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Biomedical subjects

D Berry

Publications and source records attributed to D Berry.

At least 55 records · Page 3Linked to original sources

The GABAA receptor alpha 6 subunit gene (Gabra6) is tightly linked to the alpha 1-gamma 2 subunit cluster on mouse chromosome 11.

We have established that the GABAA receptor alpha 6 (Gabra6) and alpha 1 (Gabra 1) subunit genes are tightly linked on mouse chromosome 11 by analysing the strain distribution patterns of RFLPs for the two genes and microsatellite markers flanking these genes in 26 BXD recombinant inbred strains. These results further demonstrate clustering of the GABAA receptor subunit genes on mouse chromosomes and the synteny for these clusters between the mouse and human genomes.

Animals↗

Bovine tuberculosis in free-ranging white-tailed deer from Michigan.

A 4.5 yr-old male white-tailed deer (Odocoileus virginianus) killed by a hunter during the 1994 firearm hunting season in northeastern Michigan (USA) had lesions suggestive of tuberculosis and was positive on culture for Mycobacterium bovis the causative agent for bovine tuberculosis. Subsequently, a survey of 354 hunter-harvested white-tailed deer for tuberculosis was conducted in this area from 15 November 1995 through 5 January 1996. Heads and/or lungs from deer were examined grossly and microscopically for lesions suggestive of bovine tuberculosis. Gross lesions suggestive of tuberculosis were seen in 15 deer. Tissues from 16 deer had acid-fast bacilli on histological examination and in 12 cases mycobacterial isolates from lymph nodes and/or lungs were identified as M. bovis. In addition, lymph nodes from 12 deer (11 females and 1 male) without gross or microscopic lesions were pooled into 1 sample from which M. bovis was cultured. Although more male (9) than female (3) deer had bovine tuberculosis infections, this difference was not statistically significant. Mycobacterium bovis culture positive deer ranged in age from 1.5 to 5.5 yr with a mean of 2.7 yr (median 2.5 yr) for males and 3.2 yr (median 3.5 yr) for females. This appears to be the first epidemic occurrence of M. bovis in free-ranging cervids in North America. A combination of environmental (high deer density and poor quality habit) and management-related factors (extensive supplemental feeding) may be responsible for this epizootic.

Animals↗

The significance of tumor contamination in the bone marrow from high-risk primary breast cancer patients treated with high-dose chemotherapy and hematopoietic support.

We studied the incidence and significance of tumor cell contamination of the bone marrow or peripheral blood progenitor cells of patients who had high risk primary breast cancer involving 10 or more axillary lymph nodes and who received high dose cyclophosphamide, cisplatin, and carmustine with hematopoietic support as consolidation following standard dose adjuvant chemotherapy. The autologous hematopoietic cell products were evaluated in 85 eligible patients. Eighty-three samples were available from the time of bone marrow harvest, and peripheral blood progenitor cells were evaluated from 57 of the 65 patients who additionally received these products. The screening technique utilized a panel of four anti-breast cancer monoclonal antibodies and an immunohistochemical technique. Thirty (36%) of the 83 evaluable patients had tumor cell contamination of the bone marrow. Only 2 (4%) of the 57 patients had tumor cell contamination of the peripheral blood progenitor cells. Tumor cell contamination of the bone marrow was associated with shorter disease-free survival and overall survival. In addition, the higher the number of tumor cells identified, the shorter disease-free and overall survival. There was no relationship between the tumor cell contamination of the bone marrow and the site of relapse. The combination of the log of the number of tumor cells +1 and number of positive lymph nodes predicted both disease-free and overall survival. Tumor cell contamination of the bone marrow from the harvest is associated with shorter disease-free and overall survival for patients who were treated with standard dose chemotherapy followed by consolidation with high dose alkylating agents and hematopoietic support. It is unclear what role the contaminating tumor cells have in relapse, and they may just be a high-risk marker. A comparison with other prognostic factors and characteristics of the tumor may determine the significance of the tumor contamination of the bone marrow.

Adult↗

Evidence against oppositional and pharmacokinetic mechanisms of tolerance to diazepam's sedative effects.

Acute administration of diazepam (2 mg/kg i.p.) to rats decreased the number of head-dips, locomotor activity and the number of rears made in the holeboard apparatus, indicating sedative effects. After daily treatment for 7 days with diazepam (2 mg/kg) tolerance developed to all these behavioural effects, despite serum concentrations of diazepam and N-desmethyldiazepam significantly higher than those following acute treatment. After 7 drug-free recovery days the rats were quite unresponsive to a probe dose of diazepam (2 mg/kg) and although there was a gradual recovery of responsiveness to diazepam, the reduction in rears still did not reach the level of the acute group even after 21 drug-free days. There was evidence for pharmacokinetic changes when probe doses of diazepam were given after 7, 14 or 21 recovery days. Lower levels of diazepam and higher levels of N-desmethyldiazepam than following an acute dose to the drug-naïve group were detected, indicating that the chronic treatment had resulted in a persistently enhanced rate of N-demethylation. It is argued that these changes do not fully account for the reduced responsiveness to the probe doses, and nor can they account for the gradual return of response over the 3-week recovery period. There were no detectable scrum concentrations of either compound 24 h after the end of the chronic treatment. However, no rebound increases in behavioural responses were detected at any time-point in withdrawal. Thus, the mechanism underlying this behavioural tolerance was not oppositional in nature. It is suggested that a situation-independent learned behavioural strategy is the most likely mechanism for the observed tolerance.

Animals↗

Multiple small bowel perforations in a patient on treatment of tuberculosis.

Perforation and obstruction of the small intestine are well recognized in cases of ulcero-constrictive gastro-intestinal tuberculosis and at the commencement of anti-tuberculous chemotherapy. We present a case of two metachronous perforations in a patient despite established anti-tuberculous treatment.

Adult↗

Reverse transcription-polymerase chain reaction detection of collagen transcripts in healing human wounds.

The aim of this study was to analyse the expression of COl1A1, COl1A2 and COl3A1 in 6 mm diameter punch biopsies obtained from human wounds. Total RNA was isolated from biopsies taken from Sacrococcygeal pilonidal sinus excision cavities at weekly intervals between surgery and clinical closure. cDNAs were generated from the RNA using reverse transcriptase and polymerase chain reaction (PCR) amplifications performed with oligonucleotide primer pairs specific for regions of the COl1A1, COl1A2 and COl3A1 genes. The expression of these three genes was demonstrated throughout the course of healing on 36 biopsies taken from nine patients between surgery and clinical closure. Amplification bands demonstrated on cDNAs generated from 6 mm diameter biopsies were comparable in intensity and specificity with those generated from 50 mg excised scar tissue and cultured fibroblasts. The RT-PCR technique described here allows the rapid 'routine' detection of specific gene expression in 6 mm biopsies obtained from healing wounds.

Biopsy↗

Amonafide: An active agent in the treatment of previously untreated advanced breast cancer--a cancer and leukemia group B study (CALGB 8642).

Amonafide is a new imide derivative of naphthalic acid. The drug had demonstrated significant activity in preclinical studies and some activity in Phase I trials. The drug is extensively metabolized and detected in plasma and urine. Its toxicity has previously been correlated to the formation of an active metabolite, N-acetyl-amonafide. Amonafide was chosen for inclusion in the Cancer and Leukemia Group B (CALGB) master metastatic breast cancer protocol. CALGB 8642 randomizes previously untreated metastatic breast cancer patients either to one of several Phase II agents given for up to four cycles and then followed by standard cyclophosphamide-doxorubicin-5-fluorouracil, or to immediate treatment with standard cyclophosphamide-doxorubicin-5-fluorouracil. The end point of CALGB 8642 is to assess the difference in survival, toxicity, and overall response when limited exposure to Phase II agents precedes standard chemotherapy. This report deals only with amonafide as a Phase II agent. Comparisons with the cyclophosphamide-doxorubicin-5-fluorouracil arm will not be addressed. Patients had to have histologically documented measurable breast cancer and a performance status of 0-1. Patients could not have had prior chemotherapy for metastatic disease. Prior adjuvant chemotherapy was permitted. Patients could not have visceral crisis. Amonafide was given at 300 mg/m2/day i.v. for 5 days, and repeated at 21-day intervals for a maximum of four cycles. Escalation and reduction in dose was mandated dependent on hematotoxicity or lack thereof. Toxicity was primarily hematological and bimodal: 32% had grade 3 or 4 leukopenia and 24% had grade 3 or 4 thrombocytopenia; 22% had no leukopenia and 44% had no thrombocytopenia. The response rate was 18%, including one complete response. When response was analyzed by hematological toxicity, there was a 35.7% response if patients had leukopenia grade 3/4 (versus 8.3%, P = 0.08). There was a 50% response if patients had thrombocytopenia grade 3/4 (versus 7.1%, P = <0.01). We conclude that amonafide is somewhat active in previously untreated breast cancer patients. There may be a steep dose-response curve, based on the significant correlation between myelosuppression and response. Rates of responses in patients adequately dosed (i.e., with significant hematotoxicity) with amonafide ranged from 35 to 50%. Further studies will incorporate individualized dosing based on pretreatment acetylator phenotyping.

Adenine↗

Charnley low-friction arthroplasty of the hip. Twenty-year results with cement.

The first 333 Charnley (Thackray, United Kingdom) total hip arthroplasties performed at the Mayo Clinic between 1969 and 1970 have been followed since that time. One hundred twelve patients (112 hips) remain alive at 20 years. Clinical results remain excellent. The Mayo clinical and roentgenographic hip scoring system rates the results as good to excellent in 39 of 69 hips (with all necessary data to calculate the entire score), fair in 13 hips, and poor in 17 hips. The clinical score alone showed satisfactory results in 77 of 112 hips. Some clinical deterioration was attributed to the advancing age of the patients (mean age at final follow-up evaluation, 84 years). Probable roentgenographic loosening (component migration, complete bone-cement interface, radiolucent line greater than 1 mm, cement fracture) was noted in 12 of 69 acetabular components (17%) and 28 of 69 femoral components (36%). Two patients had required revision since the last report at 15 years for a total of 38 patients (32 revised, 4 Girdlestone arthroplasties, 2 stem fractures not yet revised). The probability of surviving 20 years without revision of the components was 84% (83% for men, 85% for women). The rates of loosening, revision, and failure (revision, Girdlestone, or symptomatic loosening) remain linear over 20 years of follow-up evaluation. If the probability of revision is based on patient age at the time of the initial total hip arthroplasty, there is a significantly increased probability of revision in those patients less than 59 years of age (27%) compared to those 59-65 years of age (13%), 65-70 years (7.5%), and over 70 years (12%).

Aged↗

Analysis of vocal disorders with methods from nonlinear dynamics.

Several authors have recently demonstrated the intimate relationship between nonlinear dynamics and observations in vocal fold vibration (Herzel, 1993; Mende, Herzel, & Wermke, 1990; Titze, Baken, & Herzel, 1993). The aim of this paper is to analyze vocal disorders from a nonlinear dynamics point of view. Basic concepts and analysis techniques from nonlinear dynamics are reviewed and related to voice. The voices of several patients with vocal disorders are analyzed using traditional voice analysis techniques and methods from nonlinear dynamics. The two methods are shown to complement each other in many ways. Likely physiological mechanisms of the observed nonlinear phenomena are presented, and it is shown how much of the terminology in the literature describing rough voice can be unified within the framework of nonlinear dynamics.

Electroencephalography↗

Overexpression of p53 and HER-2/neu proteins as prognostic markers in early stage breast cancer.

OBJECTIVE: Overexpression of the p53 and HER-2/neu oncogenes are the two most common genetic abnormalities associated with breast cancer. Shorter survival time has been reported in patients with tumors with p53 or HER-2/neu. This report analyzes a retrospective cohort of early stage breast cancers for both oncogenes and relates overexpression to clinicopathologic parameters and survival. METHODS: Immunostaining for p53 and HER-2/neu was performed on 230 paraffin-embedded specimens of stage I and II breast cancers diagnosed and treated at Duke University Medical Center between 1984 and 1987. Positive staining for both p53 and HER-2/neu in paraffin-embedded tissues indicates an underlying genetic abnormality: point mutations in the p53 gene and amplification of the HER-2/neu gene. RESULTS: In this cohort of patients, 24% were positive for p53 and 17% for HER-2/neu. Four per cent were positive for both oncogenes. Significant correlations were found between p53 immunostaining and increasing tumor size, stage, and low estrogen and progesterone receptor contents. Univariate analysis showed that p53 and HER-2/neu were indicators of overall and failure-free survival. An additive effect on survival was observed in patients with both oncogene abnormalities. Nodal status, HER-2/neu, and p53 all attained independent prognostic value in a multivariate analysis. CONCLUSIONS: The p53 and HER-2/neu oncogenes have proven but limited prognostic value. An approach that combines several molecular genetic markers with established pathologic criteria may help physicians to make more accurate predictions of prognosis in patients with early stage breast cancer.

Biomarkers, Tumor↗

Mechanical lithotripsy.

Endoscopic lithotripsy is a procedure used for the removal of large stones in the common bile duct that cannot be removed after sphincterotomy. This procedure causes fragmentation of large stones, which allows easier retrieval of stones by other instruments such as balloons or baskets. There are currently two types of mechanical lithotripsy: one type uses an instrument called a mechanical lithotriptor, and the second type uses an electrohydraulic lithotriptor. This article focuses on mechanical lithotripsy. Since it is vital for the operator of this equipment to understand its function, assembly, disassembly, and maintenance, specific guidelines are provided.

Gallstones↗

Isolation and pharmacological characterization of a hamster urinary bladder neurokinin A receptor cDNA.

Functional cDNA clones for hamster neurokinin-2 receptor (NK-2R) were isolated from hamster urinary bladder using a polymerase chain reaction-based methodology. The hamster NK-2R consists of 384 amino acids with a relative molecular weight of 43,418. Hamster NK-2R shares significant amino acid sequence homology with other tachykinin receptors, particularly with rat, bovine, and human NK-2R (94.3, 84.4, and 86.5%, respectively). To examine the pharmacology of cloned hamster NK-2R, we transfected mouse erythroleukemia cells with this receptor, prepared high speed membranes, and studied the receptor properties utilizing the ligand [4,5-3H-Leu9]NKA in a receptor-binding assay. For pharmacological comparison, we also transfected the human NK-2R into mouse erythroleukemia cells. [3H]NKA bound to hamster NK-2R receptor in a protein-dependent, high affinity (Kd1 = 4.14 +/- 0.31 nM), saturable (Bmax1 = 679 +/- 26 fmol/mg of protein), and highly specific manner (89 +/- 2%). A smaller population (10% density) of lower affinity receptors (Kd2 = 150 +/- 92 nM), was also observed in competition experiments. [3H]NKA bound to the human receptor with significantly higher affinity and overall greater receptor density (Kd1 = 0.37 +/- 0.11 nM, Bmax1 = 234 +/- 175 fmol/mg of protein; Kd2 = 9.0 +/- 2 nM, Bmax2 = 1989 + 990 fmol/mg of protein). [3H]NKA binding to both hamster and human receptors was enhanced greatly by divalent cations, whereas GTP analogs weakly inhibited binding to hamster receptor, but potently inhibited binding to the human receptor. Competition experiments with agonists demonstrated binding to high and low affinity states of NK-2 receptors, with identical order of potency in hamster or human NK-2R; NKA > [Nle10]NKA(4-10) > [beta-Ala8]NKA(4-10) >> substance P >>> Senktide. However, remarkable differences were observed in studies with selective NK-2 antagonists (hamster, SR48,968 > L659,877 > R396 >> MEN10,376 versus human, SR48,968 > MEN10,376 > L659,877 > R396). The rank order of antagonist affinity is consistent with the observations of NK-2 receptor pharmacology in the native tissues.

Amino Acid Sequence↗

A diterpene epoxide from the marine brown alga Dictyota sp.: possible vasopressin V1 receptor antagonist.

A novel epoxide, in addition to eight known diterpenes, has been isolated from a marine brown alga of the genus Dictyota. The structures of these compounds were established by the interpretation and comparison of spectral data with literature data. Most of the isolates demonstrated vasopressin receptor antagonist activity in vitro with the new epoxide being the most active of the diterpenes tested.

Animals↗

Conioidines A and B, novel DNA-interacting pyrrolidines from Chamaesaracha conioides.

Two novel pyrrolidine compounds, conioidines A [1] and B [2], have been isolated from the Texas plant, Chamaesaracha conioides (Solanaceae). Their structures were determined by spectroscopic methods and hydrolysis studies. Both natural products, like doxorubicin, showed DNA-specific KB cell cytotoxicity. Dose-response data indicated a Kd value of 2.8 microM for binding of conioidine A [1] to calf thymus DNA.

Animals↗