Biomedical subjects
Publications and source records attributed to K Kamijo.
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cDNA clones of 2,4-dienoyl-CoA reductase were isolated from rat liver cDNA libraries constructed in phages lambda gt11 and lambda gt10. Hybrid selected translation analysis revealed that 2,4-dienoyl-CoA reductase was translated as a polypeptide with a molecular weight of about 36,000, which was about 3,000 molecular weight units larger than mature reductase. Sequencing analysis revealed that the open reading frame encoded a polypeptide consisting of 335 amino acid residues (predicted molecular weight = 36,132), which contained an N-terminal extension peptide of 34 amino acid residues (presequence) in addition to the mature enzyme. Thus, 2,4-dienoyl-CoA reductase is synthesized as a larger precursor polypeptide, and the N-terminal extension peptide may be acting as the mitochondrial import signal.
The 70-kDa peroxisomal membrane protein (PMP70) is one of the major integral membrane proteins of rat liver peroxisomes. cDNA clones for PMP70 were isolated and sequenced. The predicted amino acid sequence (659 amino acid residues) revealed that the carboxyl-terminal region of PMP70 has strong sequence similarities to a group of ATP-binding proteins such as MalK and Mdr. These proteins form a superfamily and are involved in various biological processes including membrane transport. Limited protease treatment of peroxisomes showed that the ATP-binding domain of PMP70 is exposed to the cytosol. The hydropathy profile, in comparison with those of several other members of the ATP-binding protein superfamily, suggests that PMP70 is a transmembrane protein possibly forming a channel. Based on these results, we propose that PMP70 is involved in active transport across the peroxisomal membrane.
In the present study, a new clinical state of transient subclinical hypothyroidism in 12 early pregnant women is documented. The incidence of transient subclinical hypothyroidism was 18 (0.19%) among 9,453 pregnant women examined in this series in Sapporo. The characteristics of transient subclinical early gestational hypothyroidism in our study may be summarized as follows: temporarily increased TSH in the blood (11.7 +/- 6.3 microU/ml; mean +/- S.D.) in early pregnant women at 8.5 +/- 2.4 weeks of gestation, accompanied with or without reduced FT4 which spontaneously return to normal at 17.9 +/- 7.1 weeks; no subjective complaints and no previous history of thyroid disease; small struma; positive titers of antimicrosome antibody and antithyroglobulin antibody; normal serum hCG; negative results for TSH receptor antibody. None of the infants show any physical abnormality such as struma and none of the patients had neck pain or fever suggesting subacute thyroiditis. The presence of autoantibody to the thyroid gland and echographical findings strongly suggest the existence of Hashimoto's thyroiditis in early pregnant women with transient subclinical hypothyroidism, although the cause of transient subclinical early gestational hypothyroidism remains obscure.
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The aim of the present study was to investigate hypothalamic-pituitary function, pituitary-thyroid function as well as pituitary-adrenal function in cancer patients. 1. Hypothalamic-pituitary function: We already reported a tumor-related paradoxical increase of serum growth hormone (GH) in oral glucose tolerance test (OGTT) and TRH test, which seemed to be due to changes in pituitary GH cell, not hypothalamus. The high incidence of the paradoxical increase of GH in OGTT was found in patients with hepatocellular cancer and pancreatic cancer, whereas in TRH test it was observed in patients with pancreatic, colonic and gastric cancer. The highly sensitive GH enzyme immunoassay demonstrated in 12 non-responder patients in OGTT a significant reduction of serum GH at 30 minutes compared to basal values. 2. Pituitary-thyroid function: We already demonstrated that a high incidence of low T3 syndrome in elderly cancer patients compared to younger patients and metabolic changes in glucose must be involved in the pathogenesis. In addition, this syndrome is significantly related to prognosis. There were no significant changes in thyroid function before and after curative operation for tumors except in patients with poor prognosis. 3. Pituitary-adrenal function: It was shown that cancer cachexia is characterized by hypercortisolemia, which must be due to a defect of negative feedback control.
cDNA clones for rat mitochondrial acetoacetyl-CoA thiolase were isolated and sequenced. The most 5'-extended clone (RT2-6) consisted of 1,460 bases and contained a 1,272-base open reading frame encoding a polypeptide of 424 amino acid residues. A coupled in vitro transcription/translation analysis of RT2-6 revealed that RT2-6 encodes the entire precursor of this enzyme. The amino-terminal sequence and amino acid composition of the purified enzyme agreed with the primary structure deduced from the cDNA. The calculated molecular masses of the precursor and the subunit of the mature enzyme are 44,694 and 41,364 Da, respectively. The primary structure of this enzyme was compared with those of four other thiolases (rat mitochondrial and peroxisomal 3-ketoacyl-CoA thiolases, acetoacetyl-CoA thiolase of Zoogloea ramigera, and cytosolic acetoacetyl-CoA thiolase of Saccharomyces uvarum). Marked homology between any two of them (34-51% identity) indicates that the genes of thiolases have evolved from a common ancestral gene. It has been reported that this enzyme has two isoenzymes A and B. However, the purified isoenzymes were indistinguishable from each other in some analyses. Though 17 independent cDNA clones were isolated, no definite evidence indicating the presence of different cDNAs was found.
An acquired partial pituitary insufficiency with selective ACTH and GH deficiency was demonstrated in two men aged 47 and 54, for which the clinical course over many years corresponds to Addison's disease. In one of the 2 cases, antibodies to anterior pituitary cell membrane, assayed by an immunofluorescence method with GH3 cells (rat GH and prolactin secreting cell) and AtT-20 cells (mouse ACTH secreting cell) as antigens, were positive. We also present a 55-year-old man with isolated ACTH deficiency associated with transient GH deficiency. In this case, hydrocortisone replacement corrected his subnormal, pre-therapy GH response to insulin tolerance and glucagon propranolol tests, although there was no response of serum GH to L-dops and arginine stimulation test before therapy. Selective ACTH and GH deficiency are very rare and the finding of transient GH insufficiency in a patient with isolated ACTH deficiency suggests that repeated testing while on hydrocortisone replacement therapy is of great diagnostic importance in order to distinguish between selective ACTH and GH deficiency and isolated ACTH deficiency accompanied by transient GH insufficiency.
The purpose of this paper was to evaluate quantitatively visual fatigue encountered in viewing stereoscopic 3D television. By examining the difference in the visual function involved in watching 2D and stereoscopic 3D displays, we could extract only the effect on visual perception in stereoscopic 3D television. Since the visual fatigue with the 3D display may be caused by the discrepancy between convergence and accommodation, the near point distances were measured by an Accommodo Polyrecorder, where Landolt's ring was pursued with binocularity. Five subjects, all employees of NEC Corporation, participated in the experiment. All subjects had normal or corrected-to-normal vision. Two of the subjects watched a 3D video movie. After a week, they watched another video movie in 2D. The rest of them watched the movies in reverse order. One video movie viewing requires about 120 minutes. The near point distances were measured before and after watching for 30, 60, 90 and 120 minutes. The 3D television system used here is a 3D video disc system with field sequence using glasses with liquid crystal shutters. In the case of 2D, each subject wore the glasses whose shutters were kept open. In the experiment, instruction to watch the video movies in a relaxed posture was given. There was a significant effect in regard to 3D/2D treatments on the change rates of the near point distance measured after watching every 30 minutes to one before watching. In addition, the change rates in 3D watching after 60, 90 and 120 minutes were significantly increased, compared with the corresponding rates in 2D.(ABSTRACT TRUNCATED AT 250 WORDS)
Paradoxical growth hormone (GH) responses in 50 g or 75 g oral glucose tolerance tests (OGTT) have been demonstrated in 24 patients with hepatocellular carcinoma, whereas no significant changes in serum GH levels after OGTT were shown in 10 normal controls, 6 patients with cirrhosis of liver, and with chronic active hepatitis. There were no significant difference in the GH responses in OGTT as well as in the incidence of paradoxical GH responses between diabetic and non-diabetic patients with HCC. Informatively, the basal somatomedin C level was very low in all cases examined.
Clinical aspects of TRH, GHRH, Somatostatin (SS) and CRH as well as an effect of glucocorticoid on GH secretion are reported.
Clinical symptoms, signs, endocrine examinations, image diagnosis of GH cell adenoma, prolactin cell adenoma, TSH cell adenoma and nonsecreting pituitary adenoma are discussed.
In order to investigate whether endogenous GHRH and somatostatin were involved in the mechanism of the paradoxical GH rise after TRH injection, changes in serum GH and plasma GHRH were examined before and after TRH injection in 12 cancer patients and changes in serum TSH and GH were similarly studied in 76 cancer patients including 31 GH-responders and 45 GH-nonresponders to TRH. TRH stimulated GH secretions without altering the circulating GHRH concentration in 4 of the 12 cancer patients. There was neither a significant correlation between the increase from the basal to maximum GH and GHRH after TRH injection in the 12 cancer patients nor a reciprocal relationship between the increase in GH and TSH after TRH injection in the 76 cancer patients. These findings suggested that the paradoxical GH rise after TRH injection in cancer patients was exerted by its direct action at the pituitary level, and not mediated through the hypothalamus.
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Changes in serum growth hormone (GH) concentrations before and after TRH injection, oral glucose tolerance test (OGTT), L-dopa, CB-154 and LHRH administration were investigated in 78 gastric, 32 hepatocellular, 23 colonic, 20 pulmonary, 11 esophageal, 9 pancreatic and 9 other types of cancer patients. In addition, the effect of 5-FU or tegafur on thyroid function was studied in 39 gastric, 12 colonic, 8 hepatocellular, 5 pancreatic and 8 other types of cancer patients. The results obtained were as follows. 1) Paradoxical responses of growth hormones to TRH and OGTT were demonstrated in cancer patients, although normal increases in GH concentrations after L-dopa and CB-154 administration were shown. Incidences of GH response to TRH were significantly higher in female cancer patients than in male cancer patients, although there was no sex difference in the paradoxical responses of serum GH concentrations to OGTT. 2) After curative surgery, paradoxical responses of serum GH levels to TRH and OGTT were gradually diminished. Immunostaining of tumors using GH Ab was negative. Anti-tumor agents showed a stimulatory effect on the paradoxical response to OGTT. 4) More than 3 months after 5-FU or tegafur administration, significant elevations of serum T3, T4 and TBG concentrations were demonstrated in cancer patients, compared to pre-treatment values or those within 2 months after therapy, although there were no significant changes in serum thyroglobulin and TSH levels before and after therapy. In conclusion, tumor-dependent hypothalamic-pituitary changes were recognized in cancer patients. Long-term administration of 5-FU or tegafur caused elevations of serum T3 and T4 through high TBG concentrations.
A tissue specimen taken from the pancreatic tumor of a patient suffering from Zollinger-Ellison syndrome associated with a concurrent Cushing's syndrome was investigated both morphologically and immunohistochemically. Histologically, the tumor cells were found to be arranged in a cord or ribbon pattern. An immunohistochemical study revealed that the tumor nodule contained both gastrin and ACTH. Further, double stainings of the same section disclosed that the same tumor nodule possessed both hormones simultaneously, thus confirming the concurrent presence of Zollinger-Ellison syndrome and Cushing's syndrome. An electron micrograph of the tumor cell showed the presence of numerous endocrine-type granules in the cytoplasm. These findings substantiate the concurrent presence of the two characteristic clinical syndromes.
In order to investigate the relation of weight loss and intravenous hyperalimentation therapy to low T3 syndrome, serum T3, T4. rT3 and TBG were determined by radioimmunoassay in 105 cancer patients. The cancer patients were classified into 3 groups, Group I, II and III depending on the grade of weight loss, ranging up to a 5% change in weight loss from a healthy condition, from 5 to 9%, and more than 10%, respectively. Cancer patients under age 59 showed no significant difference in serum T3, T4, rT3 and TBG among these 3 groups. However serum T3 and T3/T4 in cancer patients at age 60 and over were significantly reduced in group III, compared to groups I and II. Serum rT3 values were significantly elevated in group III of elderly cancer patients. The incidence of low T3 syndrome in group III of elderly cancer patients was also significantly higher than in groups I and II. In three out of 5 cancer patients with low T3 syndrome, serum T3 values increased after the intravenous hyperalimentation therapy, whereas no significant change in serum T3 values was observed in two patients who died within one day after the final examination. It is concluded that weight loss produced different effects on peripheral conversion of T4 to T3 between cancer patients under age 59 and over age 60 and glucose plays an important role in the pathogenesis of low T3 syndrome except cases with very poor prognosis.