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Biomedical subjects

M Shima

Publications and source records attributed to M Shima.

At least 163 records · Page 9Linked to original sources

Multiple associated endocrine abnormalities in a patient with pseudohypoparathyroidism type 1a.

A girl with type 1a pseudohypoparathyroidism (PHP) presented several hormonal abnormalities. Although she had eluded neonatal thyroid screening, she was diagnosed as having hypothyroidism at the age of 5 months. Thereafter, a diagnosis of PHP was made on the basis of skeletal features of Albright osteodystrophy and lack of both cyclic adenosine monophosphate (c-AMP) and phosphaturic responses after parathyroid hormone (PTH) infusion. The basal levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were higher than normal and showed exaggerated responses to luteinizing hormone-releasing hormone (LH-RH). There was no growth hormone (GH) response to arginine infusion, and the prolactin (PRL) response after thyrotropin-releasing hormone (TRH) infusion, was also impaired. The stimulating guanine nucleotide-binding protein (Ns) activity of the erythrocytes was reduced to 66.9%. The skeletal age was not delayed at the age of 5 months in spite of the hypothyroid state, and it advanced following thyroxine and vitamin D treatments.

Age Determination by Skeleton↗

1,25(OH)2D and 24,25(OH)2D production in the developing kidney.

To clarify the state of vitamin D production by the developing kidney, firstly, we measured serum levels of 1,25(OH)2D and 24,25(OH)2D in humans of different ages (pregnant and nonpregnant women, adult males, children and newborn infants) and secondly, we measured 1 alpha- and 24-hydroxylase activity in the kidney mitochondria of rats at different ages. The mean serum levels of 1,25(OH)2D in pregnant women, cord blood and newborns were significantly higher than those in children and nonpregnant women and adult males. In newborns, the level increased with gestational age. Synthesis of 1,25(OH)2D was, at least in part, under the control of the fetus and newborn, rather then being solely a reflection of the conditions prevailing in the mother. The 1 alpha-hydroxylase activity in mitochondria was highest in the 1- to 2-month-old rats, and it decreased gradually thereafter. The change in 1 alpha-hydroxylase activity with age was due to a change in the Vmax of the system.

24,25-Dihydroxyvitamin D 3↗

Microcarriers facilitate mineralization in MC3T3-E1 cells.

MC3T3-E1 cells showed mineral deposits after about 1 week of culture when incubated in the presence of microcarrier beads. These deposits appeared as white spots on the dish surface, and under light microscopy the cells showed multiple cell layers and mineralization around the microcarriers. The deposits stained positive with calcium-specific Von Kossa's method. Using conventional assay, alkaline phosphatase activity (ALP) and parathyroid hormone-stimulated intracellular cAMP production were lower in the microcarrier cultures than in the control, but using cytochemical methods, high alkaline phosphatase activity was found around the microcarriers. These results indicate that microcarriers facilitated the formation of multiple cell layers and provided a culture environment for mineralization.

Alkaline Phosphatase↗

Intrarenal localization of degradation of atrial natriuretic peptide in isolated glomeruli and cortical nephron segments.

Using isolated glomeruli and nephron segments obtained from collagenase treated rabbit kidneys, we examined the in vitro degradation of alpha-human atrial natriuretic polypeptide (alpha-hANP). The ANP-degrading activity was measured by the amount of immunoreactive ANP remaining after incubation of about 50 fmoles alpha-hANP with each tissue preparation for 7.5 min. The sequence of degrading activity among isolated nephron segments was as follows: proximal straight tubule greater than proximal convoluted tubule greater than cortical collecting tubule greater than distal convoluted tubule greater than cortical thick ascending limb. A single glomerulus exhibited the degrading activity which was comparable to approximately 50% of the activity of 1 mm proximal convoluted tubule. Phosphoramidon, an inhibitor of endopeptidase, prevented the degradation of ANP in proximal convoluted tubule and glomerulus by 68% and 89%, respectively, but not in cortical thick ascending limb and cortical collecting tubule. From these results, we conclude that the degradation of ANP by endopeptidase occurs mainly in the proximal tubule and glomerulus.

Animals↗

Dynamic study of nervous control on prostatic contraction and fluid excretion in the dog.

The effect of the section or stimulation of various nerves on prostatic contraction and fluid excretion was investigated dynamically in the dog using an apparatus devised in our laboratory. Prostatic contraction could be classified into two types from the pattern of the contracting wave. One was a prominent tonic contraction, designated as H-type contraction, observed typically after hypogastric nerve stimulation and followed always by prostatic fluid excretion. The other was a weak clonic contraction, designated as P-type contraction, occurring typically after pelvic nerve stimulation and accompanied by no fluid excretion. The periodical contraction of these two types was noticed even at rest. The H-type contraction was associated with fluid excretion with a mean rate of 0.3 ml./hr. The denervation both of the hypogastric and pelvic nerves showed no distinct influence on contraction and excretion in the resting condition. The pudendal nerve was demonstrated to have no significant effect on prostatic contraction and fluid excretion. From these results, it was considered that dynamic fluid excretion followed by prostatic contraction was regulated chiefly by sympathetic fibers from the hypogastric nerve and the physiological role of parasympathetic fibers from the pelvic nerve was something other than fluid excretion.

Animals↗

Factor VIII polypeptide specificity of monoclonal anti-factor VIII antibodies.

Four monoclonal antibodies against factor VIII, NMC-VIII/1, NMC-VIII/2, NMC-VIII/3 and NMC-VIII/4, were produced. The first three antibodies were of the IgG1 immunoglobulin subclass, while the fourth was IgM. The affinity of each antibody for factor VIII was high and anti-factor VIII clotting activity was detected in NMC-VIII/2, NMC-VIII/3 and NMC-VIII/4. NMC-VIII/1 had no inhibitory effect on factor VIII clotting activity. Immunoblotting using purified intact and thrombin-treated factor VIII identified the antibodies' factor VIII polypeptide specificities. With thrombin-treated factor VIII the factor VIII fragments for NMC-VIII/1 and NMC-VIII/2 were 80 kDa and 54 kDa, respectively, while both NMC-VIII/3 and NMC-VIII/4 recognised a 44 kDa fragment. With intact factor VIII, antibodies NMC-VIII/2-4 bound to polypeptides larger than 90 kDa, especially NMC-VIII/2, which reacted with a chain of 330 kDa thought to be a mature form of factor VIII protein. We also detected a mature form of factor VIII in hepatic sinusoidal endothelial cells by immunoperoxidase staining. Identification of the factor VIII polypeptides bearing these fragments enabled us to clarify the localization of the factor VIII thrombin cleavage site, and suggested the existence of factor VIII in hepatic sinusoidal endothelial cells.

Animals↗

Effect of phosphorus supplementation on bone formation induced by osteosarcoma-derived bone-inducing substance in X-linked hypophosphatemic mice.

In our previous report, we demonstrated normal cartilage and bone matrix formation and a defect of bone mineralization in hypophosphatemic (Hyp) mice using an ectopic bone formation system. That system consisted of an osteogenic sarcoma-derived bone-inducing substance. In this report, we describe the effect of phosphorus supplementation on abnormal bone mineralization. The osteogenic sarcoma-derived bone-inducing substance was implanted in Hyp mice or control mice. The Hyp mice were divided into two groups after implantation. One group was fed a normal laboratory chow, while the other was fed a high-phosphorus diet for 4 weeks of the experimental period. Normal control mice were fed the normal laboratory chow. The mean serum phosphorus level in the high-phosphorus diet group was normal at 2, 3 and 4 weeks after implantation. Using the method of 85Sr incorporation, the high-phosphorus diet group showed marked improvement in bone mineralization at 2 and 4 weeks after implantation, but incomplete improvement at 3 weeks. On the other hand, histological study of the high-phosphorus diet group at 4 weeks after implantation still showed a meaningful amount of the osteoid matrix formation compared to the control. These findings suggest that the abnormal bone mineralization in Hyp mice was mainly due to their abnormally low serum phosphorus level. However, still other abnormalities might exist and these might be responsible for the incomplete improvement in bone mineralization.

Animals↗

Intranasal absorption of salmon calcitonin.

Eight normal subjects and 4 children with osteogenesis imperfecta were administered salmon calcitonin (S-CT) intranasally, and the pharmacokinetics of S-CT were studied. In the normal subjects, the plasma S-CT concentration showed a dose-dependent increase over a dosage range of 200-400 IU. Maximal plasma concentrations were reached 20-60 min after intranasal administration of S-CT. The plasma calcium concentration was significantly decreased 60 min after the administration. In the children, S-CT was also absorbed through the nasal mucosa. This suggests that nasal spraying may be an efficient method for administration of S-CT.

Administration, Intranasal↗

Japanese patients with leukaemia following the use of Thorotrast including a patient with marked chromosomal rearrangements.

It is estimated that 20,000-33,000 persons have been injected with Thorotrast in Japan. By August 1984, 12 patients with leukaemia following the use of Thorotrast have been reported. Their clinical and haematological data indicate that most of the patients were males over 50 years of age and that the most frequent type of leukaemia involved the stem cells common to the granulocytic, erythroid and/or megakaryocytic lines. This assumption was supported by the evidence of marked chromosomal rearrangements in 100% of the cells from the bone marrow in our case. The median latent period from the administration of Thorotrast to the onset of leukaemia in Japan was 35 years, ranging from 16 to 45 years, which indicates that patients who were injected with Thorotrast should be carefully followed up in the future.

Acute Disease↗

In vitro characterization of various factor VIII concentrates.

The in vitro properties of 5 heat-treated Factor VIII (F VIII) concentrates were studied and compared with those of conventional non heat-treated concentrates with special reference to F VIII/von Willebrand Factor (vWF) activities. The heat-treated F VIII concentrates were found to contain about 25 U/ml of F VIII: C as indicated on the label, 59.5-103.3 U/ml of F VIII: Ag, 20.0-74.0 U/ml of ristocetin cofactor activity (RCof), and 67.3-96.0 U/ml of vWF: Ag. The F VIII/vWF activities in the heat-treated concentrates were almost the same as those in the 6 non heat-treated concentrates. The antihemophilic factor (AHF)-cryoprecipitate contained 2.3 U/ml of F VIII: C which was roughly equivalent to the amount of F VIII: Ag. In addition, it contained 7.3 U/ml of RCof which was equivalent to the amount of vWF: Ag. The ratio of F VIII: Ag to F VIII: C in the F VIII concentrates ranged from 2.5 to 4.4. The ratio of vWF: Ag to RCof in the concentrates ranged from 1.1 to 4.8. There were, however, no significant differences in F VIII/vWF activities between the heat-treated and the non heat-treated F VIII concentrates with two exceptions. These findings suggest that the inactivation of the biological activities of F VIII and RCof, and/or the denaturation of both the F VIII: C protein and the vWF protein antigen occurred during the production procedure, while the heat-treatment did not lead to further changes of F VIII/vWF.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗

[Spontaneous calcification in F344/Slc and F344/JCL rats].

F344/Slc and F344/JCL rats 2 years of age were histologically examined for the incidence and distribution of calcification. In the male rats of both strains, calcification was observed in the testis, lung, brain, kidney, heart, aorta, cornea, prostate and seminal vesicle respectively. In the female F344/JCL rats, calcification appeared in the kidney, lung, cornea, brain, stomach, ovary and heart. Among these of both sexes, the lung was one of the most affected organs for calcification. On the other hand, calcification in the kidney was more severe and frequent in the females than in the males, suggesting that the sex may be one of enhancing factors for calcification.

Animals↗

Effect of intrahepatic arterial infusion of 131I-labelled lipiodol on hepatocellular carcinoma of rat.

Intrahepatic arterial infusion of 131I-labelled lipiodol was performed to study the intrahepatic distribution of lipiodol and to determine the radiation effect on 3'-Methyl-4-Dimethylaminobenzene (DAB) induced hepatocellular carcinoma (HCC) in rats. From the findings of the softex films and scintigrams of the liver, according to the time course, lipiodol was found to accumulate in the tumour tissues parallel with the degree of perfusion, and it remained in the tumour tissues for an extended period probably due to the delay of the degradation of lipiodol compared to that in non tumour tissues. It was noticed that the lipiodol, accumulated and deposited selectively in the tumour tissues, existed mostly in the extracellular space but not in the intracellular space. In histological studies of the resected specimens of the tumours, complete necrosis of hepatocellular carcinoma was recognized 2 to 8 weeks after the infusion of 131I-labelled lipiodol, while there was none in the control group where cold lipiodol was employed. These results suggest that the most effect on hepatocellular carcinoma in this study is caused by the radiation effect of 131I-labelled lipiodol.

Animals↗

Bone gamma-carboxyglutamic acid containing protein in the perinatal period.

We measured bone gamma-carboxyglutamic acid-containing protein (BGP), calcium (Ca), phosphorus (P), and alkaline phosphatase (Al-P) in paired maternal and cord sera, and urinary gamma-carboxyglutamic acid (gamma-Gla) in neonates. The circulating BGP was 41.21 +/- 2.47 ng/ml and 7.44 +/- 0.87 ng/ml in the cord (n = 15) and the maternal (n = 14) sera, respectively. The urinary gamma-Gla in the neonates was 147.68 +/- 10.75 mumol/g creatinine (n = 15). The cord serum BGP was significantly higher than the normal adult level. The maternal serum BGP was at the same level as in other adults. It is conceivable that the fetus may produce BGP during gestation, as the cord serum BGP level was significantly higher than the maternal level and there was no correlation between the cord and maternal serum BGP concentrations. The reason for the elevated circulating BGP level in the cord serum is not known, but increased bone turnover may be a factor. The cord serum BGP may include not only carboxylated but also non-gamma-carboxylated GP because of fetal vitamin K deficiency.

1-Carboxyglutamic Acid↗