Biomedical subjects
Publications and source records attributed to S A Lynch.
We present monozygotic twin boys of a triplet pregnancy with phalangeal abnormalities, deafness, a caudal appendage and the additional features of short stature, cryptorchidism, mental retardation and facial dysmorphism.
We present a mother and daughter with clinical and radiological findings consistent with the diagnosis of campomelic dysplasia. Milder tibial bowing and significant shortening of the phalangeal bones of both hands and feet may distinguish this from the classical autosomal recessive form of the disease.
In this review, we address current progress in various facets of the immune response to cancer, including 1) the molecular identification of tumor antigens implicated in immune recognition, 2) experimental studies of cytokine gene transfer into cancer cells, and 3) adoptive transfer of immune effector cells. These studies provide strategies for the future development of immunotherapy for cancer.
The c-src proto-oncogene encodes a M(r) 60,000 phosphoprotein, pp60c-src, with tyrosine-specific protein kinase activity. We have used an immune complex protein kinase assay for pp60c-src to analyze a spectrum of B-cell neoplasms. pp60c-src activity was elevated in all five hairy cell leukemia specimens and in a number of the large cell and immunoblastic lymphomas; neoplasms representing later stages in B-cell development. pp60c-src activity was low in neoplastic cells which correspond to early and intermediate stages in B-cell development (acute and chronic lymphatic leukemia, lymphoblastic lymphoma, small lymphocytic lymphoma). The enhanced pp60c-src activity was associated with high levels of pp60c-src protein. However, increased expression of c-src was not associated with amplification or gross structural rearrangement of the c-src gene. This preliminary study demonstrates elevated levels of pp60c-src protein and tyrosine protein kinase activity in neoplasms corresponding to the later stages of B-cell ontogeny.
The current status of state mental retardation/developmental disability agency information systems related to day and employment programs for persons with disabilities was described, and data regarding the number and characteristics of persons served in different day-employment programs and the funding sources for these persons were summarized. Suggestions were made regarding data utilization and information systems design.
BACKGROUND: Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions. Selective agents might be safer and more effective. METHODS: We carried out two randomized, double-blind, crossover studies in patients with painful diabetic neuropathy, comparing amitriptyline with the relatively selective blocker of norepinephrine reuptake desipramine in 38 patients, and comparing the selective blocker of serotonin reuptake fluoxetine with placebo in 46 patients. Fifty-seven patients were randomly assigned to a study as well as to the order of treatment, permitting comparison among all three drugs and placebo as the first treatment. The patients rated the degree of pain present each day using verbal descriptors, and they also assessed the extent of pain relief globally at the end of each treatment period. RESULTS: After individual dose titration, the mean daily doses of the drugs were as follows: amitriptyline, 105 mg; desipramine, 111 mg; and fluoxetine, 40 mg. There was moderate or greater relief of pain in 28 of the 38 patients (74 percent) who received amitriptyline, 23 of the 38 patients (61 percent) who received desipramine, 22 of the 46 patients (48 percent) who received fluoxetine, and 19 of the 46 patients (41 percent) who received placebo. The differences in responses between amitriptyline and desipramine and between fluoxetine and placebo were not statistically significant, but both amitriptyline and desipramine were superior to placebo. Amitriptyline and desipramine were as effective in patients who were not depressed as in depressed patients, but fluoxetine was effective only in depressed patients. CONCLUSIONS: Desipramine relieves pain caused by diabetic neuropathy with efficacy similar to that of amitriptyline, offering an alternative for patients unable to tolerate the latter. Blockade of norepinephrine reuptake is likely to mediate the analgesic effect of these antidepressant drugs in diabetic neuropathy. Fluoxetine, which blocks serotonin uptake, is no more effective than placebo for the relief of pain.
Melanoma is a valuable model to study phenotypic traits that are regulated during cell differentiation and malignant transformation. Melanoma cells display extensive phenotypic and antigenic heterogeneity. Studies of this attribute have provided insight into events that take place during normal melanocyte differentiation and give clues to traits that contribute to malignancy. It is possible that the phenotypic and genotypic heterogeneity present among melanoma cells within a single lesion includes a subset of cells with traits that favor tumor progression and metastasis. This review discusses the identification and characterization of antigens expressed by melanoma cells and their potential contribution to melanocyte differentiation and malignant transformation.
Analysis of the cell-surface antigenic phenotypes of normal and malignant renal cells demonstrates that approximately 90% of cultured normal human kidney cells and virtually all renal cell carcinomas (RCC) derive from the proximal tubule (PT) cell of the nephron. In the present study, the v-src oncogene was introduced into cultured normal human PT cells, and the effects of the v-src-encoded protein (pp60v-src) on the biologic and genetic phenotype of these cells were determined. V-src-containing PT cells underwent a series of phenotypic changes characteristic of renal cells in vivo. These included (i) alterations in morphology, (ii) an increase in proliferative capacity, (iii) loss of contact inhibition, (iv) immortalization and (v) tumorigenicity. Moreover, v-src-infected PT cells developed non-random clonal karyo-typic abnormalities which are commonly observed in RCCs, including a deletion of chromosomal region 3p14-21, one of the most frequent deletions observed in human renal tumors. These results indicate that pp60v-src can initiate a complex process leading to the transformation of PT cells. This process includes the induction of genetic instability. Finally, these data provide experimental evidence corroborating cytogenetic and molecular data that a deletion of genes on chromosome 3p is a critical event in the transformation of the human renal cell.
Five generations of a family exhibit a unique autosomal dominant neurologic disorder characterized by the development (usually between 15 and 30 years of age) of ataxia, seizures, choreiform movements, progressive dementia, and death after 15 to 25 years of illness. Neuropathologic findings in two deceased family members revealed remarkably similar findings, including marked neuronal loss of the dentate nucleus, microcalcification of the globus pallidus, neuroaxonal dystrophy of the nucleus gracilis, and demyelination of the centrum semiovale. The clinical and pathologic findings are closely correlated. Ataxia and chorea are related to severe neuronal loss in the dentate nucleus with calcification in the globus pallidus. Dementia occurs with progressive demyelination of the centrum semiovale, and loss of posterior column function occurs with neuroaxonal dystrophy of the nucleus gracilis and nucleus cuneatus.
The expression of the cellular src gene product pp60c-src was examined in an embryonal carcinoma cell line that differentiates in vitro into neuronlike cells after being treated with retinoic acid. Quantitative and qualitative changes in c-src expression accompanied the events associated with neuronal differentiation. The levels of pp60c-src increased 8- to 20-fold during the period when the cells elaborated neuritic processes and expressed neuron-specific proteins. The electrophoretic mobility of pp60c-src induced in these cells was retarded in comparison with that in untreated cells or in treated cells before neurite elaboration. The shift in electrophoretic mobility was due to an alteration in the amino terminal 16,000 daltons of pp60c-src and similar to an alteration of c-src protein found in neural tissues and in pure primary cultures of neuronal cells. These results indicate that expression of pp60c-src induced by retinoic acid in these embryonal carcinoma cells mimics the expression of c-src in developing neurons. Therefore, this embryonal carcinoma cell line provides a model system to investigate the function of the src protein in neuronal differentiation.
Job satisfaction is a key to the retention of quality nurses. To promote staff retention and reduce costs, nursing administrators need current research on job satisfaction of home health nurses. In a study of job satisfaction of 66 home health nurses, research indicates that the most satisfying aspects of home care nursing include autonomy and independence, close nurse-client relationships, work hours, flexibility in scheduling hours, and satisfaction with peers and supervisors. When nursing administrators capitalize on these job satisfiers, staff turnover is reduced and costs are contained.
Ten uninjured subjects (ages 18 to 30 years) had electromyographic testing of the peroneus longus, peroneus brevis, and tibialis anterior muscles in response to inversion moments at two speeds (50 and 200 deg/sec) and two joint angles (neutral and 20 degrees of plantar flexion) using a hydraulically controlled tilt platform. Subjects underwent 10 trials of each type of inversion moment on Day 1 testing, which included both legs. On Day 2, subjects again underwent 10 trials of each type of inversion moment, but only on one leg. Reliability was assessed by comparing left and right leg data within muscle groups for Day 1 testing. Repeatability was assessed by comparing Day 1 with Day 2 data. The latency measurements (the time between the beginning of the inversion moment and the onset of first motor response) for the peroneus brevis and tibialis anterior muscles were found to be reliable and repeatable with no significant differences between the same muscle groups. The peroneus longus muscle had a significant difference between legs but was found to be highly repeatable. Speed of inversion moment and plantar flexion angle both caused significant changes in latency response of the peroneus muscles, with increased speed producing a shorter latency response and increased angle causing a longer latency response. Our results indicate a loss of protective reflexes with increasing plantar flexion.
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