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Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 145 records · Page 8Linked to original sources

Idiopathic genital ulcers in women infected with human immunodeficiency virus.

A national survey of investigators caring for human immunodeficiency virus (HIV)-infected women was undertaken to describe the clinical presentation of idiopathic genital ulcer disease. Patients with negative syphilis and herpes simplex testing and/or negative genital ulcer biopsy were included in this study. Study participants (n = 29) were generally severely immunocompromised (median CD4 cell count was 50/mm3, and 68% had an acquired immunodeficiency syndrome [AIDS]-defining opportunistic process). Thirty-seven percent had coexistent oral ulcers and 19% had their genital ulcer progress to fistula formation (four rectovaginal and one vaginal-perineal). There was generally a favorable response to topical, systemic, and intralesional steroid treatment. This study suggests that idiopathic or probable aphthous genital ulcers in women have similar clinical characteristics to aphthous oroesophageal ulcers. Although infrequent, these genital ulcers can cause severe morbidity. Further research is warranted to better define the pathophysiology and optimal management.

Adult↗

A ribozyme gene and an antisense gene are equally effective in conferring resistance to tobacco mosaic virus on transgenic tobacco.

Ribozymes of the hammerhead class can be designed to cleave a target RNA in a sequence-specific manner and can potentially be used to specifically modulate gene activity. We have targeted the tobacco mosaic virus (TMV) genome with a ribozyme containing three catalytic hammerhead domains embedded within a 1 kb antisense RNA. The ribozyme was able to cleave TMV RNA at all three target sites in vitro at 25 degrees C. Transgenic tobacco plants were generated which expressed the ribozyme or the corresponding antisense constructs directed at the TMV genome. Six of 38 independent transgenic plant lines expressing the ribozyme and 6 of 39 plant lines expressing the antisense gene showed some level of protection against TMV infection. Homozygous progeny of some lines were highly resistant to TMV; at least 50% of the plants remained asymptomatic even when challenged with high levels of TMV. These plants also displayed resistance to infection with TMV RNA or the related tomato mosaic virus (ToMV). In contrast, hemizygous plants of the same lines displayed only very weak resistance when inoculated with low amounts of TMV and no resistance against high inoculation levels. Resistance in homozygous plants was not overcome by a TMV strain which was altered at the three target sites to abolish ribozyme-mediated cleavage, suggesting that the ribozyme conferred resistance primarily by an antisense mechanism.

Base Sequence↗

Complications of pediatric cochlear implantation.

Cochlear implantation has been established as a method of auditory rehabilitation for selected deaf children. However, as with any surgical procedure, complications can occur and may be particularly devastating in children. In this retrospective study, complications encountered in 100 consecutive cochlear implant surgeries in children were analyzed. Surgical problems were limited to one case of delayed, transient facial paresis and one cerebrospinal fluid gusher. These findings demonstrate that cochlear implantation can be performed safely with careful preoperative planning and meticulous surgical technique.

Cerebrospinal Fluid Otorrhea↗

The human lanosterol synthase gene maps to chromosome 21q22.3.

In order to contribute to the development of the transcriptional map of human chromosome 21 (HC21) we have used exon trapping to identify portions of HC21 genes. Using pools of random HC21-specific cosmids from the LL21NC02-Q library and cosmids from 21q22.3 we have identified five different coding regions with strong homology to the lanosterol synthase genes of rat and yeast. This enzyme catalyzes the cyclization of squalene-2,3-epoxide lanosterol, which is the parental compound of all steroids in mammals. Using somatic cell hybrids and HC21 yeast artificial chromosomes (YACS) and cosmids, we mapped the human lanosterol synthase cDNA gene to 2lq22.3 between markers D21S25 and 21qter. Cosmid Q7G8 from the LL21NC02-Q library and YAC 145D8 from the CEPH HC21 contig contain this human gene. We cloned a portion of the human lanosterol synthase cDNA (almost 85% of the coding region) from a brain cDNA library and determined its nucleotide sequence. The predicted human protein shows 83% identity to its rat and 40% to its yeast homolog. No obvious candidate human disease exists for lanosterol synthase deficiency and the role (if any) of triplication of this gene in the various phenotypes of trisomy 21 is unknown.

Amino Acid Sequence↗

A novel approach to the determination and characterization of HIV dementia.

BACKGROUND: Neuropsychological studies of the pattern and extent of cognitive impairment in HIV-infected patients have mostly used deviations from control values and/or cut-off scores as criteria for classification of dementia. There is, however, no agreement as to how to define impairment, and classification is imprecise. METHOD: The current study used a dementia classification matrix, developed with a step-wise linear discriminant analysis of neuropsychological data from patients with primary neurodegenerative dementias, to classify symptomatic HIV patients as demented or non-demented, and further to differentiate cortical and subcortical dementia patterns. Thirty-two male and 2 female patients (mean age 39 +/- 2) with symptomatic HIV disease (mean absolute CD4 count 195 +/- 41) participated in the study. RESULTS: Thirty-five per cent of patients were classified as demented. Of these, 83% showed a subcortical pattern and 17% a cortical profile of deficits. Significant differences between patients classified as subcortically demented and those categorized as normal on neuropsychological measures associated with subcortical integrity further validated the classification. Measures of psychiatric status between subgroups were similar. CONCLUSION: Since certain treatments may delay or reverse cognitive deficits, the use of an objective classification method based on discriminant analysis may help to identify patients who may benefit from therapy.

AIDS Dementia Complex↗

Intracellular location of the Saccharomyces cerevisiae CDC6 gene product.

The CDC6 gene product from Saccharomyces cerevisiae is required for transition from late G1 to S phase of the cell cycle. We have investigated the subcellular localization of the CDC6 protein in yeast to explore where Cdc6p exerts its gene function (s). Using affinity-purified sera we localized Cdc6p to the cytoplasm and the nuclear matrix by both subcellular fractionation and indirect immunofluorescence microscopy. The nuclear localization was confirmed to be in the nuclear scaffold by the low-salt extraction method. The Cdc6p cannot be detected in the mitochondrial or plasma membrane fractions. Using indirect immunofluorescence, we found that a subpopulation of Cdc6p migrated into the nucleus after G1/S transition and diminished after M phase, suggesting its temporal role in nuclear DNA replication. The predicted Cdc6p polypeptide contains a conserved nuclear localization, 27PLKRKKL33, similar to that of the SV40 large T antigen and other nuclear proteins. To test whether this peptide segment plays a role in mediating nuclear transport, we have carried out site-directed mutagenesis to alter the conserved 29Lys to Thr and Arg. The wild-type nuclear localization signal of Cdc6p was found to mediate the LacZ reporter gene fused to CDC6 efficiently to the nucleus, but not the mutated versions of the nuclear localization motif. The results suggested that 29Lys is important in mediating nuclear localization, the 29Thr and 29Arg mutant versions of the CDC6 gene were also unable to complement the cdc6 temperature-sensitive mutant. However, when these mutants were expressed from a multicopy plasmid, the mutated genes could complement the mutation. Similar results were obtained in the cdc6-disrupted cells. Taken together, we suggest that (i) Cdc6p is predominantly located in the cytoplasm, (ii) the nuclear entry of Cdc6p is cell cycle dependent, and (iii) nuclear entry of Cdc6p is mediated by its nuclear localization signal. The presence of Cdc6p in both the nucleus and the cytoplasm suggests a model that Cdc6p exerts its gene function in DNA replication and mitotic restraint in the cell cycle.

Amino Acid Sequence↗

The prevalence of MEN-1 in Tasmania.

BACKGROUND: An extensive programme was undertaken to trace and screen four known families in Tasmania with multiple endocrine neoplasia type 1 (MEN-1). METHODS: Written and personal contact was made with family members over the age of 20 years recommending a review by family practitioners for the purpose of recording their medical history and collecting a blood sample. Those suspected of MEN-1 were referred to our Department for further investigation. RESULTS: In January 1993, the total number of individuals alive and known to be affected by MEN-1 was 107, giving a prevalence of MEN-1 disease in Tasmania of 23/100 000. The estimated prevalence of MEN-1 trait in Tasmania (including affected cases and those considered at 50% risk of possessing the trait) is 45/100 000. CONCLUSION: The prevalence of MEN-1 has never previously been determined accurately. The prevalence of MEN-1 in Tasmania is at the upper end of the possible range and would justify the allocation of resources for screening programmes equal to those available for the detection of several less prevalent genetic diseases.

Adolescent↗

National Asthma Education and Prevention Program working group report on the quality of asthma care.

The quality of asthma care is the second topic of the National Asthma Education and Prevention Program Task Force Report on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care. This working group recommended an asthma continuous quality improvement model as an appropriate framework for examining the quality of asthma care. This model can be implemented by various organizations and providers of care in a variety of settings. The framework consists of four steps: (1) define the opportunity for improvement, (2) set the asthma quality improvement goals (outcomes), (3) characterize the process of care, and (4) begin the improvement cycle. Several case studies are presented to illustrate the use of this model in various settings, including managed care facilities, emergency departments, teaching hospitals, physician's offices, schools, workplaces, and communities. In addition, the appendix provides an overview of asthma outcome measures in the framework of patient-centered versus organizationally based perspectives.

Asthma↗

Evaluation of a parent child drug education program.

The purpose of the study was to evaluate the effectiveness of a parent-child drug education program. One thousand four hundred and forty-seven fourth, fifth, and sixth grade students and 2,036 of their parents participated in the study. Results indicated that the program produced changes in the responses of children and their parents to questions concerning attitudes, use, perceptions of use, and intended use of drugs.

Adult↗

A survey of physician use of treatment methods for functional enuresis.

We report a survey of treatment methods used by primary care physicians in Worcester, Massachusetts in the treatment of functional enuresis. The results suggest a predominance in the use of psychobehavioral over pharmacologic treatment methods and are in contrast to previous studies. Ninety-one percent of physicians reported recommending the use of rewards to control enuresis. Eighty percent of physicians reported using the "bell-and-pad" conditioning method for treatment of functional nocturnal enuresis, contrasted with 5% of physicians reported in previous studies. Fifty-two percent of physicians reported using medication for treatment of functional nocturnal enuresis, despite substantial evidence of its dubious efficacy.

Attitude of Health Personnel↗

Impact of theophylline use in Wolff-Parkinson-White syndrome.

Methylxanthine use in the treatment of apnea of prematurity is well documented. This drug is avoided in patients with aberrant pathways of conduction such as Wolff-Parkinson-White syndrome. In theory, methylxanthines enhance precipitation and exacerbation of tachyarrhythmias to which these patients are predisposed. This article reports a case of Wolff-Parkinson-White syndrome in a preterm neonate with severe apneic episodes in which methylxanthines were used. However, no adverse effects on cardiac rate or rhythm were encountered.

Aminophylline↗

Comparison of cognitive-behavioral therapy and clonazepam for treating periodic limb movement disorder.

Many patients with periodic limb movement disorder (PLMD) display inadequate sleep hygiene, and others decline conventional pharmacologic intervention for their form of sleep disturbance. Nonetheless, the use of nonpharmacologic therapies with PLMD remains unexplored. The current study was designed to compare the short-term treatment effects of a cognitive-behavioral therapy (CBT) and conventional pharmacotherapy (clonazepam) among a group of insomniacs with PLMD. The 16 subjects participating in this study first underwent baseline assessment procedures, including completion of a sleep log for 2 weeks, an ambulatory polysomnogram (APSG) and an Insomnia Symptom Questionnaire (ISQ). They then were randomized either to CBT (n = 8) or standard clonazepam therapy (n = 8). Subjects maintained sleep logs throughout a 4-week treatment and then completed a second APSG and ISQ. Comparison of pre- and post-treatment data suggested that the two treatments led to equal improvements in sleep log measures of sleep-wake times and ISQ measures of subjective sleep concerns. Patients treated with CBT showed a decrease in daytime napping, whereas the clonazepam group reported increased napping. Conversely, those treated with clonazepam showed larger declines in periodic limb movement-arousals per hour of sleep than did the CBT group. Post-treatment interviews suggested that both CBT and clonazepam therapies were generally well tolerated by study participants. It is concluded that both treatments may be useful for PLMD but that the two treatments may have contrasting effects across selected measures of improvement. Additional research is needed to examine the long-term efficacy of CBT as a primary or adjunctive treatment for varying levels of PLMD severity.

Aged↗

[Acculturation, identity and well-being: the adjustment of Somalian refugees].

This study examines the links between acculturation and psychological adjustment of 94 Somalian refugee women. On a group level, the preferred mode of acculturation is integration. Somalian women who have lived the longest in Canada identify more as Canadians and perceive more discrimination against themselves and against Somalians in general. Moreover, the endorsement of the mode of acculturation by integration implies a refusal of other modes such as assimilation, rejection and marginalization. Important links are also established between age, the desire to take part in Canadian society and mental health. Young women especially distinguish themselves from the group as they have a tendency to have a higher level of depression. Moreover, those refugees who have emigrated for political reasons wish to return to their homeland and are less satisfied with their life in Canada.

Acculturation↗

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗