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Biomedical subjects

D Montague

Publications and source records attributed to D Montague.

16 recordsLinked to original sources
PubMed2000

Immunofluorescent microscopic investigation of the distal arrector pili: a demonstration of the spatial relationship between alpha5beta1 integrin and fibronectin.

Currently there is limited knowledge regarding the anatomy of the distal arrector pili (AP) muscle. A previous study implicated fibronectin and alpha5beta1 integrin binding as the anchor between the AP and the extracellular matrix (ECM). The purpose of this study was to strengthen this hypothesis. Serial frozen sections of human scalp skin were double-labeled via immunofluorescent staining for alpha5beta1 with fluorescein and fibronectin with rhodamine, followed by fluorescent microscopy. Granular staining for alpha5beta1 with fluorescein and smooth staining for fibronectin with rhodamine were seen at the periphery of the AP muscle bundles and along the distal fibers. Precise co-localization of alpha5beta1 and fibronectin was observed at the AP-ECM interface by means of a dual filter. Analysis of variance was used on the relative density of staining for each epitope. Staining for both epitopes was significantly brighter at the distal fibers than at the middle or proximal portions of the muscle. A computerized three-dimensional reconstruction provides a detailed picture of the microanatomy of the distal AP, which allows mathematical evaluation of the forces of contraction. The anatomic co-localization between alpha5beta1 and fibronectin strengthens our hypothesis that interaction of these epitopes mediates the attachment of the distal AP to the ECM.

Fibronectins↗
PubMed1995

Appropriate use of heparin. Empiric vs nomogram-based dosing.

BACKGROUND: A study involving two groups of patients with cardiovascular disease was conducted to compare empiric (clinician-directed) heparin therapy with therapy based on a nomogram-determined dosage. The comparison was based on (1) the average weight-referenced infusion rate yielding a therapeutic activated partial thromboplastin time (APTT) and (2) the time required to reach a therapeutic APTT (55 to 95 seconds) after empiric or nomogram-based heparin therapy was initiated. METHODS: Data were collected for patients admitted to the cardiology service at a university health science center in two phases: phase 1 (April 1 through June 30, 1992), involving 95 patients receiving heparin therapy, with 88 patients included in the data analysis, and phase 2 (March 11 through June 11, 1993), involving 156 patients receiving heparin therapy, with 45 patients receiving nomogram-guided therapy included in the data analysis. RESULTS: In phase 1, 66 patients (75.0%) achieved a therapeutic APTT some time during their heparin therapy, with an average time to therapeutic APTT of 20.7 + 19.1 hours. Regression analysis demonstrated a statistically significant relationship between the heparin infusion rate at the time of the patient's first therapeutic APTT and the patient's total body weight (r2 = .3043). An initial infusion rate based on total body weight (13 U/kg per hour) was therefore used as the basis for the nomogram in phase 2. In phase 2, 41 patients (91.1%) achieved a therapeutic APTT at some time during their heparin therapy, with an average time to therapeutic APTT of 13.1 + 11.9 hours, statistically significantly shorter than that in phase 1. A greater proportion of patients in phase 2 compared with patients in phase 1 reached the therapeutic range within 12 hours (62.2% vs 34.1%) and within 24 hours (77.8% vs 54.5%). CONCLUSIONS: Use of a weight-based nomogram to determine the initial and maintenance heparin infusion rates was associated with a higher percentage of patients admitted to the cardiology service reaching the targeted therapeutic APTT range at a time earlier in the course of therapy compared with empiric dosing.

Adult↗
PubMed1994

Inhibition of cisplatin toxicity without decreasing antitumor efficacy. Use of a dithiocarbamate.

OBJECTIVE: To demonstrate whether a dithiocarbamate derivative, N-methyl-D-glucaminedithiocarbamate, could prevent anorexia and weight loss and enhance survival without decreasing the antitumor efficacy of high-dose cisplatin therapy. DESIGN: One hundred forty-two mice were randomized into groups receiving cisplatin, 5 mg/kg per day, 7.5 mg/kg per day, or 10 mg/kg per day for three days with or without N-methyl-D-glucaminedithiocarbamate, 1000 mg/kg per day. Weight loss and morbidity were examined between groups. Antitumor efficacy of cisplatin combined with N-methyl-D-glucaminedithiocarbamate was examined using a subcutaneous melanoma model. SETTING: Institutional laboratory. MAIN OUTCOME MEASURES: N-methyl-D-glucaminedithiocarbamate intervention would decrease morbidity, weight loss, and increase survival without decreasing the antitumor efficacy of cisplatin. RESULTS: Weight loss and morbidity were significantly reduced when N-methyl-D-glucaminedithiocarbamate was coadministered with cisplatin (P < .05) at all doses of cisplatin. The antitumor efficacy of high-dose cisplatin therapy (7.5 mg/kg per day and 10 mg/kg per day) was not significantly decreased (P > .05) at all doses of cisplatin. CONCLUSION: As N-methyl-D-glucaminedithiocarbamate seems to limit morbidity and mortality of high-dose cisplatin administration without decreasing its antitumor efficacy, this drug deserves further investigation in the treatment of cancer.

Animals↗
PubMed1993

Metabolic activation, DNA adducts, and H-ras mutations in human neoplastic and non-neoplastic laryngeal tissue.

Metabolic activation, DNA adducts, and H-ras mutations were examined in human laryngeal tissue (n = 16) from both smoker and non/ex-smoker patients with laryngeal cancer. DNA adducts detected by 32P-postlabelling were evident only in smokers (n = 13); in fact, smoking cessation for as little as 10 months resulted in no DNA adducts detected (n = 3). Total DNA adduct levels in these samples were significantly correlated with levels of cytochromes P-4502C and 1A1 in laryngeal microsomes. Moreover, the P-4501A1 levels represent the highest yet found in human tissues. In contrast, laryngeal microsomes did not have detectable P-4501A2 activity, while laryngeal cytosols showed appreciable N-acetyltransferase activity for p-aminobenzoic acid (NAT1) but not sulfamethazine (NAT2). DNA was extracted from laryngeal specimens and amplified by PCR. Nylon filter dot or slot blots were hybridized with 32P-labelled probes for codons 12, 13, and 61 of the H-ras gene. Sixty percent of specimens demonstrated mutations in either codon 12, 13, or 61; a single common and specific mutation was a Gln-->Glu transversion in codon 61. This mutation appeared in 5 laryngeal specimens, all from smokers. These results implicate cigarette smoke components, bioactivated by CYP1A1 and/or CYP2C, in DNA adduct formation. These results also demonstrate a probable smoking-related H-ras Gln-->Glu transversion in codon 61.

4-Aminobenzoic Acid↗
PubMed1993

Tumor specific response to photodynamic therapy.

The exact mechanism by which photodynamic therapy (PDT) causes tumor destruction has not been elucidated. Early reports indicated that PDT causes direct cellular effects probably mediated by unstable oxygen species, resulting in cellular oxidation and death. More recently, PDT effects on tumor blood flow have been implicated, and there are questions as to whether the PDT response is specific to tumor tissue. Rats were implanted with a window chamber containing either a mammary adenocarcinoma or a piece of inert surgical sponge. After growth of the tumor was ascertained, all rats were given 5 mg/kg Photofrin intraperitoneally, and then were irradiated with 630 nm light 24 hours post-injection. Caliper thickness and reflectance measurements were performed before and after irradiation; all animals were sacrificed 72 hours post-PDT and the chambers submitted for histologic analysis. Animals implanted with tumors demonstrated marked edema of the chamber with an associated decrease in reflectance. No edema response was noted in the chambers containing inert sponge, or in any controls. Nonselective PDT effects (characterized by a marked foreign body response) in chambers containing sponge was not seen. Histologic analysis of treated specimens corroborate the above data.

Animals↗
PubMed1993

Community-based cholesterol screening and education to prevent heart disease: five-year results of the North Coast Cholesterol Check Campaign.

A cardiovascular disease screening and education campaign was conducted throughout the North Coast Region of New South Wales from 1987 to 1991. Objectives were: to screen 20 per cent of the adult population for blood cholesterol and other heart disease risk factors; to raise awareness of the risks associated with a high-fat diet; to provide nutrition counselling and referral advice for those with elevated cholesterol; and to monitor these participants' cholesterol levels with a follow-up test at three months. During the five years, 42,869 individuals or 18 per cent of North Coast adults participated, with some overrepresentation of women aged 40 to 60 years. Initially, 65 per cent of participants had elevated cholesterol levels (> or = 5.5 mmol/L) and 46 per cent were overweight (body mass index over 25). A three-month retest was offered to all participants with elevated cholesterol, of whom 53 per cent attended. Participants who received nutrition counselling generally reported dietary changes which were reflected in significant cholesterol and weight reductions. Of participants who attended retest, 63 to 87 per cent had reduced cholesterol levels and 57 to 71 per cent reduced weight. A stratified random sample of participants was retested at one and three years. Reductions in cholesterol were well maintained for one year but showed signs of relapse after three years. There was a tendency for initially lower cholesterol levels to increase over a three-year period. Contributing factors included aging, regression to the mean and complacency. Maintenance may be enhanced by regular reinforcement of nutrition changes and development of more supportive environments.

Adult↗
PubMed1993

Immunoperoxidase study of the endolymphatic sac in Menière's disease.

A growing body of evidence suggests that some cases of Menière's disease may be mediated by immune mechanisms. Because endolymphatic sac dysfunction is believed to be an underlying cause of Menière's disease, this study used immunohistochemical techniques to demonstrate the presence of immune complex deposition in the sacs of patients with Menière's disease. Positive immunoglobulin G (IgG) staining was noted in 10 of 23 sac biopsies from Menière's patients, with 2 specimens showing perivascular deposition. Only 1 of 5 control specimens was only slightly positive for IgG. Clinical correlation showed a statistically significant increase in disease bilaterality (P < .05), larger summating potential/action potential (SP/AP) ratios with electrocochleography (ECoG), and a tendency toward worse hearing and more progressive disease among the immunopositive Menière's patients. The results provided histological evidence of immune injury in the endolymphatic sacs of patients with Menière's disease.

Action Potentials↗
PubMed1983

Differences in the Elution profiles of corticotropin-releasing activity in rat plasma and hypothalamic extracts following high performance liquid chromatography.

Extracts of rat plasma and hypothalami were fractionated by reversed-phase high performance liquid chromatography (HPLC) and the fractions were assayed in an in vitro bioassay for corticotropin-releasing activity. Corticotropin releasing factor (CRF) bioactivity was found in many fractions with retention times of 20-50 min. In contrast, material derived from the plasma of rats stressed by ether anaesthesia yielded only one peak of CRF bioactivity, with a retention time of 47-48 min. These results suggest that ACTH can be released from isolated pituitary cells by a number of components derived from HPLC of extracts of rat hypothalami. It is possible, however, that some of these are artefacts of the extraction process from post-mortem material. Because the CRF activity found in plasma was homogeneous by HPLC, plasma can be used to obtain physiologically active CRF.

Animals↗
PubMed1980

Prospective study of the effect of resection of the rectum on male sexual function.

A prospective study to evaluate sexual dysfunction following resection of the rectum was performed in 21 male patients. Following proctocolectomy for inflammatory bowel disease (9 patients), the incidence of sexual dysfunction was 11%, and it was always partial. Following abdominoperineal excision of the rectum for carcinoma (7 patients), the incidence of sexual dysfunction was 50%, and it was total in 16%. After anterior resection with low colorectal anastomosis (5 patients), the incidence of sexual dysfunction was 40%. The risk of dysfunction following operations on the rectum increased with the age of the patient and was minimal below the age of 50 years. In patients with inflammatory bowel disease, careful dissection close to the rectum should avoid damage to the pelvic nerves, and the incidence of sexual dysfunction should be low.

Adult↗
PubMed1980

An improved methodology for the extraction and partial purification of porcine hypothalamic corticotrophin releasing factor.

In most previous reports material with corticotrophin releasing factor (CRF) activity has been obtained from hypothalami after extraction with dilute aqueous acid. Such conditions allow substantial proteolytic degradation. By adopting conditions designed to precipitate proteases and by using information on the nature of CRF gained from earlier studies, rapid large scale extraction and partial purification of porcine hypothalamic CRF in high yield was achieved. After extraction with 0.2 m-HCl; acetone (1:1, v/v), centrifugation and ultrafiltration, considerable preliminary purification of the CRF activity was achieved by adsorption onto carboxymethylcellulose and subsequent elution at increased salt concentration. Following ion-exchange chromatography of the extract on carboxymethylcellulose, CRF activity was obtained in good yield (minimal effective dose of about 1-2 micrograms/ml) for ACTH release in an in-vitro CRF bioassay utilizing a coupled isolated pituitary cell-adrenal cell system. The data indicated that the previously reported heterogeneous corticotrophin releasing factors of low activity may be a consequence of proteolytic degradation.

Adrenal Glands↗
PubMedDate not supplied

Prevention of cisplatin-induced toxicity by selected dithiocarbamates.

Cisplatin (CDDP) is a widely used antineoplastic agent, the administration of which is associated with dose-related toxicities. Currently, ototoxicity is the dose-limiting toxicity of cisplatin and difficult to prevent. The purpose of this study was to determine the ability of two substituted dithiocarbamates, diethyldithiocarbamate (DDTC) and N-methyl-D-glucaminedithiocarbamate (NMGDTC) to abrogate cisplatin-induced toxicity in young female Hartley albino guinea pigs. The animals were divided into saline controls, CDDP only, NMGDTC only, and CDDP-DDTC or CDDP-NMGDTC combinations with DDTC or NMGDTC given 30 minutes before or 30 minutes after CDDP. Auditory brainstem responses (ABR) were recorded periodically in sound-attenuated rooms to assess hearing thresholds. Representative cochleas were harvested at autopsy, processed, and examined by scanning electron microscopy (SEM). The NMGDTC produced marked reduction of CDDP-induced ototoxicity and weight loss. No significant ABR shift was found regardless of the order of CDDP and NMGDTC administration, but the derivative was more effective in preventing anorexia and weight loss when given prior to CDDP. Specifically, groups of guinea pigs given NMGDTC prior to CDDP showed the only weight gain among the treatment groups. Diethyldithiocarbamate, the other dithiocarbamate evaluated in this study, did not provide protection from cisplatin ototoxicity regardless of the order of administration. A CDDP-induced weight loss was reduced when DDTC was administered prior to CDDP. In summary, NMGDTC given prior to CDDP offers remarkable protection against cisplatin-induced ototoxicity and weight loss. It may help eliminate dose-limiting cisplatin-induced toxicity and allow the use of cisplatin at higher doses in cancer chemotherapy.

Animals↗