Biomedical subjects
Publications and source records attributed to C Keenan.
Lipoprotein lipase deficiency (LPLD) represents a rare ( < 1:100000), life-threatening neonatal condition, and a challenge for dietary management. We describe a neonate who developed diabetes mellitus as a feature of LPLD, without evidence of pancreatitis.
Concerns about dysfunctional alcohol use among lesbians and gay men are longstanding. The authors examined alcohol use patterns and treatment utilization among adults interviewed in the 1996 National Household Survey on Drug Abuse. Sexually active respondents were classified into 2 groups: those with at least 1 same-gender sexual partner (n = 194) in the year prior to interview and those with only opposite-gender sexual partners (n = 9,714). The authors compared these 2 groups separately by gender. For men, normative alcohol use patterns or morbidity did not differ significantly between the 2 groups. However, homosexually active women reported using alcohol more frequently and in greater amounts and experienced greater alcohol-related morbidity than exclusively heterosexually active women. Findings suggest higher risk for alcohol-related problems among lesbians as compared with other women, perhaps because of a more common pattern of moderate alcohol consumption.
The prevalence of factor V (FV) Leiden among normal populations has primarily been determined using blood donors. This control group is carefully selected and therefore may not accurately reflect the true prevalence within the population. We assessed the prevalence of FV Leiden within the Irish population using Guthrie card samples randomly selected from all newborns. We compared this result with the prevalence of FV Leiden within blood donors. A novel nested polymerase chain reaction (PCR) method for FV Leiden was developed for analysis of the Guthrie card samples. There was no significant difference between the allele frequency within the Guthrie card samples and blood donors (2.07% vs. 2.35%, P = 0.66)
The prothrombin G20210A polymorphism is associated with a threefold-increased risk of venous thrombosis. There is considerable variation in the reported prevalence of this polymorphism within normal populations, ranging from 0 to 6.5%. The prevalence within the Irish population has not been determined. A restriction fragment length polymorphism (RFLP)-based assay is commonly used for the detection of the prothrombin 20210A allele. This assay does not include a control restriction digest fragment and, consequently, failure of the enzyme activity or lack of addition of enzyme to the sample cannot be distinguished from wild-type prothrombin. We developed a RFLP-based assay, which incorporates an invariant digest site, resulting in the generation of a control digest fragment. Furthermore, we developed a nested polymerase chain reaction (PCR) method for the amplification and digestion of poor-quality or low-concentration DNA. In the Irish population studied, five of 385 (1.29%) were heterozygous and one patient was homozygous for the prothrombin 20210A polymorphism. This is the first reported data on an Irish or Celtic population and suggests that the allele frequency is similar to Anglo-Saxon populations. The nested PCR method successfully amplified and digested 100/100 (100%) of the archived samples; none of these samples could be analyzed by the standard single-round PCR method. In conclusion, nested PCR should be considered in the analysis of archived samples. Single-round PCR is appropriate for recently collected samples; however, an invariant control digest site should be incorporated in RFLP-based assays to validate the integrity of the digestion enzyme and limit the risk of false-negative results.
The Ramos-Burkitt lymphoma (BL) B cell line is driven into growth arrest and apoptosis by cross-linking surface immunoglobulin. We demonstrate that protein kinase C (PKC) activity is required for Ramos B cell proliferation and survival. A variety of PKC inhibitors trigger a significant decrease in [(3)H]thymidine incorporation with a concomitant increase in cell death. Antisense depletion of expression of the PKC-alpha isoform is sufficient to trigger cell death in the absence of any other signal, demonstrating a requirement for this isoform for survival of Ramos-BL B cells. Cross-linking surface immunoglobulin also leads to depletion of PKC-alpha levels, suggesting that this may be one mechanism by which this signals for cell death in Ramos-BL B cells.
The purpose of this study was to describe the associations between intimate relationships, characterized in terms of presence or absence of conflictive interaction with the partner, and the health and well-being of homeless women. A sample of 558 homeless women were administered structured interviews by trained nurses or outreach workers of the participants' ethnicity. Women answered questions about their general physical health, health-threatening behaviors (i.e., risky drug and sexual behaviors), health-promoting behaviors (i.e., TB and Pap testing), psychological well-being and symptomatology, self-esteem, coping, and life satisfaction. Women in nonconflictive relationships reported significantly greater psychological well-being, self-esteem, and life satisfaction and less hostility and noninjection drug use than women with conflictive relationships or those without an intimate partner. Women with conflictive relationships were significantly more anxious and depressed than those with nonconflictive relationships. Results suggest that, when possible, it is advisable to involve the intimate partner in programs to facilitate the emotional well-being of homeless women.
A qualitative research approach was used to explore the factors that influence the initiation of drug and alcohol use among homeless women and the health and social consequences of drug and alcohol use. The sample consisted of 238 women; of whom 209 women reported drug and/or alcohol use in the past month and 29 women reported no history of drug or alcohol use. Findings of the study revealed homeless women who currently used drugs and alcohol, homeless women who currently used drugs only, and to a lesser extent current alcohol users only, had suffered traumatic childhood events and family dysfunction and had to cope with low self-esteem, emotional distress, and poor physical health. The initiation of drug and/or alcohol use was strongly affected by the social influence of other users. In comparison, homeless women who did not use drugs or alcohol reported a positive self-image, few traumatic events, and chose partners who did not use drugs or alcohol. Common among current drug and/or alcohol users were the reported social benefits of drug use. Quantitative analyses revealed homeless women who were current drug users were significantly more likely to have experienced childhood and adult victimization as compared with women in the other groups. Thus, the need for social interventions and positive social support early in the lives of these women are strongly implicated in these findings.
The purpose of this study was to compare differences in personal, cognitive, behavioral, psychological, and social variables among homeless women who were current drug or alcohol users, or both, past drug or alcohol users, or both, and those who never used drugs or alcohol. The sample consisted of 1,013 women residing in 73 Los Angeles homeless shelters. Depression, anxiety, hostility, emotion-focused coping, lower self-esteem, and less social support were more prevalent among homeless women who continued to use drugs and alcohol than among past users or those who never used. AIDS knowledge was higher among past users. The results contribute important knowledge regarding the pattern of cognitive, psychological, and social differences between users and nonusers.
The protein kinase C family of serine-threonine kinases are important signal transducers participating in many different agonist-induced signalling cascades. PKC is activated by increases in diacylglycerol produced in response to agonist-induced hydrolysis of inositol phospholipids. PKC is thought to reside in the cytosol in an inactive conformation and translocate to the plasma membrane upon cell activation where it modifies various cellular functions through phosphorylation of target substrates. Increasing evidence has illustrated that this family of enzymes is capable of translocating to other subcellular sites than the plasma membrane. A key to understanding the functions of the members of this family is identifying their physiological substrates and their relationship with those target substrates. The idea that PKC may be an important regulator of cytoskeletal function has been suggested by numerous studies. Activation of PKC in a variety of different cell types leads to changes in the cell cytoskeleton including lymphocyte surface receptor capping, smooth muscle contraction and actin rearrangement in T cells and neutrophils. Given the ubiquitous expression of PKC and the diversity of cytoskeletons in different cell types it is not surprising that PKC has been shown to be associated with and/or phosphorylate a wide range of cytoskeletal components. This review examines the interaction of PKC with the cytoskeleton and discusses some of the cytoskeletal functions ascribed to PKC to date.
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Neonatal group B streptococcal infection is the primary cause of neonatal morbidity related to infection. It can often be prevented by identifying and treating pregnant women who carry group B streptococci or who are at highest risk of transmitting the bacteria to newborns. Increasing evidence and expert opinion support intrapartum treatment of women at relatively high risk of delivering an infant with group B streptococcal infection. Such women can be identified through the use of an anogenital culture for group B streptococci obtained at 35 to 37 weeks of gestation and by the presence of at least one of many risk factors associated with neonatal infection. These risk factors include preterm labor or rupture of the membranes at less than 37 weeks of gestation, previous delivery of an infant with invasive group B streptococcal disease, group B streptococcal bacteriuria during the present pregnancy, maternal intrapartum fever of 38 degrees C (100.4 degrees F) or higher and rupture of the fetal membranes for 18 hours or more. The recommended agent for intrapartum chemoprophylaxis is intravenous penicillin G; clindamycin is used in penicillin-allergic women. The use of risk markers alone to guide the administration of intrapartum antibiotics is much more cost-effective than other preventive strategies, but it exposes more women and infants to antibiotic-associated risks. Management of the infants of treated mothers is empiric and is currently guided by expert opinion.
This research examined the impact of including a supportive person on the outcomes of two culturally sensitive AIDS education programs, an education-only (traditional) program and a program combining education with self-esteem and coping enhancement (specialized). Research participants in this quasi-experimental study included 241 homeless women, who were randomly assigned by residence (drug treatment program or shelter) to one of four treatment groups. The outcomes measured at baseline, 6, and 12 months were risk behaviors, cognitive factors, and psychological functioning. Study results demonstrated significant improvements at both 6 and 12 months for the entire sample in all psychological, behavioral and cognitive outcome variables except active coping. Women in the specialized program improved more on AIDS knowledge and reduction in non-injection drug use than did those in the traditional program, but their active coping scores declined. Participation of a supportive person did not appear to have any effect on outcome.
Expression of certain mammalian protein kinase C (PKC) isoforms inhibits the proliferation of Schizosaccharomyces pombe (Goode et al., Mol. Biol. Cell 5 (1994) 907-920). We have taken advantage of this fact to determine the in vivo isoform preference of a number of PKC inhibitors, using a microtitre plate assay which allows rapid screening. This in vivo model has revealed previously unreported preferences; calphostin C is a more efficient inhibitor of the novel PKCS than chelerythrine chloride whereas the efficiencies are reversed for inhibition of the classical PKCgamma. We have also shown that the anti-leukaemic agent bryostatin 1 inhibits or activates in vivo in an isoform-specific manner.
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The repertoire of novel and atypical protein kinase C (PKC) isotypes present in human T cells and their subcellular localization have not been fully characterized. We detected calcium-independent PKC activity in whole cell fractions from unstimulated peripheral blood lymphocytes (PBL). Towards an understanding of the role of PKC isoforms in lymphocyte activation we have studied the expression of calcium-independent PKC isoforms theta, delta and eta in PBL. With isoformspecific antibodies we detected the presence of PKC theta and delta in whole cell fractions from unstimulated human PBL by Western blot analysis. In addition, immunocytochemical analysis confirmed the presence of the novel PKC isoform PKC eta in PBL. Using immunocytochemistry, PKC theta, delta and eta had distinct patterns of redistribution following activation by phorbol myristate acetate (PMA). However, signalling through the T-cell receptor (TCR) did not appear to induce such changes in isoenzyme redistribution. These findings indicate that activation of lymphocytes either through the TCR-CD3 complex or with PMA induces different signalling pathways with respect to calcium-independent isoenzymes. Signalling through receptors other than the CD3 complex may be involved in activation of these isotypes.