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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 721 records · Page 40Linked to original sources

Prolonged sensitisation of pituitary glands in vitro to repeated administration of luteinising hormone-releasing hormone: effects of pulse frequency, ovariectomy, estradiol and progesterone.

Anterior pituitary gland fragments were obtained from female Wistar-derived rats on dioestrus or pro-oestrus and perifused in Biogel columns in vitro. They were subjected at the beginning of each of 5 h of perifusion to a volley of 6 1-min pulses of luteinising hormone-releasing hormone (LHRH, 10 nM), given 4 min apart. Luteinising hormone (LH) was measured by radioimmunoassay in sequential 2-min fractions of the perifusate. Pituitary glands removed at 14.00 h on dioestrus showed a characteristic pattern of sensitisation followed by desensitisation to the repeated volleys of LHRH, whereas tissues removed at 10.00 or 14.00 h on pro-oestrus showed no evidence of desensitisation over the 5-hour period, the response to each LHRH volley being greater than the preceding one. Estradiol (E, 3-100 pg/ml) added to the medium from the start of perifusion had no significant effect on the pattern of response from tissues removed on pro-oestrus, but the highest concentration significantly enhanced the response of dioestrus pituitaries to all but the last of the LHRH volleys. Progesterone (P, 1-50 ng/ml) added to the medium produced a dose-related inhibition of the response of pro-oestrous tissues to the LHRH volleys. Groups of animals were ovariectomised (OVX) on dioestrus and used for experiment the next morning. OVX at 10.00 h on dioestrus produced the pattern of response characteristic of dioestrus the next morning, but with much higher levels of LH release, which were unaltered by the addition of E to the medium. OVX at 17.00 h on dioestrus produced an entirely different pattern of response the next day, with high basal and moderate LHRH-induced LH release, and no evidence of changes in sensitivity of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Permissive role for ornithine decarboxylase and putrescine in the luteinising hormone surge.

Anterior pituitary gland fragments removed from Wistar-derived rats at 10.00 h on pro-oestrus were perifused with Krebs-bicarbonate medium in a column and exposed to hourly volleys of 6 1-min pulses of 10 nM luteinising hormone (LH)-releasing hormone (LHRH). LH release showed a characteristic pattern of prolonged (over 5 h) sensitisation to the releasing hormone, with the response to each volley becoming progressively greater. The addition of 2 mM difluoromethylornithine (DFMO; an inhibitor of ornithine decarboxylase) to the perifusion medium completely inhibited the response to all volleys of LHRH. This effect of DFMO was reversed by the concurrent inclusion of 2 mM putrescine in the medium. Putrescine alone had a small but non-significant enhancing effect on LHRH-induced release, and no significant effect on basal LH release in this system. In a second series of experiments, tissues were loaded with 1-14C-ornithine and the radioactive carbon dioxide released into the medium during the perifusion monitored. Unstimulated pituitary tissues showed constant low levels of carbon dioxide release during 5 h of incubation, but those given hourly volleys of LHRH showed progressively increasing release of radioactivity, which was blocked by the addition of DFMO. No LHRH-stimulated increase in 14CO2 production from 1-14C-ornithine was seen from pituitary tissue removed at 10.00 h on dioestrus. Administration of DFMO (10-100 mg/rat) on the afternoon of pro-oestrus 4 h before the expected peak of the LH surge reduced the magnitude of the subsequent surge and the concentration of the hormone found in the anterior pituitary gland in a dose-related manner. In addition, the concentration of putrescine, but not of spermidine or spermine, was significantly reduced in treated animals (50 mg/rat) at the time of this attenuated surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Profile of autoantibodies in the serum of patients with tuberculosis, klebsiella and other gram-negative infections.

Autoantibody profiles were examined in the sera of untreated patients with tuberculosis, and those with klebsiella septicaemia, and klebsiella and E. coli urinary tract infections. Rheumatoid factors of the IgM, IgA and IgG isotypes, antinuclear antibodies and antibodies to poly(ADP-ribose) were all frequently detected (generally 15-40%). In contrast, antibodies to the extractable nuclear antigens and to the organ specific antigens were unusual (generally less than 10%). In comparison, in a group of lupus patients IgM rheumatoid factor, anti-nuclear antibodies, antibodies to poly(ADP-ribose) and antibodies to the extractable nuclear antigens were more frequently found, but IgA and IgG rheumatoid factors and antibodies to the organ-specific antigens were present in much the same frequency.

Antibodies, Antinuclear↗

Ontogeny of neuroendocrine cells in human fetal lung. III. An electron microscopic immunohistochemical study.

Immunocytochemistry at the transmission electron microscopic level utilizing colloidal gold spheres conjugated with secondary antisera was performed on lungs of 22 human fetuses and newborn infants of 13 to 38 weeks gestation and from birth to 5 1/2 months of postnatal life. Tissue was stained for the peptide hormones, immunoreactive (IR) bombesin, and IR calcitonin. In addition to unmatched neuroendocrine (NE) cells identified for these peptides, matched cells were identified in near-serial ribbons, each stained for an individual peptide. Based on morphology, five subtypes of NE cells were examined for these two peptides. We have confirmed the previously demonstrated developmental appearances of these peptides in human fetal lung. We also have found many cells containing both peptides in the lungs of live-born infants of 25 weeks gestation or more who survived long enough to develop chronic lung disease. The percentage of neurosecretory granules labeled for IR bombesin which overlapped with the percentage of granules labeled for IR calcitonin in cells of several dysplastic lung suggested that both peptides could be contained within a single granule. This was confirmed in NE cells of four such infants in preliminary studies utilizing double labeling immunocytochemistry at the electron microscopic level. At least two subpopulations of NE cells were not labeled for either peptide, suggesting that as yet-unidentified peptides and/or amines are contained in their granules. The possibility that large nonlabeled granules contain hormone precursors is also raised.

Bombesin↗

Evaluation of explanted polyurethane trileaflet cardiac valve prostheses.

Morphologic, chemical, and hemodynamic studies were made of eight prototype polyurethane trileaflet cardiac valve prostheses that had been implanted in juvenile sheep for 17 to 21 weeks in the mitral position. Calcification of the polyurethane leaflet surfaces was the principal finding. Quantitative chemical analyses revealed calcium values with a mean of 42.7 +/- 21 mg/gm dry weight of leaflet. Morphologically, two distinct types of calcification were observed: One was associated with the polyurethane surface or the interface between the leaflet surface and microthrombi or fibrous sheaths; the other was characterized by calcification associated with degenerated cells within thrombotic material and the fibrous sheath. These morphologic findings were in accord with the results of hemodynamic performance studies indicating that these heart valve prostheses had become both stenotic and regurgitant.

Animals↗

Panic disorder. Spectrum of severity and somatization.

One hundred++ ninety-five primary care patients were screened for panic disorder utilizing the National Institute of Mental Health Diagnostic Interview Schedule (DIS) as well as four additional questions that screened for core autonomic symptoms of panic disorder. A spectrum of severity of panic disorder was found. A subgroup of patients, labeled in the study as having simple panic, was found to have anxiety attacks associated with four or more autonomic symptoms, but they did not meet DSM-III recurrence criteria (three anxiety attacks within a 3-week period). Compared to primary care patients without panic attacks, patients with both simple panic and panic disorder exhibited multiple phobias, avoidance behavior, a high lifetime risk of major depression, and elevated scores on self-rating scales of anxiety and depression. The four autonomic screening questions that the authors added to the DIS interview increased the sensitivity of the DIS in identifying patients with panic disorder. Patients with panic disorder who selectively focus on their frightening autonomic symptoms may not be identified by screen questions that only focus on the cognitive awareness of anxiety.

Adolescent↗

Structures of mismatched base pairs in DNA and their recognition by the Escherichia coli mismatch repair system.

The Escherichia coli mismatch repair system does not recognize and/or repair all mismatched base pairs with equal efficiency: whereas transition mismatches (G X T and A X C) are well repaired, the repair of some transversion mismatches (e.g. A X G or C X T) appears to depend on their position in heteroduplex DNA of phage lambda. Undecamers were synthesized and annealed to form heteroduplexes with a single base-pair mismatch in the centre and with the five base pairs flanking each side corresponding to either repaired or unrepaired heteroduplexes of lambda DNA. Nuclear magnetic resonance (n.m.r.) studies show that a G X A mismatch gives rise to an equilibrium between fully helical and a looped-out structure. In the unrepaired G X A mismatch duplex the latter predominates, while the helical structure is predominant in the case of repaired G X A and G X T mismatches. It appears that the E. coli mismatch repair enzymes recognize and repair intrahelical mismatched bases, but not the extrahelical bases in the looped-out structures.

Bacteriophage lambda↗

The tumour.

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General Surgery↗

Growth hormone deficiency in the Rothmund-Thomson syndrome.

We describe the first proven occurrence of growth hormone deficiency in an individual with the Rothmund-Thomson syndrome. This was suspected because of the patient's severely retarded growth and bone age and her failure to respond normally to growth hormone stimulation testing with l-DOPA, arginine, and growth hormone releasing factor. In addition, we have briefly reviewed other genetic and malformation syndromes that have been found associated with growth hormone deficiency. We recommend that growth hormone deficiency be considered in these syndromes, especially when the growth failure is more marked than expected.

Arginine↗

Association of amyoplasia with gastroschisis, bowel atresia, and defects of the muscular layer of the trunk.

We reviewed 225 cases of amyoplasia, and the association of amyoplasia with gastroschisis and with monozygotic twinning was confirmed. In addition, an apparently increased association of bowel atresia and defects in the muscular layer of the trunk wall with amyoplasia was observed. The association of amyoplasia, monozygotic twinning, and these trunk wall defects strongly suggests that the pathogenesis of amyoplasia is linked to some type of vascular compromise.

Abdominal Muscles↗

Carcinoma of the breast associated with pregnancy.

A series of 178 patients in whom carcinoma of the breast was associated with pregnancy has been analysed. In 121 patients the carcinoma was diagnosed during pregnancy (CP group) and in 57 patients the pregnancy occurred subsequent to definitive treatment for primary breast carcinoma (SP group). Patients presented with more advanced disease in the CP group, 72 per cent being axillary node positive. Only 37 per cent of the 121 patients survived 5 years, although 79 per cent of the node negative patients survived 5 years. Survival was not affected by age, nor by the phase of pregnancy during which the carcinoma was diagnosed or treated. The majority of pregnancies (79 per cent) ended in the delivery of a normal child. The 5 year survival of the 57 patients in the SP group was 69 per cent. However only 26 per cent of the patients who had positive nodes at the time of primary surgery were disease free 10 years later. This fact should be borne in mind when considering the continuation of the pregnancy.

Axilla↗

Very high dose chemotherapy with autologous bone marrow rescue in adult patients with resistant relapsed lymphoma.

Seventeen patients with advanced lymphoma were treated with high-dose chemotherapy with autologous bone marrow rescue. In 11 patients with non-Hodgkin's lymphoma (NHL) there were 2 complete remissions (CRs) and 2 partial remissions (PRs), and in 6 patients with Hodgkin's disease there were 5 CRs. Three patients remain well in unmaintained remission (days 874, 446 and 351), and a further 2 are alive and still receiving treatment (days 650 and 558). This type of therapy appears useful and should now be considered earlier in the course of the disease.

Adult↗

Myocardial protective effect of amiodarone in hypertrophied hearts during global ischemia.

The effect of amiodarone on the ischemic-reperfusion injury was tested in an isolated working preparation, using hypertrophied rat heart at 37 degrees C. Constant filling and afterload pressures and similar heart rates were used. Hearts from spontaneously hypertensive rats (N = 78) had thirty minutes of ischemia. Each received a 12-ml injection, by aortic root infusion, of amiodarone in normal saline or of normal saline alone at 37 degrees C at the onset of ischemia. Heart rate, aortic output, coronary sinus output, atrial pressure, and aortic pressure were recorded before and after global ischemia under steady-state conditions. Dose-response studies were performed at concentrations of 0.01 to 1.0 mg/ml. At every dose administered, amiodarone was found to significantly ameliorate the deleterious effects of global ischemia. The maximal benefit of amiodarone (70 +/- 4.6% recovery of function [mean +/- standard error of the mean], p less than 0.01) was found to be 0.25 mg (0.021 mg/ml), or 0.11 mg/g wet heart weight. Improvement in survival (return of aortic output and heart rate following ischemia) with all doses of amiodarone was statistically significant (p less than 0.002). Decreased recovery of function following global ischemia when doses were greater than 0.25 mg may have been secondary to the known negative inotropic effects of the drug. The mechanisms for the protective effects of amiodarone may be coronary vasodilatation, antiarrhythmic stabilization, or inhibition of calcium flux at the slow channel.

Amiodarone↗

Left ventricular outflow tract obstruction with mitral valve replacement in small ventricular cavities.

The inference that mitral valve replacement (MVR) may produce left ventricular outflow tract (LVOT) obstruction has been made, but no comparative hemodynamic studies with various types of prostheses have been done. The purpose of the present study was to compare the gradients created across the LVOT with MVR in young sheep with small left ventricular cavities. Mitral valve replacement was accomplished using cardiopulmonary bypass and hypothermic cardioplegic arrest. Five animals were used for each of the following valves studied: 25-mm Ionescu-Shiley bovine pericardial valve, 25-mm Hancock porcine aortic valve, 2M-6120 28-mm Starr-Edwards ball-valve prosthesis, 25-mm Björk-Shiley 60-degree flat tilting-disc prosthesis, and 25-mm St. Jude Medical hemidisc valve. Gradients across the LVOT were measured after MVR and then during infusion of isoproterenol hydrochloride (0.05 micrograms/kg/min). Following MVR, only the Starr-Edwards valve produced an LVOT gradient (32 +/- 23 mm Hg). Substantial gradients after MVR were seen, however, with isoproterenol administration with the Ionescu-Shiley (47 +/- 4 mm Hg), Hancock (13 +/- 8 mm Hg), and Starr-Edwards (65 +/- 30 mm Hg) valves but not with the low-profile valves (Björk-Shiley and St. Jude Medical). The results of the present study demonstrate that MVR can produce LVOT obstruction. The greatest degree of obstruction was with the high-profile mechanical and bioprosthetic valves.

Animals↗