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Biomedical subjects

M West

Publications and source records attributed to M West.

At least 19 recordsLinked to original sources
PubMed1992

Characterization and purification of a novel transcriptional repressor from HeLa cell nuclear extracts recognizing the negative regulatory element region of human immunodeficiency virus-1 long terminal repeat.

Cellular transcription factors play critical roles in regulating human immunodeficiency virus (HIV) gene transcription, although the precise mechanism(s) defining their roles are not well established. Primarily it has been suggested that sequence-specific interaction of trans-activating proteins with cis-acting DNA elements plays a crucial role in regulating the target genes. The negative regulatory element (NRE) of HIV-1 long terminal repeat (LTR) is one such defined region that has been reported to down-regulate LTR-directed HIV gene expression. Information regarding the role of this region in the regulation of HIV expression is lacking. Here we describe an attempt to further characterize the role of NRE cis-elements and define any sequence-specific interaction with cellular factors. Using gel mobility shift DNA-binding and Southwestern blot assays, we have mapped a distinct region of NRE (-290 to -260, a 30-base pair (bp) domain of NRE-A) sequences of HIV-1 LTR, which recognizes a specific DNA-binding protein from HeLa cell nuclear extracts. This factor is a 38-kDa polypeptide which can be affinity-purified to near homogeneity by this 30-bp specific oligonucleotide in affinity chromatography. The cellular factor from HeLa cell nuclear extract exhibits specific interaction only with the 30-bp NRE-A domain of HIV-1 LTR and acts as a strong transcriptional repressor/inhibitor molecule in the DNA-protein gel binding, as well as in vitro transcriptional studies with the nuclear extracts from cells with productive HIV-1 infection. To our knowledge, this is the first report of a factor recognizing a distinct segment within NRE that has been shown to exert an inhibitory effect on transcriptionally active DNA-protein "pre-initiation" complex formation, suggesting a possible role in HIV-1 gene regulation.

Base Sequence↗
PubMed1992

Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic pyridobenzoxazepinones and dibenzoxazepinones.

Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)-ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as low as 19 nM. A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency. Substitution in the C-ring is generally neutral or detrimental to activity. Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted. Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.

Dibenzoxazepines↗
PubMed1992

Long-term benefits of therapy with cyclophosphamide and prednisone in patients with membranous glomerulonephritis and impaired renal function.

Long-term follow-up data are provided for a previously reported study of patients with membranous glomerulonephritis (MGN), nephrotic syndrome, and renal function impairment. Nine patients were treated with cyclophosphamide (1 to 2 mg/kg) and six of these received concurrent prednisone; they are compared with 17 concurrent controls (14 of whom had received prednisone at some time). The mean follow-up is 83 +/- 13 months in the treated patients and 64 +/- 7 months in the controls. Of the nine treated patients, four achieved a complete remission from the nephrotic syndrome (proteinuria less than 0.5 g/d), and five a partial remission (proteinuria decreased by at least 50% and to less than 3.5 g/d). One of the nine treated patients and 10 of the 17 controls have reached end-stage renal disease (ESRD) (P less than 0.05). Nine of the controls reaching ESRD had persistent nephrotic syndrome, whereas of the seven controls who have not yet reached ESRD, only two have persistent nephrotic syndrome (chi 2, P less than 0.02). There have been four relapses in three treated patients, and three of the four have responded to repeat therapy. One patient refused full therapy and remains nephrotic. Life-table analysis demonstrates significantly increased survival from ESRD in treated patients as compared with controls (P = 0.04).

Adult↗
PubMed1992

The two-view radionuclide ventriculogram. Advantages of the LPO view.

This report is a prospective study of 33 male patients who underwent both contrast ventriculography (CVG) and radionuclide ventriculography (RVG) within a 24-hour period. Expert, blinded observers graded the left ventricle's regional wall motion (RWM) in the left anterior descending (LAD), left circumflex (LCx), and posterior descending arterial (PDA) distributions on right anterior oblique (RAO), and left anterior oblique (LAO) CVGs, and on anterior (ANT), LAO, 70 degrees left anterior oblique (LAO70), and left posterior oblique (LPO) RVGs. When statistically compared with CVG RWM standard data, RVG studies composed of LAO and LPO views were equal to the RVG studies composed of ANT, LAO, and LAO70 views in assessment of the LAD and LCx distributions. The RVG with LAO and LPO views was superior to the RVG with ANT, LAO, LAO70 in the detection of the posterior descending artery RWM. The authors conclude that accurate assessment of RWM is efficiently performed with the RVG composed of LAO and LPO views.

Coronary Artery Disease↗
PubMed1992

The assessment of dimensions relevant to adult reciprocal attachment.

The development and potential clinical uses of the Adult Attachment Dimensions Questionnaire is described. The seven scales of the Adult Attachment Dimensions Questionnaire relate to the aspects of a relationship formed to promote and maintain security. The underlying theory is founded on John Bowlby's work on the attachment behavioural system. The empirical validation was accomplished through three studies involving a clinical group and a non clinical group in a hospital setting and respondents to a community survey. Psychometric validation included measures of internal reliability, test-retest reliability, and construct validity through factor analysis. The resultant 35 item questionnaire should be useful to both clinicians and researchers interested in the characterization of the attachment system for adults.

Adult↗
PubMed1992

Intergenerational geriatric remotivation.

This piece of a larger study on intergenerational geriatric remotivation discusses influential program variables. Interviews, participant observation, and videotapes were used to study a program in the Southeast and a comparison program in the Midwest. The variables examined were frequency, longevity, and constancy of intergenerational contact, problem discovery and problem resolution procedures, physical environment, and activity structure. As practitioners contemplate establishing intergenerational programs, a number of issues regarding program structure need to be considered to ensure that outcomes match expectations.

Aged↗
PubMed1992

Ultraviolet radiation and its role in wound pattern documentation.

The history of ultraviolet illumination in photography is discussed. Particular attention is devoted to the forensic aspects of ultraviolet photography as it relates to patterned injury on human skin. The authors discuss the theory underlying ultraviolet illumination of wounds on skin as well as the equipment required for this type of imaging.

Documentation↗
PubMed1991

Complications of the transsphenoidal approach to sellar lesions.

Transsphenoidal surgery is currently performed extensively for lesions of the sella turcica. The mortality and morbidity of this surgical approach are minimal, and the results satisfactory overall. Only a few studies have addressed the complications of this approach. The authors present a retrospective study of 200 transsphenoidal procedures in 196 patients over an eleven year period. There was one death due to meningitis. Major morbidity consisted of intraventricular hemorrhage in three patients, false aneurysm of the internal carotid artery in one patient and thalamic infarction in another patient. Minor morbidity details are presented. The pathogenesis of the most serious of these complications along with possible preventive measures are discussed.

Brain Diseases↗
PubMed1991

Efficacy of SIV/deltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys.

Immunization with an inactivated whole-virus vaccine is highly effective in preventing lentivirus infection. The viral protein(s) essential to the induction of protective responses, however, have not been identified. To define the role of virion components in the induction of protective immunity, we evaluated the efficacy of glycoprotein-enriched and glycoprotein-depleted simian immunodeficiency virus (SIV) subunit vaccines prepared by lentil-lectin affinity chromatography of gradient-purified virions using the immunization and challenge regimen previously found successful with an inactivated whole-virus vaccine. Infection was determined by successful recovery of virus, the induction of SIV-specific antibody responses, and infection of naive recipients by inoculation with lymph-node-derived lymphocytes from the vaccinates. Immunization with the glycoprotein-enriched preparation prevented infection in two out of four monkeys, whereas the glycoprotein-depleted vaccine failed to prevent infection in all four vaccinates tested. However, the glycoprotein-depleted vaccine appeared to moderate the progression of SIV-induced disease compared with non-immunized infected control monkeys inoculated with the same challenge dose. These data suggest that subunit vaccines containing sufficient quantities of viral glycoproteins can protect against SIV infection, whereas subunit vaccines composed predominantly of viral core proteins cannot. The development of effective vaccines against HIV infection should include studies on the optimum presentation of the viral envelope glycoproteins to produce long-term broadly protective immune responses.

Animals↗
PubMed1991

Interviewing institutionalized elders: threats to validity.

In the course of an ethnographic study of an intergenerational Geriatric Remotivation Program in a Southeastern U.S. nursing home, we encountered difficulties in interviewing institutionalized elders that threatened the validity of the data. The purpose of this paper is to explicate the difficulties and to recommend strategies for overcoming them. Four main clusters of elder characteristics threatened the validity of data: (1) physical characteristics; (2) cognitive characteristics; (3) affective characteristics; and (4) personal characteristics. Problematic data were categorized as "insufficient," "unclear," "nice" and "emotionally charged." Strategies for increasing validity when interviewing impaired institutionalized elders included increasing the sample size, returning to the setting frequently, lengthening observation periods, recognizing the value of stories, recognizing the value of socializing, using videotapes, collecting both interview and observation data, and having elders view and respond to videotaped recordings.

Affect↗
PubMed1991

Costs of operating a supported work program for traumatically brain-injured individuals.

This paper presents a preliminary analysis of costs associated with a return-to-work program emphasizing a supported employment approach for persons who had sustained severe traumatic brain injuries. This analysis spans almost three years. Results indicated that a mean of 237.8 hours of staff intervention time was required to achieve job stabilization, at a cost of +6896. Ongoing follow-along and support services averaged 1.64 hours per week at a cost of +47.56. Over 68% of total staff time and costs were expended in job-site training and advocacy efforts. Application of these findings to state-level and agency-level policies should be weighed against individual characteristics and needs of clients, program design, and outcomes which clients achieve as a result of services.

Adolescent↗
PubMed1990

A novel membrane factor stimulates guanine nucleotide exchange reaction of ras proteins.

A factor with a molecular weight of 100 kDa, which markedly enhanced the guanine nucleotide exchange reaction of ras p21 proteins, was partially purified from bovine brain tissues. The factor was predominantly associated with the plasma membrane. When the partially purified factor and excess cold GTP were added to [3H]GDP.Gly12 p21 or Val12 in the presence of 2 mM MgCl2, the nucleotide exchange rate was stimulated up to 25-fold. The stimulation of the p21-nucleotide exchange reaction by the factor was completely blocked by the Y13-259 ras-neutralizing antibody. Taken together, these results suggest that the factor may control the rate limiting GDP/GTP exchange step in recycling of p21 in ras-mediated signal transduction.

Animals↗
PubMed1990

False aneurysm of the cavernous carotid artery: a complication of transsphenoidal surgery.

Although excellent results currently are being achieved with transsphenoidal surgery, life-threatening complications may occasionally result from this approach. We present a patient with carotid injury sustained during transsphenoidal surgery, who presented 6 weeks postoperatively with a large false aneurysm in the cavernous part of the right internal carotid artery. This lesion was successfully treated by trapping. The pathogenesis of this complication is discussed and the relevant literature is reviewed.

Adenoma↗
PubMed1990

Alkaptonuric ochronosis and multiple intracranial aneurysms.

Alkaptonuric ochronosis is a heritable disorder of tyrosine metabolism, with various systemic abnormalities related to pigment deposition and degeneration of collagen and other tissues, including the heart and aorta, though no cerebrovascular abnormalities have been reported. The authors report a patient with alkaptonuric ochronosis and multiple intracranial aneurysms presenting with subarachnoid hemorrhage. The ruptured aneurysm was surgically treated, with a satisfactory outcome. In view of the well-known association of other connective tissue disorders with intracranial aneurysms, a potentially causal relationship is suggested between cerebral aneurysms and alkaptonuric ochronosis.

Humans↗
PubMed1990

Helping postacute traumatically brain injured clients return to work: three case studies.

This paper presents three case studies of individuals who had sustained a severe brain injury and who are clients of a return to work programme emphasizing a supported employment approach. The case studies illustrate the types of interventions which are utilized, including job placement; job site and off-site training, advocacy, and compensatory strategies; and ongoing assessment and maintenance of social and productive gains in order to assist with job retention. The results of the case studies may be generalized to the population of brain injury survivors who require intensive and long-term intervention and support in order to return to employment.

Adult↗
PubMed1990

Carotid artery dissection secondary to seatbelt trauma: case report.

A postmortem report of a patient with traumatic internal carotid artery dissection, along with evidence strongly suggestive of a car seatbelt as a causative factor, is presented. In this 5-foot subject, the shoulder harness could have been high, over the anterior cervical area. The authors feel this mechanism deserves consideration as one of the important causes of traumatic carotid dissection. If supported by further studies, remedial measures in the form of changes in seatbelt design, or the use of alternate protective measures may be warranted.

Adult↗
PubMed1990

Intrathoracic meningocele associated with neurofibromatosis: case report.

The authors present a case of intrathoracic meningocele associated with neurofibromatosis. Computed tomography with metrizamide myelography proved valuable in locating the lesion, thus facilitating surgical intervention. With the preoperative diagnosis established and the severity of the meningocele known, the surgeons safely employed a subpleural approach at thoracotomy.

Adult↗