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Biomedical subjects

D Moore

Publications and source records attributed to D Moore.

At least 127 records · Page 7Linked to original sources

Karyotypic heterogeneity and its relation to labeling index in interphase breast tumor cells.

We have used fluorescence in situ hybridization (FISH) with chromosome-specific probes and immunofluorescent detection of in vivo bromodeoxyuridine (BrdUrd) incorporation to evaluate simultaneously numerical chromosome aberrations and proliferative activity of breast cancers. The number of distinct hybridization domains specific for repetitive pericentromeric sequences on chromosomes 1, 7, 11, 15, 17, and X was used as an indicator of copy number of these chromosomes in interphase tumor cells from 23 human breast cancers. Every tumor analyzed showed a heterogeneous distribution of copy number for at least one chromosome type. The copy number distribution for different chromosomes within a tumor frequently showed differing patterns. Major cell populations showing monosomy were relatively rare, occurring only in five cases for chromosome 17, once for chromosome 1, and once for chromosome 15. Flow cytometric analysis of DNA ploidy correlated well with FISH analysis, although flow cytometry failed to detect aneuploidy when only a few chromosomes were affected. To determine whether cell populations with different chromosomal copy numbers have identical proliferation characteristics in vivo, BrdUrd incorporation and centromeric copy number were detected simultaneously. Comparison of the chromosome copy number distribution in BrdUrd-positive cells vs. the distribution of the entire cell population showed different distributions in seven of the 20 cases analyzed. This study demonstrates the common occurrence of chromosome copy number heterogeneity and suggests that a cell phenotype (proliferation) may be associated with genotypic subpopulations.

Adult↗

Use of thiacetazone.

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AIDS-Related Opportunistic Infections↗

Pre-introductory clinical trials of Norplant implants: a comparison of seventeen countries' experience.

This report summarizes the data collected in pre-introductory Norplant implants clinical trials in 17 countries in Latin America, Asia and Africa that were coordinated by either the Population Council or Family Health International (FHI) between 1984 and 1991. A total of 16,282 women between the ages of 18 and 40 years participated in the studies with semi-annual or annual follow-up visits for up to 5 years. Gross cumulative pregnancy rates were < 0.6 per 100 women in the first year and < 1.5 in the second year in all countries. Significant differences in cumulative 5-year pregnancy rates were observed between weight groups 40-49 and 50-59 kg and between 50-59 and 60-69 kg body weight but not between 60-69 kg and those > or = 70 kg. Total cumulative discontinuation rates after five years of Norplant implants use ranged from 35.8 to 60.0 per 100 women. Younger age and low parity were associated with a higher discontinuation rate. Cumulative discontinuation rates for menstrual reasons more than doubled between the end of the first year and second year of use in 13 of 17 countries. This analysis and one previous review provide the only comparison of Norplant contraceptive system study results across a wide diversity of countries; thus allowing an appreciation of the range of clinical experience with Norplant implants and the regional differences in that experience.

Adolescent↗

Autoimmune enteropathy with anti-goblet cell antibodies.

A 9-year-old boy with a 5-year history of severe protracted diarrhea requiring home parenteral nutrition and a 1 year history of abnormal liver function tests was admitted for duodenal, rectal, and liver biopsy. Duodenal biopsy results showed mild villus blunting, a mild lymphocytic infiltrate, and absent goblet cells. Paneth cells and endocrine cells could not be identified. Review of several previous biopsies showed an almost total absence of goblet cells by light microscopy. Anti-goblet cell antibodies of the immunoglobulin (Ig)G class were shown by immunofluorescence with a titer of 1:512. Histological examination of rectal mucosa also showed a total lack of goblet cells, orderly surface epithelial cells, and infiltration of the colonic crypts by lymphocytes. Immunoperoxidase staining of rectal mucosa showed increased numbers of lymphocytes with an excess of CD3+, CD45RO+ T cells, and increased numbers of B cells labeling with B1 and L26. Increased numbers of CD25+ (activated) lymphocytes were also observed. HLA/DR expression was striking and observed in both the crypt and surface enterocytes, as well as in the lamina propria. Immunological assessment of the patient showed an inverted CD4/CD8 ratio and IgA/IgG4 deficiency. The liver biopsy and radiological investigation were in keeping with chronic sclerosing cholangitis. Although a slight and transient improvement in histological appearances was observed with prednisolone there was no significant improvement of diarrhea. Trials of azothiaprine and oral cyclosporin did not result in clinical or histological improvement.

Autoantibodies↗

Cutaneous T-cell lymphoma in association with silicone breast implants.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a chronic malignancy of helper T cells with the CD4 phenotype. It occurs less frequently in young women but is increasing in incidence for unknown reasons. Silicone breast implants have been associated with T-cell-mediated autoimmune reactions. OBJECTIVE: Our purpose was to suggest the hypothesis that CTCL may arise after breast implants and that different patients with CTCL may be stimulated by different antigens. METHODS: Investigators with many patients with CTCL were queried regarding the occurrence of CTCL in women after breast implants. RESULTS: Three cases of confirmed CTCL after breast implants were identified and are reported. In one patient with Sézary syndrome and CTCL, the disease went into remission after removal of implants, resolution of chronic staphylococcal infection, and initiation of photopheresis and interferon alfa therapy. Another patient had progressive disease. CONCLUSION: CTCL may occur in association with breast implants in young female patients, but causality is unknown. If CTCL is antigen driven, then it is likely to result from several different antigens in different groups of patients.

Adult↗

Modified transnasal endoscopic Lothrop procedure as an alternative to frontal sinus obliteration.

Persistent frontal sinusitis traditionally has been treated with external procedures such as osteoplastic frontal sinus obliteration or the Lynch procedure. Currently, functional endoscopic sinus surgery can be used in most cases to remove disease from the frontal recess, the most frequent site of frontal sinus obstruction, thereby relieving the sinusitis. In some cases, however, frontal recess exploration has failed to relieve the obstruction of the frontal sinus, necessitating an osteoplastic frontal sinus obliteration. We present our experience with a transnasal modification of the Lothrop procedure. The Lothrop procedure, first described in 1914, uses a combined external and transnasal approach to resect the median frontal sinus floor, superior nasal septum, and intersinus septum to drain the frontal sinus. This procedure was largely abandoned and forgotten by modern otolaryngologists. However, with the advent of the computed tomography scan and endoscopic techniques, we sought to reassess the basic tenant of the Lothrop procedure (i.e., wide median frontal sinus drainage). An anatomic study of cadaver heads was performed to quantify the surprisingly large potential opening and to better understand the pertinent anatomy. This procedure was performed on 10 patients, with no resulting complications and no failure to maintain patency of the frontal sinus drainage throughout the follow-up period (mean, 7 months). We are encouraged by our initial favorable results and intend to use the procedure in the future as needs arise.

Adult↗

Three-probe fluorescence in situ hybridization to assess chromosome X, Y, and 8 aneuploidy in sperm of 14 men from two healthy groups: evidence for a paternal age effect on sperm aneuploidy.

The method of simultaneous three-chromosome fluorescence in situ hybridization (FISH) was developed using repetitive DNA sequence probes for chromosomes 8, X and Y and applied to semen of 14 men from two healthy groups who differed in their average ages (46.8 +/- 3.1 years, n = 4 v. 28.9 +/- 5.0 years, n = 10). The frequencies of disomic sperm determined by FISH compared well with frequencies obtained using the hamster-egg technique for human-sperm cytogenetics and with the frequencies of disomic and diploid sperm reported in previous FISH studies in this laboratory. The two groups of men did not differ in their baseline frequencies of sperm disomic for chromosome 8 (approximately 6.5 per 10(4) sperm), sperm with XY8 aneuploidy (approximately 9.5 per 10(4) sperm), or sperm with autodiploidy XX88 or YY88 (approximately 2 per 10(4) sperm). However, the older group had statistically higher frequencies of sperm carrying sex chromosomal disomy than the younger group (5.1 v. 2.2 per 10(4) sperm for XX8; 5.9 v. 2.0 per 10(4) sperm for YY8; P < 0.005). A recent report from this laboratory of sex-chromosomal aneuploidy in sperm of aged mice provides inter-species corroborating evidence for this preliminary finding of a paternal age effect on sperm aneuploidy in human males.

Adult↗

Glucosamine 6-phosphate deaminase in normal human erythrocytes.

In the course of an investigation of hexosamine catabolism in the human malaria parasite, Plasmodium falciparum, it became apparent that a basic understanding of the relevant enzymatic reactions in the host erythrocyte is lacking. To acquire the necessary basic knowledge, we have determined the activities of several enzymes involved in hexosamine metabolism in normal human red blood cells. In the present communication we report the results of studies of glucosamine 6-phosphate deaminase (GlcN6-P) using a newly developed sensitive radiometric assay. The mean specific activity in extracts of fresh erythrocytes assayed within 4h of collection was 14.7 nmol/h/mg protein, whereas preparations from older erythrocytes that had been stored at 4 degrees C for up to 4 weeks had a mean specific activity of 6.2 nmol/h/mg. Characterization of the deaminase by chromatofocusing gave a pI of 8.55. The enzyme was optimally active at pH 9.0 and had a Km of 41 microM. The metal chelators EDTA and EGTA were non-inhibitory; however, inhibition was observed in the presence of metal ions, especially Cu2+, Ni2+ and Zn2+. In addition, the deaminase was also inhibited by several sugar phosphates including the reaction product, fructose 6-phosphate.

Aldose-Ketose Isomerases↗

Glucosamine 6-phosphate deaminase in Plasmodium falciparum.

The pathways of glucose utilization for energy production in the malaria parasite, Plasmodium falciparum, have been studied extensively. Little is known, however, about the reactions by which glucose is converted into complex carbohydrates in the parasite, and knowledge of the catabolism of these substances is likewise scanty. The present investigation was undertaken to determine whether the parasites possess a key enzyme of glucosamine catabolism, i.e. glucosamine 6-phosphate deaminase (EC 5.3.1.40), which catalyses the conversion of the sugar phosphate to fructose 6-phosphate and ammonia. Lysates of Plasmodium-infected erythrocytes had substantially higher deaminase activity than control samples from normal erythrocytes, and an even higher specific activity was observed in extracts of isolated parasites, amounting to 20-40 times that of uninfected cells. Anion exchange chromatography indicated that the parasite deaminase eluted in a retarded position when compared to the elution profile of the erythrocyte enzyme. The charge difference suggested by these findings was established more directly by chromatofocusing, which indicated pI values of 6.85 and 8.55 for the parasite and erythrocyte deaminases, respectively. Other differences were also observed, notably a greater thermolability on the part of the parasite enzyme. These results indicated that the parasites synthesize a specific deaminase that is distinct from the normal erythrocyte enzyme. Studies on synchronized parasite cultures further indicated that the parasite deaminase is developmentally regulated, because a dramatic increase in activity levels occurred during the later stages of parasite development.

Aldose-Ketose Isomerases↗

Gender differences on thought disturbance measures among schizophrenic patients.

OBJECTIVE: This study examined gender differences on three measures of thought disturbance among patients with schizophrenia and the relation between thought disturbance and social competency. METHOD: Fifty-three male and 34 female patients diagnosed with schizophrenia according to the DSM-III-R criteria were assessed on measures of thought disturbance: subscales of the Scale for the Assessment of Positive Symptoms (SAPS), subscales of the Brief Psychiatric Rating Scale (BPRS), and the Ego Impairment Index. Gender differences on the three measures of thought disturbance and the relation of these measures to demographic variables and other variables, such as social competency, were examined. RESULTS: Male and female schizophrenic patients demonstrated similar degrees of thought disturbance on the pertinent subscales of the SAPS and the BPRS, but the male schizophrenic patients had scores showing greater impairment on the Ego Impairment Index. Furthermore, a relationship between thought disturbance and social competency was confirmed. CONCLUSIONS: These findings support other studies in which female patients were found to have a "milder" form of schizophrenia, generally characterized by better social functioning, than their male counterparts. The literature regarding gender-related differences in thought disturbance in schizophrenia has been unclear and complicated by design issues such as obtaining adequate samples of subjects and optimizing measurement selection. The findings of this study suggest that use of a converging-measures strategy allows a better assessment of thought disturbance in severely ill schizophrenic patients and an understanding of the importance of thought disorder with respect to gender-related patterns of clinical characteristics, such as social competency.

Adult↗

Three-hour paclitaxel infusion in patients with refractory and relapsed non-Hodgkin's lymphoma.

PURPOSE: Paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is a novel antimicrotubule agent with anti-tumor activity against ovarian and breast carcinomas. Its activity when administered as a 3-hour intravenous infusion in patients with relapsed non-Hodgkin's lymphoma (NHL) has not been studied. PATIENTS AND METHODS: Patients with relapsed NHL were treated with a 3-hour infusion of 200 mg/m2 of Taxol every 3 weeks in an outpatient setting. All patients received premedication (dexamethasone, diphenhydramine, and cimetidine) to prevent allergic reactions. Responses were assessed after two courses of therapy, and patients who achieved at least partial remission (PR) continued to receive Taxol for a maximum of eight courses. RESULTS: Of 60 eligible patients, 54 (90%) were assessable for treatment toxicity and 53 (88%) were for treatment response (22 with primary refractory and 31 with relapsed disease). Twelve patients (23%) achieved a PR (n = 6) or complete remission (CR; n = 6) (95% confidence interval, 12% to 36%). Responses were observed in intermediate-grade (31%), low-grade (14%), and mantle-cell (17%) lymphomas. In the intermediate-grade lymphomas, there was a trend for a higher response rate in relapsed versus primary refractory disease (54% v 13%; P = .08). Treatment-related toxicity included alopecia (100%), peripheral neuropathy (37%), myalgia or arthralgia (25%), and neutropenic fever (11%). None of the patients had allergic reactions or cardiac toxicity. CONCLUSION: At this dose and schedule, Taxol is an active agent in patients with relapsed NHL and can be safely administered in an outpatient setting. Combination programs with Taxol should be investigated for treatment of NHL.

Adult↗

Modified transnasal endoscopic Lothrop procedure: further considerations.

The Lothrop procedure resects the medial frontal sinus floor, superior nasal septum, and intersinus septum to create a large frontonasal communication. However, the external approach often allowed medial collapse of soft tissue and stenosis of the nasofrontal communication. We describe a modified transnasal endoscopic Lothrop procedure in which drills are used for cases in which frontal recess exploration fails to relieve obstruction of the frontal sinus. The lateral bony walls are preserved, and medial collapse does not occur. The mucosa of the posterior table and posterior nasofrontal duct is preserved, and a single common frontal opening is created. We have found this approach to be safe and reliable. Fourteen patients have undergone this procedure without complication, achieving resolution or improvement of their symptoms and maintaining wide patency of the frontonasal opening. We recognize that long-term follow-up will be required but remain encouraged with our favorable results to date.

Adult↗

Human cytomegalovirus induces IL-6 and TNF alpha from macrophages and microglial cells: possible role in neurotoxicity.

Human cytomegalovirus (HCMV) can frequently infect the central nervous system (CNS) in the setting of immunosuppression such as transplantation and infection with the human immunodeficiency virus (HIV). Our laboratory previously reported that HCMV infection of human brain aggregates preferentially infected a microglial/macrophage (M/M) and caused a neuropathology that differed between strains and could occur in the absence of antigen expression. We extended these studies by infecting a human brain cell aggregate model with four low passage clinical isolates of HCMV. Two patterns of cytopathology emerged after infection; a lacy eosinophilic appearance or a glial nodular formation concomitant with a decreased aggregate size. None of the infections were positive for HCMV antigen; however, all were positive for HCMV DNA. We also infected primary macrophages and microglial cells with the same HCMV isolates. Microglial cells were more susceptible to HCMV infection resulting in a lytic infection. Production of potentially neurotoxic cytokines, IL-1, IL-6 and TNF alpha, from HCMV-infected macrophages and microglial cells were evaluated to explain brain aggregate cytopathology. Supernatants from HCMV-infected macrophages and microglial cells produced similar levels of TNF alpha (< 30 pg ml-1) but showed strain and cell source variation in the production of IL-6; microglial cultures produced > 4 fold higher levels. None of the supernatants contained IL-1. Treatment of brain aggregates with either IL-6 or TNF alpha resulted in morphologic alterations and/or a decrease in size consistent with HCMV infection or supernatant treatment.

Brain↗

Altered membrane microviscosity in essential hypertension: relationship with family history of hypertension and sodium-lithium countertransport activity.

OBJECTIVE: To investigate the alterations in erythrocyte ghost membrane microviscosity in essential hypertensive patients and to determine the relationship between these changes and the sodium-lithium countertransport activity as a sensitive marker of membrane function. SUBJECTS: Forty-three normolipidaemic essential hypertensive patients (23 treated, 20 untreated) and 27 normotensive controls were studied. Patients were attending the hospital hypertension clinic or a local general practitioner's surgery. METHODS: Erythrocyte sodium-lithium countertransport activity was measured. The Michaelis constant (Km) for extracellular sodium and maximal reaction velocity for sodium-lithium countertransport were measured in a subgroup consisting of 22 essential hypertensive patients and 11 normotensive controls. Erythrocyte membrane microviscosity was measured using fluorescence polarization anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-trimethylammoniumphenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). RESULTS: There was no significant difference in the fluorescence polarization anisotropy of DPH or TMA-DPH between normotensive and essential hypertensive patients. However, the fluorescence polarization anisotropy of TMA-DPH was increased significantly (reflecting increased membrane microviscosity) in hypertensive patients with a family history of hypertension compared with in patients without a family history of hypertension. The standard sodium-lithium countertransport activity was elevated in essential hypertensive patients compared with normotensive controls, and the Km for sodium was significantly lower in patients with a family history of hypertension than in patients without a family history of hypertension. Patients with a family history of hypertension were clustered, with significantly lower Km for sodium and higher TMA-DPH anisotropies than either hypertensive patients without a family history of hypertension or normotensive controls. CONCLUSIONS: These findings suggest that a high membrane microviscosity affecting the outer region of the lipid bilayer is associated with altered sodium-lithium countertransport kinetics in a subgroup of essential hypertensive patients consisting of those with a family history of hypertension.

Antiporters↗

Elevated frequency of glycophorin A mutations in erythrocytes from Chernobyl accident victims.

In 1986, when an explosion accident occurred at the Chernobyl, Ukraine nuclear power plant, a large number of people were exposed to significant amounts of ionizing radiation. During the time between 1986 and 1992, peripheral blood samples were obtained from 102 people who either were on site during the emergency or were brought to Chernobyl shortly thereafter to assist in the cleanup of radioactive contaminants and isolate the damaged reactor from the environment. These blood samples plus samples from 13 unexposed Soviet individuals were analyzed by flow cytometry using the allele-loss somatic mutation assay for glycophorin A. Results of these assays show that the frequency of N/O variant red cells increased in proportion to the estimated radiation exposure of each individual. The radiation dose-response function derived from this population closely resembles that determined previously for atomic bomb survivors whose blood samples were obtained and analyzed 40 years after their exposure. This suggests comparable mutation induction per unit dose for these two populations and long-term persistence of the mutational damage. In addition, measurements on multiple blood samples from each of 10 donors taken over a 7-year period showed no significant changes in N/O variant cell frequencies, confirming the persistence of radiation-induced somatic mutations in long-lived bone marrow stem cells.

Dose-Response Relationship, Radiation↗