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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 199 records · Page 11Linked to original sources
PubMed1990

HPLC procedure for the pharmacokinetic study of the spin-trapping agent, alpha-phenyl-N-tert-butyl nitrone (PBN).

Considerable progress has been made in the use of spin-trapping agents for the trapping of free radicals in biological systems. Radicals have been detected in both in vitro and in vivo systems using this methodology. Free radicals have not only been identified by this procedure, but also the intensity of radical generation and the duration of their production has been assessed as well. One of the most widely used spin-trapping agents in biological systems is PBN. This spin trap appears to be relatively nontoxic at the levels required for successful trapping experiments, but there is no information concerning the possible fate of PBN in such biological systems. Metabolism of PBN could alter the concentration of PBN at the site of trapping which may affect the efficiency of radical capture, especially in in vivo systems. In this study, PBN was administered intraperitoneally to rats and the concentration of the spin trap in various organs was determined by high pressure liquid chromatography as a function of time (15 min to 12 h). The concentration of PBN in plasma peaked at 15 min while the maximum in all organs tested occurred at 30 min. The time course of PBN concentrations in all tissues followed similar curves, and declined rather steeply after the 30-min maximum with a biological half-life of 134 min. However, the amount of PBN per gram of tissue was always higher in liver and kidney than in the brain, heart, and lung. PBN was detected in the urine for as long as 24 h after injection of the compound.

Animals↗
PubMed1990

Predicting response to chemotherapy for patients with epithelial ovarian cancer using urinary polyamine excretion patterns.

Urinary polyamine (UPA) excretion patterns were measured in 39 patients with clinically evaluable epithelial ovarian cancer immediately before they were treated with a cycle of chemotherapy and 24-48 h after chemotherapy to ascertain if changes in UPA excretion patterns correlated with eventual response to treatment. Almost all of the 19 patients who responded to chemotherapy had a rise in the excretion of all UPA fractions after treatment while most patients with chemoresistant cancer showed only an increase in the excretion of the putrescine and spermine fractions. However, a two-fold increase in excretion of the spermidine fractions occurred exclusively in patients who would eventually respond to chemotherapy. This phenomenon was not seen in patients with chemoresistant cancer. If, 48 h after chemotherapy, a patient with epithelial ovarian cancer does not show at least a doubling of the urinary levels of spermidine, acetylspermidine or total polyamine excretion that chemotherapy should be stopped since it is unlikely to be effective.

Biogenic Polyamines↗
PubMed1990

Effect of vasoactive intestinal peptide on cyclic adenosine monophosphate production in enterocytes isolated from human duodenal biopsy specimens.

A modification of a cell isolation technique used in animal studies was developed to remove enterocytes from duodenal biopsy specimens. Citrate-ethylenediaminetetra-acetic acid treatment removed enterocytes from any underlying lamina propria and produced single cells and strips of cells. A mean (SEM) of 4.39 (2.06) x 10(6) cells was obtained from nine duodenal biopsy specimens. Enterocyte recovery was estimated enzymatically using alkaline phosphatase activity and was found to be 61%. Cytological assessment of the cells with CAM 5.2 showed that 98% of the cells isolated were enterocytes with an intact brush border. The cells responded well to vasoactive intestinal peptide stimulation in the absence of an exogenously added adenosine triphosphate regenerating system. The addition of vasoactive intestinal peptide to duodenal enterocytes produced a biphasic dose dependent increase in cyclic adenosine monophosphate production. Stimulation of these cells with 10(-13)M vasoactive intestinal peptide resulted in a 50% stimulation over basal value while 10(-6)M vasoactive intestinal peptide led to a fivefold increase in cyclic adenosine monophosphate production. We conclude that duodenal biopsy specimens are a good source of human intestinal cells for the study of enterocyte physiology. The cells were viable and highly responsive to vasoactive intestinal peptide.

Adult↗
PubMed1990

Dual energy radiography versus quantitative computer tomography for the diagnosis of osteoporosis.

In this study we compared dual energy radiography (DER), a new, highly precise x-ray densitometric technique recently devised for measurements of vertebral mineral density and quantitative computer tomography (QCT), a densitometric technique that selectively measures the trabecular compartment of the vertebra. DER and QCT measurements were obtained in 56 healthy (H) and 48 fractured osteoporotic (OP) women using a Hologic QDR 1000 bone densitometer and a GE 9800 scanner, respectively. DER was significantly correlated with QCT in both the H (r = 0.75; P less than 0.0001) and the OP subjects (r = 0.58; P less than 0.0001). DER decreased significantly with age in the H (P less than 0.05), but not in the OP women, whereas QCT was related to age in both the H (P less than 0.0001) and the OP subjects (P less than 0.01). The rate of bone loss with age was also higher with QCT than with DER in both normal and osteoporotic women. The difference in bone density between the H and the OP subjects was larger (P less than 0.05) with QCT than with DER. Receiver operating characteristic analysis revealed that QCT was a better predictor of vertebral fractures than DER. A larger percentage of OP subjects were 2 SD or more below the normal predicted value with QCT (41%) than with DER (29%). Furthermore, the slopes of the regressions of bone density with age for normal and osteoporotic women were significantly different (P less than 0.05) with QCT but not with DER. These findings are consistent with a disproportionate loss of trabecular bone with age in osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1990

Lateral dual energy radiography: a new method for measuring vertebral bone density: a preliminary study.

Dual energy radiography (DER) is a new technique for non-invasive measurement of vertebral bone mineral density, which because of its high precision (1%), is particularly suitable for prospective analyses of time-related changes in bone mass. However, we recently found that DER is less sensitive to demineralization of trabecular bone than quantitative computed tomography (QCT). Since the compact bone of the posterior vertebral elements are included in the standard anterior-posterior DER (APDER), but not in QCT measurements, changes in trabecular bone mass attending the early phases of the osteoporotic process go undetected with the APDER technique due to the preponderance of cortical mass. Lateral-view DER (LDER), however, would minimize the contribution of vertebral compact bone as well as intra-abdominal calcifications to the trabecular component. To determine the in vivo short-term precision of the LDER method, we obtained three measurements in 18 healthy women, aged 23 to 76, during a four-week period. In addition, both APDER and LDER measurements were obtained in 53 healthy women, aged 23 to 80. The coefficient of variation for LDER was 2.8%. LDER density values accounted for a higher percentage of the variance of bone mass measurements with age (47%) than APDER (23%). Moreover, LDER declined significantly with age in both premenopausal (r = -0.42, p less than 0.05) and post-menopausal women (r = -0.50, p less than 0.005), whereas the age-related changes in APDER values failed to reach statistical significance in either group. The rate of bone loss with age in the premenopausal group was 0.45% per year with LDER, and 0.10% per year with APDER. Postmenopausal women showed a 0.78% loss of bone mass per year with LDER and 0.47% per year with APDER. The correlation between APDER and LDER was significant (r = 0.78, p less than 0.01). The accumulated data indicate that LDER may be a more appropriate technique than APDER for detecting the initial loss of vertebral trabecular bone that characterizes early subclinical osteoporotic syndrome.

Adult↗
PubMed1990

Chlamydia trachomatis pneumonitis: a case study and literature review.

Chlamydia trachomatis was cultured from the lung and eye of an 11-day-old infant who had rapidly deteriorating respiratory symptoms. Chlamydia trachomatis inclusion bodies were identified on thick Epon sections and by electron microscopy. We discuss the unusual presentation and review the published histopathological lung findings.

Chlamydia Infections↗
PubMed1990

The play project--use of stimulus objects with demented patients.

A major problem among hospitalized demented patients relates to the patients' agitation, resistance to nursing care, and loss of meaningful activity. The limited stimulus environment and restriction to a chair in an institutional environment contribute to such responses. Demented patients display significant interest in simple toys and stimulus objects. A variety of stimulus objects were provided; most interest was shown in mechanical toys devised for young children. In selecting toys and stimulus objects for patients, care must be taken to avoid objects that can be ingested, used as weapons, thrown on the floor where they will pose a safety hazard to ambulating residents, or that require constant intervention of nursing staff. Although patients greatly enjoy fabric and plush objects, they tend to hold or stroke them in a calm and passive manner. Mechanical objects stimulate vigorous exploration and use visual inspection, turning, spinning of dials, and manipulation of moveable or mechanical parts.

Aged↗
PubMed1989

Characterization of an FMN-containing cyclohexanone monooxygenase from a cyclohexane-grown Xanthobacter sp.

A soluble cyclohexanone monooxygenase was purified 16.1-fold to homogeneity from a Xanthobacter sp. grown upon cyclohexane as sole source of carbon and energy. The native enzyme is a 50-kDa single polypeptide chain associated with FMN rather than FAD as flavin prosthetic group in a 1:1 stoichiometric relationship. The monooxygenase catalyses the transformation of cyclohexanone to the lactone 1-oxa-2-oxocycloheptane in an oxygen ring insertion reaction. Only related cycloalkanone substrates are accepted for oxygenation, no activity is shown towards straight-chain alkanones. Enzyme activity is strongly inhibited by sulphydryl-reactive agents, but is relatively insensitive to metal chelators, electron transport inhibitors and the metal ions Fe3+ and Cu2+. Cyclohexanone monooxygenase has Km values for cyclohexanone and NADPH of less than 0.5 microM and 12.5 microM respectively. Kinetic investigations under steady-state conditions demonstrate that the flavoprotein prosthetic group, FMN, is involved in the monooxygenase catalytic mechanism. The systematic name for the enzyme is cyclohexanone, NADPH:oxygen oxidoreductase (6-hydroxylating, 1,2-lactonizing) (EC 1.14.13.22).

Chromatography↗
PubMed1989

Urinary polyamine excretion patterns in patients with epithelial ovarian cancer.

Free and acetylated urinary putrescine, spermine and spermidine levels (UPA) and total polyamine excretion were measured by high-performance liquid chromatography in 57 patients with epithelial ovarian cancer (EOC) and 43 control patients. Mean UPA levels were higher and the number of abnormal UPAs per sample greater for cancer patients but maximum single UPA sensitivity was only 29%. No control subject had more than 2 abnormal UPA values compared with 42% of patients with EOC. Rising UPA levels reflected progressive disease in 83% of patients and fell with tumour response in 66%.

Adult↗
PubMed1989

Malignant melanoma lately diagnosed.

To assess the clinical impression that patients in Dublin were presenting with late, deep, poor prognosis lesions, a 10 year retrospective review of patients with malignant melanoma was performed. The pathological data on 186 patients was examined and clinical follow-up obtained on 151 of these (80%). The mean period of follow-up was 35 months. Females predominated in a ratio of 3:1. Incidence figures for the two five year periods (1976-80) and (1981-85) indicated a rise in the latter period of over 100%. There was a marked delay in presentation after the onset of symptoms i.e. new pigmented lesions or changes in pre-existing lesions (mean = 21 months). Only 45% of lesions were less than 1.5mm in depth. Females presented with a higher percentage of good prognosis lesions reflected in a superior five year survival figure of 70% compared with 43% for males. The results of this study suggest an increase in incidence and mortality from malignant melanoma in this country. Patients appear to be unaware of the significance of pigmented lesions, presenting late with deep poor prognosis tumours.

Adolescent↗
PubMed1988

Construction of an ion-exchange amino acid analyser kit for use with high-performance liquid chromatography apparatus.

A conventional ion-exchange amino acid analyser kit has been simply and economically constructed for use with existing high-performance liquid chromatography (HPLC) apparatus. Sequential elution conditions are fully programmable by virtue of a 32K BBC microcomputer interfaced with an elution buffer selection valve and a thermostatically controlled column. Post-column derivatization with o-phthaladehyde-2-mercaptoethanol reagent enables fluorimetric detection at the picomole level. The system enables sensitive amino acid analysis of complex mixtures to be carried out by clinical and research laboratories who already possess HPLC apparatus but whose sample turnover does not merit purchase of a dedicated fully automated analyser.

Amino Acids↗
PubMed1988

Expression of the cytosolic and particulate forms of transglutaminase during chemically induced rat liver carcinogenesis.

Transglutaminase (EC 2.3.2.13) activity in chemically induced rat hepatocellular carcinomas was reduced by some 65% when compared to normal rat livers. The majority of the remaining activity (approx. 85%) was found in the particulate fraction. The use of non-ionic detergent to extract the transglutaminase activity present in both normal and tumour tissue followed by its separation on a Mono-Q column revealed two distinct peaks of activity. These peaks of activity were equivalent to those previously identified as a membrane-bound transglutaminase and the more characteristic cytosolic or tissue transglutaminase. The ratio of the activity of the cytosolic enzyme to that of the membrane-bound enzyme in normal liver was calculated as 5:1. In hepatocellular carcinomas, this ratio was reduced to 0.4:1. No significant change in the activity of the membrane-bound enzyme was detectable in tumour tissue. Comparison of the cytosolic enzyme found in hepatocellular carcinomas with that found in normal liver indicated no change in its molecular weight, Km,app for putrescine incorporation into N,N'-dimethylcasein and sensitivity to activation by Ca2+. These observations suggest that the reduction in transglutaminase activity observed in the hepatocellular carcinoma is due to a selective reduction in the expression of the cytosolic transglutaminase.

Animals↗
PubMed1988

Calmodulin antagonists of improved potency and specificity for use in the study of calmodulin biochemistry.

Syntheses are described for a range of N-(omega-aminoalkyl)-5-iodo- and -5-cyanonaphthalene-1-sulphonamides. The selective activity of these compounds as inhibitors for calmodulin-dependent phosphodiesterase (EC 3.1.4.17) is compared with their activity for the calmodulin-independent but calcium-dependent enzymes protein kinase C and transglutaminase (EC 2.3.2.13). The results show a drastic improvement in the selectivity of effect for the 5-iodo-compounds compared with the widely-used drug, W7, N-(6-aminohexyl)-5-chloronaphthalene-1-sulphonamide.

Calmodulin↗
PubMed1988

Transglutaminase-catalysed cross-linking of proteins phosphorylated in the intact glucose-stimulated pancreatic beta-cell.

Incubation of intact islets in the presence of [32P]Pi and stimulatory levels of glucose followed by separation of phosphorylated islet proteins by SDS-polyacrylamide gel electrophoresis revealed the presence of a high molecular weight phosphopolymer which did not transverse a 3% (w/v) acrylamide gel. The majority of this phosphopolymer (approx. 70%) was present in the 600 x g sedimented fraction of islet homogenates. Islet homogenates obtained from intact islets previously incubated with [32P]Pi and stimulatory levels of glucose when incubated under conditions that activated the islet transglutaminase resulted in an increase in the amount of phosphopolymer present in the 600 x g sedimented fraction. Inhibitors of transglutaminase activity which are known to inhibit glucose-stimulated insulin release led to a significant reduction in the fraction of phosphopolymer present in the glucose-stimulated intact islet. These findings suggest that protein cross-linking and phosphorylation reactions may be closely linked in the pancreatic beta-cell.

Animals↗
PubMed1988

Dual energy radiography (DER): a preliminary comparative study.

Dual energy radiography (DER) has been recently proposed as a new technique for the non invasive measurement of vertebral mineral density. This preliminary study was undertaken to assess the short-term precision of DER and to compare DER to dual photon absorptiometry (DPA) measurements. Three DER measurements were obtained in 19 healthy volunteers (mean age 34.7 +/- 9.3 years) over a 3 week period. In addition, both DER and DPA measurements were obtained in 52 women (mean age 54.3 +/- 12.5 years). The coefficient of variation for the DER measurements was 1.00%. A highly significant correlation (r = 0.94; p less than 0.0001) was found between DPA and DER. Using this curve a conversion factor of -6.8% was calculated to convert DER to DPA values. Both DER and DPA were significantly and similarly correlated with age (r = -0.43, p less than 0.005; r = -0.38, p less than 0.05, respectively). The rates of bone loss, 0.66% per year for DER and 0.57% per year for DPA, were also similar with the two techniques. From these data, it is concluded that DER is a precise new method for vertebral bone mass measurements.

Adult↗