Biomedical subjects

K Bell

Publications and source records attributed to K Bell.

At least 73 records · Page 4Linked to original sources

PubMed1997

Alzheimer's disease after remote head injury: an incidence study.

OBJECTIVE: To evaluate a history of remote head injury as a risk factor for subsequent dementia due to Alzheimer's disease. METHODS: 271 participants of a community based longitudinal study of aging in north Manhattan without evidence of significant cognitive impairment were interrogated for a history of head injury on two occasions at entry into the study. The examining physician sought a history of head injury with loss of conciousness. Independently, a risk factor interviewer inquired about a history of head injury with loss of consiousness or amnesia, the duration of any loss of consiousness, and the date of the head injury. Patients were followed up with standardised annual evaluations for up to five years to determine the first occurrence of dementia. RESULTS: Over the course of the study incident dementia due to probable or possible Alzheimer's disease was diagnosed in 39 patients. Cox proportional hazards modelling showed that a history of head injury with loss of consiousness reported to the physician was associated with earlier onset of dementia due to Alzheimer's disease (relative risk (RR) = 4.1, 95% confidence interval (95% CI) 1.3-12.7). head injury with loss of consiousness or amnesia reported to the risk factor interviewer was not significantly associated with earlier onset of Alzheimer's disease overall (RR 2.0, 95% CI 0.7-6.2), but those who reported loss of consiousness exceeding five minutes were at significantly increased risk (RR 11.2, 95% CI 2.3-59.8). Incident Alzheimer's disease was significantly associated with head injury which occurred within the preceding 30 years (RR 5.4, 95% CI 1.5-19.5). CONCLUSION: The results of this cohort study are consistent with the findings of several case-control studies suggesting that head injury may be a risk factor for Alzheimer's disease.

Age of Onset↗

PubMed1997

Large scale manufacturing of TXU(anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate for clinical trials.

We have conjugated the murine monoclonal anti-CD7 antibody TXU to the plant hemitoxin pokeweed antiviral protein (PAP) to construct an effective immunotoxin against CD7 antigen positive hematologic malignancies. The scaled-up production and purification of TXU antibody, PAP toxin, and TXU-PAP immunotoxin permitted the manufacturing of a highly purified clinical-grade TXU-PAP preparation. In clonogenic assays, TXU-PAP elicited selective and potent cytotoxicity against CD7 antigen positive human leukemia cells and killed primary clonogenic leukemic cells from T-lineage acute lymphoblastic leukemia (ALL) patients. To our knowledge, this pre-IND work represents the first effort of producing a clinical-grade PAP immunotoxin for treatment of T-lineage ALL. Since the CD7 antigen is also expressed on AML cells, TXU-PAP could also be useful for the treatment of CD7 positive acute myeloid leukemia (AML) patients.

Antibodies, Monoclonal↗

PubMed1996

Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization.

Rats were pretreated with daily cocaine or saline injections for 1 week. The rats treated with daily cocaine were separated into two groups: a sensitized group of animals demonstrating > 20% increase in motor activity on the last injection compared with the first injection of daily cocaine, and a nonsensitized group showing < 20% elevation. At 2-3 weeks after the last daily injection, four experiments were performed to assess changes in excitatory amino acid (EAA) transmission in the nucleus accumbens produced by repeated cocaine administration. (1) Rats were challenged with a microinjection of AMPA into the shell or core of the nucleus accumbens. The sensitized rats demonstrated greater motor activity than did the saline-pretreated or nonsensitized animals after AMPA injection into either subnucleus. (2) It was shown that the behavioral distinction between sensitized, nonsensitized, and control rats in behavioral responsiveness to AMPA was not mediated by differences in AMPA-induced dopamine release. (3) The extracellular content of glutamate was measured after a cocaine challenge given at 21 d of withdrawal. Cocaine elevated the levels of glutamate in the core of sensitized rats, but not of nonsensitized or control rats. (4) Microinjection of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione into the core abolished the augmented motor response to a cocaine challenge in sensitized rats, but was without effect on cocaine-induced motor activity in nonsensitized animals. These results indicate that repeated cocaine administration increases EAA transmission in the nucleus accumbens only in rats that develop behavioral sensitization to cocaine.

Animals↗

PubMed1996

Modeling the influence of extrapyramidal signs on the progression of Alzheimer disease.

OBJECTIVE: To determine how the advent of extrapyramidal signs influences the progression of Alzheimer disease as measured by standard clinical measures. DESIGN: We applied growth curve models to prospective data to characterize patients' cognitive and functional changes over time. To detect changes in disease course related to extrapyramidal signs, their onset was treated as a time-dependent covariate. SETTING: Three research medical centers. PARTICIPANTS: Patients (n = 217) with probable Alzheimer disease. INTERVENTION: Patients were followed up semiannually for 5 years. MAIN OUTCOME MEASURES: Scores on the modified Mini-Mental State Examination and measures of basic and instrumental activities of daily living from the Blessed Dementia Rating Scale. RESULTS: For basic and instrumental activities of daily living, disease course was more rapid once extrapyramidal signs developed. Decline in the modified Mini-Mental State Examination score was greater at the time the signs developed, but not at subsequent visits. CONCLUSIONS: The point at which extrapyramidal signs emerge is associated with measurable acceleration in the progression of Alzheimer disease. This may in part explain why extrapyramidal signs are associated with a poorer prognosis. The differential influence of extrapyramidal signs on cognitive and functional measures suggests that the pathological changes underlying these disease features may vary.

Aged↗

PubMed1996

A simplified silver diammine method for the staining of nucleic acids in polyacrylamide gels.

High sensitivity and low background, which are the significant features of the procedure of Johansson and Skoog (J. Biochem. Biophys. Methods. 1987, 14, (Suppl.) 33) for silver staining of nucleic acids in polyacrylamide gels, have been improved by excluding ethanol from all solutions and increasing the length of washing steps after sensitisation and staining. Including a fixation step before sensitisation increased the contrast of the bands even at high concentration of nucleic acid, producing a shift in the tone of colour from black to grey instead of gold to yellow bands. This technique is superior in terms of sensitivity and background to a number of other silver staining protocols, three which utilise silver diammine and three which utilise silver nitrate ions.

Ammonia↗

PubMed1996

Plasma protease inhibitor (PI) system in the laboratory opossum, Monodelphis domestica.

Protease inhibitor (PI) polymorphism was observed in the laboratory opossum, Monodelphis domestica, by either one-dimensional acid polyacrylamide gel electrophoresis (PAGE; pH 4.6) or isoelectric focusing (pH 3.5-5.0) followed by immunoblotting with rabbit antiserum to human alpha 1-antitrypsin; but acid PAGE produced superior resolution of the PI proteins. Family studies demonstrated an inheritance of nine codominant autosomal alleles, PID, PIE, PIF, PIG, PIH, PII, PIJ, PIK, and PIM, and a population study revealed frequencies of 0.411, 0.010, 0.341, 0.034, 0.023, 0.071, 0.035, 0.020, and 0.055, respectively.

Animals↗

PubMed1996

Context-specific cross-sensitization between systemic cocaine and intra-accumbens AMPA infusion in the rat.

Two behavioral experiments were conducted in rats to evaluate the context-specificity of changes in nucleus accumbens glutamate transmission induced by systemic cocaine administration. At 2 weeks of withdrawal from daily cocaine injections (15 mg/kg, IP, daily x 7 days), subjects who had received cocaine in the test environment displayed a significantly greater motor response to intra-accumbens infusion of the glutamate receptor subtype-specific agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) than subjects who had received daily saline injections. Subjects who previously received cocaine in the home cage displayed no greater AMPA-induced motor activity within the test environment than saline-treated controls. In contrast, behavioral sensitization to an intra-accumbens challenge with the NMDA receptor-specific agonist, 1-aminocyclobutane-cis-1,3-dicarboxylic acid (cis-ACDA), was seen in both cocaine-treated subject groups. These results suggest that behavioral sensitization to psychostimulants may be mediated, in part, by a context-conditioned behavioral sensitization to glutamate transmission in the nucleus accumbens through AMPA/kainate receptors.

Animals↗

PubMed1996

Application of a growth curve approach to modeling the progression of Alzheimer's disease.

BACKGROUND: Studies using clinical measures to track AD progression often assume linear declines over the entire course of the disease, which may not be justified. The objective of this study was to model change in measures of the clinical severity of Alzheimer's disease (AD) over time. METHODS: We developed a method to apply growth curve models to prospective data and characterize AD patients' functional change over time. Data from the modified Mini-Mental State Examination (mMMSE) and measures of basic and instrumental ADL, administered semiannually for up to 5 years to 236 patients with probable AD, were modeled. RESULTS: The rate of decline in mMMS scores per 6-month interval gradually increased as scores dropped from the maximum of 57 to 20. The rate of decline then decreased as scores approached 0, resulting in an inverse "S" curve. The rate of increase in instrumental ADL scores per interval attenuated as the scores increased, while that for basic ADL scores across intervals was constant. CONCLUSIONS: Differences in the pattern of progression of the three measures is in part a function of their psychometric properties. The progression curves may also reflect content-specific features of the instruments. Superimposition of the modeled decline in these three content areas suggests a hypothetical model of the relative timing of cognitive and functional changes in AD.

Activities of Daily Living↗

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

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↗