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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 307 records · Page 17Linked to original sources
PubMed1986

Fate of influenza A virion proteins after entry into subcellular fractions of LLC cells and the effect of amantadine.

Influenza A virus entry into the host cell was studied by monitoring the fate of virion proteins in subcellular fractions of LLC-RMK2 cells under conditions of low multiplicity of infection in the absence of drugs. Adsorption but not entry could be demonstrated at 4 degrees. Restricted entry into a prelysosomal pool could be demonstrated at 20 degrees. At 37 degrees proteins entered the cell in the same relative distribution as present in virions arguing against the fusion hypothesis and for the endocytosis hypothesis. The hemagglutinin and matrix proteins were readily degraded intracellularly at 37 degrees, but the nucleoprotein was relatively resistant to degradation, also consistent with the latter hypothesis. Amantadine blocked neither entry into the host cell nor transfer between the prelysosomal and lysosomal compartments; however, it appeared to block exit from the prelysosomal and lysosomal pools. The addition of the drug reduced degradation of the matrix protein in these pools but not of the hemagglutinin, consistent with inhibition by amantadine of fusion of virion envelope and vesicle membrane.

Adsorption↗
PubMed1986

Teratoma following cisplatin-based combination chemotherapy for nonseminomatous germ cell tumors: a clinicopathological correlation.

From April 1975 through May 1981, 51 patients had teratoma resected from residual disease following cisplatin-based combination chemotherapy. All patients had normal serum markers before resection of abdominal (25), lung (12), mediastinal (5), thoracoabdominal (8) or other (1) disease. Teratoma was classified as mature in 29 cases, immature in 15 or immature with nongerm cell elements in 7. Of the 51 patients 31 (61 per cent) remain free of recurrent disease, while 20 either had recurrent carcinoma (10) or teratoma (10) requiring further therapy. Nine patients died, including 1 in whom angiosarcoma developed, which was thought to be secondary to previous radiation therapy. In 4 patients the initial relapse of carcinoma developed beyond 2 years after resection. Univariate factors predicting for relapse include tumor burden, immature teratoma with nongerm cell elements and site (mediastinum), while only immature teratoma with nongerm cell elements and site predicted for survival. Patients with immature teratoma had a comparable relapse-free and over-all survival as those with mature teratoma. Using a multivariate analysis, primary tumor site at the mediastinum was the most significant adverse factor predictive for relapse and survival. This study appears to support the various pre-clinical models that demonstrate multipotential capabilities of teratoma. Complete surgical excision of teratoma remains the most effective treatment with continued close followup recommended for high risk patients (immature teratoma with nongerm cell elements, large tumor burden and primary mediastinal tumors) with resected teratoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Left ventricular filling in hypertrophic cardiomyopathy: a pulsed Doppler echocardiographic study.

Abnormal left ventricular diastolic properties have been described in patients with hypertrophic cardiomyopathy. To evaluate the diastolic filling characteristics of the left ventricle in patients with this disease, pulsed Doppler echocardiography was used to study mitral flow velocity in 17 patients with hypertrophic cardiomyopathy (11 with and 6 without systolic anterior motion of the mitral valve) and 16 age-matched normal subjects. There were no statistically significant differences between patients with hypertrophic cardiomyopathy with and without systolic anterior motion with regard to ventricular septal thickness, left ventricular posterior wall thickness, left ventricular internal dimensions or the extent of hypertrophy evaluated by two-dimensional echocardiography. Mitral regurgitation was detected by Doppler echocardiography in all 11 patients with and in 2 (33%) of the 6 patients without systolic anterior motion of the mitral valve. Early and late diastolic peak flow velocity, the ratio of late to early diastolic peak flow velocity and deceleration of early diastolic flow were measured from Doppler mitral flow velocity recordings. There were no statistically significant differences in these four indexes between the patients with systolic anterior motion and normal subjects. In contrast, the patients with hypertrophic cardiomyopathy without systolic anterior motion showed lower early diastolic peak flow velocity, higher ratio of late to early diastolic peak flow velocity and lower deceleration of early diastolic flow compared with the patients with systolic anterior motion and normal subjects, suggesting impaired left ventricular diastolic filling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Variable expression of the translocated c-abl oncogene in Philadelphia-chromosome-positive B-lymphoid cell lines from chronic myelogenous leukemia patients.

The consistent cytogenetic translocation of chronic myelogenous leukemia (the Philadelphia chromosome, Ph1) has been observed in cells of multiple hematopoietic lineages. This translocation creates a chimeric gene composed of breakpoint-cluster-region (bcr) sequences from chromosome 22 fused to a portion of the abl oncogene on chromosome 9. The resulting gene product (P210c-abl) resembles the transforming protein of the Abelson murine leukemia virus in its structure and tyrosine kinase activity. P210c-abl is expressed in Ph1-positive cell lines of myeloid lineage and in clinical specimens with myeloid predominance. We show here that Epstein-Barr virus-transformed B-lymphocyte lines that retain Ph1 can express P210c-abl. The level of expression in these B-cell lines is generally lower and more variable than that observed for myeloid lines. Protein expression is not related to amplification of the abl gene but to variation in the level of bcr-abl mRNA produced from a single Ph1 template.

B-Lymphocytes↗
PubMed1986

Comparison of visual and photometric Bac-T-Screen results.

The Bac-T-Screen (Marion Laboratories, Kansas City, MO) was used to screen 826 urine specimens. Of these, 85 either pigmented or clogged the Bac-T-Screen filter and could not be evaluated. Results for the remaining 741 specimens were examined both visually and photometrically by a newly developed photometric card reader. The results were then compared. Screening results for all urines containing greater than or equal to 10(5) pathogens/mL were equivalent for both methods, with sensitivity and predictive negative values of greater than 98% and greater than 99%, respectively. The predictive values of positive tests were also equivalent at 57.5% for visual and 59.6% by photometry. The overall agreement varied with the card reader value used because the photometric card-reader procedure allows the user to select desired sensitivity and specificity levels.

Bacteriological Techniques↗
PubMed1986

Monoclonal antibodies specific for v-abl- and c-abl-encoded molecules.

Monoclonal antibodies specific for regions of the transforming protein of Abelson murine leukemia virus were prepared. Antibodies directed against the kinase domain inhibited the autophosphorylation of v-abl proteins, and all of the antibodies reacted with the products of the murine and human c-abl loci.

Abelson murine leukemia virus↗
PubMed1986

T cell-derived migration-inhibitory factor and colony-stimulating factor share common structural elements.

Migration-inhibitory factor (MIF) is a lymphokine that acts to localize mononuclear phagocytes (monocytes and macrophages) and perhaps to activate them. Mo cells are a human T cell leukemia virus II-infected T cell line previously shown to secrete large quantities of MIF upon stimulation with phytohemagglutinin and phorbol myristate acetate. MIF was purified from Mo cell-conditioned medium by gel filtration, phenyl-Sepharose affinity chromatography, isoelectrofocusing, and reverse-phase high-performance liquid chromatography (RP-HPLC). Overall purification was 6,000-fold. The purified MIF fraction was found to display potent colony-stimulating factor (CSF) activity when assayed on human bone marrow cells. The double peak of MIF activity as shown by C 18-RP-HPLC coincided with the double peak of CSF activity. A monoclonal antibody selected for its anti-MIF activity absorbed both the CSF and the MIF activity. These findings indicate that MIF and CSF are either identical molecules or closely related molecules with common structural elements.

Cell Line↗
PubMed1986

Resection of thoracic and abdominal teratoma in patients after cisplatin-based chemotherapy for germ cell tumor. Late results.

Fifty-one patients with primary testicular (N = 46) or mediastinal germ cell cancer (N = 5) were treated from April, 1975, through May, 1981, and had teratoma resected from residual disease after cisplatin-based combination chemotherapy. All patients had normal serum markers before resection of pulmonary (N = 12), mediastinal (N = 5), thoracoabdominal (N = 8), supraclavicular (N = 1) or abdominal disease (N = 25). Teratoma was classified as mature teratoma (N = 29), immature teratoma (N = 15), or immature teratoma with non-germ cell elements (N = 7). Thirty of 51 (60%) patients remain free of recurrent disease, whereas 20 patients have either recurrent carcinoma (N = 10) or teratoma (N = 10). One patient has a presumed second malignancy. After additional chemotherapy, four patients with recurrent carcinoma are alive and disease free and six have died. After an additional operation, eight of 10 patients with recurrent teratoma are long-term survivors. In four patients the initial relapse of carcinoma developed more than 2 years after therapy; in an additional patient carcinoma recurred after a 32 month disease-free survival period. Univariate factors predicting for relapse include tumor burden, immature teratoma with non-germ cell elements, and site (mediastinum), whereas only immature teratoma with non-germ cell elements and site predicted for survival. Immature teratoma and mature teratoma had similar relapse-free intervals and overall survival intervals. According to a multivariate analysis, primary tumor site at the mediastinum is the most significant adverse factor predictive for both relapse and survival (two of five patients survived). This study appears to support the various preclinical models that demonstrate multipotential capabilities of teratoma. Complete surgical excision of teratoma remains the most effective treatment with continued close follow-up recommended for high-risk patients (immature teratoma with non-germ cell elements, large tumor burden, or primary mediastinal tumors.

Abdominal Neoplasms↗
PubMed1986

Stability of the maxilla after Le Fort III advancement in craniosynostosis syndromes.

The purpose of this study was to assess long-term position of the maxilla after surgical Le Fort III advancement of midfacial structures in patients with craniosynostosis syndromes. Data from preoperative, short and long-term postoperative lateral head films on 21 consecutive patients with Crouzon's syndrome, Pfeiffer's syndrome, or Apert's syndrome were analyzed. A method of evaluating the position of the postoperative maxilla on lateral head films is described. On average, the position of the maxilla did not change significantly in the postoperative periods studied, although some individual variation was demonstrated. Postoperative management, utilizing a registration bite splint after the intermaxillary fixation has been removed, similar to our treatment following bone grafting procedures in patients with hemifacial microsomia, is described.

Acrocephalosyndactylia↗
PubMed1986

Effects of recombinant GM-CSF on the blast cells of acute myeloblastic leukemia.

The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) were compared to those of media conditioned by the continuous bladder carcinoma line, HTB9 (HTB9-CM), using three criteria. First, both GM-CSF and HTB9-CM stimulated blast colony formation in methylcellulose cultures, patient-to-patient variations were seen in the dose-response curves, and GM-CSF was effective, but less so that HTB9-CM. Second, GM-CSF also enhanced growth of blast progenitors in suspension culture, indicating its capacity to support self-renewal. GM-CSF was as effective as HTB9-CM in the production of adherent cells during the growth of blast cells in suspension, a finding that is interpreted to mean that GM-CSF also supports postdeterministic events in blast differentiation. Finally, colonies growing in the presence of GM-CSF were not phenotypically different than those stimulated by HTB9-CM.

Cells, Cultured↗
PubMed1985

Structure of covalent insulin-receptor complexes (I-S-S-R) in isolated rat adipocytes and human placental membranes.

The structure of naturally-formed covalent disulphide-linked complexes between insulin and its receptor was examined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. To prevent destabilization of disulphide bonds at alkaline pH the standard discontinuous electrophoresis conditions were changed to a continuous buffer system at pH 7.0. 125I-insulin was first bound to either rat adipocytes or human placental membranes for 10 min at 37 degrees C. After washing, non-dissociable radioactivity was extracted from cells or membranes in Triton X-100 and immunoprecipitated with an antiserum (B-2) to the insulin receptor. Electrophoresis of the immune precipitate revealed the two smaller of the three reported species of native insulin receptor (Mr values approx. 350 000, 290 000 and 260 000); in addition, a species of Mr 200 000 was also frequently observed in adipocytes. When non-dissociable 125I-insulin was chemically crosslinked to adipocytes or placental membranes, prior to solubilization and immunoprecipitation, all three species of the native receptor were labelled; after reduction, only a single species of Mr 130000 was observed. These findings indicate that disulphide exchange of insulin occurs with the Mr 130000 (alpha) binding subunit within partially reduced species of the native, oligomeric receptor. The degree of disulphide binding of insulin could therefore depend on the relative abundance of partially reduced receptor species and on the redox state of the cell membrane.

Adipose Tissue↗
PubMed1985

Clinical characteristics of fibrositis. II. A "blinded," controlled study using standard psychological tests.

Twenty-two patients with fibrositis and 22 control patients selected from a general medical outpatient population were given 3 standardized psychological questionnaires: the Beck Depression Inventory, the Spielberger State and Trait Anxiety Inventory, and the SCL-90-R. There were no statistically significant differences between fibrositis patients and control patients on any of these tests, a finding at variance with a commonly held belief that patients with fibrositis have an underlying psychological disorder. While psychological factors may be important in some patients with fibrositis, these results indicate that the presence of a psychopathologic condition is not mandatory for the persistence of fibrositis.

Adult↗
PubMed1985

Insulin resistance, acanthosis nigricans, and polycystic ovaries associated with a circulating inhibitor of postbinding insulin action.

A 21-yr-old moderately obese woman with hirsutism, acanthosis nigricans, and oligomenorrhoea was diagnosed as having polycystic ovary syndrome. Despite hyperinsulinemia, binding of insulin to her red cells was within the range for normal, young adult subjects. Her serum did not bind or degrade [125I]insulin or alter its binding to fat cells, and was negative for insulin receptor antibodies. However, her serum caused a dose-dependent inhibition of insulin-stimulated lipogenesis (conversion of [3-3H]glucose to [3H]lipid) in rat fat cells significantly greater than that produced with control serum (relative potency, 3.5:1) and (at a 1:20 dilution) markedly impaired the response of both lipogenesis and 2-deoxy-D-glucose uptake to maximum concentrations of insulin. After the patient was treated with clomiphene for 4 months, her menses resumed, hair growth slowed, fasting blood glucose and plasma insulin concentrations decreased, and serum inhibitory activity decreased to the control range. Serum inhibitory activity was stable to freezing and thawing and to heating at 56 C for 30 min, and could be extracted into acid-ethanol. By dialysis, its mol wt was below 1000, whereas by ultracentrifugation, it was above 3500; both high and low mol wt forms were detected after Sephadex G-50 gel chromatography of serum, suggesting that the inhibitor was of low mol wt but loosely bound to a higher mol wt component in serum. These findings indicate that insulin resistance in this patient with acanthosis nigricans and polycystic ovaries could be attributed to a circulating low mol wt inhibitor of postbinding insulin action.

Acanthosis Nigricans↗
PubMed1985

Interaction of alpha 1 with alpha 2 region in class I MHC proteins contributes determinants recognized by antibodies and cytotoxic T cells.

The structure-function relationship of individual coding regions of class I mouse major histocompatibility complex proteins was studied by a combination of recombinant DNA, gene transfer techniques, and serologic and functional characterization. To examine the role of alpha 1 and alpha 2 regions in antibody and CTL recognition, the third exon of H-2Dd, Kd, and Ld transplantation antigen genes was replaced by the homologous coding region of the Qa-2-coded class I gene, Q6. We have chosen to carry out the exon shuffling experiments between these two different types of class I genes, because they are structurally similar and did not evolve to carry out identical functions. Therefore, it is less likely that the hybrid proteins will fortuitously recreate alpha 1-alpha 2 controlled functionally important determinants. The replacement of H-2 alpha 2 coding region with its Q6 counterpart had different effects on the expression of the three genes. The mutant H-2Dd gene transfected into L cells was expressed at high levels and retained several of the serologic determinants found on parental H-2Dd and Q6 domains. The serologic epitopes on the mutant H-2Kd-transfected cells were detectable at very low levels, whereas the product of the mutant H-2Ld gene could not be identified at all. Analysis of cells transfected with mutant H-2Dd gene with alloreactive and minor antigen(s)-restricted cytotoxic T cells indicated that the hybrid proteins lost the ability to be recognized by T cells. Our data suggest that cytotoxic T cells recognize conformational determinants composed of amino acids from alpha 1 and alpha 2 regions. Alternatively, it could be proposed that T cell recognition sites located in a single alpha 1 or alpha 2 protein region are susceptible to distortion upon alpha 1-alpha 2 interactions. Such susceptibility to conformational changes of the amino-terminal domain of transplantation antigens could be of functional importance for H-2-restricted antigen presentation.

Animals↗
PubMed1985

A nursing diagnosis approach to the patient awaiting cardiac transplantation.

The most common reason to perform cardiac transplantation is dilated cardiomyopathy. Alterations in cardiac output secondary to decreased contractility and increased preload and afterload will, over time, lead to progressive deterioration of the patient with this type of end-stage cardiac disease. Heart transplantation is now an accepted therapy for these patients. This article focused on the patient in the period awaiting cardiac transplantation. Five pertinent nursing diagnoses were identified and discussed. A case study approach was utilized to highlight patient problems and nursing interventions.

Adaptation, Psychological↗
PubMed1985

A double blind crossover trial of prednisone versus placebo in the treatment of fibrositis.

Twenty patients with a diagnosis of fibrositis were entered into a double blinded crossover study to compare the effects of prednisone versus placebo. Each patient was randomly assigned to either prednisone 15 mg/day or placebo for 14 days of therapy and then therapy was switched for a further 14 days. The following measurements were assessed at baseline, end of Week 2 and end of Week 4: analogue scores for pain, sleep disturbance, morning stiffness and fatiguability, and dolorimetry readings of pain tolerance over 14 representative tender points. Overall there was no improvement while taking prednisone, indeed most measured variables showed a trend towards deterioration with this therapy.

Adult↗