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Biomedical subjects

S Bell

Publications and source records attributed to S Bell.

At least 19 recordsLinked to original sources

DLA-DRB1 polymorphisms in dogs defined by sequence-specific oligonucleotide probes (SSOP).

To date, DNA sequences for 29 dog DLA-DRB1 alleles have been reported. However, no data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether there is interbreed variation of allele distribution. We have addressed this by establishing a molecular based sequence-specific oligonucleotide probing (SSOP) method to identify all of the known broad DRB1 types and we have used this to type a random panel of dogs. A series of oligonucleotide probes were designed to detect known polymorphisms in the three DRB1 hypervariable regions, together with two distinctive motifs in other regions of exon 2. This set of probes enabled us to assign broad DRB1 types. Two hundred and eighteen dogs were SSOP typed for DRB1. All but 4 of the published DLA-DRB1 alleles were identified in these animals. Interbreed variation in both allele distributions and allele frequencies were observed, which may be useful in the study of genetic variation between breeds. This variation also has implications for the selection of control groups for studies aimed at identifying MHC associations with disease susceptibility in the dog.

Animals

Effect of beta-glucan from oats and yeast on serum lipids.

Heart disease is the leading cause of death in the U.S. One way to reduce the risk of developing the disease is to lower serum cholesterol levels by making dietary changes. In addition to reducing intake of total fat, saturated fat, and dietary cholesterol, serum cholesterol can be further reduced by added fiber, especially from sources rich in beta-glucan. In this review, two sources of beta-glucan are described; one source is oats and the other yeast. Their chemical structures and physical properties are compared, and their effect on serum lipid levels is described. Oat beta-glucans are found in various breakfast cereals and snacks. Usually, several servings of these products are required to meet the Food and Drug Administration's claim of reducing the risk of heart disease. The yeast-derived fiber is a more concentrated source of beta-glucan than the oat product. It is currently being tested in a wide variety of food products.

Avena

Blood-brain barrier disruption for the treatment of malignant brain tumors: The National Program.

Chemotherapy delivery for the treatment of malignant brain tumors is markedly enhanced when given in conjunction with osmotic opening of the blood-brain barrier. Osmotic opening or disruption of the blood-brain barrier is achieved while the patient is under general anesthesia, by the infusion of mannitol into the internal carotid or vertebral artery circulation. The mannitol infusion is followed by administration of intraarterial chemotherapy. A National Blood-Brain Barrier Program now exists and includes six universities. Within the National Program over 4200 blood-brain barrier disruption procedures have been performed in over 400 patients. Patients with primary central nervous system (CNS) lymphoma, glioma, primitive neuroectodermal tumor (PNET), germ cell and metastatic cancer are eligible for treatment. Results in patients with primary CNS lymphoma, recently reported in the Cancer Journal, include the first example of a durable response in a primary brain tumor without loss of cognitive function and without use of radiotherapy. Results with PNET and germ cell tumors are also very encouraging. Advanced practice nurses coordinate the care of blood-brain barrier disruption patients. Care includes patients selection, education, close neurological observation, maintenance of fluid and electrolyte balance and managing effects of high-dose chemotherapy. Both acute and long-term medical and psychological follow-up are an essential component of the program, as well as patient and family support.

Antineoplastic Agents

Systemic scleroderma. Multicenter trial of 1 year of treatment with recombinant interferon gamma.

OBJECTIVE: To confirm significant improvement of the skin score in systemic sclerosis by treatment with interferon gamma in a larger group of patients and to investigate on a molecular level the influence of interferon gamma on collagen type I messenger RNA expression. DESIGN: Open, noncontrolled multicenter study. SETTING: Five outpatient clinics specializing in the care of systemic scleroderma. PATIENTS: Thirty-two patients suffering from the diffuse or limited form of systemic sclerosis and progressive disease were recruited; 20 patients finished the study. INTERVENTION: Each patient received interferon gamma, 50 micrograms subcutaneously 3 times a week for 1 year. MAIN OUTCOME MEASURE: Skin score, collagen type I messenger RNA in skin biopsy specimens. RESULTS: The patients who completed the study showed an unchanged median skin score after 1 year of therapy. In addition, similar collagen type I messenger RNA levels were detected in skin biopsy specimens taken from involved skin before and after therapy in these patients. CONCLUSIONS: Treatment of systemic scleroderma with interferon gamma is associated with stabilization of the skin score and lack of worsening of visceral involvement.

Female

The effects of extending cognitive-behavioral therapy for binge eating disorder among initial treatment nonresponders.

OBJECTIVE: The study was designed with the aim of determining whether extending group cognitive-behavioral therapy (CBT) would enhance outcome among individuals with binge eating disorder (BED) who failed to stop binge eating after an initial 12-week CBT intervention. METHOD: Forty-six participants who met diagnostic criteria for BED were randomly allocated to either a 12-week group CBT intervention or a waiting list control condition. At the end of 12 weeks, treated participants who met clinical criteria for improvement subsequently received 12 sessions of behavioral weight loss. Remaining participants received 12 additional sessions of CBT for binge eating. RESULTS: Fifty percent of treated participants improved with the initial 12-week course of CBT. There was a strong trend for the extension of CBT to affect improvement in binge eating among initial nonresponders (6 of 14 subjects no longer met diagnostic criteria for BED). Overall, extending CBT led to clinical improvement in 66.7% of all treated participants, with treatment gains occurring through session 20. DISCUSSION: The results suggest that an extended course of CBT (i.e., longer than 12 weeks) will likely maximize the number of potential responders to treatment.

Adult

Altered expression of troponin T isoforms in mild left ventricular hypertrophy in the rabbit.

Alterations in troponin T (TnT) isoforms have been reported in severe human and experimental heart failure (HF), and may play a role in the depressed myofibrillar ATPase activity observed in this condition. It is unclear whether these alterations reflect very severe hemodynamic derangement or are a component of mild hypertrophic stress. Therefore, we studied the expression of TnT isoforms (SDS-PAGE, Western blots), myosin isoforms, myofibrillar ATPase activity, and left ventricular (LV) mechanoenergetics (rbc perfused, isovolumically contracting isolated heart) in a rabbit model of mild hypertrophy (LVH) due to gradual hypertension caused by 12 weeks of cellophane wrap of the kidneys (n=12). LV/body weight ratio increased by 28% in LVH compared to shams (P<0.001); no animals had evidence of HF. In LVH, the percentage of TnT2 was modestly but significantly increased compared to shams [6.2+/-1.9 (+/-S.D. ) v 3.7+/-1.0%, P<0.05], mainly as a consequence of a parallel decrease in TnT4 (P=0.07). Sham hearts ranged from 75-100% V3 isomyosin, whereas all LVH hearts had 100% of the V3 form. There were no significant differences in myofibrillar ATPase activity or mechanical variables, including contraction and relaxation rates. The slope of the VO2-pressure-volume-area relation (a measure of the energy conversion efficiency of the contractile machinery) was also unchanged. We conclude that in the rabbit, shifts in TnT isoforms toward a more "fetal" pattern occur during mild LVH and, therefore, are likely to be a general feature of the response to hemodynamic stress, rather than a phenomenon confined to end-stage disease. These modest shifts are not associated with major alterations in LV myofibrillar ATPase activity or mechanoenergetics.

Adenosine Triphosphatases

Double-blind, placebo-controlled study of intralesional interferon gamma for the treatment of localized scleroderma.

BACKGROUND: Localized scleroderma is characterized by circumscribed fibrotic plaques and may progress to widespread skin involvement and fibrosis. Interferon gamma (IFN-gamma) has been shown to be a potent inhibitor of collagen synthesis and of the migration and proliferation of dermal fibroblasts. OBJECTIVE: Our purpose was to determine whether IFN-gamma is effective in the treatment of localized scleroderma. METHODS: A double-blind, randomized, placebo-controlled, multicenter study was conducted. Twenty-four patients with progressive lesions received 100 micrograms of IFN-gamma or placebo subcutaneously on 5 consecutive days for 2 weeks followed by 100 micrograms of IFN-gamma or placebo once weekly for 4 weeks. Thereafter patients were observed for 18 weeks. To determine whether improvement could be related to an altered level of collagen messenger RNA (mRNA), biopsy specimens were taken from uninvolved and involved skin before and after therapy. RESULTS: The patients treated with IFN-gamma or placebo showed no significant difference in size or fibrosis of lesions or collagen type I mRNA synthesis. However, a reduction in the number of new lesions was observed in the IFN-gamma-treated group. The biopsy specimens obtained from involved skin showed a moderate increase of type I collagen and a significant decrease in the small proteoglycan decorin mRNA levels. CONCLUSIONS: The results indicate that IFN-gamma is ineffective in the treatment of localized scleroderma, but may inhibit the development of new lesions.

Collagen

S. cerevisiae and sulfur: a unique way to deal with the environment.

Saccharomyces cerevisiae is by far the best-studied unicellular eukaryote. Although yeast cells are very similar to higher eukaryotes in many respects, there is striking evidence that S. cerevisiae is not a perfect model for a eukaryotic cell (cf. 1). Here we report that yeast proteins contain a significantly lower amount of cysteine residues compared to other eukaryotes. Explanations for this phenomenon could not be found in the sulfur metabolism of yeast, which showed no major differences from other organisms (2-4). However, previous examinations could link a defect in sulfate uptake of S. cerevisiae to an increased resistance against toxic substances like selenate and chromate in the environment, which share the same permeases (5-7). This environmental problem might have caused S. cerevisiae to down-regulate its sulfate uptake and therefore lead to a lower amount of available sulfur in the cell, making it necessary to replace all dispensable sulfur amino acids in proteins. We show in two examples that S. cerevisiae proteins contain only such cysteine residues that are structurally or functionally needed. Therefore, we conclude that S. cerevisiae has solved a widespread environmental problem in a specific way which might be unique among eukaryotes.

Base Sequence

Site-directed and linker insertion mutagenesis of herpes simplex virus type 1 glycoprotein H.

The gH-gL complex of herpes simplex virus type 1 (HSV-1) is essential for virion infectivity and virus-induced cell fusion, but functional domains of the gH molecule remain to be defined. We have addressed this question by mutagenesis. A set of linker insertion mutants in HSV-1 gH was generated and tested in transient assays for their ability to complement a gH-negative virus. Insertions at three sites in the C-terminal third of the external domain affected the ability of gH to function in cell-cell fusion and virus entry, while insertions at six sites in the N-terminal half of the external domain induced conformational changes in gH such that it was not recognized by monoclonal antibody LP11, although expression at the cell surface was unchanged. A recombinant virus in which a potential integrin-binding motif, RGD, in gH was changed to the triplet RGE entered cells as efficiently as the wild type, indicating that HSV-1 entry is not mediated by means of the gH-RGD motif binding to cell surface integrins. Furthermore, mutagenesis of the glycosylation site which is positionally conserved in all herpesvirus gH sequences in close proximity to the transmembrane domain generated a recombinant virus that grew in vitro with wild-type single-step kinetics.

Animals

Prevention of hepatitis A and B.

The vaccine preventable hepatitides, hepatitis A and hepatitis B, cause a great burden of illness in both developing and industrialized nations. There is increased community awareness of the problems of viral hepatitis, and it is important for general practitioners to be aware of current recommendations for prevention of hepatitis A and B.

Adolescent

An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes.

Homologous recombination in embryonal stem cells has been used to produce a fusion oncogene, thereby mimicking chromosomal translocations that frequently result in formation of tumor-specific fusion oncogenes in human malignancies. AF9 sequences were fused into the mouse Mll gene so that expression of the Mll-AF9 fusion gene occurred from endogenous Mll transcription control elements, as in t(9;11) found in human leukemias. Chimeric mice carrying the fusion gene developed tumors, which were restricted to acute myeloid leukemias despite the widespread activity of the Mll promoter. Onset of perceptible disease was preceded by expansion of ES cell derivatives in peripheral blood. This novel use of homologous recombination formally proves that chromosomal translocations contribute to malignancy and provides a general strategy to create fusion oncogenes for studying their role in tumorigenesis.

Acute Disease

Neonatal osteofibrous dysplasia: report of two cases.

Skeletal neoplasms of the newborn and neonatal period are infrequently encountered and often misdiagnosed. Osteofibrous dysplasia is a tumor of childhood that may be seen in the newborn. Because of its unique natural history, with and without surgical treatment, and the similarity in radiographic appearance of this tumor to other lesions, a high index of suspicion must be maintained when a tibial lesion is encountered in the newborn. We present two additional cases of neonatal osteofibrous dysplasia and discuss the differential diagnostic considerations.

Diagnosis, Differential

Improving outpatient clinic staffing and scheduling with computer simulation.

Patient flow in an appointment-based, outpatient internal medicine clinic involving multiple, sequential providers-registrar, triage nurse, physician, and discharger-was studied using computer simulation. Provider task time distributions were obtained through a time-motion study and then input into the computer program, which simulated the clinic situation well. Time interval and sensitivity analyses yielded insights into staffing levels, appointment times, and clinic dynamics. A bottleneck provider was shown, and patient time in the clinic was related to the time of appointment and was slowed by having too many doctors in the clinic. Subsequent operational changes significantly decreased the average observed patient total time in clinic from 75.4 (SD 34.2) minutes to 57.1 (SD 30.2) minutes (p < .001, t test).

Appointments and Schedules