Skills learned in oncology nursing prove valuable in psychiatry.
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Humans↗
Biomedical subjects
K Thomas
Publications and source records attributed to K Thomas.
Newly synthesized calsequestrin, destined for the sarcoplasmic reticulum, is contained in early/intermediate Golgi-derived clathrin-coated vesicles.
We have examined the possible role of clathrin-coated vesicles (CVs) in the genesis of the sarcoplasmic reticulum (SR) in developing chick skeletal myotubes. Calsequestrin (CSQ) a luminal Ca2+ binding protein of the terminal SR cisternae, is contained within the vesicle lumen of skeletal muscle CVs in substantial amounts, approximately four molecules/CV. Employing 3-day cultures of chick skeletal myotubes we demonstrate that after a 30-min labeling with [35S]methionine and cysteine, radioactivity in CSQ remains high in the CVs 45 min later and then declines, while labeled CSQ in the SR continues to rise. No CSQ appears to be secreted. All of the CSQ in both the CVs and SR is sensitive to the activity of endoglycosidase H, and a significant fraction also binds to wheat germ agglutinin. Based on these results, we discuss the hypothesis that a selective CV-mediated pathway exists in developing skeletal muscle cells for the transport of CSQ from the early/intermediate Golgi apparatus to the SR.
Acetylcholinesterase↗
Intracellular transport, sorting, and turnover of acetylcholinesterase. Evidence for an endoglycosidase H-sensitive form in Golgi apparatus, sarcoplasmic reticulum, and clathrin-coated vesicles and its rapid degradation by a non-lysosomal mechanism.
Tissue-cultured muscle cells synthesize several oligomeric forms of acetylcholinesterase (AChE) destined for the cell surface or secretion. Previous studies on the biogenesis of AChE polypeptide chains have shown that only a small fraction become assembled into catalytically active oligomers which transit the Golgi apparatus and acquire endoglycosidase H (endo H) resistance. Most of the AChE polypeptides remain endo H-sensitive and are rapidly degraded intracellularly. We now show that all newly synthesized AChE polypeptides are transported from the rough endoplasmic reticulum to the Golgi apparatus where they acquire N-acetylglucosamine. However, approximately 80% of these AChE polypeptides remain endo H-sensitive and are degraded intracellularly with a half-life of about 1.5 h by a mechanism which is insensitive to lysosomotropic agents. These endo H-sensitive AChE molecules can be chased into clathrin-coated vesicles and/or the sarcoplasmic reticulum prior to degradation. Pulse-chase studies of isotopically labeled or catalytically active AChE molecules suggest that there are at least two discreet populations of clathrin-coated vesicles which leave the Golgi, one whose origin is cis/medial and one whose origin is trans. These studies indicate the existence of a post-rough endoplasmic reticulum, non-lysosomal degradative pathway for intra-luminal proteins and suggest that post-translational events at the levels of protein sorting and degradation may play a role in regulating the abundance of exportable proteins.
Acetylcholinesterase↗
Development of a murine gastric distension model for testing the emetic potential of new drugs and efficacy of antiemetics.
A small animal model for emesis would allow preclinical testing of antiemetics and new drugs. Mice treated with cisplatinum develop stomachs distended with food. This effect is reduced by metoclopramide and parallels the gastric nausea experienced by patients receiving cisplatinum. To assess gastric distension as a more general model for paralleling the human emetic response, groups of five BALB/c mice were given intravenous nitrogen mustard, adriamycin, cyclophosphamide, 5-fluoruracil (5FU), vincristine and intraperitoneal DTIC at doses equivalent to those used clinically (mg/kg mouse = 12 X mg/kg per man). The mice were allowed free access to food pellets and water. At 48 h they were sacrificed and gastric distension quantitated as a ratio of average stomach to body weight. Significant gastric distension occurred with nitrogen mustard, DTIC, adriamycin and cyclophosphamide but not 5FU or vincristine. This parallels the emetic potential of these drugs in humans. Similarly cisplatinum was compared to its analogues, carboplatin and JM40 and produced gastric distension at lower doses than carboplatin. The model was then used to test the antiemetic efficacy of escalating doses of prochlorperazine against cisplatinum induced gastric distension in groups of 10 BALB/c mice. Doses ranged from 2.5 mg/kg. Only a high dose (19.2 mg/kg) significantly reduced the gastric distension. This parallels a clinical dose response relationship recently reported for prochlorperazine and suggests the further potential use of this model.
Animals↗
Hormonal changes induced by short-term administration of gonadotropin-releasing hormone agonist during ovarian hyperstimulation for in vitro fertilization and their consequences for embryo development.
Several regimens have been developed to administer gonadotropin-releasing hormone agonists in association with human menopausal gonadotropins (hMG) during follicular growth stimulation for in vitro fertilization. The aim of this study was to characterize hormonal changes induced by short-term administration of agonist, and to evaluate a putative impact of the flare-up effect on follicular recruitment and subsequent IVF. Eighteen highly selected patients were randomely divided in two groups. Nine patients received a short-term administration of Buserelin (Hoechst, AG, Franfurt/Main, FRG) (day 1). They were compared with 9 patients who were exposed to a long-term protocol (day 21), and 13 control patients. Agonist-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increase, in early follicular phase, stimulated follicular growth, shortened follicular phase, and induced a transient rise in progesterone. This was followed by a phase of reduced LH secretion associated with a significant modification of LH immunoreactivity. The short-term regimen did not improve the follicular recruitment, and appeared to reduce the oocytes fertilization rate and embryo quality when compared with prolonged administration of peptide.
Buserelin↗
Immunoradiometric assays of total renin and gonadotropins in serum during the menstrual cycle.
The contribution of the ovary to the circulating total renin pool is linked to its secretory activity in relation with its reproductive function. In a longitudinal study of 13 normal women, total renin levels measured in serum by an immunoradiometric assay were lower in the midfollicular phase (180 +/- 59 pg/ml) than in the midluteal phase (291 +/- 100 pg/ml). Peak levels were encountered 1 day after the luteinizing hormone (LH) surge (375 +/- 97 pg/ml). Rapid circhoral fluctuations were observed in all periods of the cycle, unrelated to the LH pulses. In case of ovarian function inhibition (induced by gonadotropin-releasing hormone agonists), total renin levels were lower than in the midfollicular phase (126 +/- 56 pg/ml). Low levels also were encountered in the prepubertal period (153 +/- 89 pg/ml). Very high levels (17,600 +/- 11,400 pg/ml) were found in follicular fluids from stimulated cycles. These results show that circulating total renin levels follow a complex pattern in which LH, but possibly also follicle-stimulating hormone and gonadal steroid hormones (estradiol and progesterone), may play a role.
Adult↗
Use of a gonadotropin-releasing hormone agonist during ovarian stimulation leads to significant concentrations of peptide in follicular fluids.
The penetration of a gonadotropin-releasing hormone agonist (GnRH-a), Buserelin (Hoechst AG, Frankfurt, West Germany), into human follicular fluids (FF) was studied by means of a radioimmunoassay (RIA) and a bioassay. Acute nasal administration of a therapeutic dose of Buserelin (300 and 600 micrograms) before the ovum pickup for in vitro fertilization leads to significant concentrations of Buserelin in one-third of the FF. These concentrations ranged between 28 and 124 pg/ml, which represents 10% to 50% of the serum concentrations achieved in these patients. Follicular penetration of this agonist is time-dependent. Chronic administration during the follicular phase leads to low but significant concentrations of peptide 36 hours after the last inhalation. A very good correlation was observed between the RIA and the bioassay. This demonstrates the accuracy and the specificity of the RIA. In addition, it indicates that the Buserelin that reaches follicles is intact and is not the inactive product of degradation. Intranasal administration of Buserelin stopped 35 hours before ovum pickup appears to be an adequate way of minimizing the exposure of maturing oocytes to the GnRH-a.
Adult↗
Evaluation of a synthetic serum substitute to replace fetal cord serum for human oocyte fertilization and embryo growth in vitro.
A comparison was made between a serum substitute. UltroSer G (Gibco, Ghent, Belgium) (2%) (medium B) and 10% human fetal cord serum (medium A), as regards their ability to support 1-cell and 2-cell mice embryo development in vitro. Sixty percent and 56% of the 1-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. Eighty-four percent and 88% of 2-cell embryos reached the expanded blastocyst stage when cultured in media A and B, respectively. A prospective randomized study was then performed to evaluate this synthetic serum substitute in human in vitro fertilization. Among 141 ovum pick-up (OPU), oocytes retrieved in 74 cases were processed in medium A and oocytes retrieved in 67 others in medium B. In media A and B, the fertilization rate was 67% and 44.3% respectively, and the pregnancy rate/OPU 23% and 9%, respectively. The pregnancy rate/transfer was 28.8% and 12.2% respectively, and the implantation rate/transferred embryo 9.5% and 4.2%. In the human sperm survival assay, the vitality and residual motility after 24 hours of incubation were significantly lower in medium B. In conclusion, UltroSer G successfully sustained the development in vitro of mouse embyros. However in human, it reduced sperm survival, oocyte fertilization, and embryo viability.
Animals↗
Hearing threshold in patients with diabetes mellitus.
Hearing threshold of 30 diabetic patients and 30 healthy controls attending the medical outpatient department were determined using pure tone audiometry (Arphi Digital 900). All subjects were less than 50 years old. Subjects with otological and other metabolic diseases were excluded from the study. The patients were categorized into groups according to age, duration of disease, complications and control of diabetes. These observations were compared with those from the control subjects using appropriate statistical methods. It was found that diabetics had a poorer hearing threshold than the non-diabetics; all age groups with diabetes showed a significant high frequency hearing loss, as compared to the control population; poorly controlled and complicated diabetics have significant, high frequency hearing loss as compared to those who were well controlled and uncomplicated; there was no relationship between duration of the diabetes and the level of hearing loss.
Adolescent↗
In-vitro fertilization: how many attempts before success?
Repeated attempts increase the overall rate of success of sterility therapy by in-vitro fertilization. The present study, using data collected between 1983 and 1987 in a Belgian hospital, attempts to investigate the expected number of treatment cycles before success is achieved. The answer requires some knowledge about the degree of independence between success probability and treatment duration. Using mathematical models of implantation, it can be shown that success probability actually decreases during treatment. A method for updating individual probabilities is suggested; it could be used as a prognostic estimation for women undergoing this kind of therapy.
Evaluation Studies as Topic↗
Inhibin and renin in follicular fluids of patients with one or two ovaries stimulated with a GnRH agonist and gonadotrophins.
Follicular fluids from eight patients with one ovary and from ten patients with two ovaries were investigated for bioactive inhibin, total renin, oestradiol (E2) and progesterone (P4) concentrations. Four follicular fluids were pooled per patient before assessment. All women had been stimulated similarly using a protocol including a GnRH agonist, HMG and HCG. Renin levels were significantly lower and P4 significantly higher in pools of follicular fluid from patients with one ovary, whereas inhibin and E2 concentrations were similar in both patient groups. A significant negative correlation was found in the pools of follicular fluid between inhibin and E2 in both groups. These results suggest a role for inhibin and renin in the paracrine and autocrine control of stimulated follicular development.
Adult↗
Studies on the circulation in normotensive febrile patients.
Normotensive febrile patients were studied in a constant-temperature room during stable fever, They were restudied later while afebrile and after heating the trunk. Finger and forearm blood flow were measured by venous occlusion plethysmography. The ability of cutaneous vessels to constrict on dependence of the limb was measured by laser Doppler flowmetry. The volume, velocity and acceleration of the blood in the ascending aorta were determined using pulsed Doppler ultrasound with a probe in the supra-sternal notch; measurements of systolic time intervals were made. While febrile, patients had a tachycardia and shortened systolic ejection times; cardiac output and total peripheral resistance were unchanged on average as compared to when afebrile. There was no evidence of any change in left ventricular contractility during fever from measurements of the peak velocity, maximum acceleration of blood or from the systolic time intervals. As compared to when heated, febrile patients had a skin blood flow that was relatively reduced for their skin temperature and had preservation of postural vasoconstriction.
Adult↗
Estimates of general practitioner workload: a review.
This paper reviews four studies sponsored by the Department of Health which have attempted to measure workload in general practice and compares these with data from the general household survey. Despite the considerable differences in the objectives and methods employed by the four studies, they were found to contain remarkably consistent measurements of general practitioner workload. In a 'normal working week' general practitioners spend 38 hours on general medical service duties (including 24 hours of patient contact and five hours of travel to home visits), they see 150 patients or their representatives in surgery, and make 26 home visits. In an 'annual average week', taking into account holidays and sick leave, general practitioners undertake 90% of this workload. The studies show consistently large variations in the workload of general practitioners measured in this way, but fail to identify the key determinants of such variations. The reasons underlying the variation in general practitioner workload will remain unclear until we can distinguish between the expected, measurable variation and the residual, unexplained variation which may be due to the personal preferences of general practitioners.
Appointments and Schedules↗
Fluctuations in response to L-dopa in Parkinson's disease may be explained by changes in striatal dopamine turnover.
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Animals↗
Kawasaki syndrome.
Kawasaki and associates first described a mucocutaneous lymph node syndrome from Japan. Since then this febrile illness has been reported from several countries. The patient described in this report had all the clinical manifestations of this entity excepting coronary aneurysms.
Adolescent↗
[Clinical value of inhibin in women].
Inhibin is a peptide secreted in women by the granulosa cells, the corpus luteum and the placenta. This hormone specifically inhibits pituitary FSH secretion. Recent studies have shown that the serum concentration of bioactive and immunoactive inhibin may represent a valuable marker of follicular and luteal functions. Inhibin may also contribute with estrogen and progesterone to FSH suppression during the luteal phase and in pregnancy. Evidence was found that a defect in inhibin secretion is involved in premature ovarian failure and the menopause but not in the polycystic ovary syndrome.
Female↗
[Leukocyte immunization and early spontaneous abortions].
Forty patients who had had at least two early spontaneous abortions, i.e. before the 12th week of pregnancy without known aetiology factors (anatomical, chromosomal, infectious or hormonal) were immunised with their husband's leucocytes. These immunisations were carried out by repeated intravenous injections of leucocytes taken from the husband's peripheral blood. In 24 patients the search for anti-HLA antibodies was shown to be positive after a varying number of injections (2 to 10). Twelve patients are still being treated, 4 did not make antibodies. Eighteen pregnancies have been observed, of whom 11 have so far come to term, 4 are following a normal course and 3 pregnancies were interrupted late of different reasons. The success rate, by which is meant pregnancies without early abortion, was 17/21, i.e. 81%. A comparison of the number of HLA A, B or DR antigens found to be shared between the couple in 40 couples studied, when compared with a series of 64 fertile couples (who had had at least 2 children without any abortions) shows no differences. These couples as compared with fertile couples do not show either differences in the frequency of HLA antigens. After leucocyte immunisation an inhibition in the mixed lymphocyte culture is found between the patient's lymphocytes and her husband's in the wife's serum if this has made anti-HLA antibodies.
Abortion, Habitual↗
Localization of the mdx mutation within the mouse dystrophin gene.
We have mapped human and mouse X chromosome-specific genomic and cDNA probes through an interspecies Mus musculus/spretus pedigree which contains the mdx mutation. The positions of these markers relative to one another and to the mdx mutation were delineated. Using probes corresponding to segments of the human Duchenne muscular dystrophy (DMD) gene transcript, the position of a cross-hybridizing mouse equivalent gene (mDMD) was located. In more than 200 animals mapped, three were identified which show recombination within this mDMD gene. Analysis of these three animals shows that the mDMD gene is oriented with its 5' end centromeric and its 3' end telomeric on the mouse X chromosome. Furthermore, their recombinational breakpoints are on either side of the mdx mutation, thus providing the first unequivocal demonstration that the mdx mutation is located within the mDMD gene and defining limits within that gene between which the mutation must lie. Within that segment the evidence indicates that there is no major deletion of an exon as detectable by Southern blot analysis in mdx animals. The mdx mouse becomes important as an animal model for the study of the expression of the DMD gene and its developmental consequences, for transgenic and other corrective manipulations.
Animals↗