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Biomedical subjects

J D Turner

Publications and source records attributed to J D Turner.

105 records · Page 6Linked to original sources

Association between acute glaucoma and the weather and sunspot activity.

The dates of presentation of 191 cases of acute closed-angle glaucoma which presented at the Birmingham and Midland Eye Hospital between 1971 and 1974 were analysed and the seasonal incidence of acute glaucoma confirmed (P less than 0-001). These data were compared with meteorological data for air temperature, rainfall, hours of sunshine, atmospheric pressure, cloud amount, terrestrial magnetic field level, and sunspot numbers. A statistically significant direct association (P less than 0-05) was found with hours of sunshine and an inverse association (P greater than 0-05) with cloud amount. A statistically significant inverse association (P less than 0-05) was found with sunspot count, and this assumed high significance (P less than 0-0005) on consideration of sunspot activity in the preceding period. The literature is reviewed and the significance of these findings discussed.

England↗

Control of ventilation in the hypercapnic skate Raja ocellata: I. Blood and extradural fluid.

In order to study the role of CO2 and acid-base status in contributing to ventilatory drive, skate were exposed to normoxic hypercapnia (PICO2 = 7.5 Torr) under conditions where the primary O2 drive would remain unaltered. Blood O2 transport was markedly insensitive to CO2, with no Root effect and only a small Bohr effect. Red blood cell pHi was not preferentially regulated, and there was no evidence of RBC swelling or nucleoside triphosphate adjustment. Although there were no changes in arterial O2 levels during hypercapnia, ventilation immediately increased 2.7-fold through large changes in stroke volume and small changes in frequency, and declined only slightly through 24-48 h. PaCO2 equilibrated rapidly with PICO2, driving down arterial pHa, which was 65% corrected through HCO3- accumulation by 24 h. In contrast, the extradural fluid outside the brain equilibrated only very slowly, and was clearly not involved in the ventilatory stimulation. Increased ventilation during hypercapnia may be related to depression in pHa.

Acid-Base Equilibrium↗

Control of ventilation in the hypercapnic skate Raja ocellata: II. Cerebrospinal fluid and intracellular pH in the brain and other tissues.

This study examined the possible role(s) of central acid-base stimuli in the increase in ventilation induced by hypercapnia in the skate, a response that is not due to an O2 signal (Graham et al., Respir. Physiol., 1990, 80: 251-270). Skate were sampled for cerebrospinal fluid (CSF) acid-base status, intracellular pH of the brain (14C-DMO method), and pHi in other tissues throughout 24 h of exposure to PICO2 = 7.5 Torr. CSF PCO2 rapidly equilibrated with the elevated PaCO2. Despite the much lower non-HCO3- buffer capacity in the CSF, CSF pH was not depressed to the same extent as blood pHa. CSF pH was also regulated rapidly, returning to control levels by 8-10 h, whereas pHa remained significantly depressed at 24 h. Similarly, the pHis of the weakly buffered brain and heart ventricle were initially compensated more rapidly than those of more strongly buffered white muscle and red blood cells. However, brain pHi adjustment slowed markedly after 4 h and stabilized at only 70% compensation by 20-24 h, suggesting that brain intracellular acidosis may play a role in the long-term increase in ventilation. CSF and brain were the only compartments which did not exhibit an apparent compounding metabolic acidosis during the initial stages of hypercapnic exposure. While these results illustrate the primacy of central acid-base regulation, they do not support a role for CSF pH in the long-term elevation of ventilation in response to hypercapnia. Depressions in pHa and brain pHi appear the two most likely candidates for proximate stimuli.

Acid-Base Equilibrium↗

Peptidases involved in the catabolism of neurotensin: inhibitor studies using superfused rat hypothalamic slices.

In order to identify which peptidases are involved in the catabolism of neurotensin in the CNS, [3H-Tyr3,11]-neurotensin was superfused over rat hypothalamic slices in the presence and absence of peptidase inhibitors. The degree of degradation of the peptide was determined by reverse phase HPLC separation of 3H-labelled neurotensin from 3H-labelled products. Very little degrading activity was released from the slice into the medium during the superfusion. In the absence of inhibitors, 20 to 50% of 3H-neurotensin was degraded giving mainly 3H-Tyr along with other unidentified 3H-labelled products. Inhibitors of endopeptidase 24.11 (phosphoramidon) and proline endopeptidase (antibody) had no effect on the degradation. Captopril, an inhibitor of angiotensin converting enzyme, had a small inhibitory effect. In contrast, dynorphin(1-13), an inhibitor of a soluble, thiol dependent metallopeptidase which hydrolyses neurotensin at Arg8-Arg9, gave greater than 80% inhibition of 3H-neurotensin degradation in the slice preparation. 1,10-Phenanthroline, an inhibitor of metallopeptidases, was also an effective inhibitor. The dynorphin sequence responsible for the inhibition contains the Arg6-Arg7 bond. Other peptides (bradykinin and angiotensin) which are substrates of the soluble metallopeptidase also inhibited neurotensin breakdown by the slice. This evidence suggests that this thiol dependent metalloendopeptidase is the major neurotensin catabolizing enzyme in hypothalamic slices.

Animals↗

Changes in tissue-type plasminogen activator-like and plasminogen activator inhibitor activities in granulosa and theca layers during ovarian follicle development in the domestic hen.

Changes in plasminogen activator (PA) and PA inhibitor (PAI) activities were measured during follicular development in granulosa cells (GC) and theca tissue (TT) isolated from the six largest yolk-filled preovulatory follicles (F1, F2, F3, F4, F5, F6) and large white follicles (LWF) of the domestic hen. PA activity increased and PAI activity decreased during follicular development, with the peak PA value and minimum activity for PAI observed in the largest preovulatory follicle (F1) 12-14 h before expected time of ovulation. The PA activity in GC and TT appears to be principally of the tissue (t)-PA type judging from its substrate specificity and biochemical characteristics. The enzyme cleaved the chromogenic substrate specific for t-PA (Spectrozyme TM t-PA; CH3SO2-D-CHT-Gly-Arg-p-nitroanilide) more efficiently (4-6 x) than that for u-PA (Spectrozyme TM UK; Cbo-L-Glu-(alpha-t-BuO)-Gly-Arg-p-nitroanilide), suggesting that t-PA may be the predominant PA in the chicken preovulatory follicle. Determination of PA activity following sodium dodecyl sulphate-polyacrylamide gel electrophoresis and isoelectric focussing suggested the presence of two forms of the enzyme in GC and TT. The predominant form of PA had a molecular weight of 75,000 and an isoelectric point (pI) of 7.7, characteristics similar to those reported for t-PA in humans, pigs, and rodents. The other form of PA had a molecular weight of 35,000 and pI of 8.4. PAI present in GC and TT had a molecular weight of 50,000 and pI of 4.7. In GC, an acid-labile PAI was detected with biochemical characteristics similar to those of the protease, nexin I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lipid peroxidation is associated with the inhibitory action of all-trans-retinoic acid on mammary cell transformation.

BACKGROUND: Retinoids are effective in reducing transformation of various cell types; however the role of lipid peroxidation has not been studied in this regard. MATERIALS AND METHODS: Retinoic acid (RA) and retinol were tested on several SV-40 large-T-antigen transformed bovine mammary fibroblast (MFB) lines that form foci on plastic with long-term culture. RESULTS: Dose response studies revealed that RA at 10(-6) M was the most potent dose in delaying the onset of foci formation and reducing total foci number. RA was always more effective than retinol. Addition of RA (10(-6) M) to MFB cells increased lipid peroxide (LPO) concentrations by approximately three-fold relative to untreated MFB cells or to RA or control treated normal mammary fibroblasts. The lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), acted synergistically with RA to increase LPO and cell death in MFB cells. The combination of the cyclooxygenase inhibitor, indomethacin, at 10(-4) M with 10(-6) M RA lowered MFB fibroblast cell numbers when compared to fibroblasts cultured singly with either RA or indomethacin. CONCLUSIONS: These data indicate that an increase in lipid peroxidation occurs specifically in tumor cells treated with RA and this may play a role in RA-mediated suppression of cellular transformation in the mammary gland. Additionally, eicosanoid inhibitors may have an additive or synergistic effect with RA on the inhibition of mammary tumor cell transformation and proliferation.

Animals↗