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Biomedical subjects

R Pugh

Publications and source records attributed to R Pugh.

At least 37 records · Page 2Linked to original sources
PubMed1988

Structural and immunochemical aspects of Brucella abortus endotoxins.

Smooth lipopolysaccharide (sLPS) of Brucella abortus, which is the most immunodominant component among the antigens of B. abortus isolated, has been used for diagnosis for decades. High yields of sLPS can be prepared by a modification of the procedures of Moreno et al. (J. Bacteriol. 138:361-369, 1979). Washed B. abortus cells can be disrupted by 21 freeze-quick thaw cycles and ultrasonication to separate non-membrane-bound material; then phenol extraction is performed 3 times and the phenol fraction is washed with H2O intensively. The membrane-bound sLPS can be fractionated into 3 to 5 groups according to the extent of dialysis and centrifugation. These membrane bound sLPS fractions show marked individual differences in their precipitin profile and chemical composition. Their protein content varies from 16% to 42% as determined by dye binding test and 17 to 60% by Lowry phenol method using bovine serum albumin as the standard, which indicates that these proteins associated with LPS may play important roles in the immunochemical interactions, solubility, and the heterogeneity of B. abortus lipopolysaccharides. Compared to previously published methods, a higher yield of sLPS, ranging from 3.6% to 7.7% of dried bacteria, is obtained. Group f5A, which has a standard bell shaped curve in the precipitin assay, is one of the major fractions in all three strains (1119.3, 19, 2308). The protein free sLPS (less than 1% of Lowry reactive component) can be prepared by pronase digestion. The immunochemical reactivity remains about the same before and after this treatment. The O-chains of the major fraction (f5A) of B. abortus (Strains 2308 and 19) membrane bound smooth lipopolysaccharide (sLPS) are obtained by hydrolysis of f5A native sLPS in 1% acetic acid at 100 degrees C for 2 hours. After hydrolysis, the O-chains are separated from the lipid A protein complex by centrifugation, and from small fragments by ultrafiltration of a molecular weight cut-off (MWCO) of 1.0 x 10(3). These carbohydrate haptens can be identified by precipitin-inhibition assay and further fractionated by both membrane filtration and dialysis. The size distributions of carbohydrate haptens of the endotoxins (f5A) ranged from several oligosaccharides up to 1.0 x 10(4) MWCO. Three major fractions of MWCO 8.0-10.0 x 10(3), 3.5-5.0 x 10(3), and less than 1.0 x 10(3) for both strains 2308 and 19 contain more than 85% of the total immunreactive materials.(ABSTRACT TRUNCATED AT 400 WORDS)

Brucella abortus↗
PubMed1987

Short-term chemotherapy of poor-prognosis metastatic breast cancer with three non-cross resistant chemotherapy regimens. A Southwest Oncology Group Study.

A Southwest Oncology Group pilot study was designed to evaluate a brief, 4.5-month induction course of chemotherapy with three presumably non-cross resistant regimens in poor-prognosis metastatic breast cancer. Sixty-three patients were treated with doxorubicin, cyclophosphamide, plus vincristine on day 1, methotrexate followed 30 minutes later by 5-fluorouracil (5-FU) on day 22, and mitomycin C plus 3 days of vinblastine on day 43. All three sequential regimens were repeated once and therapy was then discontinued in responding patients. The same chemotherapy was reinstituted at the time of relapse. The overall response rate to the induction chemotherapy was 35% and included only one complete response (2%). Median response duration was 9 months. Respondents were off all therapy for a median of 5 months (range, 1-12+ months) and were followed without evidence of progressive disease. Response to retreatment was 30% with no complete responses seen. Overall median survival from the data of diagnosis of metastatic disease was 24 months, with a median survival of 14 months from the date of initiation of therapy. Toxicity for this induction regimen was moderate with two treatment-related deaths secondary to myelosuppression. While the results of this pilot study fail to support the use of non-cross resistant regimens in breast cancer, short-term therapy appears to have no adverse effect on survival and resulted in significant periods during which no therapy was given, resulting in a reduction in overall toxicity.

Adult↗
PubMed1987

Immunochemical and partial chemical characterization of fractions of membrane-bound smooth lipopolysaccharide-protein complex from Brucella abortus.

Smooth lipopolysaccharide (sLPS) of Brucella abortus was prepared and fractionated by a modification of the procedures of Moreno et al. (J. Bac. 138:361-369, 1979). Washed B. abortus cells were disrupted by 21 freeze-quick thaw cycles with ultrasonication to separate the non-membrane-bound material. Ultrasonicated bacteria were used for preparation of membrane-bound sLPS (approximately f5, the main crude sLPS fraction described by Moreno et al.). Phenol extraction was repeated 3 times and then washed with H2O 10 times to remove most of the chromogen, polysaccharides and nucleic acids, eliminating the need for enzyme treatment as described previously. The membrane-bound sLPS was fractionated into 3 to 5 groups according to the extent of dialysis and centrifugation, these fractions required only 80 ng for positive ELISA, about 0.2 ng for positive Limulus lysate tests, and reacted well with precipitating antibodies in the serum from a strain 2308 infected cow. They had marked differences in precipitin curves and chemical composition. The protein content varied from 16% to 42% as determined by dye binding test and 17 to 60% by Lowry phenol method using bovine serum albumin as the standard, which implies that the proteins associated with LPS may also play important roles in the complex for the immunochemical interactions and the heterogeneity of B. abortus lipopolysaccharide protein complex. As compared with previous reports, a higher yield of sLPS, ranging from 3.6% to 7.7% of dried bacteria, was obtained. Group f5A, which had a standard bell shaped curve in the precipitin assay, is one of the major fractions in all three strains (1119.3, 19 and 2308). The amount of other subfractions obtained varied with batches or strains of B. abortus. These results provide a new profile of the immunochemical reactivities and the heterogeneity on B. abortus smooth membrane-bound endotoxins.

Antigen-Antibody Complex↗
PubMed1987

Doxorubicin and methotrexate on a weekly schedule in patients with sarcomas.

Fifty-five sarcoma patients with advanced measurable disease were treated with a doxorubicin and methotrexate combination in which both drugs were given on a weekly schedule. Patients received doxorubicin and methotrexate at three prospectively evaluated treatment levels with doxorubicin dosage ranging from 0.5 to 0.725 mg/kg/week and methotrexate dosage ranging from 0.25 to 0.375 mg/kg/week. Objective responses were seen in 11 of 39 (28%) patients receiving the two higher doxorubicin-methotrexate treatment levels where doxorubicin dose was greater than 0.5 mg/kg/week compared to only 2 of 16 (12%) patients receiving lower doxorubicin levels (p less than 0.05), suggestive of a dose-response relationship. Toxicity of this regimen was manageable but stomatitis was appreciable, seen in 30% of patients. These results support the activity of weekly doxorubicin in sarcoma therapy. However, no apparent improvement was associated with addition of conventional dose methotrexate to weekly doxorubicin treatment.

Adolescent↗
PubMed1985

Thresholds of the dog for detection of inhaled eugenol and benzaldehyde determined by electroencephalographic and behavioral olfactometry.

Electroencephalographic olfactometry and behavioral olfactometry were developed to evaluate objectively the olfactory function of 12 dogs. These techniques were used to determined normative thresholds for benzaldehyde, a mixed olfactory and trigeminal stimulant, and eugenol, a suspected pure olfactory stimulant, in 12 dogs. Both techniques were effective in obtaining a mean threshold for clinically normal dogs. Electroencephalographic olfactometry was demonstrated to be more sensitive than was behavioral olfactometry. The techniques measured olfactory function by failure to evoke responses in dogs after ablation of olfactory mucosa. The contribution of trigeminal stimulation to the thresholds was not determined.

Animals↗
PubMed1984

Expression of viral arthritis-tenosynovitis infection in immunosuppressed chickens.

Previously untreated chicks and those treated neonatally with either cyclophosphamide (CY) or infectious bursal disease virus (IBDV) were subcutaneously inoculated with viral arthritis virus ( VAV ) to determine whether suppression of humoral immunity would affect VAV pathogenicity. No difference was apparent in the disease process that occurred in the immunosuppressed versus the nonimmunosuppressed chickens. However, in the immunosuppressed birds, VAV was recovered from the heart and tendon tissues earlier in the postinoculation (PI) period. Also, VAV inoculated immunosuppressed birds carried higher levels of serum gamma globulins at certain PI intervals than the VAV inoculated positive controls or the untreated negative control chickens. It is suggested that the suppression of the bursa of Fabricius (BF) by CY or IBDV did not interfere in the antibody production to VAV , but the antibody produced was qualitatively defective.

Animals↗
PubMed1983

Doxorubicin and CCNU with or without vincristine in patients with advanced refractory breast cancer. A randomized trial.

Thirty-five patients with advanced breast cancer refractory to initial chemotherapy were randomized to receive two-drug doxorubicin-CCNU or three-drug doxorubicin-CCNU-vincristine (VCR) treatment. Doxorubicin (25-40 mg/m2) and VCR (1.4 mg/m2) were given intravenously every 21 days; CCNU (65-90 mg/m2) was given orally every 42 days. Patients with liver or bone marrow metastases initially received the lower range doses. All patients failed prior chemotherapy with cyclophosphamide and 5-FU with or without methotrexate and prednisone; 67% received prior hormonal therapy. Pretreatment patient characteristics were comparable in both groups. Objective responses (greater than 50% reduction in tumor size) were seen in 7 of 18 patients (39%) on the VCR containing arm and in 8 of 17 patients (46%) on the doxorubicin-CCNU arm. Survival was not improved by VCR addition with overall survival on the doxorubicin-CCNU arm, approximately 10% greater at all intervals (median 9.1 versus 7.0 months; not statistically significant). However, neurotoxicity was significantly greater in the VCR arm (36% versus 0%; P less than 0.05). In advanced breast cancer, no benefit to VCR addition was seen in prior randomized studies of first-line combinations where VCR was the treatment variable. Such results, combined with our experience with VCR in a salvage regimen, question the value of VCR addition to combination regimens in advanced breast cancer.

Breast Neoplasms↗
PubMed1983

An association between hostility and poor adherence to treatment in patients suffering from depression.

Direction of hostility, as measured by the Hostility and Direction of Hostility Questionnaire, was found to be associated with poor compliance during a treatment trial of a new tricyclic antidepressant. An association with other factors such as the type and severity of depression was not found. There are other studies in the literature which support these observations although some controversy surrounds the role played by personality variables in adherence to treatment. Hostility has been shown to be a possible factor in the aetiology of depression, an important factor in the classification of depression, and a symptom of depression which improves with treatment. Hostility may have a particularly large importance in compliance with treatment for depression or may have been overlooked in studies in compliance with treatment for non-psychiatric disorders.

Adolescent↗
PubMed1982

Does lofepramine have fewer side effects than amitriptyline? Results of a comparative trial.

A double blind trial was carried out comparing the tricyclic antidepressant lofepramine with amitriptyline in the treatment of patients suffering from moderate to markedly severe depression. No difference was demonstrated between the two drugs in terms of their antidepressant effect, but patients treated with lofepramine suffered from significantly less side effects than patients treated with amitriptyline. Both groups of patients had a high drop out rate but this was less marked in the groups of patients treated with lofepramine.

Adolescent↗
PubMed1982

Cisplatin hydration with and without mannitol diuresis in refractory disseminated malignant melanoma: a southwest oncology group study.

In a prospective phase II randomized trial, a dose of 100 mg/m2 iv cisplatin every 3 weeks plus forced hydration with or without mannitol diuresis was tested in patients with previously treated advanced malignant melanoma. A total of 67 patients were evaluated: 33 not given mannitol and 34 in the mannitol arm. Two partial remissions (of 2+ and 6.5 months) were achieved in the no-mannitol arm and one complete response and four partial responses (of 1, 2, 2.5, 5.5, and 8 months) were seen in the mannitol arm. Moderate, severe, and life-threatening renal toxicity was less in the mannitol arm, and patients tolerated more doses of cisplatin. The renal toxicity occurred mostly after the first dose of chemotherapy and did not seem to be cumulative. Other side effects were comparable in both arms. We concluded that renal toxicity is less severe in patients treated with cisplatin, hydration, and mannitol and that the use of cisplatin alone or in combination with other active agent(s) should be considered for further evaluation in previously untreated patients with malignant melanoma.

Cisplatin↗