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Biomedical subjects

J Sinclair

Publications and source records attributed to J Sinclair.

At least 73 records · Page 4Linked to original sources

Induction of cytochrome P-450 by alcohols and 4-substituted pyrazoles. Comparison of structure-activity relationships.

A comparison was made between 4-substituted pyrazoles and short-chain alcohols as inducers of cytochrome P-450. A quantitative structure-activity analysis of the data led to the following equations: (I) Pyrazoles: Log 1/C = 0.85 (+/- 0.21) Log P + 1.93 (+/- 0.38), r = 0.970 (II) Alcohols: Log 1/C = 0.78 (+/- 0.14) Log P + 1.46 (+/- 0.13), r = 0.988 where C is the concentration that caused a 50% increase in cytochrome P-450, is the partition coefficient between octanol and water, and r is the correlation coefficient. The results suggest that induction of cytochrome P-450 by these compounds depends on hydrophobicity alone. Electronic and steric factors have insignificant roles.

Alcohols↗

Treatment of diabetic gastroparesis with oral domperidone.

Three patients with severe diabetic gastroparesis unresponsive to metoclopramide were found to have markedly prolonged gastric half-emptying times (t1/2) using a radionuclide-labelled test meal. They all showed symptomatic improvement and normal t1/2 within one week of taking oral domperidone 10 mg q.d.s. Oral domperidone may have a role in the treatment of severe diabetic gastroparesis particularly in metoclopramide-resistant cases.

Administration, Oral↗

The interaction of nitrite with photosynthetic electrom transport under anaerobic conditions.

Chlorella cells were examined in a modulated oxygen polarograph under aerobic and anaerobic conditions. At light intensities below about 600 ergs . cm-2 . s-1 of 650 nm light, the oxygen yield and phase lag are lower under anaerobic conditions. Addition of 25 mM sodium nitrite increases both these parameters to values close to those found in the presence of oxygen. It is proposed that nitrite is reduced by Photosystem I thus diverting electrons from the cyclic electron transport pathway. The intersystem electron transport chain becomes more oxidized and this suppresses a backflow of electrons to the oxidizing side of Photosystem II, hence increasing the oxygen yield and the phase lag. The removal of oxygen from the bathing medium also alters the response of dark adapted Chlorella to a series of saturating light flashes. In terms of the Kok model of Photosystem II (Kok, B., Forbush, B. and McGloin, M. (1970) Photochem. Photobiol. 11, 457-475) there is a large increase in the parameter alpha. Addition of nitrite reverses this change and virtually restores the response seen in the presence of oxygen. The deactivation of the S2 state is greatly speeded up in the absence of oxygen but the addition of nitrite again reverses this.

Anaerobiosis↗

Factors influencing in vitro production of colony-stimulating factor by mononuclear leukocytes from humans.

The purpose of this study was to identify factors that influence the production of colony-stimulating factor by leukocytes of humans. The use of nonadherent light-density bone marrow cells is semisolid agar cultures to assay the concentrations of colony-stimulating factor in the supernatant of monocyte and mononuclear leukocyte cultures made it possible to distinguish between colony-stimulating factor, which stimulates colony-forming cells directly, and monocyte-dependent stimulating activity, which acts indirectly, by increasing the monocyte production of colony-stimulating factor. Colony-stimulating factor was not detectable in the cytosol of monocytes; that detected in culture must, therefore, have been newly synthesized. Synthesis was enhanced independently by heat-inactivated human serum and by semipurified serum fractions enriched with monocyte-dependent stimulating activity. The kinetics of the production of colony-stimulating factor in the presence and absence of monocyte-dependent stimulating activity indicated that the latter facilitated monocyte production of the former. Factors released from neutrophils were shown to reduce the production of colony-stimulating factor and thr proliferation of colony-forming cells and thus may provide a feedback control mechanism limiting the proliferation of neutrophils.

Colony-Stimulating Factors↗

A backflow of electrons around photosystem II in Chlorella cells.

A study was made with a modulated oxygen electrode of the effect of variations of oxygen concentration on photosynthetic oxygen evolution from algal cells. When Chlorella vulgaris is examined with a modulated 650 nm light at 22 degrees C, both the oxygen yield and the phase lag between the modulated oxygen signal and the light modulations have virtually constant values between 800 and 120 ergs . cm-1 . s-1 if the bathing medium is in equilibrium with the air. Similar results are obtained at 32 degrees C between 1600 and 120 ergs . cm-2 . s-1. Under anaerobic conditions both the oxygen yield and the phase lag decrease if the light intensity is lowered below about 500 ergs . cm-2 . s-1 at 22 degrees C or about 1000 ergs . cm-2 . s-1 at 32 degrees C. A modulated 706 nm beam also gives rise to these phenomena but only at significantly lower rates of oxygen evolution. The cells of Anacystis nidulans and Porphyridium cruentum appear to react in the same way to anaerobic conditions as C. vulgaris. An examination of possible mechanisms to explain these results was performed using a computer simulation of photosynthetic electron transport. The simulation suggests that a backflow of electrons from a redox pool between the Photosystems to the rate-limiting reaction between Photosystem II and the water-splitting act can cause a decrease in oxygen yield and phase lag. If the pool between the Photosystems is in a very reduced state a significant cyclic flow is expected, whereas if the pool is largely oxidized little or no cyclic flow should occur. It is shown that the effects of 706 nm illumination and removal of oxygen can be interpreted in accordance with these proposals. Since a partial inhibition of oxygen evolution by 3-(3.4-dichlorophenyl)-1,1-dimethylurea (10(-8) M) magnifies the decreases in oxygen yield and phase lag, it is proposed that the pool which cycles back electrons is in front of the site of 3-(3,4-dichlorophenyl)-1,1-dimethylurea inhibition and is probably the initial electron acceptor pool after Photosystem II.

Anaerobiosis↗

Histological and ultrastructural changes in rat kidney following cadmium injection.

Cadmium injection in rats affects the genito-urinary system. The renal effects are generally considered to be mainly tubular. Light microscopy of 29 specimens confirms cellular damage in the glomeruli with changes in glomerular capillaries. Electron microscopic changes in the glomerulari confirm changes in the podocytes, thickening of the basement lamina, the occurrence of electron dense deposits in association with the capillary endothelium with platelet and polymorphonuclear cell accumulations which suggests opening of the endothelial junction of the glomerular vessels.

Animals↗

An investigation of water splitting in the Kok scheme of photosynthetic oxygen evolution.

The involvement of OH bond breaking in the 4 dark reactions of the Kok scheme of photosynthetic oxygen evolution was investigated using Chlorella and spinach chloroplasts. When the photosynthetic material was suspended in a 2H2O based medium, the reaction rates in all 4 cases were only slightly reduced as compared to the rates observed in an H2O based medium. This was evidence that these rate processes were probably not limited by the breaking of an OH bond. Observations were also made on the yields of O2 from dark adapted Chlorella subjected to a sequence of brief saturating light flashes. The oscillating flash yield sequence observed with algai suspended in 2H2O showed greater damping of the oscillations than when the algae were suspended in H2O. A computer fit of the Kok model to these results revealed a slightly higher proportion of misses, alpha (i.e. absorbed quanta that do not drive photochemistry) in the 2H2O case.

Chlorella↗

The incidence of deep vein thrombosis in prostatectomised patients following the administration of the fibrinolytic inhibitor, aminocaproic acid (EACA).

Forty patients undergoing prostatectomy for benign prostatic hypertrophy were included in a double blind trial of epsilon aminocaproic acid, and the incidence of postoperative deep vein thrombosis determined, using 125I-fibrinogen technique. There was no significant difference between the groups, the overall incidence of abnormal scans being 50 per cent, but of the patients undergoing enucleative prostatectomy 68 per cent developed significant scan findings compared with 33 per cent following transurethral surgery.

Aged↗

Studies on the rate-limiting reaction of photosynthetic oxygen evolution in spinach chloroplasts.

The modulated oxygen polarography has been used to study the rate-determining steps of photosynthetic oxygen evolution in spinach chloroplasts. The rate constant, k, of the reaction has a value of 218 +/- 10 (S.E.) s-1 at 23 degrees C and an activation energy of 7 +/- 2 (S.E.) kcal-mol-1. A kinetic isotope experiment indicated that this step is probably not the water-splitting reaction. These findings resemble previous results with the unicellular alga Chlorella (Sinclair, J. and Arnason, T (1974) Biochim. Biophys. Acta 368, 393-400). In other experiments we changed the pH, O2 concentration and osmolarity of the medium, and treated the chloroplasts with 1 mM NH4Cl without detecting any significant change in k. These results suggest that the step is irreversible. However, a significantly lower value of k, 110 +/- 20 (S.E.) s-1 was obtained when all salts except 1 mM MgCl2 were removed from the medium bathing the chloroplasts.

Chloroplasts↗

The results of 100 small tissue biopsies of testis in male infertile patients.

The value of testicular biopsy in male infertility has recently been emphasized by Meinhard, McRae and Chisholm (1973), and the present authors agree with them that a biopsy is essential for the following reasons: (1) to establish a firm diagnosis; (2) to rationalize therapy on the basis of histological findings; (3) new developments in drug therapy and electronmicroscopic techniques will help to clarify many areas of doubt and uncertainty in this difficult field; (4) the diagnosis of 'sloughing' by itself may mask changes in germinal cell development which may be amenable to hormone therapy.

Androgens↗

Effect of temperature on growth of newborn rabbits.

The effect of cold exposure upon rabbits was investigated in order to study the interrelationships of food intake, growth and metabolic rate. Newborn rabbits were raised in 2 groups at environmental temperatures that produced a 50-100% difference in metabolic rate. No difference in growth rate or milk intake was apparent. Nucleic acid and protein content of several organs were measured and were similar. The paradox of a similarity in weight gain between the groups in the face of a similar intake of milk but different oxygen consumptions is discussed.

Animal Nutritional Physiological Phenomena↗

The complexity of satellite deoxyribonucleic acid in a higher plant.

Purified satellite DNA from melon (Cucumis melo) was shown to contain at least two components from thermal-denaturation and renaturation studies. Two components were separated after partial renaturation, a fast-renaturing fraction similar in complexity to mouse satellite DNA, and one with 6000 times greater complexity. Both components renatured very accurately, indicating a minimum of sequence divergence. Centrifugation of the purified satellite DNA in Ag+/Cs2SO4 gradients resolved two major and several minor fractions. The two major fractions were only slightly enriched for fast- or slow-renaturing sequences.

Base Sequence↗

The Relationship between Satellite Deoxyribonucleic Acid, Ribosomal Ribonucleic Acid Gene Redundancy, and Genome Size in Plants.

The buoyant density of ribosomal DNA is similar in species with or without satellite DNA, and in all species examined was distinguishable from that of the satellite DNA. In melon tissues (Cucumus melo) the percentage satellite DNA is not correlated with the percentage hybridization to ribosomal RNA. Satellite DNA sequences do not appear to be dispersed between those coding for ribosomal RNA. There is no correlation between the presence of satellite DNA and high ribosomal RNA gene redundancy, but there is a correlation between satellite DNA and small genome size, which results in a correlation between satellite DNA and a high percentage hybridization to ribosomal RNA. Satellite DNAs are defined as minor components after CsCI centrifugation.

Journal Article↗