Captopril-induced creatine kinase elevations: a possible role of the sulfhydryl group.
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Biomedical subjects
Publications and source records attributed to S Komine.
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In the early stage of mammary gland involution, biochemically detectable lysosomal damage occurs. The mechanism(s) underlying this damage is not well understood. We found that alpha-lactalbumin from mouse milk induced the release of enzymes from the lysosomes of mouse mammary epithelial cells in vitro, and this induction also occurred with bovine alpha-lactalbumin. This enzyme release was accelerated by the addition of whey proteins with a molecular weight of 50 000 to 60 000. We also found that the lysosomal membrane of mammary epithelial cells had a strong affinity for alpha-lactalbumin.
We previously reported that alpha-lactalbumin combines with the lysosomal membrane of mammary epithelial cells and that it acts to release lysosomal enzymes. However, the details of this combination within the cells remained undetermined. We now report that 125I-bovine-alpha-lactalbumin in the medium entered mouse mammary epithelial cells, and about 13 per cent of the alpha-lactalbumin that entered the cell bound to lysosomes. About 75 per cent of the alpha-lactalbumin that reached the lysosome was tightly bound to the lysosomal membrane. It appears that alpha-lactalbumin in the secretory vesicles does not migrate out, because murine and bovine whey did not induce the release of Golgi enzymes in vitro.
Growth hormone (GH) responses to growth-hormone-releasing hormone (GRH) and thyrotropin-releasing hormone (TRH) were studied in 17 diabetic patients. Ten patients (group 1) had retinopathy corresponding to stage III-V (Scott's classification), and the remaining seven patients (group 2) had no retinopathy despite longer duration of diabetes in comparison with the patients in group 1. There were no differences in age, percent of ideal body weight, and serum HbA1 levels between the two groups. Basal serum GH levels were 1.9 +/- 0.4 ng/ml (mean +/- SEM) in group 1, and not different from the values in group 2 (1.6 +/- 0.7 ng/ml). However, GH responses to synthetic human GRH-44 (1 micrograms/kg body wt, i.v. bolus) were significantly greater in group 1, as judged by the maximal response or integrated GH secretion after the administration of GRH. There were no differences in serum insulin-like growth factor I (IGF-I) levels between group 1 (262 +/- 35 ng/ml) and group 2 (232 +/- 30 ng/ml), and no significant correlation was found between serum IGF-I levels and GH responses to GRH in either of the two groups. Paradoxical GH responses to TRH (500 micrograms, i.v. bolus) were found in only one patient in each group. We have thus demonstrated that GH responses to GRH are more pronounced in diabetic patients with retinopathy than in patients without this complication, although it remains to be determined whether or not greater GH responses to GRH are causally related to the development of diabetic retinopathy.
Ninety patients with spinal cord injury were managed by aseptic intermittent catheterization program I (preventing the over-distension of the bladder) and program II (allowing overdistension) in which recovery of bladder function and the clinical effects were comparatively investigated. Using program I, cases with positive BCR restored the automaticity of the bladder on average 8 weeks after injury. When urinary incontinence first occurs during aseptic intermittent catheterization, urinary training may be commenced since the bladder has then recovered from spinal shock. Cases with no BCR do not restore automatic bladder contraction. Program II delayed or weakened the recovery of bladder function considerably. Patients with incomplete lesions and sacral sparing, particularly those with urinary sensation, should be managed by program I which does not impair recovery of the bladder. It is possible to prevent urinary incontinence and infection, if paraplegics with complete lesions are managed by program II. The percentage of urinary infection was 22.6 +/- 16.0% (N = 90) during aseptic intermittent catheterization (non-touch technic) among whom no statistically significant difference between those with trigger voiding (22.2 +/- 17.2%, N = 57) and those with self-catheterization (23.2 +/- 14.0%, N = 33) was found.
Over-distension therapy was performed in 60 patients during the period of spinal shock after complete spinal cord injury. Forty-five developed upper motor neurone (UMN) hypo-active decompensated bladder function and 39 achieved satisfactory social activity without urinary incontinence using self-catheterisation. Self catheterisation appeared a safer and more comfortable means of urinary management than trigger voiding in paraplegics with complete spinal cord injury. This is a preliminary communication as it is hoped that a comparative study will follow in due course.
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The lipolytic activity in crude extracts prepared from mouse mammary glands during lactation and pregnancy or that in extracts partially purified with anion exchange chromatography and ammonium sulfate precipitation depended on the ratio of the extract volume to the substrate amount in the assay emulsion. When the ratio was high, the fatty acid release ceased within a short time of incubation. In this case, the substrate concentration available for the lipase dropped. This decline was considered to occur due to the interaction of the substrate with some substance in the extracts.
Mammary epithelial cells from lactating mice were used to compare the in vitro casein synthesis by membrane-bound and free polysomes with that of messenger ribonucleic acid extracted from free- and bound polysomes (polysomal system and a rabbit reticulocyte lysate system). Casein synthesis was detected by incorporation of hydrogen-3 labeled amino acids in the reaction mixture into synthesized casein molecules. Membrane-bound polysomes synthesized considerably more casein than free polysomes; this difference was abolished by deoxycholate treatment of free polysomes. The synthesizing activity of messenger ribonucleic acid was similar whether extracted from free- or membrane-bound polysomes. Casein synthesis may be controlled by factors on the polysomal membrane.
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Rat mammary glands contain cyclic AMP-independent casein kinase and cyclic AMP-dependent histone kinase. The former was easily isolated from cyclic AMP-dependent histone kinase by MgCl2 treatment. Mammary casein kinase was not activated by cyclic nucleotides, and Mg++ and ATP were required for activation. The specific activity of casein kinase in cytosol of rat mammary epithelial cells increased 2 to 3-fold during pregnancy and lactation. Cytosol of mouse mammary epithelial cells also contained cyclic AMP-independent casein kinase, and the activity of this enzyme was about three times that of the Golgi fraction.
The lipolytic activities with acid pH optimum were extracted from the acetone powders of the pregnant and lactating mouse mammary glands. Since the activities were strongly inhibited by human serum and albumin which were required for lipoprotein lipase assay, they were considered to be ascribable to lipase(s) other than lipoprotein lipase. Despite the fact that the amount of fatty acid released by the extract prepared from the glands in pregnancy (P-extract) was proportional to the incubation time, the release of the fatty acid by the extract from those in lactation (L-extract) ceased during incubation for a short time. The cessation, however, was avoided by preincubating the L-extract at 50 degrees C for 10 min before assay. In the presence of L-extract, the lipolytic activity in the P-extract was also almost completely lost after a short incubation. From these results, the existence of a heat labile inactivator of the lipolytic activities in lactating mouse mammary glands was suggested.
The amount of free fatty acid in the mouse mammary gland continuously increased throughout pregnancy and lactation, while the amount of triglyceride which had been stored in the gland rapidly decreased after parturition. Higher lipolytic activity in the gland was observed in pregnancy than in nonpregnant and lactating animals. The optimum pH of the activities before and after parturition were about 6 and 7, respectively, and the activities did not decrease at high ionic strength in contrast to the ion dependent inactivation described in lipoprotein lipase. Incubation of the enzyme extract of the lactating mouse mammary gland at 50 degrees C for 10 min led to a remarkable increase in the lipolytic activity measured at pH 6.0, suggesting the existence of either an inactive form of the lipase whose optimum pH is 6.0 or some heat sensitive inhibitor(s) or inactivator(s) of the enzyme in the lactating mammary gland. The triglyceride stored in the gland in pregnancy will be consumed within the first 3rd days after parturition, and the lipases play an important role in the decomposition of the triglyceride.
The relationships between hormonal action and cyclic AMP as the second messenger of hormones have recently been discussed on many hormones. Lactation is influenced by various hormone, especially, insulin, prolactin, and hydrocortisone. Whether adenyl cyclase activity in the mammary gland of mouse epithelial cells has parallel relations with casein biosynthesis ability or not was examined using the mammary gland organ culture method. Female, mid-pregnant (11-14 days), mice of DDY strain were used. Organ culture was done by the Chen's floating lens' paper method, using the hormone-added MEM media and non-added ones. Casein biosynthesis ability was measured by observing 32P incorporation into the casein molecules. Adenyl cyclase activity was estimated by the amount of 14-C-cyclic AMP produced out of adenine-8-14C by the Kuo and Krishna's method. Radio isotope compounds were pulsed for 4 hours in the medium. The experiments revealed that the added hormones had a remarkable effect on caein biosynthesis ability, but none on adenyl cyclase activity. No parallel fluctuation was observed between adenyl cyclase activity and casein biosynthesis ability, that is, the change of adenyl cyclase activity was found to have nothing to do with casein biosynthesis ability. Consequently, the cyclic AMP addition to the media showed no effect on casein biosynthesis ability.
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