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The kinetic properties and subcellular distribution of an esterifying enzyme in the pigment epithelium of bovine retina have been studied using both [1-3H]retinol and [3H]retinol bound to cellular retinol-binding protein as substrates. The most active esterifying fraction in pigment epithelial cell preparations was the microsomes, but the lysosome plus mitochondria fraction also showed some activity, probably due to endoplasmic reticulum present as an impurity. The microsomal enzyme showed optimum activity at pH 7.5, and the reaction was linear up to 30 microgram protein and for the first 10-15 min. The apparent Km values were 16.6 . 10(-6) and 5.5 . 10(-6) M for [3H]retinol and bound [3H]retinol, respectively. This is the first time that retinol bound to cellular retinol-binding protein has been shown to undergo metabolic transformation. The microsomal esterifying activity was destroyed by boiling for 1 min, or after freezing for 2 months. No clear requirement for ATP, CoA or fatty acid could be demonstrated. Of all the other tissues examined under the same experimental conditions as those used for the pigment epithelium, only intestine showed measurable activity. With larger amounts of tissue protein and longer incubation periods, activity was also detectable in microsomes of liver, testis and retina.

Most secretagogues, in addition to their acute stimulatory effect on insulin release, modify the responsiveness of the islet to subsequent stimulations. According to the nature and duration of the stimulus, the generated islet memory may either amplify [time-dependent potentiation, (TDP)] or diminish [time-dependent inhibition (TDI)] the responsiveness of the beta-cell. This work characterizes the kinetic parameters of TDI in the isolated rat pancreas. When subjected to a low dose (8.3 mmol/liter) glucose stimulus, maximal TDI was observed after 5 min of priming, while at a higher dose (16.7 mmol/liter) shorter exposures were sufficient. Longer periods of stimulation (10-40 min) resulted in the predominance of TDP, thus amplifying the release rate. TDI was not affected by previous generation of TDP; 40-min priming with 16.7 mmol/liter glucose markedly augmented the subsequent insulin responses to a pair of 6.9 mmol/liter stimuli, but the response to the second stimulus was inhibited, as in unprimed pancreas. Stimulation with arginine (5.0 mmol/liter) in the presence of basal (3.3 mmol/liter) glucose activated TDI only, and hence revealed monophasic insulin release. Tolbutamide (100 micrograms/ml), glucagon (5 micrograms/ml), and isobutylmethylxanthine (0.1 mmol/liter) also demonstrated TDI when given as a pair of 10-min stimuli; they all elicited monophasic insulin responses during prolonged stimulation. Arginine was chosen for detailed characterization of TDI because of its potency. Using identical concentrations of arginine for the generation and expression of TDI, a similar degree of inhibition (60-80%) was observed at all doses tested (0.5-5.0 mmol/liter). However, there existed competition between TDI and the acute secretory signal. Thus, TDI generated by 1.0 mmol/liter arginine had a minimal effect on insulin release induced by 2.0-5.0 mmol/liter amino acid, while it was fully inhibitory of the response to 1.0 mmol/liter arginine. Similarly, inhibition of the insulin response to 5.0 mmol/liter arginine was dependent on the dose (0.5-5.0 mmol/liter) of the priming pulse of arginine. The generation of TDI was unaffected by the insulin release rate during priming, since synergistic augmentation (combined arginine-glucose or arginine-isobutylmethylxanthine stimulation) or partial inhibition (arginine plus epinephrine) of the response had no effect on the subsequent expression of TDI. It is concluded that TDI and TDP are two distinct regulatory systems that independently control the rate of insulin release, most probably operating through different mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)

The implications of left-handedness for intellectual functioning in monozygotic (MZ) twinships remain unresolved. Two proposed explanations of hand-discordance in MZ twin pairs, elevated birth stress and delayed zygotic splitting, were used to generate hypotheses and predictions concerning IQ, both within and between twin pairs. A comparison of Full Scale IQ, Verbal IQ and Performance IQ scores for MZ twin children, from 67 twin pairs, organized according to concordance or discordance for handedness and relative birth weight, is presented. The results support the hypothesis that left-handedness in lower birth weight MZ co-twins may be associated with pre-natal pathological events, while left-handedness in higher birth weight left-handed MZ co-twins may be associated with delayed zygotic splitting and disrupted asymmetry determination. Birth weight status within MZ twin pairs may predict a lower IQ for the lower birth weight twin only when lower birth weight co-occurs with left-handedness. Pre-natal insult similarly reduced Verbal IQ, but not Performance IQ, within these particular twinships.

An in vitro perfusion system at 37 degrees C for the assessment of rabbit kidney function is described. The purpose of this assay system is to evaluate the effects of cryobiological manipulation on kidney function. The effect of the colloids dextran (MW = 70,000, 80,000, and 180,000) in the perfusate at 110 mm Hg were compared to a reduced perfusion pressure, colloid-free perfusate. Better function was obtained at lower perfusion pressure with the colloid-free perfusate. Less damage was noted histologically on light and electron microscopy. Investigation of energy substrates on rabbit kidney function demonstrated that butyrate, or lactate, in addition to glucose resulted in increased sodium and glucose reabsorption over glucose alone. Substrate-free perfused kidneys exhibited depressed Na transport. Lactate, and to some extent butyrate, decreased net glucose utilization. An alpha-adrenergic blocking agent, isoxsuprine, in the initial flush solution did not appear to be beneficial. An increase of perfusion pressure from 50 to 75 mm Hg resulted in an increase in GFR. Tubular function was enhanced by inclusion of small amounts of BSA in the perfusate.

In a prospective, randomized, multicenter study, the efficacy and safety of cefoperazone and the combination ampicillin-tobramycin as initial therapy for patients with severe acute biliary tract infections were compared. Of 77 patients initially entered in the study, definite severe biliary tract infection was confirmed in 67. Sixty-four patients completed treatment. At the end of treatment, 35 of 36 (97%) patients given cefoperazone and 23 of 28 (82%) given ampicillin-tobramycin were cured of their infection (P = 0.07). Pathogens were recovered from the bile in 32 patients; microbiological cures were observed in 18 of 19 (94%) patients receiving cefoperazone and 8 of 13 (62%) receiving ampicillin-tobramycin (P = 0.03). Thirteen patients had septicemia. None (0%) of the eight septicemic patients from the cefoperazone group, but two of five (40%) from the ampicillin-tobramycin group, were clinical failures. Of the isolated pathogens, 51% were resistant to ampicillin, while the resistance rate was 4% for tobramycin and 1% for cefoperazone (P less than 0.001). Biliary concentrations of cefoperazone were maintained at high levels--236 +/- 87 micrograms/ml up to 12 h after administration. Even in the presence of severe obstruction, cefoperazone levels in the bile and gallbladder wall were above MICs for most pathogens. Cefoperazone may be considered as an excellent alternative in the therapy of severe biliary tract infections.

A review of 102 total ankle arthroplasties performed during a four-year period revealed that complications occurred in 41%. 22% with impingement of various types 6.9% with loosening and 2.9% with deep sepsis. The best results were obtained in patients with rheumatoid arthritis and those with posttraumatic osteoarthritis who were older than 60 years of age. Total ankle arthroplasty currently should not be considered in patients with posttraumatic osteoarthritis who are younger than 60 years old. Arthrodesis remains the only acceptable method of treatment in these individuals. Total ankle arthroplasty seems indicated in patients who have significant ankle joint disability secondary to rheumatoid arthritis and in elderly patients with disabling posttraumatic degeneration whose physical demands are limited.

We administered the Multidimensional Personality Questionnaire (MPQ) to 217 monozygotic and 114 dizygotic reared-together adult twin pairs and 44 monozygotic and 27 dizygotic reared-apart adult twin pairs. A four-parameter biometric model (incorporating genetic, additive versus nonadditive, shared family-environment, and unshared environment components) and five reduced models were fitted through maximum-likelihood techniques to data obtained with the 11 primary MPQ scales and its 3 higher order scales. Solely environmental models did not fit any of the scales. Although the other reduced models, including the simple additive model, did fit many of the scales, only the full model provided a satisfactory fit for all scales. Heritabilities estimated by the full model ranged from .39 to .58. Consistent with previous reports, but contrary to widely held beliefs, the overall contribution of a common family-environment component was small and negligible for all but 2 of the 14 personality measures. Evidence of significant nonadditive genetic effects, possibly emergenic (epistatic) in nature, was obtained for 3 of the measures.

The author tries to change the opinion still prevailing today according to which any pigmentary retinopathy may represent a handicap to the descendants. Pigmentary retinopathy may have several etiologies--hereditary, sex-linked, dominant autosomal or recessive autosomal, metabolic, within the framework of various mucopolysaccharidoses, secondary post inflammatory or post traumatic. Hereditary transmission is discussed recalling for isolated cases the empirical calculus of H. Maumenee on 1000 Swiss families. Genetic advice, the same as other medical prognosis must form integral part of clinical medical practice. Genetic advice must be based on perfect knowledge of the patient and his family, yet the final decision remains with the family.

The hydrolysis of 3H-retinyl ester was examined in the retinal pigment epithelium (RPE) and neural retina of cattle eyes and compared to that in homogenates of rat liver. The optimum pH for hydrolysis was 4.0-4.5 for RPE and 7.5-8.0 for liver. The RPE activity, which shows no variability between individual animals, is localized mainly in the lysosomal fraction of the cell. It is strongly inhibited by bile salts at concentrations as low as 0.2-0.5% and conversely, is strongly activated by Triton X-100, with maximum stimulation found at a concentration of approximately 1%. The apparent Vmax for hydrolysis of labeled retinyl ester in the RPE is 2.7 nmoles/hr/mg protein, a value approximately 1/150 to 1/200 of the rate of retinol esterification in these cells. Little or no hydrolytic activity could be detected in neural retina or in rod outer segments. Studies on the specificity of the RPE retinyl ester hydrolase activity revealed unexpectedly high hydrolytic activity toward both cholesteryl oleate and triolein, approximately 20 and 5 times greater, respectively, than in rat liver. The hydrolytic activity for cholesteryl oleate in the RPE was mainly at pH 3.5, while that for triolein showed three pH maxima, one at pH 4.5-5.0, a second near neutral pH and the third at pH 8. These findings reflect an active and complex pattern of fatty acyl ester lipid-metabolizing enzymes in cattle RPE whose interrelationships to one another require further clarification.

The immediate global impressions of zygosity (based upon physical similarity) were recorded by the investigator at initial meetings with 105 pairs of twins. The accuracy of these ratings, as well as classifications provided by two objective procedures (physical resemblance questionnaire; dermatoglyphic analyses) and two subjective procedures (parental impressions; physician's impressions), were evaluated by comparison with results from bloodtyping for 53 pairs. The judgments of the investigator furnished the most accurate indication of zygosity (94-96% accuracy). Laboratory tests were repeated for five pairs when the results proved incompatible with the investigator's ratings. In all five cases, the investigator's judgments were confirmed, indicating that a laboratory error had occurred. It appears that the opinion of a skilled observer of twins can provide a convenient and highly effective alternative to bloodtyping.