[Regulatory control and physiopathology of the hypothalamic pituitary system].
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Biomedical subjects
Publications and source records attributed to A Shimazu.
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The purpose of this study was to investigate the relationship between changes in parathyroid hormone (PTH) receptor levels and chondrocyte maturation during endochondral ossification. Chondrocytes were isolated from the growth plate of rabbit ribs and maintained in the presence of 10% serum in mass cultures. Treatment with PTH-(1-84) and a PTH-(1-34) fragment suppressed the increases in alkaline phosphatase activity and in type X collagen and 1 alpha,25-dihydroxyvitamin D3 receptor levels and abolished 45Ca incorporation into mineral, all of which occurred in parallel untreated cultures in the hypertrophic (terminal) stage. These effects of PTH were observed at low concentrations (10(-10) to 10(-9) M) and within 24-48 h of treatment. PTH-(1-84) and PTH-(1-34) also increased [35S]sulfate incorporation into newly synthesized proteoglycans. In contrast, the middle and carboxyl-terminal fragments of PTH tested had little effect on proteoglycan synthesis or terminal differentiation. The binding of 125I-PTH-(1-34) to cells in the growth plate was greater than that to cells in liver, skin, muscle, brain, or kidney. When the correlation between binding levels and stage of maturation was examined, we found that 125I-PTH-(1-34) binding to its 72-kDa receptor was low in resting and proliferating chondrocytes, increased 10-fold in matrix-forming chondrocytes, and thereafter decreased in hypertrophic chondrocytes both in vitro and in situ. Scatchard analysis revealed that the changes in PTH binding were due to changes in the number, and not in the affinity, of the receptor. The changes in PTH-(1-34) binding paralleled those in [35S]sulfate incorporation into proteoglycans. These findings suggest that stage-dependent increases in PTH/PTH-related peptide receptor levels localize the hormone stimulation of proteoglycan synthesis and inhibition of precocious hypertrophy in the matrix-forming zone of growth plates.
The Kanagawa Rehabilitation Hospital was established by Kanagawa Prefecture 20 years ago. The hospital has a 40 bed SCI unit and has been providing comprehensive medical and rehabilitation services for SCI patients of this prefecture. A letter of enquiry to 404 major surgical units within this prefecture revealed that 630 SCI patients had been under care in this prefecture during a period of 3 years. Of these, the Frankel grade A, B and C patients, were assumed to be rehabilitation candidates, totalling about 130 in this prefecture per year. The inpatient medical record revealed that we treated 770 SCI patients from 1986 to 1991. From this data, we estimated that the hospital accepted an average of 54.5 SCI patients per year for rehabilitation purposes. Other inpatients were rehospitalised for various complications. According to the study of 125 patients who were hospitalised for comprehensive rehabilitation, they waited an average of 139 days and stayed in the hospital for 288 days. The increasing number of chronic patients who required treatment of complications appeared to be delaying the early admission of rehabilitation patients. The medical treatment cost for those with spinal cord injuries was less than that for the average patient with other types of medical conditions.
Three patients with metastatic thyroid follicular carcinoma developed thyrotoxicosis. Two had mild T3 toxicosis without detectable TSH binding inhibitor immunoglobulins (TBII) or thyroid stimulating antibodies (TSAb). Considerable concentration of 131I by tumours occurred, although serum TSH was undetectable. The third patient developed thyrotoxicosis several months after treatment with 131I had commenced and this was associated with concurrent increase in both TBII (90%; normal, less than 11%) and TSAb (2100%). We conclude that thyrotoxicosis in patients with metastatic thyroid carcinoma may result from a large bulk of tumour functioning either autonomously or after stimulation by TSH receptor antibodies.
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OBJECTIVE: To investigate the effects of hyaluronic acid (HA) on the release of proteoglycan by cultured rabbit chondrocytes. METHODS: Articular cartilage chondrocytes were isolated from the knee joints of New Zealand white rabbits. Proteoglycan synthesis after incubation with HA was determined by measuring 35S-sulfate incorporation. Cells incubated with HA were labeled with 3H-glucosamine and applied to a Sepharose CL-2B column. After incubation of confluent cells with 35S-sulfate and then with HA in various concentrations in the presence or absence of cytokines, proteoglycan release from the cell matrix layer was measured. RESULTS: HA (M(r) 3 x 10(5) to 19 x 10(5)), at 10 micrograms/ml to 1 mg/ml, had little effect on the incorporation of 35S-sulfate or 3H-glucosamine into cartilage matrix proteoglycans, or on the hydrodynamic size of proteoglycan monomers, in rabbit chondrocyte cultures. However, at 10-1,000 micrograms/ml, HA suppressed the release of 35S-proteoglycans from the cell matrix layer into the medium in the presence and absence of interleukin-1, tumor necrosis factor alpha, or basic fibroblast growth factor. CONCLUSION: These results suggest that HA is a potent inhibitor of the displacement of matrix proteoglycan into culture medium.
Residual dorsal tilt is one of the main deformative factors in the malunion of fractures of the distal radius. We investigated the effect of such tilt on the range of wrist motion and on carpal alignment in a cineradiographic study of wrist motion in 30 patients with extra-articular Colles' fracture. With increased dorsal tilt, the range of wrist motion became more restricted and abnormalities of carpal alignment during wrist motion became apparent. When the dorsal tilt was less than 10 degrees, the effects on the range of motion and on the dynamic carpal alignment were small.
To see if symptoms such as sensory disturbance or numbness worsen during exercise as is thought to occur in entrapment neuropathy, we studied the interaction between sensory and muscle nerve fibres in a mixed nerve in cats. Stimulation electrodes were placed on both the deep (muscle) and superficial (sensory) branch of the radial nerve at the elbow. High frequency stimulation at 100 Hz was applied to one branch for five minutes and the nerve action potential of the other branch was recorded at the axilla where the radial nerve is mixed. The stimulation decreased the amplitude of the nerve action potential and prolonged its latency. Recovery from these changes was gradual, and changes were the same whichever branch was stimulated. When a cat's leg was made ischaemic, the changes were more pronounced. The changes in the nerve action potential may have arisen from ischaemia in the nerve, possibly caused by high frequency stimulation.
Three patients were treated for coronary artery-pulmonary artery fistula. Each was asymptomatic due to a coronary artery fistula. There was one instance each of myocardial infarction, mitral stenosis and a large closed ruptured aneurysm including a thrombus. All the fistulas were comprised of several small plexiform arranged vessels. The left to right shunt ratio was approximately 8 percent or less. A surgical operation was performed to close the drainage orifice of the fistulas through pulmonary arteriotomy under cardiopulmonary bypass in two patients while one patient underwent a ligation of a large abnormal vessel to the aneurysm followed by a resection of the aneurysm without cardiopulmonary bypass. A large saccular aneurysm of such fistulas is rare and a rupture of such an aneurysm is even more rare. The surgical management of coronary artery fistulas is also discussed herein.
Phosphoenolpyruvate phosphomutase (PEPPM) catalyzes C-P bond formation by intramolecular rearrangement of phosphoenolpyruvate to phosphonopyruvate (PnPy). We purified PEPPM from a gram-negative bacterium, Pseudomonas gladioli B-1 isolated as a C-P compound producer. The equilibrium of this reaction favors the formation of the phosphate ester by cleaving the C-P bond of PnPy, but the C-P bond-forming reaction is physiologically significant. The C-P bond-forming activity of PEPPM was confirmed with a purified protein. The molecular mass of the native enzyme was estimated to be 263 and 220 kDa by gel filtration and polyacrylamide gel electrophoresis, respectively. A subunit molecular mass of 61 kDa was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the native protein was a tetramer. The optimum pH and temperature were 7.5 to 8.0 and 40 degrees C, respectively. The Km value for PnPy was 19 +/- 3.5 microM, and the maximum initial velocity of the conversion of PnPy to phosphoenolpyruvate was 200 microM/s/mg. PEPPM was activated by the presence of the divalent metal ion, and the Km values were 3.5 +/- 1.4 microM for Mg2+, 16 +/- 5 nM for Mn2+, 3.0 +/- 1.5 microM for Zn2+, and 1.2 +/- 0.2 microM for Co2+.
A new polypeptide inhibitor, AI-409, that inhibits human salivary alpha-amylase, was purified from a fermentation broth of Streptomyces chartreusis strain No. 409. This protein consists of a single-chain polypeptide of 78 amino acid residues, and includes two disulfide bridges. The primary structure of AI-409 and the locations of the disulfide bridges were identified by enzymatic digestion and the automatic Edman technique. Enzymatic digestion was done with trypsin, carboxypeptidase Y, and chymotrypsin. One of the disulfide bridges was between Cys(10) and Cys(26), and the other between Cys(44) and Cys(71).
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As a result of screening for inhibitors of glycerol-3-phosphate dehydrogenase, which may be effective to prevent corpulence, we isolated two inhibitors named adipostatin A and adipostatin B from the culture broth of Streptomyces cyaneus 2299-SV1. Their structures have been established to be 5-n-pentadecylresorcinol and 5-isopentadecylresorcinol, respectively. Adipostatin A and adipostatin B inhibited glycerol-3-phosphate dehydrogenase at the IC50 values of 4.1 microM and 4.5 microM, respectively. These compounds prevented triglyceride accumulation in 3T3-L1 cells at a concentration of the microM level.
Possible enhancement of myocardial protection by adding DBcAMP and oxygenation of a crystalloid cardioplegic solution (CCS) was evaluated in a three group study. The patients having coronary bypass operation or valvular operation were divided into three groups, each consisting of 15 patients, and differing only in the type of CCS employed. Group I was protected by nonoxygenated CCS (PO2 190 mmHg, PCO2, 32 mmHg, pH 7.78, K 30 mmEq/L), Group II by adding DBcAMP to nonoxygenated CCS and Group III by adding DBcAMP to oxygenated CCS (PO2 790 mmHg, PCO2 26 mmHg, pH 7.87). Group III had significantly improved CI and double product (p less than 0.05) compared with Group II. However, CPK, CPK-MB, and myoglobin in the serum were similar in each group. Lactate and pyruvate ratio (L/P) in the coronary sinus bloods were improved to lower value after the pump than before the pump only in Group III. Base excess in the coronary sinus held on alkalosis after aortic declamp only in Group III. The refunction time was significantly shortest with Group III than with other groups (p less than 0.01, 0.05) and Group II was significantly shorter than Group I (p less than 0.05). It is concluded that oxygenation and adding DBcAMP to CCS are effectual for the myocardial metabolism and protect the myocardial damage during cardiac arrest.
Rat cartilage tissue was found to produce two types of proteoglycan monomers distinguished by density gradient centrifugation under dissociative condition and with different molecular size (PG I and PG II) as observed in cultured rabbit costal chondrocyte and human cartilaginous tissues. The incorporation of 35S-sulfate and distribution of the molecular size of proteoglycan (PG) were studied to determine the differentiated phenotypes of chondrocyte in adjuvant induced arthritis of rats. The cartilaginous tissue from the acute inflammatory phase shows a low incorporation of 35S-sulfate into PGs but produce the same hydrodynamic size as that of the control. After that acute phase the incorporation recovered suggesting of a repair phase. But in the chronic phase both the incorporation and the produced hydrodynamic size of PGs were severely alternated. With our method this paper shows the drastic alternation about the cartilaginous properties of rat chondrocytes under these circumstances.
Basic fibroblast growth factor (bFGF) stimulates proliferation of chondrocytes and their extracellular matrix synthesis but inhibits terminal differentiation to hypertrophic cells (Kato, Y., and Iwamoto, M., (1990) J. Biol. Chem. 265, 5903-5909). In the present study, we examined changes in bFGF binding during chondrocyte cytodifferentiation. In cultures of pelleted growth plate chondrocytes, binding of 125I-bFGF to 140-kDa receptors was observed during the mitotic and matrix-forming stages but decreased to a very low level as chondrocytes became hypertrophic. Scatchard plot analysis showed that the decrease in binding of bFGF was due to a decrease in the number not in the affinity of the receptor. The loss of bFGF receptor was associated with a decrease in biological responses to bFGF. On the other hand, the binding of transforming growth factor-beta and epidermal growth factor was constant throughout all stages of growth plate chondrocytes. A rapid decrease in bFGF binding was not observed with articular chondrocytes or bFGF-exposed growth plate chondrocytes, perhaps because they scarcely underwent terminal differentiation. A decrease in bFGF binding associated with terminal differentiation in situ was also demonstrated by examination of sequential slices of growth plates. These observations suggest that rapid reduction in bFGF receptor is a special event during terminal differentiation.
A 44 year old man underwent successful surgery for a thoracoabdominal aortic aneurysm using a permanent bypass graft and aneurysmoplasty. This technique reduces visceral ischemia to a minimum and the aneurysmoplasty, through total preservation of the intercostal and lumbar arteries, can avoid paraplegia caused by spinal cord ischemia. Our technique is recommended as it can be performed easily, safely, and effectively without heparinization, temporary shunts or bypass perfusion.
To measure the pressure distribution in the radiocarpal joint, a biomechanical study was done with fresh cadavers and pressure-sensitive film. With a load of 100 newtons, the contact locations were identified for 27 different wrist positions and the peak articular pressures and contact area were measured. Normal wrists were studied first, then modified to show different ulnar variances, and then to be models of malunited Colles' fractures of increasing severity. The contact locations of the scaphoid and the lunate were separate, and the mean peak articular pressures were 2.8 and 2.7 megapascals, respectively, for the normal wrists. In the radiolunate articulation, this mean increased by 27% with 2.5 mm ulnar minus variance and decreased by 22% with 2.5 mm ulnar plus variance. In the models of malunited Colles' fracture, the contact locations shifted from volar to dorsal, and the contact area decreased as the deformity became worse.