SAKEMI, K., HAYASAKA, K., TAHARA, M., SANADA, Y. and TAKADA, G. TheEffect of Carnitine on the Metabolim of Valproic Acid in Epileptic Patients. Tohoku J. Exp. Med., 1992, 167 (2), 89-92 -The half-life of valproic acid (VPA) was studied in 8 epileptic and severely mental retarded patients before and after one month of carnitine supplementation. Serum carnitine concentration was significantly decreased and VPA half-life was prolonged especially in adult patients before carnitine supplementation. After the treatment with carnitine, serum carnitine concentration was increased, and prolonged half-lives of VPA were corrected near to the normal range (from 12.2±4.2hr to 9.7±2.2hr; p<0.05). ontroled state of epilepsy was unchanged during the short period of observation.
KITAMOTO, Y., YIDE, C., TOMITA, M, and SATO, T. The Mechanism ofGlomerular Dysmorphic Red Cell Formation in the Kidney. Tohoku J. Exp. Med., 1992, 167 (2), 93-105- The mechanism of glomerular dysmorphic cell formation was studied in a in vitro system simulating the process of concentrated acidic urine formation along the nephron. Red cells suspended in phosphate buffer were exposed to three sequential pH gradients, (1) pH 7.4-6.6, (2) pH 6.6-6.5, and (3) pH 6.5-5.2, accompanying osmolality gradients, (1) 280-1200mOsm/kg H2O, (2) 1, 200-140mOsm/kg H2O, and (3) 140-1, 100mOsm/kg H2O, respectively, for 15 to 60min, and red cell shapes were observed by differential interference microscopy. The appearance rate of glomerular dysmorphic cells was 37.7 to 47.1% after finishing all the gradients. The last gradient, simulating the work of the collecting duct, was essential for the dysmorphic cell formation; maximal formation was at the final pH of 5.0 and osmolality of 1, 000mOsm/kg H2O. No dysmorphic cells were observed in gradients simulating alkaline or diluted urine formation. In 10 glomerulonephritic patients, glomerular dysmorphic cells appeared over five times as frequently in concentrated acidic urine as in alkaline or diluted urine. Results of in vitro and patient studies coincided well with each other, suggesting that in glomerulonephritic patients, dysmorphic cells might be produced while red cells are passing through the tubules, where concentrated acidic urine is formed.
INOUE, T., TANI, K., TAJIRI, M., ISHIDA, Y., SEGUCHI, M., TANAKA, H., ASANO, S., KANEKO, T. and MATSUMOTO, N. A Case Report of Familial Cyclic Neutropenia. Tohoku J. Exp. Med., 1992, 167 (2), 107-113-A 34-year-old female with cyclic neutropenia is reported. Family studies showed that her three sons and her mother were also involved. Oscillations in the blood neutrophil counts were almost regular, with a periodicity of 21 days. Numbers of colony- forming unit -granulocyte macrophage (CFU-GM) formed from the bone marrow cells of normal volunteers co-cultured with the patient's serum or mononuclear cell-conditioned medium (MNC-CM) were examined. Her serum prepared during the neutropenic phase inhibited the growth of CFU-GM, while her MNC-CM stimulated it. Human granulocyte colony-stimulating factor (hG-CSF) level in her serum was persistently high, with the peak occurring during the neutropenic phase. These results suggest that some inhibitory factors in the serum may be pathophysiologically important for cyclic neutropenia. To control infections, a pharmacological dose of hG-CSF was administered for 7 days around the early neutropenic phase. Her peripheral neutrophil counts oscillated from 1, 200/mm3 to 17, 000/mm3 with G-CSF, and from 150/mm3 to 1, 800/mm3 without G-CSF.
IRIUCHIJIMA, J. Supraspinal Origin of Abnormal Hindquarter VasoconstrictorTone in Spontaneously Hypertensive Rats. Tohoku J. Exp. Med., 1992, 167 (2), 115-119-The object of this study was to determine whether the abnormal hindquarter tone in spontaneously hypertensive rats (SHR) is of spinal origin or not. SHR were implanted with a catheter in the left common carotid and an electromagnetic flow probe around the terminal aorta. About three days after implantation, the spinal cord was transected at Th 1 under ether anesthesia. One hour later, when the rat restored consciousness and the arterial pressure recovered partially to a new plateau level which was significantly higher than that in similarly treated normal rats, ganglionic blockade with hexamethonium did not significantly decrease hindquarter (terminal aortic) resistance, calculated as arterial pressure divided by hindquarter flow. It was concluded that there was no appreciable sympathetic vasoconstrictor tone in the hindquarters of SHR after spinal transection and that the origin of the abnormal tone was at the supraspinal level.
NAGAKURA, K., TSUTSUMI, Y., MORIYA, H., NAKAZAKI, H. and KAWAI, K. Serologic Findings in Hepatic Ascariasis: A Case Report. Tohoku J. Exp. Med., 1992, 167 (2), 121-126-A 56-year-old Japanese woman underwent partial hepatectomy for intrahepatic cystic masses. Before operation, the patient had been diagnosed as liver abscess due to Ascaris infection serologically. The excised hepatic lesions consisted of encapsulated old abscesses, with a few calcified parasitic ova and numerous Charcot-Leiden's crystals microscopically seen in necrotic exudate. However, no parasitic worms were found in the cystic cavity. The eggs in the tissues were indistinguishable from other helminthic ova morphologically, but stained positively for Ascaris antigens by the indirect immunoperoxidase method. The results indicate that the serologic diagnosis of intrahepatic ascariasis may be feasible, practical, and reliable.
SUZUKI, T., YAMANAKA, H., NAKAJIMA, K., SUZUKI, K., KANATANI, K., KIMURA, M., OHMA, C. and OTAKI, N. Immunohistochemical Study of Metallothioneinin Human Seminal Vesicles. Tohoku J. Exp. Med., 1992, 167 (2), 127-134 -Metallothionein (MT) in human seminal vesicles was examined by use of the avidin-biotin-peroxidase complex method. Tissues were obtained from six patients with prostate cancer who underwent luteinizing hormone-releasing hormone agonist or estrogen therapy before radical prostatectomy (group 1) and from 18 patients without hormone therapy (three with prostate cancer, three with urinary bladder cancer, and twelve free of urogenital diseases at autopsy) (group 2). MT was localized in the cytoplasm and nuclei of epithelial cells and also in secretory products in the lumen. The epithelial cells lacked uniformity in immunoreaction; for instance, some stained strongly while others stained weakly. Smooth muscle cells were found to have positive immunoreaction, but other connective tissues had no immunoreaction. The number of strongly positive cells in group 1 was fewer than that in group 2 (not significant), and the secretory products in group 1 had no immunoreaction. These results suggest that MT is synthesized in the epithelial cells of the seminal vesicles and secreted into the fluids, and that the synthesis of MT is suppressed by the hormone therapy.
MEGURO, K., YAMAGUCHI, S., DOI, C., NAKAMURA, T., SEKIZAWA, K. and SASAKI, H. Prevention of Respiratory Infections in Elderly Bed-Bound NursingHome Patients. Tohoku J. Exp. Med., 1992, 167 (2), 135-142-A procedure to prevent silent aspiration, which results in frequent respiratory infections, was conducted on elderly bed-bound nursing home patients who suffered mainly from cerebral infarction and dementia. We cleaned the mouth with povidone iodine and kept them in a sitting position for 2hr after each meal in order to restrict respiratory bacterial infection and to prevent aspiration of gastric juices, respectively. Patients with urinary tract infections were excluded from the present protocol. During the treatment for 103 days the number of febrile days was significantly decreased in the treated group compared with the control group, probably due to minimizing of respiratory infections.
YAMAGUCHI, S., FUKAO, T., KANO, M., WAKAZONO, A., ORII, T., SAKURA, N. and HASHIMOTO, T. Further Analysis of Mutant Thiolase Protein in Fibroblastsfrom a Japanese Boy with 3-Ketothiolase Deficiency. Tohoku J. Exp. Med., 1992, 167 (2), 143-153 -We examined the mutant protein of mitochondrial acetoacetyl-CoA thiolase (mutant T2) in fibroblasts from a Japanese boy with 3-ketothiolase deficiency. The molecular size of the mutant T2 protein, determined by pulse labeling and SDS/PAGE, was intermediate between the mature subunit and the precursor of T2. To characterize the mutant T2 protein, pulse-labeling and rhodamine 6G inhibition of mitochondrial transport in fibroblasts, cell-free translation experiments, and family studies by thiolase assay, immunoblotting, and pulse-labeling were carried out. The mutant T2 was detectable as early as a 10-min pulse. The probable precursor of the mutant T2 was not detectable in either the rhodamine 6G inhibition or cell-free translation experiments. In the parents, the K+ ion dependency of acetoacetyl-CoA thiolase activity was low and the T2 bands in immunoblots were faint. It would thus appear that the parents are heterozygotes of this disease. In pulse-labeling, only a band for the mutant T2 was detected in the patient and a single band for the normal mature subunit of T2 in the father; both bands were detected in the mother. These findings suggested that the mutant T2 in the patient was inherited from the mother, and that the expression of another mutant allele of the father may be either abolished or scanty.
OHNO, Y., CHIBA, S., UCHIGASAKI, S., UCHIMA, E., NAGAMORI, H., MIZUGAKI, M., OHYAMA, Y., KIMURA, K. and SUZUKI, Y. The Influence of Tetrodotoxin onthe Toxic Effects of Aconitine in vivo. Tohoku J. Exp. Med., 1992, 167 (2), 155-158 -Both aconite toxins (aconitine, mesaconitine, and hypaconitine) and a pufferfish toxin (tetrodotoxin, TTX) were detected in the blood of a legal autopsy case. In order to elucidate the in vivo influence of TTX on the toxic effects of aconitine, a mixture of aconitine and TTX was administered to male ICR mice orally or intraperitoneally. The animal experiments revealed that the time of death due to aconitine was significantly delayed in proportion to the dose of TTX compared with the case for aconitine alone, and that the mortality of aconitine was lowered by TTX when the dose ratio of the two toxins was in a particular range. Accordingly, it is thought that the toxic effects of aconitine are attenuated by TTX in vivo.
KONDO, S., FUSHIMI, E., MORITA, T. and TASHIMA, Y. Direct Measurement ofEndothelin Receptor in Human Bladder Base and Dome Using 125I-Endothelin. Tohoku J. Exp. Med., 1992, 167 (2), 159-161-The amount of endothelin receptor in human bladder base and dome was measured by radioligand binding techniques using 125I-endothelin-1 (125I-ET). Specimens were obtained from 5 patients who underwent total cystectomy under diagnosis of bladder cancer. 125I-ET bound to the bladder base with the KD value of 0.004±0.003nM and to the bladder dome with the KD value of 0.007±0.003nM. These values were not significantly different. The Bmax values (fmol/mg protein) of 125I-ET binding to human bladder were 2.74±2.81 to the base and 47.3±9.52 to the dome. There were much larger amount of endothelin receptors in the dome compared to the base. The existence of endothelin receptors in human bladder suggests the possible roles of endothelin on the human bladder function.
KONDO, S., TASHIMA, Y. and MORITA, T. Effect of Cimetidine on the Densityof Adrenergic Alpha-1 and Alpha-2 Receptors in the Rat Whole Prostate. TohokuJ. Exp. Med., 1992, 167 (2), 163-166-In order to study the antiprostatic effect of cimetidine, we measured adrenergic α-1 and α-2 receptors of the whole prostate of cirmetidine-administered rats using radioligand binding techniques. Saturation e×periments using 3H-prazosin and 3H-yohimbine revealed that there were significant amounts of α-1 and α-2 receptors in the rat whole prostate. There were more α-1 receptors than α-2 receptors in both the control and treated groups. In the treated group, the density of α-1 receptors showed little change, while that of α-2 receptors showed a significant decrease in comparison to the control group without changes in KD values. These data suggest that cimetidine affects the prostatic alpha receptors and consequently decreases the density of adrenergic α-2 receptors in the prostate.
KONDO, S., KAGAYA, M., TASHIMA, Y. and MORITA, T. The QuantitativeDifference in Adrenergic Alpha-1, Alpha-2 and Beta Receptors between the Prostaticand Epididymal Ends of Dog Vas Deferens. Tohoku J. Exp. Med., 1992, 167 (2), 167-169-In order to study the regional differences in the distribution of adrenergic receptors of the vas deferens, we measured the amounts of adrenergic α-1, α-2 and β receptors in prostatic, intermediate, and epididymal portions of the dog vas deferens using radioligand binding techniques. Saturation experiments with 3H-prazosin, 3H-yohimbine, and 3H-dihydroxyalprenolol demonstrated that there were significant amounts of adrenergic α-1, α-2, and β receptors, respectively, in these three portions. α-1 receptors existed most densely in the whole vas deferens. The prostatic portion was found to have the largest amounts of α-1 and α-2 receptors among three portions studied. β-Receptors were distributed most densely in the intermediate portion. α-1, α-2, and β adrenergic receptors show different distribution patterns throughout the whole length of vas deferens.