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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 19 recordsLinked to original sources
PubMed1992

Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity.

Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors alpha and beta, respectively.

Amino Acid Sequence↗
PubMed1992

Models of insulin action on metabolic and growth response genes.

In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription.

3T3 Cells↗
PubMed1992

Characterization of the bovine peripheral lymph node homing receptor: a lectin cell adhesion molecule (LECAM).

The phenomenon of tissue-specific homing of lymphocyte populations has been most clearly shown in larger domestic animals, such as the sheep and cow, yet the molecular interactions which control these processes in these animals have not been defined. Here we tested the cross-reactivity of four anti-human peripheral lymph node homing receptor (LECAM-1) (also known as LAM-1, LEC-CAM-1, Leu-8, TQ-1, or human equivalent of gp90 MEL-14) antibodies on bovine lymphocytes. These antibodies stained all bovine neutrophils and monocytes, and variable numbers of peripheral blood lymphocytes, as determined by flow cytometry. In young calves (less than 1 month old) virtually all circulating lymphocytes expressed LECAM-1, whereas the percentage of positive lymphocytes in older animals (greater than 1 year) varied from 17%-67%. Bovine LECAM-1 was rapidly lost from the cell surface of PMA-activated and chymotrypsin-treated cells. Anti-LECAM-1 monoclonal antibody blocked greater than 80% of bovine lymphocyte binding to peripheral lymph node high endothelial venules (HEV). Since the lectin domain of LECAM-1 is thought to mediate lymphocyte-HEV adhesion, we sought to establish further the similarity of the bovine, mouse, and human molecules by comparing nucleotide sequences in this region of the molecule. The polymerase chain reaction (PCR) was used to specifically clone the bovine lectin domain from single-strand cDNA. Subsequent sequencing showed an identity of greater than 80% at the nucleotide level with the human and mouse molecules. The predicted amino acid sequences were also highly conserved. Though striking similarities were seen between the bovine, mouse and human molecule, indicating evolutionary conservation of this family of proteins, notable differences were detected. The nucleotide sequence of the bovine lectin domain predicts one additional N-linked glycosylation site compared to mouse and human. Preliminary analysis suggested a more tissue-restricted expression of LECAM-1 in the compared to the human and mouse, which correlates with a better separation of lymphocyte homing phenotypes seen in these larger animals. Virtually all peripheral lymph node lymphocytes in 6-month-old calves expressed LECAM-1, whereas, ileal Peyer's patch lymphocytes were predominantly negative. Finally, by testing anti-human LECAM-1 antibodies in a different species we have established the co-expression of antigenic epitopes on leucocyte LECAM-1 and a molecule(s) expressed by endothelial cells.

Amino Acid Sequence↗
PubMed1992

Transient expression of somatostatin peptide is a widespread feature of developing sensory and sympathetic neurons in the embryonic rat.

Previous studies from this and other laboratories demonstrated that many embryonic sensory ganglion cells in the rat transiently express the catecholamine synthesizing enzyme tyrosine hydroxylase (TH), a trait not expressed by most mature sensory neurons. We, therefore, sought to determine whether transient expression was uniquely associated with catecholaminergic traits, or, alternatively, whether embryonic ganglion cells transiently expressed peptidergic properties as well. Of the four peptides examined (somatostatin [somatotropin release inhibiting factor] (SRIF), galanin (Gal), calcitonin gene-related peptide (CGRP), and substance P (SP)), only SRIF was found to be transiently expressed during early stages of sensory gangliogenesis. Surprisingly, SRIF immunoreactivity was observed in virtually all cranial and spinal sensory ganglion cells on embryonic day (E) 12.5. In addition to perikaryal labeling, intense SRIF immunoreactivity was also observed in the central and peripheral processes of E12.5 sensory neurons, suggesting the peptide may be released from nerve endings. The time course of SRIF appearance in cranial ganglion cells paralleled that previously described for TH, and double-labeling studies revealed extensive co-localization of these two phenotypes. By E16.5, however, the number of neurons expressing SRIF had diminished markedly, indicating that SRIF is only transiently expressed by most sensory neurons during early stages of ganglion development. An unexpected finding was that transient expression of SRIF is also a prominent feature of sympathetic ganglion cells; however, the temporal pattern of staining in the sympathetic and sensory ganglia differed substantially. Whereas virtually no SRIF staining was observed in E12.5 sympathetics, the vast majority of cells in the E16.5 superior cervical ganglion (SCG) were labeled. This contrasted sharply with the adult SCG, in which only low levels of SRIF expression were found. These findings demonstrate that SRIF peptide is transiently expressed at high levels in peripheral sensory and sympathetic neurons during embryogenesis. The time course and widespread distribution of SRIF expression indicates that the peptide may play a role in early stages of ganglion cell growth and development. Moreover, these data, in conjunction with previous studies demonstrating SRIF immunoreactivity in developing central neurons, suggest that transient expression of this peptide is a common property of diverse neuronal cell types.

Animals↗
PubMed1992

Preconception and preimplantation diagnosis for cystic fibrosis.

Preimplantation diagnosis provides couples at high genetic risk the possibility of avoiding genetic disease without the need for prenatal diagnosis and selective abortion of the affected pregnancy. Following extensive background work on the reliability of genetic diagnosis in a single cell, we offered on a research basis preimplantation diagnosis to five couples at risk for offspring with the delta-F508 mutation (the major mutation causing cystic fibrosis). There was no detrimental effect from polar body removal on either fertilization or preimplantation development. Genetic analysis, undertaken in 22 polar bodies and 15 corresponding blastomeres, identified 21 embryos of which ten were transferred.

Biopsy↗
PubMed1992

Postoperative analgesia using a computerised infusion of alfentanil following aortic bifurcation graft surgery.

A Psion microcomputer controlled infusion system for alfentanil was assessed for the provision of post-operative analgesia in 14 patients who had undergone aortic bifurcation graft surgery. The system employed a pharmacokinetic model working in real time to deliver any selected target plasma concentration of alfentanil. The alfentanil infusion system was used for a mean time of 39 hours and for 96% of this time, patients were scored as having no pain or only mild pain. Severe pain was recorded for only 0.05% of the study time. The use of a pharmacokinetic delivery system may offer a convenient and simple method of providing postoperative analgesia with alfentanil.

Adult↗
PubMed1992

A portable target controlled propofol infusion system.

A portable target controlled infusion system for propofol has been developed based on a Psion hand-held microcomputer and the Ohmeda 9000 syringe pump. The system uses a pharmacokinetic model which describes the distribution and elimination of propofol to achieve and maintain any selected target blood concentration. Target blood concentrations of 1 micrograms/ml, 3 micrograms/ml and 5 micrograms/ml were selected in laboratory trials and the cumulative volumes delivered by the Psion system each minute were compared with the theoretical output calculated by the pharmacokinetic model. The results obtained showed that the computer system delivered volumes which were always within 2% of the theoretical values. This system offers a convenient and simple method of maintaining anaesthesia using propofol.

Anesthesia, Intravenous↗
PubMed1992

Analyses of 95 first-trimester spontaneous abortions by chorionic villus sampling and karyotype.

PURPOSE: Our purpose was to determine the incidence of chromosomal aneuploidy in first-trimester pregnancy losses using chorionic villus sampling (CVS). STUDY DESIGN: All patients presenting for CVS with no fetal cardiac activity were offered CVS. RESULTS: Cytogenetic results were completed in 95 of 96 cases (99%). Eighty-three percent of the karyotypes were aneuploid. The 16 euploid fetuses had no excess of females. CONCLUSION: CVS is the most reliable method of determining the karyotype of spontaneously aborted fetuses. The incidence of aneuploidy is much greater than in previous reports that analyzed passed products of conception. CVS should be offered to women who present with first-trimester spontaneous abortions.

Abortion, Spontaneous↗
PubMed1992

The relationship between a nutritional index and acute physiology score in critical illness.

Prognostic indices derived from available physiological data (SAPS), complex nutritional and biochemical tests (PNI), grip strength and serum albumin were calculated in 16 critically ill patients receiving intravenous nutrition over a six week period. The aim was to compare these independently derived prognostic indices, to assess their response to feeding, and to determine suitability for use in Irish intensive care units. Mean SAPS (7.6 +/- 0.92), PNI (3.1 +/- 0.29), serum albumin (30.3 +/- 1.03 g/l) and grip strength (17.9 +/- 1.3%) were all suggestive of an "at risk" group. Significant associations were found between the accepted SAPS index and both PNI (r = 0.6, p < 0.001, n = 35) and grip strength (r = -0.68, p < 0.001, n = 44) but not with serum albumin. No consistent improvement was seen in response to feeding in any of the derived indices. The close correlation between prognostic indices derived from either physiological, nutritional or grip strength data in this study and the failure of prognostic indices to improve during hyperalimentation would support a common mechanism, e.g. endogenous mediators, for metabolic and physiological disturbance in critical illness. It suggests that the role of hyperalimentation is supportive rather than therapeutic and re-iterates the importance of managing underlying disease processes. Simple grip strength may be a useful alternative to complex nutritional indices.

Critical Illness↗
PubMed1992

Babesia bovis: analysis of and preliminary vaccination studies with a defined infected erythrocyte membrane binding antigen.

Murine monoclonal antibodies (MAB) were produced against the 'beta' fraction of Babesia bovis. A MAB, W11C5, selected on the criterion of its staining of erythrocytes infected with B. bovis, was purified. The antigen identified by MAB W11C5 was extracted from B. bovis infected erythrocytes by affinity chromatography and used in a vaccination trial to test its vaccine efficacy against homologous B. bovis infection in splenectomized calves. The vaccinated group showed significantly different parasitaemias from the control group and it was concluded that the B. bovis antigen 11C5 induced a protective immune response when used as a vaccine. This antigen should be synthesized using recombinant DNA techniques to determine its efficacy and suitability as a commercial vaccine against B. bovis infection.

Animals↗
PubMed1992

Typing of HLA-DQA1 and DQB1 using DNA single-strand conformation polymorphism.

The technique of single-strand conformation polymorphism (SSCP), which is capable of distinguishing DNA sequence variability, was adapted to the identification of the HLA-DQA1 and DQB1 alleles. Eight DQA1 alleles and 12 DQB1 alleles were distinguished by amplifying the second exon of the genes in the presence of radioactive deoxynucleotide, denaturing the products with heat, and separating the single strands by electrophoresis in nondenaturing gels. For DQA1, it was possible to distinguish the eight alleles with standard bis-acrylamide or with a Hydrolink gel matrix. Twelve DQB1 alleles were identified by a protocol employing a combination of oligohybridization and SSCP using products amplified by specific DQB1 primers.

Alleles↗
PubMed1992

Cryptococcal meningitis: outcome in patients with AIDS and patients with neoplastic disease.

A retrospective analysis of 41 patients with cryptococcal meningitis and AIDS or neoplastic disease was done. Patients with AIDS were younger and predominantly male; they had a shorter duration of prior illness, higher initial serum cryptococcal antigen titers, and lower initial cerebrospinal fluid white blood cell counts than those with neoplastic disease. The median overall survival for patients with AIDS was 9 months compared with 2 months for those with neoplastic disease (P = .004). Seventy-eight percent of patients with AIDS and 43% of those with neoplastic disease were cured or improved 6 months after diagnosis (P = .039). Toxicity from amphotericin B and flucytosine was similar for both groups. One patient with AIDS relapsed. Multivariate predictors of survival included headache (P = .007) and an AIDS diagnosis (P = .009). Examination of outcomes for other opportunistic infections associated with AIDS and other immunosuppressive illness may distinguish prognostic features for different patient populations.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Induction of anaesthesia with propofol using a target-controlled infusion system.

Sixty patients premedicated with temazepam were allocated randomly to receive an infusion of propofol designed to achieve and maintain a target blood concentration of 3, 4 or 5 micrograms.ml-1. Induction time was measured from the start of infusion to loss of verbal contact. The success rate of inducing anaesthesia within 3 min of achieving the target concentration was 40% when the predicted target concentration was 3 micrograms.ml-1, 75% when the predicted target was 4 micrograms.ml-1 and 90% when the target was 5 micrograms.ml-1. There were no significant differences between the three groups for time to loss of verbal contact in patients who were induced successfully within 3 min. There were significant reductions in arterial pressure 3 min after achieving the target concentrations within the groups but not between them. The frequency of apnoea and pain on injection was small in all groups. Selecting a target concentration of 5 microgram.ml-1 would successfully induce anaesthesia in the majority of patients premedicated with temazepam without major haemodynamic or respiratory side effects.

Adolescent↗
PubMed1992

Translation of an instrument. The US-Nordic Family Dynamics Nursing Research Project.

Translation of a research instrument questionnaire from English to another language is analyzed in relation to principles involved, procedures followed, and problems confronted by nurse researchers from the US-Nordic Family Dynamics Nursing Research Project. Of paramount importance in translation are translation equivalency, congruent value orientation, and careful use of colloquialisms. It is important to recognize that copyright guidelines apply in the translation of an instrument. Approaches to solving instrument translation problems are discussed.

Copyright↗
PubMed1992

Reducing and managing restraints in long-term-care facilities.

OBJECTIVE: To evaluate a management system designed to improve staff adherence to a federal regulation that stated restrained residents should be released, exercised, and repositioned every 2 hours. DESIGN: A delayed intervention, controlled, cross-over design with three phases. During phase one, baseline, the length of intervals that residents remained in restraints was monitored. The intervention was implemented at site A in Phase two while site B remained in baseline. During Phase three, the intervention was replicated at site B. SETTING: Two long-term care proprietary nursing facilities. PATIENTS: Sixty-three physically restrained residents in the two facilities. INTERVENTION: The intervention was a system of restraint release using colored pads corresponding to specific hours. The management rule was that the resident should be on a different colored pad every 2 hours. Staff had to lift residents to place the pad, and the colors made the system easy for supervisors to check. MAIN OUTCOME MEASURES: Checks by research personnel by black light and invisible ink, to detect movement of the knot tying the restraints. RESULTS: During the baseline phase, the majority of residents at both sites were inappropriately restrained longer than 2 hours (site A: 54.1%; site B: 60.1%). The percentage of residents restrained over 2 hours was significantly reduced during the intervention phase to 13.9% (site A) and 19.4% (site B). Three weeks after the end of the intervention, inappropriate use of restraints remained low, 14.2%, but rose to 47.7% after another 3 weeks. CONCLUSION: The management system is an effective way to increase the consistency with which nursing-home staff release and reposition restrained residents.

Aged↗
PubMed1992

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia.

The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater than or equal to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less than or equal to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents.

Animals↗
PubMed1992

Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.

Over a 7-year period, we analyzed 261 dose regimens of antimicrobial drugs in the treatment and prevention of Pneumocystis carinii pneumonia in an immunosuppressed rat model. These compounds ranged from drugs in clinical use to newly synthesized agents. Drug efficacy was expressed as the magnitude of the reduction in median P. carinii cyst or nucleus counts on a scale ranging from inactive (less than 5-fold) to very markedly active (greater than or equal to 1,000-fold). The classification system was reproducible and allowed drugs studied at different times to be compared with each other. The system demonstrated a hierarchy of anti-P. carinii activity not only among classes of compounds but also among individual members of a drug class. Sulfonamides, sulfones, and diamidines were the most active agents; some purine nucleosides and nitrofurans also showed promising activity; and most antiparasitic, antifungal, antibacterial, and antiviral drugs were inactive. We conclude that this classification system represents a simple, quantitative method of comparing the activities of antimicrobial drugs against P. carinii. Information gained from this system should be helpful in developing new anti-P. carinii compounds and establishing standard procedures for their evaluation.

Animals↗