myelin-associated glycoprotein are dystrophic but not apoptotic.

Although MAG-null mice myelinate relatively normally except for subtle structural abnormalities in the periaxonal region of myelin sheaths, they develop more severe pathological changes as they age. The purpose of this study was to further define the biochemical aspects of CNS pathology caused by an absence of MAG. Proteins associated with myelin and oligodendrocytes were quantified by densitometry of western blots in whole brain homogenates, as well as in isolated myelinated axons and myelin. Neither myelin yields, nor levels of myelin basic protein and proteolipid protein, were decreased in comparison to control levels in 14-month-old MAG-null mice. On the other hand, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and the 120 kD neural cell adhesion molecule (N-CAM) were substantially reduced in whole brain, myelinated axons, and myelin. Tubulin, Na(+)K(+)ATPase and Fyn tyrosine kinase were also reduced significantly in myelin-related fractions, but not in whole brain homogenate. The decreased levels of these proteins suggest pathological abnormalities in oligodendrocytes. Furthermore, significant reductions of CNPase and 120 kD NCAM were also present at 2 months, indicating that the oligodendroglial abnormalities begin at a relatively early age. Neither TUNEL assays nor multiplex RT-PCR for mRNAs of apoptosis-related proteins in the aging MAG-null mice provided evidence for apoptotic oligodendrocytes. These biochemical findings suggest oligodendroglial damage in MAG-null mice and support the morphological observations pointing to a progressive "dying-back oligodendrogliopathy" as a consequence of MAG deficiency.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Variability in the binding of anti-MAG and anti-SGPG antibodies to target antigens in demyelinating neuropathy and IgM paraproteinemia.

Densitometry of immunostained Western blots or thin layer chromatograms and enzyme-linked immunosorbent assays (ELISAs) were used to compare the relative strengths of IgM binding to myelin-associated glycoprotein (MAG), P0 glycoprotein, peripheral myelin protein-22 (PMP-22), sulfate-3-glucuronyl paragloboside (SGPG), and other potential target antigens in a series of eleven patients with sensory or sensorimotor demyelinating neuropathy and IgM paraproteinemia. The IgM from all patients exhibited reactivity with both MAG and SGPG, and there was a statistically significant correlation between the overlay assays and ELISAs for measuring the strength of IgM binding to MAG and to SGPG. However, the data revealed variations in the relative strengths with which the antibodies bound to the potential target antigens and heterogeneity in their fine specificities. First, there was a poor correlation between the strength of binding to MAG and to SGPG, respectively. Second, reactivity with MAG or SGPG in a few of the patients was only detected by one of the two assay systems. Third, about one-third of the patients' IgM absolutely required the sulfate on SGPG for reactivity, whereas the others retained some reactivity after removal of the sulfate. Fourth, IgM from two of the patients exhibited unusually strong reactivity with the proteins of compact myelin, P0 and PMP22. These relative differences in strengths of antibody binding to the potential antigens were compared with the patients' clinical presentations and with their responses to intravenous immunoglobulin (IVIg) therapy in a clinical trial in which they participated. For the most part, these variations did not correlate with clinical presentation, which was relatively homogeneous in this series of patients. However, an inverse relationship was noted between degree of reactivity to MAG by ELISA and response to IVIg. Two of the patients who responded had only mild elevations of IgM antibodies to nerve glycoconjugates and exhibited some unusual immunochemical and clinical characteristics in comparison to the other patients. The results demonstrate differences in the relative strengths with which anti-MAG and anti-SGPG IgM antibodies from different patients bind to potential neural target antigens which may affect pathogenic mechanisms and response to therapy.

Aged↗

Autoantibodies associated with peripheral neuropathy.

High titers of serum antibodies to neural antigens occur in several forms of neuropathy. These include neuropathies associated with monoclonal gammopathy, inflammatory polyneuropathies, and paraneoplastic neuropathies. The antibodies frequently react with glycosylated cell surface molecules, including glycolipids, glycoproteins, and glycosaminoglycans, but antibodies to intracellular proteins have also been described. There are several correlations between antibody specificity and clinical symptoms, such as anti-MAG antibodies with demyelinating sensory or sensorimotor neuropathy, anti-GM1 ganglioside antibodies with motor nerve disorders, antibodies to gangliosides containing disialosyl moieties with sensory ataxic neuropathy and Miller-Fisher syndrome, and antibodies to the neuronal nuclear Hu antigens with paraneoplastic sensory neuronopathy. These correlations suggest that the neuropathies may be caused by the antibodies, but evidence for a causal relationship is stronger in some examples than others. In this review, we discuss the origins of the antibodies, evidence for and against their involvement in pathogenic mechanisms, and the implications of these findings for therapy.

Antibody Specificity↗

Standardizing work injury care in aligned systems.

Standardizing work injury care in aligned systems requires commitment toward the same goal from all system entities. One of the keys to the success of this process improvement is involvement of all stakeholders, including external customers, in the improvement process. Strengthening the communication processes between providers and company representatives is one step in helping employers to manage the high cost of health care for their employees.

Accidents, Occupational↗

Molecular mimicry in chronic inflammatory demyelinating polyneuropathy and melanoma.

Polyclonal immunoglobulin M antibodies to the monosialoganglioside GM2, sulfoglucuronyl glycolipids, and sulfatide were detected by thin-layer chromatography and enzyme-linked immunosorbent assay in the serum of a patient with melanoma and chronic inflammatory demyelinating polyneuropathy. Both the patient's serum and polyclonal antibodies against GM2 reacted strongly with a biopsy of melanomatous tissue from the patient, suggesting a process of molecular mimicry.

Aged↗

Temperature-sensitive repetitive discharges in paramyotonia congenita.

A 47-year-old female with paramyotonia congenita was studied with electromyography and showed minimal myotonic discharges but prominent repetitive discharges in hand muscles at room temperature. With cooling the hand, the repetitive discharges ceased as the myotonic potentials became prominent. With exercise and further cooling, the myotonic discharges increased and the strength of the muscle and recruitment pattern decreased. With warming, the myotonic discharges decreased as the repetitive discharges reappeared. This is the first report of repetitive discharges occurring in a patient with temperature-sensitive sodium channel myotonia. It is postulated that the repetitive discharges as well as the myotonic discharges are the manifestation of muscle membrane hyperexcitability secondary to the abnormal, noninactivating sodium channels.

Electromyography↗

Hospital based occupational health services: meeting community needs.

1. Community health plans must include comprehensive approaches to meeting employment related health care needs. 2. To be effective, occupational health services should be based on a complete assessment of the needs of employers in the community. 3. Integration of community health care resources requires strong communication links, cooperation, and collaboration among providers.

Continuity of Patient Care↗

Nurse attendee purchasing patterns.

Retention of nursing professionals is crucial in responding to the increasing demand for and complexity of nursing care. Augmenting the decision-making role of nurses is one important retention-related strategy. Purchasing patterns reflect one aspect of nurses' decision-making role. National meetings provide nurses with an opportunity to investigate educational and employment options, as well as to preview technological advances in patient care products and supplies. Yet, the purchasing patterns of nurses related to the marketing of patient care supplies, or educational material at national meetings have rarely been acknowledged or researched. This study investigated the purchasing patterns of nurse attendees as revealed at a national meeting and how attendance influenced purchasing input following the meeting. The study addressed differences in purchasing patterns between specific groups of nurse attendees, as well as the relationship between meeting attendance motivators and purchasing patterns. A descriptive methodology utilizing participant observation at four national nursing meetings and mail survey in four phases was used to determine if there were: (1) identifiable purchasing patterns for nurses attending specific nursing-organization sponsored national meetings, (2) differences in purchasing patterns between nurse attendees from these meetings, (3) differences in self-reported post-meeting purchase input, and (4) relationships between meeting attendance motivators and purchasing patterns. The findings demonstrate that nurse attendee purchasing patterns can be identified and do vary among nursing groups. Nurse attendees at specialty meetings were more likely to act as specifiers, have a more dominant role in purchasing and were more likely to influence product purchases than were nurse attendees from generalist meetings. Self-reports of post-meeting purchasing input demonstrated that nurse attendees utilized information gained at national meetings in subsequent patient care product selections, product utilization and specification of new products/equipment/protocols for trial within the practice site. Positive relationships between meeting attendance motivators and purchasing patterns were most evident for those nurse attendees with greater purchasing involvement and influence.

Adult↗

Relocating families. An overlooked market segment for nursing.

Occupational health nurses are capable of supporting the coping skills of families during relocations. However, nurses must "market" this expertise to human resource personnel. Relocation affects the family's ability to adapt to stress, disruption of health care provider service, child care for working parents, and continuity of care for chronic health problems. Encouraging planning, effective goal setting, and efficient time management skills can augment coping strategies.

Adaptation, Psychological↗

Primary small cell carcinoma of the paranasal sinuses.

An unusual case of small cell carcinoma of the ethmoid sinuses is reported in which electron microscopy confirmed the presence of dense-core granules. The relationship to Pearse's "neuroendocrine programmed" cells is cited. With increasing numbers of different extrapulmonary primary sites for this tumor now being identified, it is believed that these sites must be investigated in any case of suspected small cell carcinoma that cannot be readily attributed to the lung.

Aged↗

Tracheal involvement in laryngeal papillomatosis.

A review of 39 laryngeal papilloma patients at The Johns Hopkins Hospital revealed an incidence of subglottic and tracheal extension much higher than previously reported. Subglottic disease was present in 69% of patients and tracheal involvement in 26%. Factors associated with distal spread were the presence of subglottic papillomas, history of tracheostomy, total number of endoscopic resections, and the duration of disease. The relationship to the presence of viral antigen was cited. Detection and elimination of all papillomas is felt to be the key for the prevention of distal spread. The strategy of management is described.

Adult↗

Implementing total quality management and reshaping delivery systems in a community hospital.

In today's healthcare marketplace, leadership requires more than the delivery of technologically sophisticated patient care. Leadership can be accomplished only by an organization energized with a mission that focuses on providing high-quality, technologically sophisticated, and cost-effective primary healthcare. The paradigm shift to total quality management at the authors' not-for-profit community hospital involved not only the adoption of the philosophy, tools, and techniques espoused by quality experts, but also a restructuring of the organization from a hierarchical format to one focused on the patient.

Community-Institutional Relations↗

Glutamine synthetase: a key enzyme for intestinal epithelial differentiation?

BACKGROUND: We have previously shown that glutamine synthetase protein and mRNA are concentrated in the crypt region of the rat small intestine and that the activity of this enzyme is highest around the time of weaning. This anatomical location and time of peak activity are sites and periods of active enterocyte differentiation. This led to our current hypothesis that glutamine synthetase is important in the differentiation of enterocytes. METHODS: To test our hypothesis, we treated Caco-2 cells with physiologic (0.6 mM) glutamine concentrations in cell culture medium. The experimental group was treated with methionine sulfoximine, an irreversible glutamine synthetase inhibitor, and the control group with phosphate buffered saline. Three standard and well-defined markers of intestinal differentiation-sucrase-isomaltase activity, microvillus formation, and electrical impedance in transwell plates-were compared between the two groups. RESULTS: The methionine-sulfoximine-inhibited group was found to have lower sucrase-isomaltase activity, a lower density of microvilli, and lower electrical impedance values over time compared with the control group. CONCLUSION: The experimental group was found to be less differentiated by all three markers of differentiation. Therefore, glutamine synthetase is important for Caco-2 cell differentiation.

Caco-2 Cells↗