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Biomedical subjects

J Murray

Publications and source records attributed to J Murray.

At least 199 records · Page 11Linked to original sources
PubMed1996

Effects of recombinant human hemoglobin on opossum sphincter of Oddi motor function in vivo and in vitro.

Nitric oxide (NO) acts as a nonadrenergic, noncholinergic inhibitor neurotransmitter that regulates sphincter of Oddi (SO) motor function. Hemoglobin blocks NO activity by binding it after it is synthesized. We hypothesized that recombinant human hemoglobin (rHb1.1) affects SO motor function by scavenging NO. Under anesthesia, 12 opossums underwent biliary tract manometry. Following a stabilization period, six animals were given rHb1.1 (0.28 g/kg over 30 min), while six received bovine albumin (0.28 g/kg over 30 min). Recordings were made during the infusion and for 3 hr after the infusion. In an in vitro preparation, force transducers were used to record spontaneous contractions at two sites along the sphincter segment. After a control period, rHb1.1 (0.1 mM) or cyanomethemoglobin (0.1 mM) was added to the tissue bath and recordings continued for another 2 hr. Recombinant human hemoglobin decreased the frequency of contractions, increased resting tone, and blocked the relaxation phase of contraction in vivo. It increased the baseline amplitude, the frequency, and the peak amplitudes of contractions in vitro. Albumin or cyanomethoglobin, which are unable to bind NO, had little effect on SO motor activity. We conclude that rHb1.1 may alter SO motor function by binding endogenous NO.

Analysis of Variance↗
PubMed1996

Natural bites, food consistency and feeding behaviour in man.

Complete feeding sequences (bite to terminal swallow) were recorded in 11 individuals (Class I occlusions) feeding on apple, banana and biscuit (hard cookie) to establish whether jaw movements characteristic of the stage I transport, chewing, stage II transport and swallowing processes found in non-human mammals could be identified in man. All participants took large natural bites (known weight) of each food, but seven were supplied standard 6-g pieces of apple. Jaw movements (three axes) were recorded using a locally calibrated Sirognathograph. Discrete stage I transport movements (bite moved from incisors to postcanines), were found in most records, but least frequently for banana. The number of chewing cycles before the first in-sequence swallow increased in the order: banana, ( = ) apple without peel, apple with peel, biscuit. Chewing cycles showed subtle changes in gape profile but significant variation in mediolateral movement cycle to cycle. Morphologically distinct stage II transport cycles could not be identified. Swallows occurred intermittently during chewing (79% of all sequences, n = 146) with cycle durations in excess of 1 s in contrast to the range for chewing (0.6-0.7 s). Almost all sequences ended with a period, clearance, of highly irregular jaw movements often including swallows. Clearance has not been described in other mammals. Food consistency affected feeding behaviour. The "chew/swallow' ratio (total number of chews/total number of swallows) increased with food hardness. The number of chewing cycles before the first in-sequence swallow also increased. Food type significantly affected sequence duration. The duration of clearance was also affected by bite weight and food hardness. It is concluded that initial food consistency determines the number of chewing cycles before the first swallow and overall sequence duration. The change in the pattern of jaw movement in both the vertical and mediolateral directions cycle to cycle suggests continuous sensory modulation of the motor output to the mandibular musculature.

Adult↗
PubMed1996

Penetrating cardiac injuries.

Penetrating cardiac injuries pose a tremendous challenge to any trauma surgeon. Time, sound judgment, aggressive intervention, and surgical technique are the most important factors contributing to positive outcomes. This article extensively reviews the history, surgical management, and techniques needed to deal with these critical injuries. This year commemorates the one hundredth anniversary of the first successful repair of a cardiac injury.

Animals↗
PubMed1996

F-actin sequesters elongation factor 1alpha from interaction with aminoacyl-tRNA in a pH-dependent reaction.

The machinery of eukaryotic protein synthesis is found in association with the actin cytoskeleton. A major component of this translational apparatus, which is involved in the shuttling of aa-tRNA, is the actin-binding protein elongation factor 1alpha (EF-1alpha). To investigate the consequences for translation of the interaction of EF-1alpha with F-actin, we have studied the effect of F-actin on the ability of EF-1alpha to bind to aa-tRNA. We demonstrate that binding of EF-1alpha:GTP to aa-tRNA is not pH sensitive with a constant binding affinity of approximately 0.2 microM over the physiological range of pH. However, the sharp pH dependence of binding of EF-1alpha to F-actin is sufficient to shift the binding of EF-1alpha from F-actin to aa-tRNA as pH increases. The ability of EF-1alpha to bind either F-actin or aa-tRNA in competition binding experiments is also consistent with the observation that EF-1alpha's binding to F-actin and aa-tRNA is mutually exclusive. Two pH-sensitive actin-binding sequences in EF-1alpha are identified and are predicted to overlap with the aa-tRNA-binding sites. Our results suggest that pH-regulated recruitment and release of EF-1alpha from actin filaments in vivo will supply a high local concentration of EF-1alpha to facilitate polypeptide elongation by the F-actin-associated translational apparatus.

Actins↗
PubMed1996

A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3.

Knobloch syndrome (KS), characterized by high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele, was recently confirmed as autosomal recessive. Here we report the assignment of the gene for this syndrome to 21q22.3 with the marker D21S171 through homozygosity mapping in a highly inbred Brazilian family with 11 affected individuals. A total of nine markers spanning a region of 15.2 cM of the chromosome 21q22.3 were tested and the candidate region was restricted to an interval of 4.3 cM.

Abnormalities, Multiple↗
PubMed1996

Identification of cell subsets expressing intracytoplasmic cytokines within HIV-1-infected lymph nodes.

OBJECTIVE: To describe the endogenous cytokine profile of HIV-1-infected lymph nodes (LN) and to identify the phenotype of individual cells expressing intracytoplasmic cytokines. DESIGN AND METHODS: Whole LN biopsies were collected from three HIV-seronegative controls and four HIV-1-positive individuals with persistent generalized lymphadenopathy. Three had established infection (Centers for Disease Control and Prevention 1993 criteria, stages A2, C1 and C3) and one was undergoing seroconversion illness. A combination of three methods was used to assess the impact of HIV-1 on LN architecture and endogenous cytokine expression. Immunocytochemistry was used to locate follicular dendritic cells (FDC), interdigitating cells and T and B cells. Reverse transcriptase-polymerase chain reaction was used to assess mRNA for interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in collagenase-digested LN cells. Three-colour flow cytometry was used to identify intracytoplasmic cytokine expression within cell subsets. RESULTS: Germinal center (GC) hyperplasia was observed in LN from two patients with established HIV-1 infection, and the third, coinfected with Mycobacterium tuberculosis, showed extensive necrosis. In the patient undergoing seroconversion, there was an extensive FDC network within the expanded and confluent GC which covered expansive areas of the LN. There was varied expression of IL-1 beta, IL-4, IL-6, IL-10 and TNF-alpha mRNA from the four HIV-1-infected LN and the patient undergoing seroconversion showed evidence for a mixed cytokine profile, which also included IL-2 and IFN-gamma. Flow cytometry revealed intracytoplasmic IL-1 beta protein restricted to cells expressing CD19, CD21 and CD38 antigens. CONCLUSIONS: Cytokines were detected in freshly isolated HIV-1-infected LN cells without requiring an exogenous stimulus. Seroconversion was associated with an expanded FDC network within enlarged GC, bounded by defined mantle zones containing B cells. There was diverse cytokine mRNA expression and IL-1 beta protein was restricted to cells expressing B-cell-associated antigens.

Adult↗
PubMed1996

Transcervical gunshot injuries: mandatory operation is not necessary.

BACKGROUND: It has been suggested that all transcervical gunshot wounds should be explored surgically because of the high incidence of injuries to vital structures. The present prospective study investigated the clinical presentation, the role of various diagnostic investigations, and the need for surgery in patients with transcervical gunshot injuries. METHODS: Ninety-seven patients sustained gunshot injuries to the neck and 33 of them (34%) were transcervical. All victims were assessed clinically according to a written protocol and subsequently were evaluated angiographically, and, in the appropriate case, by means of endoscopy and esophagography. RESULTS: Overall, 24 (73%) of the 33 patients with transcervical gunshot wounds had injuries to cervical structures. Vascular injuries were found in 48%, spinal cord injuries in 24%, and aerodigestive tract injuries in 6% of patients with transcervical injuries. In the 64 patients without midline crossing, the incidence of cervical structure injuries was 31%. Despite the high incidence of injuries to cervical structures in transcervical wounds, only 21% of the patients had a therapeutic operation. The overall mortality was 3%. There were no in-hospital deaths or local complications in the nonoperatively managed group. CONCLUSIONS: The results of the present study do not support the current recommendations of mandatory operation for all transcervical gunshot wounds. A careful clinical examination combined with the appropriate diagnostic investigations should determine the treatment modality. About 80% of these patients can safely be managed nonoperatively.

Adolescent↗
PubMed1996

Mortality and prognostic factors in penetrating injuries of the aorta.

PURPOSE: This study was designed to investigate the epidemiology and prognostic factors determining survival in penetrating injuries of the aorta. PATIENTS AND METHODS: This was a retrospective analysis of all patients with penetrating aortic injuries, admitted to a large, level I trauma center. The following factors were analyzed for their role in determining survival: mechanism of injury, anatomical site of the aortic injury, initial blood pressure on admission, need for emergency room thoracotomy, and the introduction of a dedicated trauma program with an attending surgeon in-house. RESULTS: There were 93 patients with penetrating aortic injuries over a 5-year period. The abdominal aorta was injured in 67 patients (72%) and the thoracic aorta in 26 (28%). Most of the victims (82.5%) were admitted in shock and 41% had an unrecordable blood pressure on admission. Victims with injury to the thoracic aorta were more likely to have an unrecordable blood pressure on admission than patients with abdominal aortic injuries (73% vs 28.4%), and more likely to require an emergency room thoracotomy (76.9% vs 20.9%). Thirty-four patients (36.6%) required an emergency room thoracotomy and there were no survivors. The overall mortality was 80.6% (87.5% for gunshot injuries, 64.7 % for knife injuries). Patients with abdominal aortic injuries were three times more likely to survive than those with thoracic aortic injuries (23.9% vs 7.7%). The introduction of a dedicated trauma program, which resulted in significant reduction of mortality in other types of severe trauma, had no effect on the outcome in aortic injuries. CONCLUSIONS: Penetrating aortic injuries still have a very high mortality rate with no improvement in survival despite improved trauma services. Injury to the thoracic aorta, gunshot wounds, unrecordable blood pressure on admission, and the need for emergency room thoracotomy, are important predictors of high mortality.

Adolescent↗
PubMed1996

Risk behavior and HIV seroincidence among out-of-treatment injection drug users: a four-year prospective study.

We monitored trends in HIV risk behaviors and seroconversion among out-of-treatment injection drug users (IDUs) receiving street-based outreach intervention. Beginning in 1988, 641 HIV-seronegative IDUs were recruited by targeted sampling methods to reflect broader IDU populations and were followed for 4 years (1988-1992). All were active injectors not in treatment when recruited. Cohort members were targets of HIV-prevention outreach. The intervention was guided by the Indigenous Leader Outreach Model: Exaddicts deliver HIV-prevention services targeting IDU social networks in community settings. Primary outcome measures were HIV seroconversion and HIV risk behaviors. Observed incidence of HIV infection decreased, from 8.4 to 2.4 per 100 person-years. Prevalence of drug risk behaviors also decreased, from 100 to 14%. Seroconversion was associated with injection risk behavior [risk ratio (RR) = 9.8]. Sex risk behavior also decreased, but less dramatically, from 71 to 45%. Out-of-treatment IDUs in Chicago have reduced their rates of new HIV infection by reducing their injection risk behavior. New infections were strongly associated with injection risk behavior but not with sex risk behavior.

Adolescent↗
PubMed1996

Characterization of epitopes involved in the neutralization of Pasteurella haemolytica serotype A1 leukotoxin.

Defined segments of the leukotoxin A gene (lktA) from an A1 serotype of Pasteurella haemolytica were cloned into a plasmid vector and expressed as LacZ alpha fusion proteins. These fusion proteins were electrophoresed in SDS-PAGE gels and their immunoblotting reactivities with several monoclonal antibodies characterized. The epitope recognized by a strongly neutralizing monoclonal antibody was localized to a 32 amino acid region near the C terminus of the leukotoxin A (LktA) molecule. The epitope recognized by a non-neutralizing antibody was localized to a 33 amino acid region immediately adjacent. Smaller recombinant peptides containing these epitopes were not antigenic, but a polypeptide encompassing 229 amino acids at the C terminus evoked neutralizing antibodies when used to immunize specific-pathogen-free lambs. The distributions of linear epitopes recognized by this antiserum and by antisera raised to full-length recombinant LktA and to native LktA produced by P. haemolytica serotype A1 were determined by their reactivities with a set of overlapping 10 amino acid synthetic peptides. This revealed a complex distribution of linear epitopes at the C-terminal end of LktA. Toxin-neutralizing antibodies in convalescent sheep serum were shown to be directed against conformational epitopes by selective absorption of antibodies directed against linear epitopes.

Amino Acid Sequence↗
PubMed1996

Antenatal screening for cystic fibrosis.

OBJECTIVE: To assess the practicality of implementing antenatal screening for cystic fibrosis in Yorkshire. DESIGN: Prospective study in which all pregnant women were offered testing for the delta F508 mutation which accounts for about 85% of carriers in Yorkshire. The reproductive partners of those found to be cystic fibrosis carriers were then tested and any carrier referred for genetic counselling. SETTING: Antenatal clinics in two hospitals and eight general practices. POPULATION: Six thousand and seventy-one pregnant women. RESULTS: A total of 3773 women (62%) accepted the screening offer. This was a lower uptake rate than in other published UK studies: Aberdeen (85-91%), Manchester (85%), Edinburgh (76-84%) and Oxford (67%). Nonetheless there were large and statistically significant differences in the uptake rate between centres within the study: 78% and 60% for the two hospitals and 67% for the general practices. One hundred and thirty women (3.4%) were found to be carriers and three carrier couples were identified. The median time interval for the laboratory to produce a result was five days and the cost was pounds 16 on average. CONCLUSIONS: Antenatal screening for cystic fibrosis does not pose any special practical difficulties. It would be feasible to introduce it into routine practice in Yorkshire.

Attitude to Health↗
PubMed1996

Chronic TPA treatment inhibits expression of proximal tubule-specific properties by LLC-PK1 cells.

Confluent LLC-PK1 cell populations expressed progressively proximal tubule-specific properties, including gamma-glutamyl transpeptidase activity, sodium hexose symport activity, alkaline phosphatase activity, and villin protein. This was paralleled by an increase in villin protein manifested at the single cell level. Chronic treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited expression of proximal tubule-specific properties at the levels of enzyme activity, protein content, and mRNA content. Inhibition occurred in all cells of the population. TPA treatment induced a decrease in total protein kinase C (PKC)-alpha protein content and a change in subcellular localization from predominantly soluble to predominantly particulate. PKC-epsilon protein content was unchanged by TPA treatment. PKC-epsilon was localized in both soluble and particulate fractions of control cells but was localized predominantly in particulate fractions after TPA treatment. PKC-delta was barely detectable in control cells, but content was markedly increased by TPA. These results suggest that TPA-induced inhibition of expression of proximal tubule-specific properties is mediated through modulation of content and/or subcellular localization of one or more PKC isozymes, likely PKC-alpha.

Alkaline Phosphatase↗
PubMed1996

Occupational disease trends in black South African gold miners. An autopsy-based study.

The change in prevalence in silicosis and pulmonary tuberculosis in black South African gold miners dying from unnatural causes from 1975 to 1991 was studied. Data were analyzed for 16,454 black gold miners. Information on age at death, duration of service, year of autopsy examination, and the prevalence of silicosis and tuberculosis was collected. Analyses were done to assess secular trends in the prevalence of tuberculosis and silicosis, and to determine predictors of the diseases at death. The prevalence of tuberculosis increased from 0.9% in 1975 to 3.9% in 1991. The prevalence of silicosis increased from 9.3% to 12.8%. The prevalence of both diseases increased with age and duration of service. Silicosis was the most significant predictor of tuberculosis (odds ratio [OR] = 1.78, confidence limits [CL] = 1.27 to 2.30). A significant trend for tuberculosis, for year of autopsy, remained after adjustment for the other variables in the model, such as age and duration of service (p = 0.0046). In view of current labor stabilization in the South African mines, one can expect further increases in the prevalence of tuberculosis and silicosis. Lowering of dust levels in the mines is urgently required to prevent the increase of disease burden.

Adolescent↗