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Biomedical subjects

E Wolinsky

Publications and source records attributed to E Wolinsky.

At least 19 recordsLinked to original sources
PubMed1997

Genes controlling ion permeability in both motorneurons and muscle.

Genetic data suggest that unc-8 is a member of the epithelial sodium channel (ENaC) gene family (shreffler et al., 1995). Consistent with this idea, cosmid R13A1, containing an ENaC homolog, can restore normal locomotion to unc-8 mutants after germline transformation. To identify other genes encoding proteins that regulate ENaC function, extragenic unc-8 suppressor and enhancer mutations were sought. This report describes two new unc-8 suppressor mutations, sup-42(lb88) X and sup-43(lb141) II, and an enhancer mutation, enu-2(lb140) III. sup-43(lb141) and enu-2(lb140), cause vacuoles within body wall muscle, similar in appearance to those of unc-105(n490) II mutants, consistent with their proposed role in ENaC function. Single and double mutant phenotypes observed in this and previous work suggest that sodium channels in different tissues utilize an overlapping set of gene products: at least six in motorneurons, unc-8, mec-6, and sup-40-43, and at least five in muscle, sup-43, unc-8, enu-2, unc-105, and mec-6.

Animals↗
PubMed1995

Mycobacterial lymphadenitis in children: a prospective study of 105 nontuberculous cases with long-term follow-up.

Cases of nontuberculous mycobacterial lymphadenitis were analyzed in a prospective study spanning 32 years, from 1958 to 1990. The results are based on personal observations and long-term follow-up. There were 105 cases, all of which occurred in children aged 9 1/2 months to 12 years (median age, 2.92 years). The patients were predominantly female, and the cases occurred more often in the winter and spring. The cervical or facial nodes were involved in 96 cases. An abrupt change in the predominant etiologic agent (from Mycobacterium scrofulaceum to Mycobacterium avium complex) was noted in the 1970s. Positive tuberculin skin tests were the rule, and reactivity was long lasting. Complications included a prolonged initial phase of infection (n = 6) and recurrences 3 1/2 months to 7 years later (n = 5). Resection during the early stage of infection produced the most satisfactory healing.

Child↗
PubMed1995

The unc-8 and sup-40 genes regulate ion channel function in Caenorhabditis elegans motorneurons.

Two Caenorhabditis elegans genes, unc-8 and sup-40, have been newly identified, by genetic criteria, as regulating ion channel function in motorneurons. Two dominant unc-8 alleles cause motorneuron swelling similar to that of other neuronal types in dominant mutants of the deg-1 gene family, which is homologous to a mammalian gene family encoding amiloride-sensitive sodium channel subunits. As for previously identified deg-1 family members, unc-8 dominant mutations are recessively suppressed by mutations in the mec-6 gene, which probably encodes a second type of channel component. An unusual dominant mutation, sup-41 (lb125), also co-suppresses unc-8 and deg-1, suggesting the existence of yet another common component of ion channels containing unc-8 or deg-1 subunits. Dominant, transacting, intragenic suppressor mutations have been isolated for both unc-8 and deg-1, consistent with the idea that, like their mammalian homologues, the two gene products function as multimers. The sup-40 (lb130) mutation dominantly suppresses unc-8 motorneuron swelling and produces a novel swelling phenotype in hypodermal nuclei. sup-40 may encode an ion channel component or regulator that can correct the osmotic defect caused by abnormal unc-8 channels.

Alleles↗
PubMed1992

Mycobacterial diseases other than tuberculosis.

The incidence of tuberculosis in the United States declined steadily until 1985, while at the same time, for at least the past 15 years, the frequency of disease attributable to other mycobacteria increased both in actual numbers and in the proportion of the total burden of mycobacterioses. Chronic pulmonary disease, lymphadenitis in children, skin and soft-tissue involvement, and infections of the skeletal system were predominant, and the principal etiologic agents were Mycobacterium avium/Mycobacterium intracellulare complex. Mycobacterium kansasii, Mycobacterium marinum, Mycobacterium fortuitum/Mycobacterium chelonae complex, and Mycobacterium scrofulaceum. Since 1986 disseminated disease has become not only more common, especially in association with opportunistic infections in patients with AIDS, but also attributable in part to the growing population of patients who are immunocompromised because of malignancy, receipt of an organ transplant, and administration of steroids. Treatment of these patients has been difficult because of the frequency of severe underlying conditions and the natural resistance of most of the nontuberculous mycobacteria to the presently available drugs.

Humans↗
PubMed1990

The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans.

The dominant mutation deg-1(u38) results in a toxic gene product that leads to the late-onset degeneration of a small number of neurons in the nematode Caenorhabditis elegans. Both intragenic and extragenic mutations as well as changes in wild-type gene dosage can delay or block the time of onset of the neuronal deaths. The deg-1 gene has been cloned and a partial complementary DNA reveals that the gene encodes a novel protein that may act as a membrane receptor. Because the late-onset loss of specific sets of neurons, often as a result of dominant mutations, is characteristic of several human neurodegenerative diseases, the analysis of the deg-1 gene and its suppressors may provide a means of understanding the mechanisms underlying some of these human diseases.

Age Factors↗
PubMed1990

The behavioral genetics of Caenorhabditis elegans.

Caenorhabditis elegans, a small free-living soil nematode, is an ideal organism for the genetic dissection of simple behaviors. Over 150 genes required for normal behavior have been identified. We review here the neural and genetic pathways underlying four of the best-studied C. elegans behaviors: locomotion, response to gentle touch, egg-laying, and chemotaxis. Mutations affecting these behaviors have identified genes which specify neuronal cell lineage, neuronal cell fate, and the formation of cell matrix cues involved in axonal guidance. Molecular analysis of genes required for normal behavior offers the prospect of characterizing functionally important nervous system proteins, regardless of their abundance or biochemical role.

Animals↗
PubMed1989

Infections due to Lancefield group C streptococci.

Our experience with group C streptococcal infection over the past 15 years demonstrates an important and emerging role for this hemolytic organism as an opportunistic and nosocomial pathogen. Significant risk factors in this predominantly male population included chronic cardiopulmonary disease, diabetes, malignancy, and alcoholism. Bacteremia occurred in 74% of cases seen in our series. Nosocomial acquisition of infection was observed in 26%, and infection was frequently polymicrobial in nature with gram-negative enteric bacilli isolated most commonly along with group C streptococci. We observed a broad spectrum of infections including puerperal sepsis, pleuropulmonary infections, skin and soft-tissue infection, central nervous system infection, endocarditis, urinary tract infection, and pharyngeal infections. Several cases of bacteremia of unknown source were observed in neutropenic patients with underlying leukemia. New syndromes of infection due to group C streptococci observed in our series included intra-abdominal abscess, epidural abscess, and dialysis-associated infection. Response to therapy and outcome was related to the underlying disease. While the literature suggests that patients with group C endocarditis respond better to synergistic penicillin-aminoglycoside regimens, patient numbers are too small to draw definite conclusions. The clinical significance of antibiotic tolerant group C streptococci remains uncertain. In patients with serious group C infections including endocarditis, meningitis, septic arthritis, or bacteremia in neutropenic hosts, we advocate the initial use of cell-wall-acting agents in combination with an aminoglycoside.

Abdomen↗
PubMed1983

Elastin fibers in the sputum of patients with necrotizing pneumonia.

We have observed five patients for whom the presence of fibers of elastin in potassium hydroxide (KOH) preparations of sputum represented the first evidence of necrotizing pulmonary disease. In four cases, the discovery of elastin fibers in sputum provided additional evidence supporting initiation or modification of antibiotic therapy. Necrotizing disease was confirmed in all cases by autopsy or by the development of cavitation on chest x-ray film. Cytochemical staining, electron microscopy, and elastase digestion all suggest that the refractile fibers seen on KOH wet mount of sputum are elastin. The test, first described in 1846, is simple to perform, requires little experience to read, and may be a valuable adjunct to the chest roentgenogram in the diagnosis of pulmonary parenchymal destruction.

Adult↗
PubMed1983

Tyrosine hydroxylase activity decreases with induction of cholinergic properties in cultured sympathetic neurons.

Establishment of transmitter phenotype is an essential step in neuronal development. Studies on rat sympathetic neurons both in vivo and in vitro have provided evidence that mature cholinergic sympathetic neurons arise from previously noradrenergic neurons. Cultured rat superior cervical ganglion neurons can be influenced by their environment to remain noradrenergic, to acquire dual transmitter function, or to become predominantly cholinergic. Several other neuronal traits, such as a variety of surface molecules and released proteins, change simultaneously with levels of catecholamine and acetylcholine production, suggesting that various components of transmitter phenotype are regulated in concert. In this report, tyrosine hydroxylase levels are compared in neurons cultured under noradrenergic, dual function, or cholinergic conditions. Both enzyme activity in cell extracts and immunocytochemical staining were measured. These methods showed significantly less tyrosine hydroxylase enzyme activity and immunoreactive material in cholinergic cultures compared to noradrenergic and dual function cultures. These data support the interpretation that a switch in transmitter status from noradrenergic to cholinergic has occurred. This interpretation contrasts with that of Iacovitti et al. (Iacovitti, L., T. H. Joh, D. H. Park, and R. P. Bunge (1981) J. Neurosci. 1: 685-690), who conducted their experiments under critically different culture conditions.

Adrenergic Fibers↗