Biomedical subjects
Publications and source records attributed to Robert Hunter.
The first atom transfer radical graft copolymerisation at ambient temperature in water from a soluble polysaccharide is demonstrated for a range of monomer types.
The synthesis of several novel aza-stilbene derivatives was carried out. The compounds were tested for their c-RAF enzyme inhibition. Compound 27 possesses significant potency against c-RAF and demonstrates selectivity over other protein kinases. A hypothesis for the binding mode, activity, and selectivity is proposed.
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Arylamine N-acetyltransferase (NAT) genes were targeted for inhibition using short hairpin RNA (shRNA) using two different RNA polymerase III promoters. Constructs were developed for NAT1 and NAT2, the endogenous mouse genes, and for human NAT1. There were fetal and neonatal deaths with these constructs, perhaps due in part to an interferon response as reflected in increases in oligoadenylate synthetase I mRNA levels. Seven out of 8 founders with the U6 promoter generated offspring but only 2 gave positive offspring. Out of 15 founders for H1 promoted constructs, only 4 had positive offspring. When transgenic lines were successfully established, the expression of the targeted genes was variable between animals and was not generally inhibitory.
We report the selective catalytic cleavage of the HIV coat protein gp120, a B cell superantigen, by IgM antibodies (Abs) from uninfected humans and mice that had not been previously exposed to gp120. The rate of IgM-catalyzed gp120 cleavage was greater than of other polypeptide substrates, including the bacterial superantigen protein A. The kinetic parameters of gp120 cleavage varied over a broad range depending on the source of the IgMs, and turnover numbers as great as 2.1/min were observed, suggesting that different Abs possess distinct gp120 recognition properties. IgG Abs failed to cleave gp120 detectably. The Fab fragment of a monoclonal IgM cleaved gp120, suggesting that the catalytic activity belongs to the antibody combining site. The electrophoretic profile of gp120 incubated with a monoclonal human IgM suggested hydrolysis at several sites. One of the cleavage sites was identified as the Lys(432)-Ala(433) peptide bond, located within the region thought to be the Ab-recognizable superantigenic determinant. A covalently reactive peptide analog (CRA) corresponding to gp120 residues 421-431 with a C-terminal amidino phosphonate diester mimetic of the Lys(432)-Ala(433) bond was employed to probe IgM nucleophilic reactivity. The peptidyl CRA inhibited the IgM-catalyzed cleavage of gp120 and formed covalent IgM adducts at levels exceeding a control hapten CRA devoid of the peptide sequence. These observations suggest that IgMs can selectively cleave gp120 by a nucleophilic mechanism and raise the possibility of their role as defense enzymes.
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BACKGROUND: Müllerian agenesis, the second most common cause of primary amenorrhea, affects 1 in 4,000 to 10,000 women. Although the majority of these women have complete absence of the uterus, a small percentage can have a rudimentary uterus. CASE: A menopausal nulligravida with known müllerian agenesis developed a large pelvic mass and an inguinal hernia. The patient underwent an exploratory laparotomy, which revealed a large leiomyoma growing from a small rudimentary uterus, an indirect inguinal hernia, and bilateral benign serous cystadenofibroma. CONCLUSION: Women with müllerian agenesis and rudimentary uteri can develop gynecologic pathology similar to women with normal genital tracts.
This study evaluated the gross and microscopic effects of serial blood collection from six ball pythons (Python regius) by using cardiocentesis. We collected 39 blood samples from each snake over a 120-day period. Cardiocentesis was performed on manually restrained snakes, with each sample requiring approximately 15 sec to collect. No clinically apparent complications were noted in any of the snakes after the cardiocentesis procedures, and all snakes survived until they were euthanized 73 days after the last blood sample. Minimal gross lesions were noted at necropsy; faint brown pigmentation of the pericardium was present in five of six snakes, and three snakes had approximately 0.5 ml dark pigmented fluid in the pericardial space. One snake had a small, organized hematoma in the pericardial space. Microscopic findings were limited to moderate and regularly arranged collagen fibrosis and focal thickening of the epicardium. The pericardial sac in all snakes had a mild infiltrate of hemosiderin-laden macrophages and small numbers of heterophils. The results suggest that serial cardiocentesis is well tolerated in ball pythons.
HIV infection usually results in a gradual deterioration of the immune system. It is evident that early recognition of progression markers during HIV infection from asymptomatic to symptomatic state is needed. In the present cross-sectional study, peripheral blood lymphocytes from 63 HIV-infected Puerto Rican individuals were analyzed by two-color flow cytometry to study the co-expression CD45RA and CD45RO on both CD4+ and CD8+ T-cells and its correlation with age, gender, CD4 count, CD4:CD8 ratio, anti-retroviral therapy, clinical status, and viral load. Measurement of T-cell subsets in these patients showed an excessive increase of CD3+CD8+, CD8+CD45RA+, and CD8+CD45RO+ T-cells as disease progresses. In contrast, it was also observed a significant decrease in CD3+CD4+, CD4+CD45RA+ and CD4+CD45RO+ T-cells. The distribution of CD8+CD45RA+ T-cells did not change significantly between HIV and AIDS cases suggesting that this T-cell subset is not a good progression marker. Interestingly, CD4+CD45RA+ T-cells were significantly difference between genders, and CD44+CD45RA+ and CD8+CD45RO+ T-cells were influenced by age. In conclusion, the distribution of naïve/memory CD4+ T-cells and memory CD8+ T-cells significantly correlate with HIV infection in disease progression. It is also important to mention that these T-cell subpopulations may be influenced by both gender and age. Overall, these results suggest that a loss in the generation of new immune response and function may be occurring during disease progression. This study open new windows of understanding that will be beneficial for future studies on immunopathogenesis, diagnosis, prognosis, and treatment monitoring for HIV/AIDS.
Greater Glasgow Health Board's strategy for the development of community mental health services includes the establishment, over a 7-year period, of multi-disciplinary community mental health resource centres throughout Glasgow. An evaluation of the first phase of the development was carried out in three resource centres. This focused on three key themes: the establishment of multi-disciplinary teams, targeting of those with the most severe illnesses and the participation of users in the care process. The evaluation exercise comprised five substantive elements: analysis of the clinical database; interviews with staff within each of those centres, interviews with representatives of key external agencies associated with each centre; a survey of general practitioners; and a survey of the views of clients, their carers, their key workers, and their general practitioners (GPs). Clients were generally very satisfied with the services and felt that the resource centres met all their mental health needs. Although the majority of current centre cases had severe mental illnesses and those with the more severe conditions had the highest contact rates there was evidence that in the absence of a clear framework for referral the centres were also providing services for those with less severe illnesses. Despite a wish by centre staff to move towards modes of working less dominated by health professionals and more inclusive of other resources and especially of clients themselves, these goals remained to be achieved: there was a lack of clarity in the definition of the appropriate target groups for the centres; access to crisis support was regarded as problematic; the concept of multi-disciplinary team working had yet to be fully realized with evidence suggesting that some psychiatrists working in the resource centres had not embraced many aspects of the new approach to service delivery including a focus on the severely ill; and progress towards the ideal of active client involvement had been slow.
To examine the prevalence of problem gambling and its relationship to other risk-taking behaviors, the authors surveyed 1,350 undergraduates at the 4 campuses of Connecticut State University (CSU) during fall 2000. On the basis of a modified version of the South Oaks Gambling Screen, a widely used screening instrument, they found that 18% of the men and 4% of the women reported that gambling had led to at least 3 negative life consequences (eg, felt guilty, gambled more than intended), commonly defined as problem gambling. Students identified as problem gamblers, compared with other students, were significantly more likely to be heavy drinkers, report negative consequences of alcohol consumption, and be regular tobacco and marijuana users. Problem gambling was related to binge eating and greater use of weight-control efforts. University athletes were also found to have significantly greater problem gambling rates than nonathletes. The majority of students gambled but experienced few of the negative consequences reported by problem gamblers.