Zidovudine-resistant variants of HIV-1 in lung.
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Biomedical subjects
Publications and source records attributed to D Mitchell.
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1. We measured body core and scrotal temperatures (Tbody and Tscrotum, respectively) of rams during 5 h of hot (40 degrees C) and cold (6 degrees C) exposure, for 6 h following intravenous injections of saline (0.9% NaCl) or 0.4 micrograms kg-1 of the purified lipopolysaccharide endotoxin of Salmonella typhosa (LPS), during 40 min of treadmill exercise, and for several days in their pens. 2. At 20-23 degrees C ambient temperature there were significant, but out of phase, circadian variations in Tbody and Tscrotum. Tscrotum was 3.30 +/- 0.03 degrees C lower than Tbody on average. 3. During cold exposure the tunica dartos muscles contracted, nevertheless Tscrotum fell and Tbody-Tscrotum increased. During heat exposure the tunica dartos muscle relaxed and scrotal sweat glands were activated, nevertheless Tscrotum rose and Tbody-Tscrotum decreased. There was no change in Tscrotum after LPS injection or during exercise, but Tbody increased in both cases. 4. We suggested that Tscrotum is regulated independently of Tbody via a feedback circuit involving scrotal thermoreceptors and effectors in the form of tunica dartos muscle activity and scrotal sweat gland activity. This local circuit is not affected by adjustments to the general thermo-regulatory control system during fever. The effector mechanisms were insufficient to maintain Tscrotum during the extremes of heat and cold exposure.
Three methods for preparing hydrophilic coatings on polysiloxane bonded CElect H-type capillary electrophoresis columns have been shown. The polyalkylsiloxane-bonded phase is the first coating layer on the capillary surface, and nonionic surfactant, hydrophilic polymer, or polymer surfactant, adsorbed onto this first later through hydrophobic interactions, forms the second coating layer. The resultant capillary surfaces are inert, hydrophilic, and suitable for highly efficient protein separations. The effectiveness and applicability of these capillary surface modification methods were tested for the separations of a variety of proteins over a wide range of buffer pH values under different capillary electrophoretic operations modes.
Following induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87-99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87-99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against interleukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in the lesion.
Our understanding of the epidemiology of astrovirus-associated gastroenteritis has changed markedly with each improvement in detection method. In early surveys based on electronmicroscopy (EM), astroviruses appeared to be a rare cause of gastroenteritis, being found in fewer than 1% of children with diarrhea, usually in small outbreaks of disease and primarily during the winter season. The development and use of monoclonal antibodies and enzyme immunoassays (EIA) to detect astroviruses led to reports of a higher prevalence (2.5%-9%) of astrovirus infection among patients hospitalized with diarrhea. Astroviruses appeared second only to rotaviruses as a cause of hospitalization for childhood viral gastroenteritis. Studies based on EIA detection of astroviruses indicate that astroviruses are common causes of diarrhea in children worldwide, and that most children are infected during their first two years of life. The elderly and the immunocompromised represent high-risk groups as well. The observations that newborns monitored prospectively rarely have repeat disease and that the rate of detection decreases with increasing age suggest that immunity to astroviruses, as immunity to rotaviruses, may develop early in life. The cloning and sequencing of astroviruses have led to more sensitive assays to detect the viruses by reverse transcription, polymerase chain reaction (RT-PCR). Application of RT-PCR for detection of astroviruses in children in day-care centers showed a marked increase in the detected prevalence of astrovirus-associated diarrhea, the rate of asymptomatic infection, and the duration of shedding of virus among those infected, when compared with studies that used other methods. As with rotaviruses, neither the mode of transmission nor the reservoir of astrovirus infection has been identified. Both immune and molecular-based assays to detect astrovirus serotypes indicate that serotype 1 is most common worldwide, although the predominant serotypes may vary by region and time. In the absence of obvious strategies to prevent astrovirus-associated diarrhea, vaccines might be considered if further studies establish that the disease burden would render such a vaccine cost-effective.
OBJECTIVE: To determine change in nutrient intakes, number of servings, and contributions of total fat from food groups in children who lowered their dietary fat intake. DESIGN: A research and demonstration study designed to lower plasma low-density lipoprotein cholesterol level. There were four study groups: two intervention and two control groups. All children had hypercholesterolemia except for those in one control group. There 24-hour dietary recalls were collected on randomly assigned days over a 2-week period at baseline and 3 months after the intervention. SUBJECTS: Three hundred three 4-to 10-year old children from suburbs north of Philadelphia, Pa. INTERVENTIONS: One intervention involved a home-based, parent-child autotutorial program (PCAT group) with audiotaped stories and print materials for the children and their families; the other intervention involved one face-to-face counseling session with a registered dietitian (counseling group). OUTCOME MEASURES: Change in mean nutrient intakes compared with the Recommended Dietary Allowance (RDA); change in number of servings and mean grams of total fat contributed from 10 different food groups. STATISTICAL ANALYSES PERFORMED: Analyses of variance and chi 3 analyses. RESULTS: Children in every study group had mean intakes of all nutrients (except vitamin D) greater than 67% of the RDA 3 months after the baseline measurement. Several food groups (ie, meats, dairy products, fats/oils, and desserts) provided less total fat to the diets of children who reduced their dietary lipid intake after 3 months (i.e., PCAT and counseling groups). These children also reduced the mean number of servings selected from these food groups. Within these same food groups, some children consumed fewer servings of higher fat foods and more servings of lower fat foods. APPLICATIONS/CONCLUSIONS: Children who lowered their dietary fat intake after intervention reported both quantitative and qualitative changes in food choices from several food groups. These choices did not significantly reduce their nutrient intakes.
The Kamami technique of laser-assisted uvulopalatoplasty has recently been introduced into British practice as an office-based multistage procedure for the treatment of snoring and, in certain cases, for obstructive sleep apnoea. We have treated 50 patients with simple snoring, with a minimum follow-up of six months. Six-month telephone interview follow-up has assessed partner and patient satisfaction, as well as willingness to undergo the procedure again. We have found the procedure easy to perform with no serious intra-operative complications. Thirty-four (68 per cent) of patients' partners have been definitely satisfied with the results of treatment, with 11 (22 per cent) definitely unsatisfied. However, only 25 of these 34 satisfied patients (76 per cent) would be prepared to undergo the treatment again with post-operative pain and discomfort cited as the reason in those who would not. The failure rate doubled between one and six months post-operatively. There have been no serious complications but a 40 per cent minor side-effect rate is noted. These results are discussed in the context of previously reported results, with consideration of future strategies to improve outcome.
A case of left otalgia in a patient suffering from longstanding ulcerative colitis is reported. The patient was treated for an exacerbation of his disease with courses of mesalazine and sulphasalazine during which time he developed otalgia. The otalgia disappeared with cessation of the drugs. It is concluded that in the absence of any other head and neck cause that the otalgia was a complication of the drug therapy.
Current data from in vitro and in vivo animal models indicate that fibronectin-binding integrin receptors expressed by colon cancer cells may regulate tumour growth. While individual members of the beta 1 subfamily of integrins have now been clearly identified in colorectal cancer, little information exists with respect to the alpha V subfamily. In the present study we show that alpha V can associate with multiple and different beta subunits capable of binding fibronectin in this tumour type. This is likely to have functional implications for growth and spread of colorectal cancer.
We measured somatosensory-evoked potentials in athletes to determine whether there were differences in somatosensory pathways related to sports performance or training. Seven sedentary subjects, 10 endurance runners, and seven elite gymnasts of similar height and weight were investigated. Peak latencies and amplitudes were measured of P9, P11, P13/14, N20, P25, and N30 waves, following electrical stimulation of the median nerve at the wrist. Central and peripheral conduction speeds of the sensory pathway were calculated. The subjects also completed a simple reaction test to a visual stimulus. There were no significant differences between the groups in any of the attributes we measured. The was a positive correlation between years of training undergone and the amplitude of N20, a negative correlation between the amplitudes of P11 and P13/14 and the number of hours of training undertaken per week, and a positive correlation between the amplitude of N30 and the simple visual reaction time. We conclude that the gymnasts, runners and sedentary subjects had no differences in somatosensory pathways, as measured using standard clinical procedures for evaluating somatosensory-evoked potentials.
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Nitric oxide (NO) has been shown to be a potent vasodilator released from endothelial cells (EC) in large blood vessels, but NO release has not been examined in the capillary bed. Because the capillary bed represents the largest source of EC, it may be the largest source of vascular NO. In the present study, we used intravital microscopy to examine the effect of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the microvasculature of the rat extensor digitorum longus muscle. L-NAME (30 mM) applied locally to a capillary (300 micron(s) from the feeding arteriole) reduced red blood cell (RBC) velocity [VRBC; control VRBC = 238 +/- 58 (SE) micron/s; delta VRBC = -76 +/- 8%] and RBC flux (4.4 +/- 0.7 to 2.8 +/- 0.7 RBC/s) significantly in the capillary, but did not change feeding arteriole diameter (Dcon = 6.3 +/- 0.7 micron, delta D = 5 +/- 7%) or draining venule diameter (Dcon = 10.1 +/- 0.6 micron, delta D = 4 +/- 2%). Because of the VRBC change, the flux reduction was equivalent to an increased local hemoconcentration from 1.8 to 5 RBCs per 100 micron capillary length. L-NAME also caused an increase in the number of adhering leukocytes in the venule from 0.29 to 1.43 cells/100 micron. L-NAME (30 mM) applied either to arterioles or to venules did not change capillary VRBC. Bradykinin (BK) locally applied to the capillary caused significant increases in VRBC (delta VRBC = 111 +/- 23%) and in arteriolar diameter (delta D = 40 +/- 5%). This BK response was blocked by capillary pretreatment with 30 mM L-NAME (delta VRBC = -4 +/- 27%; delta D = 5 +/- 9% after BK). We concluded that NO may be released from capillary EC both basally and in response to the vasodilator BK. We hypothesize that 1) low basal levels of NO affect capillary blood flow by modulating local hemoconcentration and leukocyte adhesion, and 2) higher levels of NO (stimulated by BK) may cause a remote vasodilation to increase microvascular blood flow.
OBJECTIVE: Clinicians should have information about patients' sexual abuse history as early as possible, because a history of sexual abuse may affect psychiatric patients' presentation of symptoms and response to treatment. The authors surveyed a nationwide sample of acute inpatient psychiatric facilities to determine whether a history of sexual abuse was completed on admission. METHODS: A survey questionnaire about current practices relating to assessment of patients' history of sexual abuse was sent to nurse managers at every general hospital in the U.S. that offered inpatient psychiatric services (N = 1,410). RESULTS: Although respondents at 69 percent of the 466 facilities that participated in the survey believed that the admission assessment of psychiatric patients should always include a history of sexual abuse, only 43 percent of responding facilities included such histories in the admission assessment. Reasons for not including the history included patients' and staff members' unwillingness to discuss sexual abuse, lack of staff competence in discussing the issue, and duplication of data collection that occurs later in the patient's hospital stay. CONCLUSIONS: Nurse managers of inpatient psychiatric services in general hospitals recognize the importance of including an assessment of patients' history of sexual abuse in the admission assessment but report several obstacles to implementing this procedure.
This paper considers the place of learning disability nursing within the profession in the 1940's and 1950's. A number of sources are discussed, which throw light on the problem of recruitment to this branch of nursing as well as its future as seen at the time. Comparisons are drawn between it and other types of nursing and conclusions are drawn about the extent to which it was a valued part of the profession.
The concentration of MoFe protein (Av1) in Azotobacter vinelandii whole-cell crude extract was measured by electron paramagnetic resonance spectroscopy at g = 3.7 resonance. The Av1 concentration was also measured from the activity of crude extract to which increasing amounts of purified Av1 and Av2 were added. The Av2 concentration was determined by fitting activity measurements of crude extract and crude extract to which purified Av2 was added. The Av1 concentration was found to be 26-28 microM and that for Av2 was 42-45 microM in whole cells, with a Av2/Av1 ratio of 1.6. In vitro activity measurements carried out as a function of Av1 concentration at Av2/Av1 ratios of 1 and 4 showed a dilution effect below 0.08 microM, a factor of 2 below that observed for nitrogenase reactivity for Klebsiella pneumoniae. No deviations from linearity were observed up to 26 microM for the Av1-Av2 interaction. The flavoprotein (AvFlp) was shown to enhance nitrogenase reactivity at low Av2/Av1 ratios, a result attributed to decreasing the Km for Av2-Av1 interaction. Direct reduction of bound Av2 is possibly the source of this kinetic enhancement. The kinetic results are considered in terms of the Thorneley and Lowe scheme.
Melanin is thought to serve in photoprotection. To investigate this, we have compared the responses of cultured human melanocytes derived from different pigmentary phenotypes (skin types I-VI) to a single irradiation with different doses of UVB light, ranging between 11.7 and 70.1 mJ/cm2. After UVB irradiation, heavily pigmented melanocytes had the same percent survival but a greater capacity to resume proliferation than their lightly pigmented counterparts. A significant increase in melanin content was observed in heavily pigmented but not in lightly pigmented melanocytes. Irradiation with UVB light blocked melanocytes, regardless of their melanin content, in G1, and induced the expression of the tumor suppressor p53 protein within 4 h. This induction steadily increased up to 48 h in lightly pigmented melanocytes; however, in heavily pigmented melanocytes, p53 level peaked at 24 h after UVB treatment and declined thereafter. Additionally, DNA from lightly pigmented melanocytes contained significantly higher numbers of cyclobutane pyrimidine dimers than did DNA from heavily pigmented melanocytes after irradiation with increasing doses of UVB light. We speculate that the prolonged induction of p53 in lightly pigmented melanocytes arrests them in G1 for a long time period in order to repair extensive DNA damage. The above described differences might partially explain the increased susceptibility of individuals with lightly pigmented skin compared to individuals with dark skin to the photodamaging and photocarcinogenic effects of sun exposure.