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Biomedical subjects

M Griffin

Publications and source records attributed to M Griffin.

At least 181 records · Page 10Linked to original sources
PubMed1992

Cell cycle kinetics, tissue transglutaminase and programmed cell death (apoptosis).

Studies were undertaken on a highly metastatic hamster fibrosarcoma cell line with a view to assessing whether cells entering into apoptosis, measured by counting the number of transglutaminase mediated detergent insoluble envelopes, has any synchrony with a particular phase of the cell cycle. A double exposure of thymidine was used to block cells in early S-phase. Flow cytometry in combination with [3H]thymidine incorporation into DNA was used to assess the degree of synchrony and progression through the different phases of cell cycle. The apoptotic index was found to be at its maximum in mid-S-phase. Measurement of transglutaminase activity in each phase of the cell cycle indicated that the specific activity was also at its greatest during mid S-phase. The level of enzyme was relatively unchanged throughout the cell cycle indicating that the regulation of transglutaminase activity occurs primarily through effects on catalytic activity rather than enzyme synthesis.

Animals↗
PubMed1992

Long-term use of depot-norethisterone enanthate: effect on blood lipid fractions.

This is the third report of a metabolic study on 56 long-term users (24 for 2-5 yr; 32 for over 5 yr) of the injectable contraceptive norethisterone enanthate (Net-En) and deals with the effects on the blood levels of lipoprotein fractions. There was no significant difference between this group and a group of 30 non-users in serum concentrations of triglycerides, total cholesterol, low density and very low density lipoproteins. There was a significant reduction in mean high density lipoprotein levels between the controls and the user groups (16% for the intermediate duration and 12% for the longer duration). Age, ethnic group, body-mass index and a close family history of cardiovascular disease were taken into account, as were various lifestyle factors: diet, exercise, alcohol consumption and smoking. In a smaller group, levels of apoproteins A and B were also assayed. There was a significant reduction in apoprotein A between controls and all users, but the significance was lost on adjusting for confounding variables. Consideration was given to the ratio of total cholesterol to high density lipoprotein cholesterol as an index of coronary risk. There were no significant differences in the total cholesterol:HDL-C ratio between controls and user groups. There was a significant interaction with ethnic group (Caucasian or Afro-Caribbean) in the response to duration of use.

Adult↗
PubMed1992

Prolactin bioassay in schizophrenia before and after neuroleptics.

Fifteen drug-free schizophrenic male inpatients and 14 normal control subjects were studied. The schizophrenic subjects had a significantly lower ratio of bioassay prolactin to radioimmunoassay prolactin before neuroleptic treatment than they did after treatment. The ratio was lower in the drug-free patients as compared with normal controls. These findings suggest that neuroleptic medications may alter the molecular forms of serum prolactin. The results also suggest that drug-free schizophrenic patients may have a different pattern of prolactin variants than normal subjects and that this difference could be secondary to a disordered tuberoinfundibular dopamine system or long-term effects of neuroleptic drugs.

Adult↗
PubMed1992

Oral delivery of a renin inhibitor compound using emulsion formulations.

The oral delivery of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L- leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylhetane (I), a new renin inhibitor, was studied in the in vivo rat model using emulsion formulations. The components of the emulsion formulations were chosen based on their proposed effects on membrane structure, membrane fluidity, and solute transport. The percent absolute bioavailability (%AB) of I was increased from 0.3% (water suspension) to 5.1% when long-chain unsaturated fatty acid (oleic acid, linoleic acid, etc.)- and mono- and diglyceride (monolein, dilaurin, etc.)-containing emulsion formulations were used. Considering very high first-pass liver extraction of the compound (80%), it is suggested that emulsion formulations increased the intestinal transport of the compound significantly. The solubility of I in aqueous media with and without bile salt (20 mM) was found to be low (approximately 1 micrograms/ml). Incubation in 0.01 N HCl did not affect the particle size of the emulsion. The titration of oleic acid/monoolein emulsion in a pH 6.5 medium with a mixed bile salt system indicated reduction in the particle size of the emulsion. Drug precipitation was observed above 30 mM bile salt concentrations. No drug crystals could be detected in the intestinal contents of the rats when emulsion formulations were ingested. These results suggest that in the intestine of the animals, the particle size of the emulsions is reduced in the presence of bile fluid while the drug resides primarily in the oil phase. The mechanism of enhanced transport of I from the emulsion formulations is discussed along with the possibility of cotransport for the drug and oil. Emulsion formulations can be a potential delivery form for low-bioavailable lipid-soluble drugs.

Absorption↗
PubMed1992

Cardiac growth after pediatric heart transplantation.

BACKGROUND: To assess whether normal cardiac growth occurs after heart transplantation in the pediatric age group, we performed a study of 13 infants and children who underwent orthotopic heart transplantation at Stanford. METHODS AND RESULTS: The echocardiographic data from a population of 93 normal children were analyzed to determine estimates of the fifth, 25th, 50th, 75th, and 95th percentiles of the normal pediatric population. Growth curves for each of the cardiac dimensions were stratified into six classes representing each of the percentile bands, and dimensions for the 13 patients were tracked between early postoperative (early) and point of maximal follow-up (late). Results were compared by Student's paired t test to determine whether normal growth was occurring. The mean age at transplant was 5.0 +/- 1.3 years (mean +/- SEM) (range, 0.4-12.8 years), duration of follow-up was 3.1 +/- 0.4 years (1.3-5.8 years), and change in body surface area was 0.24 +/- 0.03 m2 (0.12-0.50 m2). Both right ventricular (RV) and left ventricular (LV) chamber dimensions were within the normal range at both early and late time points and grew normally as assessed by a lack of class changes. Early wall thickness measurements were above the 95th percentile in seven of 13 patients (LV), 12 of 13 patients (septum), and four of 13 patients (RV). Wall thickness measurements remained above normal, and there were no significant class changes at late follow-up. Histological examination in five patients showed markedly increased septal myocyte width, indicating myocyte hypertrophy. Atrial and great vessel anastomotic sites showed no evidence of obstruction by Doppler and catheterization studies. CONCLUSIONS: These data demonstrate that normal cardiac chamber dimensional growth occurs at greater than 3 years' follow-up after pediatric heart transplantation. Significant LV and septal (and to a lesser extent RV) hypertrophy persists and may have implications for long-term allograft growth and function.

Body Surface Area↗
PubMed1991

High affinity human IgE receptor (Fc epsilon RI). Analysis of functional domains of the alpha-subunit with monoclonal antibodies.

The binding of IgE to the high affinity Fc epsilon receptor (Fc epsilon RI) on mast cells and basophils is mediated by the alpha-subunit of the tetrameric receptor complex. Based on sequence homologies, the 50-kDa alpha-subunit is a member of the immunoglobulin superfamily of proteins and has two predicted disulfide-bonded loops. Monoclonal antibodies specific for the human alpha-subunit have been identified and separated into two major classes: inhibitory and noninhibitory antibodies. Inhibitory antibodies (i.e. 15A5) block 125I-IgE binding to a recombinant chimeric alpha-subunit (ch-alpha-protein) expressed on Chinese hamster ovary cells and immunoprecipitate 125I-labeled purified ch-alpha-protein. Noninhibitory antibodies (i.e. 22E7) immunoprecipitate both 125I-labeled ch-alpha-protein and the soluble complex of 125I-IgE cross-linked to ch-alpha-protein but do not block 125I-IgE binding to the ch-alpha-protein expressed on Chinese hamster ovary cells. Both classes of antibodies bind to natural Fc epsilon RI present on human basophils and induce histamine release from these cells. Inhibitory antibody 15A5 specifically binds to a peptide corresponding to amino acids 125-140 of the putative second domain of the alpha-subunit sequence. All the inhibitory antibodies compete with 125I-15A5 for binding to the ch-alpha-protein, indicating that these antibodies recognize inhibitory epitopes that are either identical or sterically overlapping. Noninhibitory antibodies (i.e. 22E7) do not block 125I-15A5 binding to the ch-alpha-protein. These data suggest that antibodies binding to the predicted second domain of the alpha-subunit can inhibit IgE binding to the alpha-subunit, while antibodies binding at a distance from this site do not inhibit IgE binding. These inhibitory antibodies may block IgE binding to the ch-alpha-protein by direct overlap, steric inhibition, or induced conformational changes of the receptor contact points for IgE.

Animals↗
PubMed1991

Apoptosis: a potential role for cytosolic transglutaminase and its importance in tumour progression.

The relationship between transglutaminase activity, apoptosis and the propensity of a tumour to metastasise, was investigated in a series of metastatic variants of an HSV-2 induced hamster fibrosarcoma and two metastatic variants of the B16 mouse melanoma. The data suggest an inverse relationship between metastatic potential and cytosolic transglutaminase activity. A direct relationship was found between measured cytosolic activity and the levels of the endogenous product of transglutaminase, the protein crosslink epsilon(gamma-glutamyl)lysine. Increasing metastatic potential and decreasing cytosolic transglutaminase activity was accompanied by a corresponding decrease in the number of detergent-insoluble apoptotic envelopes isolated from variant cell lines. These apoptotic envelopes were found to be highly crosslinked structures, containing more than 85% of the cells content of epsilon(gamma-glutamyl)lysine. These data are in keeping with the idea that a major role for the cytosolic transglutaminase is in the formation of the highly crosslinked apoptotic envelope during programmed cell death and that perturbation of this function may be an important determinant in the development of the metastatic phenotype.

Animals↗
PubMed1991

Long-term use of depot-norethisterone enanthate: effect on blood coagulation factors and menstrual bleeding patterns.

Fifty-six women using depot-norethisterone enanthate injections for contraception for 2 years or more were compared with a control group of 48 women not using hormonal contraception. No significant difference was found between the study group and controls for Factors VIIc and Antithrombin III. Factor Xc was reduced in women who had used the injections for over two but less than five years [controls: mean 90.3% SD31.2 vs users for 2-5 yr: 78.7% SD17.1, 95%CI difference in means -0.3, -22.9]. In the group using Net-En for five years or more, Factor Xc was significantly higher than in the control group, but only by 14% of the mean control value [users for over 5 yr: 103.2% SD15.2, 95%CI difference in means 3.1, 22.7]. Haemoglobin levels, red cell count and packed cell volume were higher in those using the injections than in the control group. Changes in the platelet count were not statistically significant. Twenty-three women using the injection agreed to keep menstrual diaries. Of these, 20 experienced amenorrhoea for more than two consecutive injection intervals (112 days). It is concluded that long-term use of norethisterone enanthate is not associated with any markedly deleterious effects on Factor VIIc, Xc, or antithrombin III or haemoglobin levels. Amenorrhoea of 4 months or more can be expected after two years of continuous use.

Adult↗
PubMed1991

Calmodulin independence of human duodenal adenylate cyclase.

The calmodulin and calcium dependence of human adenylate cyclase from the second part of the duodenum was assessed in washed particulate preparations of biopsy specimens by investigating (a) the concentration dependent effects of free [Ca2+] on enzyme activity, (b) the effects of exogenous calmodulin on enzyme activity in ethylene glycol bis (b-aminoethyl ether)N,N'-tetra-acetic acid (EGTA) washed particulate preparations, and (c) the effects of calmodulin antagonists on enzyme activity. Both basal (IC50 = 193.75 (57.5) nmol/l (mean (SEM)) and NaF stimulated (IC50 = 188.0 (44.0) nmol/l) adenylate cyclase activity was strongly inhibited by free [Ca2+] greater than 90 nmol/l. Free [Ca2+] less than 90 nmol/l had no effect on adenylate cyclase activity. NaF stimulated adenylate cyclase activity was inhibited by 50% at 2.5 mmol/l EGTA. This inhibition could not be reversed by free Ca2+. The addition of exogenous calmodulin to EGTA (5 mmol/l) washed particulate preparations failed to stimulate adenylate cyclase activity. Trifluoperazine and N-(8-aminohexyl)-5-IODO-1-naphthalene-sulphonamide (IODO 8) did not significantly inhibit basal and NaF stimulated adenylate cyclase activity when measured at concentrations of up to 100 mumol/l. These results suggest that human duodenal adenylate cyclase activity is calmodulin independent but is affected by changes in free [Ca2+].

Adenylyl Cyclases↗
PubMed1990

The existence of an inactive form of transglutaminase within metastasising tumours.

Separation by anion exchange chromatography of detergent extracts from a poorly metastatic HSV-2-induced hamster fibrosarcoma, its highly metastatic variant and a highly metastatic rat fibrosarcoma indicated the presence of an inactive form of transglutaminase antigen, when eluent fractions were assayed for transglutaminase activity and antigen. This inactive antigenic transglutaminase was clearly separable from the particulate and cytosolic forms of the transglutaminase enzyme. Unlike tumours, its presence could not be demonstrated in extracts from normal rat liver. Measurement of activity levels during tumour growth indicated that the progression of the two highly metastatic tumours was accompanied by a decrease in cytosolic transglutaminase activity, whilst the activity of this enzyme form remained constant in the poorly metastatic tumour. Measurement of antigen levels indicated an inverse relationship between the level of inactive transglutaminase and the level of cytosolic transglutaminase activity, suggesting that the two forms are inter-related. Gel filtration indicated the molecular weight of the inactive form to be greater than both the particulate and cytosolic forms, and it was estimated to be 120,000. Partial proteolysis of the semi-purified inactive form, by either trypsin or thrombin, led to its activation and to the appearance of a transglutaminase similar in molecular weight and ionic mobility, both by anion-exchange chromatography and electrophoresis, to the cytosolic transglutaminase.

Animals↗
PubMed1990

Immunological similarities between cytosolic and particulate tissue transglutaminase.

At the present time it is uncertain whether or not the cytosolic and particulate forms of tissue transglutaminase are distinct and discrete enzymes. In this study a number of physical and immunological similarities between the two forms are demonstrated, indicating that they share some common epitopes, although their native confirmations may differ.

Animals↗
PubMed1990

Characterisation of the cellular substrates for transglutaminase in normal liver and hepatocellular carcinoma.

The transglutaminase-mediated incorporation of [14C]methylamine into tissue slices obtained from normal rat liver and diethylnitrosamine-induced hepatocellular carcinomas was used as a means of characterising the endogenous substrates of the transglutaminase enzymes present in these tissues. The amount of radiolabel incorporated was found to be similar in both tissues with the major radiolabelled protein identified as a high molecular weight polymer unable to traverse a 3.0% (w/v) acrylamide gel and with a molecular weight of at least 5 x 10(6) Da. Measurement of the crosslink, epsilon-(gamma-glutamyl)lysine, in the hepatocellular carcinoma and in normal liver indicated a 3-fold reduction in the levels found in tumour tissue when compared to normal liver. In contrast, the levels of covalently bound polyamines present in the hepatocellular carcinoma were found to be comparable or greater than those found in normal liver. Considering that there is a selective reduction (approx. 5-fold) in the activity of the cytosolic transglutaminase present in hepatocellular carcinomas with no change in the activity of the particulate enzyme (Hand et al. (1988) Biochim. Biophys. Acta 970, 137-145) these results suggests that the two enzymes may be differentially activated and that they may act on different substrates within the cell.

Animals↗
PubMed1990

Transglutaminase involvement in the secretion of insulin from electropermeabilised rat islets of Langerhans.

Ca(2+)-Induced insulin release from electropermeabilised islets is inhibited by the transglutaminase inhibitors monodansylcadaverine, glycine methylester, methylamine and cystamine but not by the control compounds dimethyl monodansylcadaverine and sarcosine methylester which lack the primary amine group. Neither monodansylcadaverine nor glycine methylester inhibited insulin secretion induced by either cAMP or the phorbol ester PMA at basal levels (10 nM) of Ca2+. These data provide further evidence for the involvement of transglutaminase in Ca2+ induced insulin secretion, they also suggest that insulin secretion induced by either cAMP or PMA may act in part by a mechanism independent of that induced by Ca2+.

Animals↗
PubMed1990

Intrahospital relocation of psychiatric patients and effects on aggression.

Aggression is a recurring problem with psychiatric patients and can pose special problems on inpatient units. The purpose of this study were to identify changes in patients aggression as a consequence of routine individual relocation and to identify the relationship of certain variables with patterns of aggression. Using an adaptation of the Overt Aggression Scale (Yudofsky, Silver, Jackson, Endicott, & Williams, 1986), data were collected from the patient records of 201 individuals who had been admitted to a state hospital and subsequently transferred to another ward in the same hospital. There was a phase by day interaction with the day-to-day pattern of aggression in the pretransfer phase differing significantly from that in the posttransfer phase. The highest mean aggression for a single day was the day following transfer; the second highest was the day before transfer. There were main effects for age and number of hospital admissions.

Adult↗
PubMed1990

Forced relocation of hospitalized psychiatric patients.

By virtue of their disability and hospital program requirements, severely and chronically mentally ill patients are subject to involuntary transfer from the community to hospitals, within hospitals, between hospitals, and from hospitals to the community. These forced relocations, no matter how humanely they were initially conceived to be, have become highly routine. The consequence is loss of the sense of the patient as a human being with individual needs. This research elicited the patients' own descriptions and the meanings they attached to the experience of forced relocation. The findings point to the need for greater success of programs designed to keep patients in their home communities to the greatest extent possible. The findings also suggest the need for hospital staff to eliminate or reduce intrahospital transfers and to develop and maintain humane transfer procedures when forced relocation becomes necessary.

Adult↗