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Biomedical subjects

T Ohishi

Publications and source records attributed to T Ohishi.

At least 37 records · Page 2Linked to original sources

The relationships between the degree of beta-isomerization of type I collagen degradation products in the urine and aging, menopause and osteoporosis with fractures.

We have evaluated the effect of aging, menopause and osteoporosis on the measurements of both nonisomerized type I collagen C-telopeptide breakdown products (alpha-CTx) by radioimmunoassay (RIA) and beta-isomerized type I collagen C-telopeptide breakdown products (beta-CTx) by enzyme-linked immunosorbent assay (ELISA). In 86 premenopausal healthy women (PRE), 144 postmenopausal healthy women (POST), 74 patients with vertebral fractures (VX) and 61 patients with hip fractures (HX), urinary CTx excretion was measured by both ELISA and RIA assays. Samples were collected more than 6 months after fracture in the VX group and within 48 h after fracture in the HX group. In all subjects a highly significant correlation was found between alpha-CTx and beta-CTx (r = 0.85). The values of beta-CTx in the POST group greatly increased compared with those in the PRE group (% mean increase: 82%), while the values of alpha-CTx in the POST group moderately increased compared with those in the PRE group (% mean increase: 47%). The values of both alpha-CTx and beta-CTx in the HX group were significantly higher than those in the other groups, but particularly the increase in mean alpha-CTx (211% for HX versus POST) was very high compared with the increase in mean beta-CTx (68% for HX versus POST). Moreover, the alpha-CTx/beta-CTx ratio in the HX group was significantly higher than in the other groups. These results suggest that both assays well reflect the increase in bone resorption associated with high bone turnover, especially, in osteoporotic patients with hip fracture. However, there was a difference between the urinary excretion of alpha-CTx and beta-CTx in patients with hip fracture, so the alpha-CTx/beta-CTx radio might be a good indicator reflecting the characteristics of bone metabolism for osteoporosis with hip fracture.

Adolescent↗

Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time.

OBJECTIVE: Whether patients, who have lost bone mass, can be restored to age-matched control levels by some means is still controversial. We investigated how the thyroid status after antithyroid drug therapy for various periods of time affects bone metabolism in patients with hyperthyroidism by assessing currently used biochemical markers of bone turnover and distal radius bone mineral density (BMD). DESIGN AND PATIENTS: The biochemical markers of bone turnover and BMD at the distal one third of the radius were measured in 79 women with hyperthyroidism treated with antithyroid drugs for various periods of time. The patients were divided into two groups according to thyroid function at the time of study: a hyperthyroid group (serum thyroid stimulating hormone (TSH) < 0.4 mU/l) and an euthyroid group (TSH 0.4-4.0 mU/l). Second, each group was further divided according to the duration of therapy: short-term (less than 3 years) and long-term (3 or more years). MEASUREMENTS: Urinary type I collagen degradation products (CTx) were measured by the CrossLapsTM ELISA kit. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured by high performance liquid chromatography (HPLC) after acid hydrolysis. Serum N-mid osteocalcin (OCN-mid) was measured by a recently developed enzyme-linked immunosorbent assay. Serum alkaline phosphatase (ALP) was determined by routine laboratory methods. Bone mineral density (BMD) at the distal one third of the radius was measured using dual energy X-ray absorptiometry (DEXA; DCS-600EX, Aloka, Tokyo). RESULTS: There were statistically significant positive correlations of FT3 and FT4 with the biochemical markers of bone turnover. There were significant negative correlations between the biochemical markers and BMD only in patients undergoing long-term therapy. In a comparison between hyperthyroid and euthyroid groups based on duration of treatment (long-term and short-term), and in a comparison without regard for length of treatment (all patients), it was evident that ALP and CTx levels were significantly higher in the hyperthyroid than in the euthyroid groups. Significantly lower BMD Z-scores in the hyperthyroid group compared to those in the euthyroid group were observed only in patients undergoing long-term therapy. CONCLUSIONS: Urinary type I collagen degradation products were a sensitive marker for evaluating the bone turnover in patients with hyperthyroidism. Our data suggested that it might be important to control the levels of TSH within normal ranges during long-term antithyroid drug therapy in order to prevent bone loss.

Adult↗

Adaptation of Comamonas testosteroni TA441 to utilization of phenol by spontaneous mutation of the gene for a trans-acting factor.

Comamonas testosteroni TA441 adapts to utilization of phenol upon incubation with phenol as the major carbon source. Strain TA441 has a cluster of genes (aphKLMNOPQB) encoding the catabolic enzymes phenol hydroxylase and catechol 2,3-dioxygenase, and a divergently transcribed regulatory gene (aphR), but these genes are silent until adaptation occurs. We found another regulatory gene (aphS) downstream of aphR. AphS belongs to the GntR family of transcriptional regulators. All adapted strains were found to have mutations in the aphS gene or in the aphR-aphS intervening region. The adapted strains expressed phenol hydroxylase and catechol 2, 3-dioxygenase activity in the presence of phenol. The transcriptional activity of both the aphK and the aphR promoters was elevated in the adapted strains. A strain whose aphS gene was artificially disrupted was found to be able to grow using phenol, and the cells showed high levels of the above-mentioned transcriptional and enzymatic activities, indicating that adaptation was caused only by the mutation in the aphS gene. Gel retardation analysis revealed that AphS bound to two specific sites in the promoter region between aphK and aphR. These results indicate that the active aphS gene product acts as a trans-acting factor and represses transcription of the aph genes in strain TA441.

Adaptation, Physiological↗

Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: comparison with generalized osteoarthritis.

OBJECTIVES: To compare plasma levels of matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) between patients with knee osteoarthritis and normal subjects, to investigate whether the degree of knee joint involvement is related to those measurements, and to compare patients with and without generalized osteoarthritis. METHODS: Eighty-three women with knee osteoarthritis (OA patients) were studied. Plasma levels of MMP-3, MMP-9 and TIMP-1 were measured by enzyme immunoassays. Knee and hand radiographs were taken of all patients. The joints of the knee and hand were graded from 0 to 4 according to Kellgren and Lawrence criteria. All OA patients were divided into a generalized OA (GOA) group (n = 37) and a knee OA (KOA) group (n = 46) according to Doherty's criteria. MMPs and TIMP were also measured in 19 normal subjects. RESULTS: Plasma levels of MMP-3 and TIMP-1 were significantly higher in OA patients than in normal subjects. In contrast, MMP-9 was lower in OA patients than in normal subjects. Plasma levels of MMP-3 and MMP-9 were not influenced by the grade of knee OA. TIMP-1 was influenced by the grade of knee OA. Plasma levels of MMP-3 were significantly elevated in GOA compared to KOA. In contrast, there were no significant differences in plasma levels of MMP-9 and TIMP-1 between GOA and KOA. CONCLUSION: Since the plasma level of MMP-3 in GOA was higher than that in KOA patients, it may be a superior indicator for whole-joint degeneration.

Aged↗

Genetic organization and characteristics of the 3-(3-hydroxyphenyl)propionic acid degradation pathway of Comamonas testosteroni TA441.

Comamonas testosteroni TA441 degrades 3-(3-hydroxyphenyl)propionate (3HPP) via the meta pathway. A gene cluster required for degradation of 3HPP was cloned from strain TA441 and sequenced. The genes encoding six catabolic enzymes, a flavin-type hydroxylase (mhpA), extradiol dioxygenase (mhpB), 2-keto-4-pentenoate hydratase (mhpD), acetaldehyde dehydrogenase (acylating) (mhpF), 4-hydroxy-2-ketovalerate aldolase (mhpE) and the meta cleavage compound hydrolase (mhpC), were found in this cluster, encoded in this order. mhpD and mhpF were separated by two genes, orf4 and orf5, which were not necessary for growth on 3HPP. The gene mhpR, encoding a putative transcriptional activator of the IcIR family, was located adjacent to mhpA in the opposite orientation. Disruption of the mhpB or mhpR genes affected growth on 3HPP or trans-3-hydroxycinnamate. The mhpB and mhpC gene products showed high specificity for 3-(2,3-dihydroxyphenyl)propionate (DHPP) and the meta cleavage compound produced from DHPP, respectively.

Aldehyde Oxidoreductases↗

Biochemical markers of bone turnover do not decline after menopause in healthy women.

OBJECTIVES: To investigate the duration of high bone turnover after menopause in normal healthy women. DESIGN: Study recruited from three screening studies for health care in the elderly held in the area of Hamamatsu city. SETTING: Department of Orthopaedic Surgery, Hospital at Hamamatsu University School of Medicine, Hamamatsu. PARTICIPANTS: Ninety-two healthy postmenopausal women aged 47-81 years and 18 premenopausal women. MAIN OUTCOME MEASURES: Bone mass was determined by densitometry of the spine and the os calcis, or by ultrasound of the os calcis. Biochemical markers of bone turnover were measured including total and bone-specific alkaline phosphatase, osteocalcin, C-terminal propeptide of type I procollagen, free deoxypyridinoline and urinary degredation products of type I collagen. RESULTS: All markers except the C-terminal propeptide of type I procollagen were significantly higher in early postmenopausal women than in premenopausal women. Postmenopausal women were divided into four groups according to years since menopause. There was no difference in biochemical markers among those women in whom years since menopause were 1 to 5, 6 to 15, 16 to 25 and >26. There were no correlations between biochemical markers and age in postmenopausal women. When the postmenopausal women were divided into three groups according to t-scores of bone mass, there was no significant difference in the biochemical markers among the groups. CONCLUSIONS: High bone turnover occuring after menopause lasts for >25 years during the postmenopausal period.

Aged↗

[A case of advanced gallbladder cancer responding to neoadjuvant intra-arterial chemotherapy].

The patient was a 52-year-old female who had been diagnosed as advanced gall bladder cancer by various imaging studies. The cancer responded to neoadjuvant intra-arterial chemotherapy and was curatively resected. Since cancer had invaded the median widely, the posterior and the lateral segments of the liver according to CT imaging, neoadjuvant chemotherapy was used. The combination chemotherapy included intra-arterial chemotherapy (CDDP 10 mg + 5-FU 250 mg/day/week x5 times, EPI 10 mg + 5-FU 250 mg/day/week x3 times) through the hepatic artery and oral chemotherapy (UFT 300 mg/day for 106 days). No severe side effects were found during this chemotherapy. Imaging studies after the chemotherapy showed a partial response (PR) and curative resection (hepato-pancreato-duodenectomy with regional lymph nodes dissection) could be performed successfully. She has been disease-free without any sign of recurrence for 18 months after surgery. We conclude that this combination chemotherapy will be useful for advanced gall bladder cancer if the appropriate combinations, dosages, and administration routes are chosen.

Adenocarcinoma↗

[A case of recurrent ampullary carcinoma of the papilla of Vater, in which a complete response was induced by combination therapy using radiotherapy and oral chemotherapy employing UFT and cyclophosphamide].

A 38-year-old male patient underwent a pylorus-preserving pancreatoduodenectomy for an ampullary carcinoma of the papilla of Vater. One year after surgery a regular examination with CT and an echogram revealed a solitary recurrent tumor at a lymph node near the superior mesenteric artery. He was treated with radiotherapy at a total of 60 Gy and chemotherapy with UFT at 300 mg/day daily and oral administration of cyclophosphamide at 50 mg/day every other day. Four months after the initiation of the therapy the tumor had completely disappeared and the objective response was evaluated as a CR. The patients is now disease-free and continues to be treated with oral UFT and cyclophosphamide on an outpatient basis.

Administration, Oral↗

Urinary excretion of type I collagen degradation products in healthy women and osteoporotic patients with vertebral and hip fractures.

We have evaluated both the effect of normal aging and menopause on urinary CrossLapstrade mark (u-CTx) excretion and the bone resorption status by u-CTx in patients with vertebral fracture and hip fracture. In 246 healthy women, 76 patients with vertebral fracture, and 63 patients with hip fracture, u-CTx excretion was measured by ELISA. The age-related changes of u-CTx in healthy females reflected the marked increase of bone resorption associated with modeling at childhood. The values in the subgroups of postmenopausal women 1-3 years since menopause and </=10 years since menopause were significantly higher than those in the subgroups of premenopausal adult women. The values in the vertebral fracture group were significantly higher than those in the premenopause group, but not those in the postmenopause groups. The values in the hip fracture group were significantly higher than those in the other groups. Of the 70 postmenopausal subjects aged 45-64 years, 43% had u-CTx values more than 2 SD above premenopausal mean. The corresponding values in the patients with vertebral fracture and those with hip fracture were 58% and 64%, respectively. This marker reflects well the increase of bone resorption associated with bone modeling at childhood and with high bone turnover after menopause. The excretions in the patients with hip fracture were much higher than those in the age-matched subjects and also higher than those in the patients with vertebral fracture. These findings indicate that the abnormality of bone resorption in the patients with hip fracture is more severe than in the patients with vertebral fracture.

Adolescent↗

Changes of biochemical markers during fracture healing.

The aim of this study was to evaluate the changes of biochemical markers during fracture healing in patients with osteoporosis. The study included 26 patients; 9 underwent hip hemiarthroplasty (mean age +/- SD: 71.0 +/- 10.2 years, group EN) for femoral neck fractures. 7 underwent osteosynthesis (75.3 +/- 8.2 years, group OS) for trochanteric fractures, and 10 subjects had spinal compression fractures (68.2 +/- 12.0 years, group CO). No operative procedures were performed in group CO. Urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr) by high performance liquid chromatography (HPLC), Crosslaps by both enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA) (CTx-ELISA and CTx-RIA) and serum N-terminal mid-fragment osteocalcin (OCN-Mid) by ELISA were analyzed at the time of admission and at weeks 1, 2, 4, 8 and 24 after operation or, in the case of group CO, after admission. As a whole, bone resorption markers started to increase from week 1, with various peak values between weeks 4 and 8 depending upon the particular marker, but returned to the initial vales at week 24. OCN-Mid started to increase from week 8 and remained at elevated levels at week 24. In groups EN and OS, bone resorption markers changed in the same manner as they did as a whole group. OCN-Mid did not change in group EN, although it increased significantly from week 8 in group OS. No biochemical markers changed significantly in group CO. In conclusion, bone resorption was accelerated at an early stage due to acute osteonecrosis or bed rest, followed by bone formation due to callus or mechanical stress later on. As far as bone resorption markers are concerned, 24 weeks are enough to eliminate the effect of fracture.

Aged↗

Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with immune complex-mediated glomerulonephritis in chronic active EB virus infection.

Renal involvement is rare in chronic active Epstein-Barr (EB) virus infection. We report a case of a 7-year-old girl with recurrent EB virus infection. She had fever, lymphadenopathy, hepatosplenomegaly, and persistently high titres of IgG to EB virus capsid antigen (VCA) and IgG to EB early antigen with low titres of IgM to VCA. She showed mild haematuria and proteinuria, but had no symptoms of renal failure. Renal biopsy revealed immune complex-mediated glomerulonephritis, which may have been due to a persistently high titre of antibody against EB virus. In addition, a peculiar form of tubulointerstitial nephritis was found. The morphology was characterized by a papillary infolding of the tubular epithelial cell layer into the tubular lumen. The interstitium was surrounded by the infolded epithelium and contained a large number of B-cell dominant lymphocytes. EBV-encoded RNA 1 (EBER-1) gene was detected in the nuclei of some tubuloepithelial cells by in situ hybridization and may have been associated with the pathogenesis of tubulointerstitial nephritis.

Biopsy↗

Circadian variation of urinary type I collagen crosslinked C-telopeptide and free and peptide-bound forms of pyridinium crosslinks.

This study was performed to investigate the circadian variation of urinary CrossLaps (CTx), which was the type I collagen peptide released during bone matrix degradation, and peptide-bound and free forms of urinary pyridinium crosslinks. Urine was obtained during the 24 h of the study in seven separate collections as follows: from 23:00 h to the first void (FV) followed by FV at 11:00, 11:00-14:00, 14:00-17:00, 17:00-20:00, 20:00-23:00, and 23:00 h to FV the next morning. Total, free, and peptide-bound pyridinoline (Pyr) and deoxypyridinoline (Dpyr) excretion measured by high-performance liquid chromatography (HPLC) and CTx measured by enzyme-linked immunosorbent assay in nine premenopausal women aged 22-40 years and nine osteoporotic women aged 65-83 years was analyzed. Among three parameters of Pyr measured by HPLC, a significant day and night difference was found only in total Pyr (21.9% higher at night than during the day in premenopausal women and 24.0% in osteoporotic women, whereas no significant day and night variation was found in free and peptide-bound Pyr in either group. In contrast, total and peptide-bound Dpyr were significantly (37.9% and 66.9%) higher at night than those during the day in premenopausal women (38.0%) and osteoporotic women (48.8%). For free Dpyr, there were no day and night differences in the two groups. The day and night variances were significantly greater in peptide-bound Dpyr than with total Dpyr in both groups. In urinary CTx, a significant circadian variation with a peak at night and a nadir at 17:00 h was found (p < 0.0001) (premenopausal was 54.0% higher at night than during the day; osteoporotic was 38.4%. In conclusion, urinary CTx represented remarkable circadian variation compared with urinary pyridinium crosslinks measured by HPLC. Furthermore, free pyridinium crosslinks did not undergo a circadian variation. Peptide-bound crosslinks might contribute mostly to the circadian variation of total excretion of pyridinium crosslinks.

Adult↗

Urinary collagen crosslinks reflect further bone loss of femoral neck in osteoporotic patients undergoing vitamin D therapy.

Bone mineral density (BMD) of the lumbar (L2-LA) spine and femoral neck was measured annually for 2 years (3 times beginning at the beginning of year 1 and after each subsequent year) in 39 female patients with osteoporosis undergoing 0.5 or 1.0 microg daily doses of vitamin D therapy. At the time of the first BMD measurement, biochemical markers including serum alkaline phosphatase (ALP), urinary pyridinoline (Pyr), deoxypyridinoline (Dpyr) and hydroxyproline (Hyp) were also measured. Urinary Pyr and Dpyr correlated with the percent changes of femoral neck BMD measurements taken the year following the sampling (Pyr: r=-0.622, p<0.001, Dpyr: r=-0.385, p<0.05). Only urinary Pyr correlated with the percent changes of femoral neck BMD measurements taken the following 2 years (r=-0.532, p<0.05). Neither serum ALP nor urinary Hyp correlated with the percent changes of spine or femoral neck BMD measurements taken the year or 2 years after the sera and urine sampling. In summary, we believe urinary Pyr and Dpyr can reflect subsequent bone loss of the femoral neck BMD having been measured only once during the course of a year.

Alkaline Phosphatase↗

[Estimation of probiotics by infection model of infant rabbit with enterohemorrhagic Escherichia coli O157:H7].

We examined the preventative effect against enterohemorrhagic Escherichia coli O157:H7 (EHEC) infection in rabbits on administration of probiotics contained in Streptococcus faecalis, Clostridium butyricum and Bacillus mesentericus. The probiotics were administered to 5 days old Japanese white rabbits throughout the experiment. Inoculation of 10(6) colony forming units (CFUs) of EHEC per rabbit was tried 8 days after birth. Three days after EHEC inoculation, in the control group (not administered probiotics), diarrhea was observed in approximately 80% of the rabbits, on the other hand, in the group administered probiotics, rabbits showed diarrhea in 15%. In necropsy, the number of EHEC in the contents of the cecum and the number of attaching and effacing (AE) lesions were fewer in the probiotics group than in the control group. These results suggest that infant rabbits are useful as a colitis model for EHEC, and the probiotics are effective for the prevention of the growth of EHEC in the intestine and for diarrhea.

Animals↗

Application of in situ hybridization technique for quantitative assessment of ongoing symptomatic Epstein-Barr virus infection after living related liver transplantation.

For quantitative assessment of ongoing symptomatic Epstein-Barr virus (EBV) infection in pediatric recipients of liver transplantation, we determined the number of peripheral blood mononuclear cells (PBMC) infected by EBV by in situ hybridization (ISH) and related the results with clinical courses of those patients. Twenty-four patients had symptomatic EBV infection between February 1995 and March 1996. Blood samples were obtained from these 24 patients at the time of acute phase, from 13 of them during convalescence, and 37 pediatric patients before transplantation. ISH was performed on the PBMC and polymerase chain reaction (PCR) on DNA from whole blood. Oligonucleotide probes for ISH were chosen from coding sequences of EBV-encoded small nuclear RNA 1 (EBER1). Results of ISH were reported in a number of cells expressing EBER1/5 x 104 PBMC (#EBER1). Fever, diarrhea, upper respiratory symptoms, pleural effusion, ascites, lymphadenopathy, and lymphoproliferative disease (LPD) accompanied with EBV infection proven by serology, viral-specific stain or PCR were regarded as EBV related diseases (EBVD). All samples with positive #EBER1 were accompanied by positive EBV PCR. #EBERI was 68.2 +/- 144.9 (mean +/- SD) ranging from 0 to 621 in the acute phase, 0.20 +/- 0.41 ranging from 0 to 2 in the convalescence phase, 0.27 +/- 0.77 in 23 preoperative patients with positive serology, and 0 in all 14 preoperative patients with negative serology. The #EBER1 in ongoing EBVD was significantly greater than that of patients in convalescence or before transplantation. Patients with #EBERI greater than 10 had a significantly lower chance of convalescence and a higher mortality than patients with #EBER 1 less than 10. We conclude that #EBER1 could be a specific and quantitative marker of EBVD and might predict progression to LPD.

Child↗

Promoter structure-dependent functioning of the general transcription factor IIE in Saccharomyces cerevisiae.

General transcription factor (TF) IIE is an essential component of the basal transcription complex for protein-encoding genes, which is widely conserved in eukaryotes. Here we analyzed requirement for TFIIE for transcription in vivo by using yeast Saccharomyces cerevisiae cells harboring mutations in the TFA1 gene encoding the larger one of the two subunits of TFIIE. Deletion analysis indicated that the N-terminal half of Tfa1 protein has an essential function to support the cell growth. In a temperature-sensitive tfa1 mutant cell, the steady-state level of bulk poly(A)+ RNA decreased rapidly at the restrictive temperature. Surprisingly, levels of several mRNAs, whose transcription is directed by the promoters lacking the typical TATA sequence, were not affected in the mutant cells at that temperature. This promoter-specific functioning of TFIIE was reproduced in a cell-free system composed of TFIIE-depleted nuclear extracts. These results strongly suggest that requirement for TFIIE varies in each gene depending on the promoter structures in vivo.

Fungal Proteins↗