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Biomedical subjects

K Bell

Publications and source records attributed to K Bell.

At least 91 records · Page 5Linked to original sources
PubMed1996

Disseminated epidemic Kaposi's sarcoma treated with radiation and chemotherapy.

When a 40-year-old patient with end-stage acquired immunodeficiency syndrome (AIDS) had bloating and abdominal pain, a large epidemic Kaposi's sarcoma (EKS) lesion was found obstructing the pylorus. Treatment consisted of single-agent chemotherapy for the disseminated lesions and external beam irradiation to the obstructing lesion. Within days of radiation therapy, symptoms began to resolve, and by completion of therapy, the patient was virtually asymptomatic. Although EKS is common in homosexual men infected with the AIDS virus, these patients usually succumb to overwhelming opportunistic infections. Nevertheless, palliative courses of radiation, which can produce a complete response in 50% to 100% of treated KS lesions, can substantially improve the quality of life in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Unequivocal identification of the equine Dcfmqr phenogroup.

An alloimmune reagent has been produced that distinguishes the equine factor Df in the D phenogroup, cfmqr, from that occurring in cefmqr and dfklr. Using this reagent it has been possible to correctly genotype Dc, d, f, k, l, m, q and r positive cells without recourse to family data.

Animals↗
PubMed1996

Quality of life in patients with Alzheimer's disease as reported by patient proxies.

OBJECTIVE: To measure behaviors indicative of quality of life (QOL) in patients with Alzheimer's disease and to examine correlates of patient QOL. DESIGN: Cross-sectional investigation. SETTING: Multi-center study. PARTICIPANTS: Sample of 130 diagnosed patients. PRINCIPAL OUTCOME MEASURES: Proxy ratings of (1) the frequency, opportunity, and enjoyment of 15 non-ADL activities potentially within the capacity of a demented person, and (2) the frequency of a series of positive and negative affects, evident in clearly demarcated facial and bodily expressions. RESULTS: QOL ratings were reliably elicited. Family and institutional caregivers differed only in reports of opportunity for patient activity. Frequency of activities declined with increasing severity of dementia. The frequency of negative affects increased and positive affects declined with increasing severity of dementia, but correlations were weak. High QOL, defined by frequent activity and positive affect, was evident in a quarter of the sample. In multivariate models, functional and cognitive status independently predicted QOL among community-resident older adults; only absence of antipsychotics was related to QOL among older people in nursing homes. Patient education, a marker of premorbid state, independently predicted some activity patterns. CONCLUSIONS: Although the subjective world of the demented patient is not directly accessible, readily observable behaviors offer a basis for assessing QOL.

Affect↗
PubMed1996

Expression of proliferating cell nuclear antigen in gastrointestinal tract lesions and its relationship to bcl-2 expression.

We report the relationship between proliferation as measured by the expression of proliferating cell nuclear antigen (PCNA) and the proto-oncogene bcl-2 in inflammatory and neoplastic lesions of the gastrointestinal tract and associated normal tissues. We found that (1) PCNA and bcl-2 are coexpressed in the stem cell-regenerative compartments of normal tissues but are not coexpressed in carcinomas or adjacent histologically normal epithelium, (2) there is marked heterogeneity of PCNA and bcl-2 expression in neoplastic lesions of the gastrointestinal tract, and (3) overexpression of PCNA is frequently seen in histologically inactive ulcerative colitis. We postulate (1) increased bcl-2 expression in epithelium adjacent to tumors represents an inherent change in the morphologically normal epithelium because it occurs without the corresponding high proliferative state seen in the normal crypt-regenerative compartment, (2) heterogeneity may provide a mechanistic explanation for chemotherapeutic resistance in tumors since cells having high bcl-2 but low proliferative activity would have prolonged survival and might show resistance to chemotherapeutic agents, and (3) the increased proliferative state in histologically inactive ulcerative colitis may provide a partial explanation for the increased risk of colon carcinomas in these patients.

Adenocarcinoma↗
PubMed1996

Neurologic consequences of HTLV-II infection in injection-drug users.

Several case reports have suggested an association between human T-cell lymphotropic virus type II (HTLV-II) infection and chronic neurologic disease. We performed serial neurologic examinations in injection-drug users (IDU), a group known to be at increased risk for HTLV-II infection. At baseline, those infected with HTLV-II alone, human immunodeficiency virus (HIV) alone, or both were significantly more likely to have neurologic disability than uninfected subjects. Longitudinally, HTLV-II infection was independently associated with the development of global neurologic disability and neuropathy, suggesting that HTLV-II causes neurologic disease.

AIDS Dementia Complex↗
PubMed1996

Gender Differences in HIV-Related Neurological Progression in a Cohort of Injecting Drug Users Followed for 3.5 Years.

We evaluated potential gender differences in the development of HIV related neurologic impairment, by matching 38 pairs of HIV positive male and female injecting drug users on their baseline age, education, disease stage and CD4 counts, and following them for 3.5 years. Adjusting for age, education, drug use, history of head injury and baseline CD4 count, more women had sensory abnormalities and symptoms than men at baseline, but the odds of having neurological impairment, particularly extrapyramidal signs and sensory abnormalities were increased over time in men but not in women. Men with ARC or AIDS had more neurological impairment than women in similar stages of illness. This study suggests further investigations of gender differences in HIV disease progression.

CD4 Lymphocyte Count↗
PubMed1996

The measurement of complexity in surgical pathology.

The quantitation of effort both within and among surgical pathology laboratories is data which is being increasingly sought by physician managers, hospital administrators and managed care organizations. Simple measurement of case numbers fails to adequately represent the work of a laboratory. The complexity of the cases reviewed is likely to explain a significant portion of the variance in the time required to bring a case to final diagnosis. Measures which adequately reflect complexity in surgical pathology cases have not been developed. We have studied a variety of extractable report features and correlated these with the time required for case sign-out. Numbers of slides reviewed and total lines of factual data provided were strong correlates of the time required to complete case review, report construction and verification. Such data suggests that models can be constructed based on data that can be gleaned from case reports and records which will relate such data to actual work time.

Analysis of Variance↗
PubMed1995

Expression of CD25 defines peripheral blood mononuclear cells with productive versus latent HIV infection.

The present studies were designed to further determine whether the CD25 marker could distinguish between cells productively and latently infected with HIV. This was accomplished by combining immunotoxin (IT)-mediated killing of CD25+ cells, highly sensitive indirect immunofluorescence to detect remaining CD25+ cells, and PCR-mediated amplification of proviral DNA in immunotoxin-treated vs untreated HIV-infected cells. Our results demonstrate that: 1) By direct immunofluorescence 3 to 8% of PBMCs are CD25+, whereas by indirect immunofluorescence 30% are CD25+. The increased number of CD25+ cells is due to their detection by the highly sensitive indirect immunofluorescence assay. Up to 60% of the CD25+ cells are CD4+ and 12% are CD8+. 2) Treatment of HIV-infected PBMCs with an anti-CD25 IT for 6 days eliminated both CD25high and CD25low cells and decreased the production of p24 by 99%. 3) Differences in the HIV proviral genome were detected in the unfractionated PBMCs vs PBMCs from which CD25+ cells had been eliminated by IT treatment. Hence, PBMCs containing both CD25+ and CD25- cells express all intermediate proviral species and full-length double-stranded proviral DNA. In contrast, CD25- quiescent cells contain predominantly intermediate species. These results confirm and extend our previous observations that expression of CD25 can distinguish latently infected cells from cells producing virus.

Base Sequence↗
PubMed1995

Synthesis and biological evaluation of 14-alkoxymorphinans. 11. 3-Hydroxycyprodime and analogues: opioid antagonist profile in comparison to cyprodime.

A series of 3-hydroxy-substituted analogues (3-7) of the mu selective opioid antagonist cyprodime has been synthesized in order to evaluate the role of a hydroxy group at C-3 concerning mu opioid antagonist selectivity. Compounds 3-7 were tested in bioassays (electrical stimulated mouse vas deferens preparation and myenteric-plexus longitudinal muscle preparation of the guinea pig ileum) and opioid receptor binding assays. Antagonism of mu receptor-mediated responses induced by the mu selective agonist DAMGO afforded equilibrium dissociation constants in the mouse vas deferens preparation (Ke values) for compounds 3-7 which agreed closely with their affinities as determined by opioid receptor binding assays (Ki values). At kappa and delta receptors differences were apparent. Although the compounds had high affinity for both kappa and delta receptors in opioid receptor binding, they were very poor at antagonizing agonist responses mediated by kappa and particularly delta agonists in the mouse vas deferens preparation. None of the compounds tested showed agonist potency in the mouse vas deferens preparation or the myenteric-plexus longitudinal muscle preparation of the guinea pig ileum.

Animals↗
PubMed1995

Clinical correlates of Alzheimer's disease with and without silent radiographic abnormalities.

OBJECTIVE: To determine whether patients with Alzheimer's disease (AD) who do not have historical or clinical evidence of stroke but who do have computed tomographic or magnetic resonance imaging evidence of noncortical lesions smaller than 2 cm or periventricular "caps" differ from other patients with AD. METHODS: The computed tomographic or magnetic resonance imaging scans of 158 patients meeting criteria of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were reviewed by one neuroradiologist. Two measures of disease severity--the Modified Mini-Mental State examination and the Blessed Dementia Rating Scale (Part I)--were subjected to two-way analysis of variance with scan type (computed tomography or magnetic resonance imaging) and lesion number as between-group factors and age and disease duration as covariates. RESULTS: No relationship was seen between lesion number or periventricular caps and disease severity. CONCLUSION: In this cross-sectional analysis using these clinical measures, patients with AD who have well-defined radiographic abnormalities cannot be differentiated from patients with AD who do not have them.

Adult↗
PubMed1995

Neuropsychologic impairment in early HIV infection. A risk factor for work disability.

OBJECTIVE: To explore the functional significance of incident neuropsychologic impairment among initially asymptomatic subjects infected with human immunodeficiency virus. DESIGN: Prospective, observational cohort study of homosexual and bisexual men to examine the incidence of work disability related to the onset of neuropsychologic impairment. SETTING: A university clinical and behavioral research site in New York City. PARTICIPANTS: Sample of 207 homosexual and bisexual men; 123 were seropositive and 84 were seronegative. PRINCIPAL OUTCOME MEASURES: Incident work disability in the course of 4.5 years of follow-up, with disability defined as a persistent (> or = 24 months) change in work hours (from 20 or more to less than 20 h/wk). RESULTS: Compared with seronegative control subjects (n = 72), the relative risk of work disability among initially asymptomatic seropositive men (n = 44) was 2.76 (95% confidence interval, 1.2 to 6.5), nearly a threefold increase. Proportional hazards models show that this increased risk is attributable to the development of major neuropsychologic impairment in a subset (eight of 44) of the initially asymptomatic men, which is significantly associated with incident work disability (6/8 [75%]). Adjusting for symptom status and CD4+ cell count at the time of disability did not eliminate the increased risk associated with neuropsychologic impairment. CONCLUSIONS: In this cohort, the increased risk of work disability among initially asymptomatic human immunodeficiency virus-positive men was related to incident neuropsychologic impairment; such impairment predicted work disability independently of symptom status and CD4+ cell count over the follow-up period. Neuropsychologic impairment in the course of human immunodeficiency virus infection may indicate increased risk for poor outcomes over and above that associated with systemic disease.

Cohort Studies↗
PubMed1995

A standardized technique for establishing onset and duration of symptoms of Alzheimer's disease.

OBJECTIVES: To develop an informant-based semistructured interview to determine the onset and duration of symptoms of Alzheimer's disease, and to use this instrument with informants to characterize a cohort of mildly impaired patients with Alzheimer's disease. DESIGN: In study 1, interrater and interinformant reliability was examined for the date of onset and the order of appearance for specific symptoms that were elicited by the semistructured onset interview. In study 2, the instrument was used to characterize disease onset in a cohort of patients with Alzheimer's disease who were participating in a large multicenter study. SUBJECTS: Informants of patients with Alzheimer's disease. RESULTS: In study 1, interrater reliability for duration of illness was excellent (intraclass correlation coefficient = .99, P < .001), and interinformant reliability was good (intraclass correlation coefficient = .86, P < .001). Agreement for the presence of a given symptom was highest for those that were most commonly reported (eg, memory and performance difficulty). In study 2, 89% of the cohort had memory problems, and 63.9% had performance difficulties as the first or second symptom. Depression and language problems were less commonly reported. Psychosis and behavioral disturbances were rarely reported as the first problem. CONCLUSION: This instrument provides a reliable procedure for standardizing the estimation of duration of illness based on retrospective report.

Aged↗
PubMed1995

Risk of human immunodeficiency virus type 1-related neurologic disease in a cohort of intravenous drug users.

BACKGROUND: Although the proportion of cases of acquired immunodeficiency syndrome related to intravenous drug use has increased dramatically over the past decade, there has been no longitudinal examination of primary neurologic disease in this group. OBJECTIVE: To study the development of neurologic disease in human immunodeficiency virus (HIV)-negative and HIV-positive men and women who were intravenous drug users over a 3.5-year period. DESIGN: Prospective observational cohort study. SETTING: Subjects were recruited from an infectious disease clinic at a New York City Hospital or from a methadone maintenance program. PARTICIPANTS: Ninety-nine HIV-negative (62 men and 37 women) and 124 HIV-positive (85 men and 39 women) intravenous drug users volunteered. MAIN OUTCOME MEASURE: The development of clinically significant manifestations in six neurologic domains. RESULTS: With multivariate adjustment for current and past substance abuse, age, education, and head injury, we examined the odds of developing HIV-related neurologic disease. Extrapyramidal signs and reduced motor ability became increasingly apparent over time in HIV-infected men as their CD4 cell count declined and as the subjects developed the acquired immunodeficiency syndrome. Fewer neurologic signs were seen in the women. CONCLUSIONS: The impact of HIV infection among intravenous drug users parallels that in homosexual men and is independent of alcohol and other drug use.

Adult↗
PubMed1995

GABAergic projection from the ventral pallidum and globus pallidus to the subthalamic nucleus.

There exists a topographically organized projection from the globus pallidus and ventral pallidum to the subthalamic nucleus and adjacent lateral hypothalamus. The participation of GABA as a neurotransmitter in this projection was evaluated by retrograde labeling of cells in the pallidal area from an iontophoretic deposit of Fluor-Gold in the subthalamus combined with in situ hybridization for mRNA of the GABA synthetic enzyme, glutamate decarboxylase (GAD). A rostrocaudal gradient in the contribution of GABA to the projection was demonstrated with a relatively small percentage of retrogradely labeled cells in the rostral ventral pallidum containing GAD mRNA (7%) compared to the caudal globus pallidus which had over 70% of the Fluoro-Gold containing cells double-labeled for GAD mRNA. Overall the ventral pallidum contribution to the subthalamic nucleus was less GABAergic than the portion arising from the globus pallidus (35% vs. 61%, respectively).

Animals↗
PubMed1995

A generic method for expression and use of "tagged" soluble versions of cell surface receptors.

A general method for expression, purification, immobilization, detection and radiolabeling of extracellular domains (ECD) of type I membrane proteins. The type I interleukin-1 receptor (IL-1RtI), the alpha-subunit of interleukin-2 receptor (IL-2R alpha) and E-selectin are used as illustrative examples of cell surface receptors. DNA encoding the ECD of the proteins are fused at their 3' end to a chimeric DNA which serves to generically "tag" the recombinant ECD. The resulting fusion protein contains a substrate sequence for protein kinase-A (PKA) adjacent to the signal sequence from human placental alkaline phosphatase (HPAP), The HPAP signal sequence directs the formation of the phosphatidylinositol-glycan (PI-G) anchorage of the protein at the cell surface. When these chimeric genes are expressed in CHO cells, the ECDs are detected on the cell surface and can be released by treatment with phosphatidylinositol-specific phospholipase-C (PI-PLC). Based on protein processing known to occur for native HPAP, twenty amino acids from the HPAP signal sequence remain at the C-terminus of the ECD. A high affinity monoclonal antibody was generated against this common epitope. This antibody can be used to detect, purify and immobilize the ECDs. In addition, the ECDs can be radiolabeled with 32P by treatment with PKA and maintain the ability to bind their natural ligands. This "tagging" method has been successfully applied to many other type I proteins which serve as cell surface receptors.

Alkaline Phosphatase↗
PubMed1995

Mutations in the equine plasma transferrin and esterase systems.

Eleven apparent mutations of the equine plasma transferrin and esterase gene (10 in TF and one in ES) were found in an analysis of approximately 240,000 thoroughbred horses. Eight of the transferrin mutations produced variants not previously recognized in horses. In the two remaining transferrin mutations and the esterase mutation, reduced plasma concentrations of the proteins were demonstrated by immunological techniques and together with the family data indicated the existence of 'null' alleles.

Animals↗
PubMed1995

Consistency of clinical diagnosis in a community-based longitudinal study of dementia and Alzheimer's disease.

We evaluated the consistency of the diagnosis of dementia in a multicultural, longitudinal community-based study of cognitive impairment and dementia. We diagnosed dementia using a fixed neuropsychological paradigm; the diagnosis also required historical evidence of functional impairment. In a sample of 656 subjects with at least one annual follow-up examination, dementia was confirmed at 1 year in 89% of the 304 subjects initially demented, and in 90% of the 136 subjects with the initial diagnosis of probable Alzheimer's disease (AD). The 34 initially demented subjects who failed to meet criteria for dementia at follow-up included 13 with an initial diagnosis of probable AD. All 34 still had evidence of cognitive impairment; this group was more likely to have a history of pulmonary disease, multiple medication use, or chronic alcohol use than other demented patients. Consistency of dementia diagnosis did not vary according to educational attainment or ethnic background. The use of a neuropsychological paradigm such as ours in large longitudinal studies of dementia may minimize interobserver diagnostic variability or diagnostic drift over time while contributing the benefits of a comprehensive cognitive evaluation to the diagnostic process.

Aged↗