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Biomedical subjects

R Reynolds

Publications and source records attributed to R Reynolds.

At least 145 records · Page 8Linked to original sources

The surgical treatment of blunt and penetrating injuries of the popliteal artery.

Thirty-six patients sustaining blunt and penetrating injuries to the popliteal artery underwent vascular reconstruction with an average ischemic interval of eight and one-half hours (range: four to 14 hours). There were 16 associated venous injuries, 15 nerve injuries, and 20 fractures with or without knee dislocations. Arterial repair was performed by saphenous vein interposition graft in 23 patients and by end-to-end anastomosis in 16 patients (three patients had more than one operation). Eight of the venous injuries were reconstructed and the remaining eight veins were ligated. Fasciotomy was performed in 22 patients. Skeletal stabilization by external support was necessary in 12 instances and by internal fixation in eight patients. Five patients required amputation after vascular reconstruction failed. The presence of an ischemic interval greater than ten hours, associated fractures, and/or knee dislocation carried a serious prognosis for limb survival.

Adolescent↗

Phospholipid synthesis in S. cerevisiae strain GL7 grown without unsaturated fatty acid supplements.

In the absence of exogenous unsaturated fatty acids (UFA), Saccharomyces cerevisiae strain GL7 synthesizes low levels of UFA and large amounts of decanoic, dodecanoic and tetradecanoic fatty acids. Supplementation with hemin leads to slightly higher levels of UFA, but synthesis of the medium-chain saturated fatty acids (SFA) continues. Under these conditions of limited UFA availability, strain GL7 incorporates most of its UFA into phosphatidylethanolamine (PE), whereas phosphatidylcholine (PC) and phosphatidylserine + phosphatidylinositol (PS+PI) are enriched with the medium-chain SFA. The association of specific fatty acids with the various phospholipids is not accompanied by changes in the proportions of newly synthesized phospholipids, demonstrating that the fatty acid composition of PE can be modulated independently of the other phospholipids. The effect of sterol structure on the fatty acid composition of cells grown with limiting UFA was also examined. Yeast cells grown with either ergosterol or stigmasterol contained less UFA and more medium-chain SFA in their phospholipids than did cholesterol-grown cells, suggesting that the former sterols allow strain GL7 to grow with a lower UFA content.

Cholesterol↗

Effects of intake of L-ascorbic acid on the incidence of dermal neoplasms induced in mice by ultraviolet light.

We have carried out a study of large malignant skin tumors (squamous cell carcinomas) and other lesions in hairless mice (groups of 38-45) intermittently exposed to ultraviolet light over a period of 15 weeks, beginning when the mice were about 10 weeks old. The several groups were given a standard diet with 0%, 0.3%, 5%, and 10% added L-ascorbic acid (vitamin C) throughout the study. No lesions developed in unirradiated control groups. The lesions were counted every 14 days for 4 months, beginning 4 weeks before the end of the period of irradiation. The observed incidence of lesions of several sizes during successive time periods was analyzed by the statistical method recommended by a committee of the International Agency for Research on Cancer. A pronounced effect of vitamin C in decreasing the incidence and delaying the onset of the malignant lesions was observed with high statistical significance.

Animals↗

Incidence of squamous cell carcinoma in hairless mice irradiated with ultraviolet light in relation to intake of ascorbic acid (vitamin C) and of D, L-alpha-tocopheryl acetate (vitamin E).

We have carried out a study of large malignant skin tumours (squamous-cell carcinomas) and other lesions in "hairless" mice (in groups of 45 or 60 mice) intermittently exposed to ultraviolet light over a period of 15 weeks, beginning when the mice were about 8 weeks old. Various groups were given a standard diet (Wayne Lab-Blox) or the same food with added vitamin C or vitamin E throughout the study. Lesions, classified by histopathologic study as atypical squamous-cell proliferations varying from early actinic keratoses to invasive poorly differentiated squamous-cell carcinomas, had begun to develop by the end of the period of irradiation. They were counted twice a month for five months. The observed fraction of mice that developed lesions during successive time periods was analyzed by the statistical method recommended by a committee of the International Agency for Research on Cancer. A pronounced effect of vitamin C in decreasing the incidence of the malignant lesions was observed with very high statistical significance. No significant effect of vitamin E was observed. We conclude that vitamin C should be given special attention with respect to the relation between diet and cancer.

Animals↗

Proline and glucose transport by renal membranes from dogs with spontaneous idiopathic Fanconi syndrome.

The uptake of proline and glucose by renal brush border membrane vesicles isolated from Basenji dogs exhibiting a spontaneous Fanconi syndrome was examined. The magnitude of the 1-min, Na+-gradient uptake of proline (0.02 mM) and glucose (1.0 mM) by vesicles from affected dog kidney was lower than normal. Concentration-dependent 15-sec uptake in vesicles from normal and affected dogs reveals a two-component transport system for proline and glucose. Kinetic analysis shows altered Km and Vmax values for both proline and glucose transport in the affected dogs. The data suggest that, in this model of Fanconi syndrome, the defective renal reabsorption of proline and glucose is associated with an alteration of luminal transport system.

Animals↗

Significance of relapse after adjuvant treatment with combination chemotherapy or 5-fluorouracil alone in high-risk breast cancer. A Western Cancer Study Group Project.

Beginning in 1974, patients undergoing mastectomy at high risk for recurrence (greater than or equal to 4 nodes positive; median, 9.4 positive; range, 4 to 28) were randomized after stratification for menopausal status and radiotherapy to receive either 5-fluorouracil (5-FU, 500 mg/sq m i.v. every week) or cyclophosphamide, 400 mg/sq m; methotrexate, 30 mg/sq m; and 5-FU, 500 mg/sq m (CMF; all given i.v. every 2 weeks) in a 12-month program. All 62 patients remain evaluable with median follow-up now exceeding 70 months (range, 60 to 80 months). CMF significantly prevented early disease recurrence (97% relapse free on CMF versus 75% on 5-FU at 12 months; p less than 0.05) and demonstrated survival advantage during the initial 40-month follow-up. This significance was subsequently lost, and the percentages of relapse free and overall survival after 70 months are: (formula, see text) The apparently paradoxical relationship between relapse and survival on the 5-FU arm was related to survival after recurrence. Survival after recurrence was significantly longer on the 5-FU compared to the CMF arm (median of greater than 38 versus 10 months, respectively; p less than 0.01). These results suggest (a) long-term survival in adjuvant trials cannot be accurately predicted by short-term differences in relapse frequency, (b) survival after relapse may be influenced by the antecedent adjuvant therapy received, and (c) disease relapse does not necessarily preclude long-term survival.

Breast Neoplasms↗

Penetration of topical clindamycin into comedones.

Comedones were removed from patients on topical clindamycin and assayed for that antibiotic by of two methods. Prominent levels were found in eight of ten patients by one bioassay method. Once whole comedones from a patient were found to be positive, other comedones were microdissected to separate the external and internal portions. Prominent levels of clindamycin were found in the inner portion as early as 2 weeks. Further, the antibiotic could always be found in the internal portion when it was present in the external layers. Using the more sensitive of two bioassay methods, the whole comedonal level of clindamycin ranged from 0 to 5 microgram/mg of comedonal material, with an average level of 0.824 microgram/mg. The significance of this is discussed.

Acne Vulgaris↗

Surface morphology of isolated cardiac myocytes from hypertrophied hearts of aging spontaneously hypertensive rats.

Morphologic features of the cell surface were studied in isolated cardiac myocytes obtained from 12 and 48 week old Spontaneously Hypertensive Rats (SHR) and normotensive Wistar-Kyoto (WKY) control rats. Hearts obtained from ether-anesthetized animals were perfused with Ca++-free Hanks' solution containing EGTA and 0.1% collagenase. The hearts were minced and the suspended cells fixed in 2% phosphate buffered glutaraldehyde. Cells mounted on Nuclepore membrane filters were dehydrated in alcohol and critical point dried for SEM. Quantitative evaluation of myocyte length, width and volume was done with a sonic digitizer on H and E stained cells by light microscopy. At both ages studied there was a significant increase in heart weight to body weight ratio, systolic blood pressure and cell size in SHR compared to WKY controls. In the older animals there appeared to be increased numbers of cell junction areas and deep grooves in the cell surface which appeared more pronounced in SHR than in WKY. The cell surface of the myocytes from 48 week old animals had deep capillary grooves surrounded by protruding longitudinal bundles of myofibrils. These changes would result in increased surface area of the larger cells and diminish the effect of increased cell size on diffusion distance from capillary to tissue. These changes in cell morphology were interpreted as providing a protective effect against development of functional impairment in the hypertrophied hearts.

Animals↗

The effect of diamide on amino acid transport by rat renal cortex slices.

Diamide directly added to renal cortical slices inhibits the uptake of amino acids. Steady-state kinetic analysis indicates an inhibition of alpha-amino acid influx without effect on efflux. The effect could be reversed by addition of pyruvate to the incubation medium. Although there was a good correlation of the transport effect of diamide with its ability to decrease cellular reduced glutathione concentration, there did not appear to be a necessary connection between them. This was shown by the fact that renal cortical slices stored at 4 degrees C have no alteration in amino acid uptake despite the fact that GSH concentration is as low as that seen with diamide. Diamide was shown to have a direct effect on the uptake of glycine by isolated renal brush border membrane vesicles.

Amino Acids↗

Amino acid content of rat renal cortex and the response to in vitro incubation.

The concentration of aspartic acid, threonine, serine, glycine, and alanine is significantly higher in newborn rat renal cortex than in the adult tissue, while phenylalanine and histidine are higher in the adult. When adult cortical slices are placed in bicarbonate buffer at room temperature for 20 min there is a 30-60% decrease in the levels of all amino acids except for lysine, which is slightly higher, and methionine and serine, which do not change. Under the same conditions, newborn cortical slices reveal a similar decrease in only glycine, tyrosine, histidine, and the branched-chain amino acids. On subsequent in vitro incubation of the cortical slices at 37 degrees C for 120 min the concentrations in adult tissue remain at the lower values observed on removal from buffer at room temperature except that glutamic acid, glycine, and lysine levels decrease further and serine increases to the concentration found in fresh tissue. Newborn tissue when incubated at 37 degrees C for 120 min shows amino acid concentrations comparable to unincubated fresh tissue for all except aspartic acid, glutamic acid, serine, and phenylalanine, which reach levels higher than unincubated tissue. The ability of newborn tissue to maintain amino acid pools may play a role in the enhanced transport of some amino acids resulting from preincubation at 37 degrees C (Reynolds et al. Science 184: 68-69, 1974; Reynolds and Segal, Biochim. Biophys. Acta 406: 513-525, 1976).

Aging↗

The fanconi syndrome in Basenji dogs: a new model for renal transport defects.

The renal defects resulting in a Fanconi syndrome were seen in eight Basenji dogs by measuring renal clearance and in vitro amino acid and sugar uptake and performing histopathologic evaluations. Renal tubular handling of glucose, phosphate, sodium, potassium, uric acid, and amino acids was abnormal, and in vitro uptake of labeled lysine, glycine, and alpha-methyl-D-glucoside by renal cortical slices was impaired. Histopathology was normal except for enlarged nuclei in some renal tubule cells. These Basenji dogs, which may be genetically affected, represent a likely model for idiopathic Fanconi syndrome in humans.

Amino Acids↗

On the development of glycine transport systems by rat renal cortex.

The initial uptake of glycine by renal cortical slices from newborn Sprague-Dawley and Long-Evans rats is the same as that observed in adult tissues. Both newborn and adult tissue possess similar high and low affinity glycine transport systems which require an examination of velocity measurements over a wide range of concentration (0.02--50.0 mM) for their discernment. Initial rates of glycine uptake by isolated renal tubule fragments from newborn and adults are similar at a physiological substrate concentration but at high glycine levels there appears to be a decrease in velocity of uptake (V) associated with the high Km system in the young. Whatever preparation of renal cortex is studied, there is a consistent finding that immature tissue is able to accumulate much higher intracellular levels of glycine than the adult, a finding consistent with slower efflux from the cell. An interpretation of the etiology of physiologic aminoaciduria in young animals should take this into account.

Aging↗