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Biomedical subjects

D White

Publications and source records attributed to D White.

At least 19 recordsLinked to original sources
PubMed1992

HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy.

Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.

Drug Administration Schedule↗
PubMed1992

Early treatment with parenteral penicillin in meningococcal disease.

OBJECTIVE: To measure the effect of parenteral antibiotics given before admission to hospital on mortality and on bacteriological investigations in meningococcal disease. DESIGN: Retrospective review of hospital notes and laboratory and public health medicine department records. SETTING: Three health districts in south west England. SUBJECTS: Patients with meningococcal disease in Gloucester district presenting between 1 January 1982 and 31 December 1991 (n = 190); patients with meningococcal disease in Plymouth (n = 118) and Bath (n = 73) districts presenting between 1 January 1988 and 31 December 1991 (total = 381). MAIN OUTCOME MEASURE: Number of deaths from meningococcal disease. RESULTS: Parenteral antibiotic given by general practitioners was associated with a substantial reduction in mortality (from 9% to 5%; relative risk 0.6, 95% confidence interval 0.2 to 1.5); patients with a rash were more likely to be given parenteral antibiotics, and mortality was further reduced (from 12% to 5%; 0.5, 0.2 to 1.4). In a district where such treatment was regularly encouraged its use increased from 5% to 40% of cases over 10 years (p = 0.00001). Treatment with parenteral antibiotics before admission made isolation of meningococci from blood and cerebrospinal fluid less likely but did not affect nasopharyngeal cultures. CONCLUSIONS: General practitioners should carry benzylpenicillin in their emergency bags at all times and should administer it promptly, preferably intravenously, whenever meningococcal disease is suspected, unless the patient has had an anaphylactic reaction to penicillin. Specimens for culture should include a nasopharyngeal swab.

Humans↗
PubMed1992

A phenotypically and karyotypically stable human thyroid epithelial line conditionally immortalized by SV40 large T antigen.

Primary cultures of normal human neonatal thyroid follicular cells were transfected with a plasmid expressing a temperature-sensitive (tsA58) mutant of SV40 large T antigen. An epithelial cell line, designated B-thy-ts.1, was obtained which showed tight temperature-dependent growth. In sharp contrast to previous such lines, which were derived from adult thyroid, B-thy-ts.1 has retained a well-differentiated phenotype as reflected in its morphology and cytokeratin expression pattern. In addition to phenotypic stability the line also displays an unusually stable karyotype, lacking the usual clastogenic effects of SV40, which we speculate to result from a greater DNA repair capacity of its cell of origin. B-thy-ts.1 should be a particularly useful tool with which to study the effects of activated oncogenes on epithelial growth and differentiation.

Antigens, Polyomavirus Transforming↗
PubMed1992

A thin-layer chromatographic method to determine process impurities in leucovorin calcium.

A densitometric thin-layer chromatographic method for the analysis of process impurities in leucovorin calcium was developed and validated. Using this method, folic acid, N10-formyldihydrofolic acid, p-aminobenzoic acid, and N-(4-aminobenzoyl)-L-glutamic acid were monitored with a limit of detection of approximately 0.1% each. Both absorbance and fluorescence densitometric evaluations were utilized; fluorescence evaluation selectively detected impurities that were not chromatographically resolved from leucovorin.

4-Aminobenzoic Acid↗
PubMed1992

Pituitary-gonadal function during sleep in healthy aging men.

There is limited information on the relation between age-related changes in pituitary-gonadal function and sleep physiology in older men. In this cross-sectional study of 67 healthy volunteers free from sleep complaints, aged 45-75 yr, we (1) assessed peak fluctuations and hourly variations in plasma testosterone, LH and prolactin sampled every 20 min during sleep, and (2) explored the relation between sleep parameters, respiratory and periodic leg movement disturbances, and circulating concentrations of the aforementioned hormones. We hypothesized that alterations in sleep architecture or presence of sleep disorders may contribute to hormonal variations in aging subjects. Bioavailable testosterone decreased and LH increased with age, but there were no differences in total testosterone and prolactin and no major changes in peak hormonal release. There were positive associations, independent from the age effect, between sleep efficiency, decreased latency to onset of REM activity, and number of REM episodes, and circulating testosterone. Sleep-disordered breathing significantly increased with age. The degree of respiratory disturbance was associated with decreased overnight plasma bioavailable testosterone, but this relationship lost its significance after age-adjustment. The findings demonstrate a decrease in gonadal function during sleep in healthy aging men and suggest that changes in sleep efficiency and architecture are associated with alterations in gonadal activity in these older individuals.

Adult↗
PubMed1992

Bacillus methanolicus sp. nov., a new species of thermotolerant, methanol-utilizing, endospore-forming bacteria.

The generic position of 14 strains of gram-positive bacteria able to use methanol as a growth substrate was determined. All are obligately aerobic, thermotolerant organisms that are able to grow at temperatures of 35 to 60 degrees C. Nine of the strains produce oval spores at a subterminal-to-central position in slightly swollen rod-shaped cells. DNA-DNA hybridization studies, 5S rRNA sequence analysis, and physiological characteristics revealed that all 14 strains cluster as a well-defined group and form a distinct new genospecies. Analysis of the 16S and 5S rRNA sequences indicated that this new species is distinct from Bacillus brevis but closely related to B. firmus and B. azotoformans. The name proposed for this new species is B. methanolicus. The type strain, PB1, has been deposited in the National Collection of Industrial and Marine Bacteria as NCIMB 13113.

Bacillus↗
PubMed1992

Cell surface modifications induced by calcium ion in the myxobacterium Stigmatella aurantiaca.

Calcium ion induces in the myxobacterium Stigmatella aurantiaca the ability to glide on solid surfaces and to become cohesive (D. F. Gilmore and D. White, J. Bacteriol. 161:113-117, 1985; B. J. Womack, D. F. Gilmore, and D. White, J. Bacteriol. 171:6093-6096, 1989). The addition of calcium ion to the growth medium resulted in the formation of extracellular fibrils, the appearance in the membrane fractions of a 30-kDa protein, and the accumulation in a low-speed centrifugal pellet of 10 polypeptides that cross-reacted with affinity-purified antibody to one of the polypeptides. One of the polypeptides, a 55-kDa protein, was present in the membrane fraction of control cells not incubated with calcium ion and was apparently translocated to the extracellular matrix during incubation in medium containing calcium ion. The 55-kDa protein was immunologically related to a 65-kDa protein located on the fibrils of another myxobacterium, Myxococcus xanthus.

Bacterial Proteins↗
PubMed1991

Functional and ultrastructural effects of a missense mutation in the indirect flight muscle-specific actin gene of Drosophila melanogaster.

A single-site mutation of the flight-muscle-specific actin gene of Drosophila melanogaster causes a substitution of glutamic acid 93 by lysine in all the actin encoded in the indirect flight muscle (IFM). In these Act88FE93K mutants, myofibrillar bundles of thick and thin filaments are present but lack Z-discs and all sarcomeric repeats. Dense filament bundles, which are probably aberrant Z-discs, are seen in myofibrils of pupal flies, but early in adult life these move to the periphery of the fibrils and are not seen in skinned adult fibres. Consistent with this observation, alpha-actinin and other high molecular weight proteins, possibly associated with Z-discs, are not detected on SDS/polyacrylamide gels or Western blots of skinned adult IFM. The mutation lies at the beginning of a loop in the small domain of actin, near the myosin binding region. However, that the mutant actin binds myosin heads is shown by (1) rigor crossbridges in electron micrographs, (2) the appropriate rise in stiffness when ATP is withdrawn in mechanical experiments, and (3) equal protection against tryptic digestion provided by rigor binding between actin and myosin in both wild-type and mutant fibres. Reversal of rigor chevron angle along some thin filaments reflects reversal of thin-filament polarity due to lattice disorder. The absence of Z-discs, alpha-actinin and two high molecular weight proteins, and binding studies by others, suggest that the substitution at residue 93 affects the binding of the mutant actin to a protein, possibly alpha-actinin, which is necessary for Z-disc assembly or maintenance.

Actins↗
PubMed1991

The magnetic properties of some materials affecting MR images.

We have compared the magnetic properties of various types of materials known to affect MR images. The materials compared were: (i) MR contrast agents based on chelates of paramagnetic metals (Gd-DTPA, Dy-DTPA); (ii) biological forms of iron (horse spleen ferritin and deoxyhemoglobin); and (iii) a superparamagnetic iron oxide (AMI-25). The properties compared were the magnetic susceptibility and the magnetization. The magnetization and susceptibility of superparamagnetic AMI-25 are far larger than that of ferritin or low molecular weight, paramagnetic chelates. Superparamagnetic iron oxide colloids, like AMI-25, are a uniquely powerful class of magnetic materials.

Animals↗
PubMed1991

CGS 22745: a selective orally active inhibitor of 5-lipoxygenase.

CGS 22745, and aralkyl hydroxamic acid, inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) synthesis in guinea pig leukocytes (IC50 = 0.6 microM). The compound did not appreciably affect cyclooxygenase (ram seminal vesicles), 12-lipoxygenase and thromboxane synthase (human platelets) or 15-lipoxygenase (human neutrophils). CGS 22745 inhibited A23187-induced formation of LTB4 in blood (IC50's of 4.3, 0.56 and 3.2 microM for human, dog and rat, respectively). At 1 mg/kg i.v. in dogs, it caused 96% inhibition of A23187-stimulated LTB4 formation ex vivo after 5 min. Its effective biological half-life was greater than 160 min. In dogs at 3 and 10 mg/kg p.o., CGS 22745 inhibited ex vivo A23187-stimulated LTB4 formation at 3 hr by 48% and 97%, respectively. The inhibition persisted up to 6 hr (26% at 3 mg/kg; 49% at 10 mg/kg). CGS 22745 (3, 10 and 30 mg/kg p.o.) inhibited exudate formation, mononuclear cells and PMN accumulation in a dose-dependent manner during the late phase (48 and 72 hr) of carrageenan-induced pleurisy in the rat.

Administration, Oral↗
PubMed1991

Histologic, immunophenotypic and genotypic analyses of bone marrow trephines from patients with non-Hodgkin's lymphoma.

Marrow involvement in 20 patients with non-Hodgkin's lymphoma (NHL) were studied by histology, immunophenotypic and genotypic methods. Eighteen of these trephines were histologically involved with recognizable lymphomatous infiltrates and five of these were the primary disease site. In the remaining two cases (with histologically involved lymph nodes) the trephines were uninvolved with tumour. Three B-cell cases expressing surface immunoglobulin (sIg) and/or CD37 and one case not analysed phenotypically showed Ig gene rearrangements. The two remaining cases with B NHL showed no gene rearrangements, however, in one of these the trephine was histologically uninvolved with tumour. Twelve out of 14 T-cell cases were characterized by variable or absent expression of one or more T-cell antigens from the tumour population, one case was negative for all T-cell antigens and the remaining case was not histologically involved with tumour. All three lymphoblastic lymphomas and only 4/11 peripheral T-cell lymphomas (PTCL) cases revealed T-cell receptor (TcR) gene rearrangements. One of the latter cases also exhibited Ig JH gene rearrangements. This study demonstrates the usefulness of bone marrow trephines (BMT) in histologic, phenotypic and genotypic analyses. However, although genotypic data confirm clonality in B NHL and the lymphoblastic lymphomas there was genotypic heterogeneity within the PTCL group.

Antigens, CD↗
PubMed1991

Registered nurse stress in intensive care units--an Australian perspective.

This paper describes a study of stressors and coping mechanisms in different grades of registered nurses in Intensive Care Units (ICUs). The research demonstrated that significant correlation existed between relating what and when to report clinical patient changes and relating theory to practice. Significant differences existed between groups with regard to the stress associated with caring for acutely ill patients, role conflict with medical staff and relationships with senior medical and nursing staff. The findings confirm that environmental stressors are the major stressors in ICU and demonstrate that sound knowledge and clinical assessment skills are important factors in reducing perceived stress, thus supporting the continued need for competency and skills focused post registration courses and in-service education.

Adaptation, Psychological↗
PubMed1991

Coordinating community and public-institutional mental health services: some unintended consequences.

Where a target group such as the mentally ill tend to use multiple and varied services over a long period of time, service coordination is often seen as the key to continuity of care. This article argues that coordination also has its perverse effects. To demonstrate, two types of community organizations (COs) working in mental health in the Canadian province of Québec are examined: alternative COs, which have their roots in community action and maintain few formal links with each other or with institutional resources; and transitional structures, COs which are developed with the cooperation of psychiatric professionals, are closely linked to hospitals and are often part of a tightly coordinated system of community services. With respect to access, continuity, programs, internal structure and flexibility, each type of community resource has particular strengths and weaknesses. In the first part of the article, these are described and compared. In the second part of the article, we examine the possible effects of Québec's new mental health policy on COs working in mental health. The policy seeks to create comprehensive systems coordinating all services at the regional level-including alternative organizations, transitional structures and public institutions. The imperatives of the complex planning process risk diluting or even eradicating the differences between the two types of mental health COs described earlier. The process may thus rob certain service users of the particular advantages they found in alternative COs. For those mentally ill who, by choice or by chance, remain marginal to the coordinated system, there may ultimately be no resources available at all.

Community Mental Health Services↗
PubMed1991

Induction of long-term survival of hamster heart xenografts in rats.

The aim of this study was to determine the mechanisms responsible for concordant xenograft rejection using the hamster-to-rat heart graft model. Even though it was known that rat CD4 positive T cells proliferated to hamster stimulators in mixed lymphocyte reactions, the depletion of CD4 positive T cells in rat recipients did not lead to an extension of xenograft survival. Suppression of T cell immunity using other monoclonal antibodies or cyclosporine also failed to improve survival. Only by depleting complement with cobra-venom factor could hamster xenograft survival be prolonged, and long-term survival was achieved by combining CsA with COF. High-antibody titers to hamster cells were found after transplantation of hamster hearts, and evidence is presented that rejection of these "concordant" xenografts is mediated primarily by antibody-complement mechanisms. The antihamster antibodies were produced in the absence of T cell help, which suggests that antibody-mediated graft destruction cannot be inhibited by suppression or depletion of T cells. Pharmacologic depletion of complement for the clinical application of concordant xenografts is a promising avenue of future research.

Animals↗