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Biomedical subjects

M Shiraki

Publications and source records attributed to M Shiraki.

At least 91 records · Page 5Linked to original sources

The ultra long-term treatment of senile osteoporosis with 1 alpha-hydroxyvitamin D3.

We have attempted to examine the effects of long-term treatment with 1 alpha-hydroxyvitamin D3 (1 alpha-OHD3; 0.5-1.0 microgram/day) on bone and chemical parameters in osteoporosis, retrospectively. Twenty-six pairs of age-, period of observation- and initial bone mineral density-matched patients with or without treatment were selected from 86 patients with osteoporosis. An 11% decrease (-2.2%/year) and a 6% increase in radial mineral density at the peripheral cortical bone site was observed in the control and the treated group after 5 years, respectively (P < 0.05-0.01). There were no patients who showed hypercalcemia nor an abnormally high blood urea nitrogen (BUN) level in both groups. These results indicate that 1 alpha-OHD3 treatment in osteoporosis is effective and has no serious adverse effects. Although the facts were obtained from observations only at the peripheral cortical bone site, 1 alpha-OHD3 treatment may be considered as a potential mode of therapy for osteoporosis.

Aged↗

ELISA detection of glycosaminoglycan (GAG)-linked proteoglycans in gingival crevicular fluid.

The purpose of this study was to develop an ELISA method to detect chondroitin sulfate isomer-linked proteoglycans in gingival crevicular fluid (GCF), and to elucidate the role played by the glycosaminoglycans (GAGs) in GCF during experimentally-induced periodontitis in dogs. Experimental periodontitis was induced by placement of a silk ligature below the gingival margin of the molar teeth in 3 mongrel dogs. GCF was collected using microcapillary tubes at 0, 7, 21 and 60 days after ligature placement. To compare with GAG in GCF, bovine nasal cartilage proteoglycan monomer, dog's serum and supernatant of homogenized gingival tissue were prepared. Combination of monoclonal antibodies, 3B3 and 9A2, and specific enzymatic digestion made possible the identification of chondroitin 4 sulfate (C4S), chondroitin 6 sulfate (C6S) and dermatan sulfate (DS). The ELISA method detected very small amount of chondroitin sulfate (CS) isomers (15-1000 ng/ml of bovine nasal cartilage proteoglycan). The ELISA value of CS isomers in GCF was lower than that of homogenized gingival tissue but higher than that of the serum. The ELISA value of C4S, C6S and DS, although fluctuating, increased in proportion to the severity of the inflammation.

Animals↗

Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas.

PURPOSE: This three-armed phase III study in adults with advanced soft tissue sarcomas was planned as a comparison of objective regression rates, toxicity, and survival of patients receiving doxorubicin alone, ifosfamide plus doxorubicin, and mitomycin plus doxorubicin plus cisplatin. PATIENTS AND METHODS: Between December 1987 and July 1990, 279 patients with histologically confirmed sarcomas were enrolled to receive treatment A (doxorubicin 80 mg/m2), treatment B (ifosfamide 7.5 g/m2 plus doxorubicin 60 mg/m2), or treatment C (mitomycin 8 mg/m2 plus doxorubicin 40 mg/m2 plus cisplatin 60 mg/m2). RESULTS: Of 262 assessable patients, 74 (29%) achieved objective tumor regression. Objective regression occurred in 20% of the 90 patients who received doxorubicin alone (complete remission [CR] rate, 2%), in 34% of the 88 who received ifosfamide plus doxorubicin (CR rate, 3%), and in 32% of the 84 who received mitomycin plus doxorubicin plus cisplatin (CR rate, 7%). With grade 3 or greater myelosuppression in 53% of group A, 80% of group B, and 55% of group C, regimen B was significantly more myelosuppressive than either regimen A or C (P = .01) with two, three, and one treatment-related deaths, respectively. Synovial sarcomas were responsive to ifosfamide plus doxorubicin, especially among patients younger than 40 years of age. CONCLUSION: Ifosfamide plus doxorubicin produced a significantly higher regression rate (P = .03) than did doxorubicin alone; however, this was achieved at a level of myelosuppression significantly more intense than that produced by the single agent or by the three-drug combination. Mitomycin, doxorubicin, and cisplatin also appeared to be more active than the single agent; however, at a myelosuppression level similar to that of doxorubicin alone, this trend (P = .07) did not attain the usual level for significance. No significant survival differences were observed.

Adult↗

Risk factors for development of retinopathy in elderly Japanese patients with diabetes mellitus.

OBJECTIVE: To define the risk factors for the development of diabetic retinopathy in elderly patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: We studied 110 diabetic outpatients > 60 yr of age who were free of diabetic retinopathy at the first visit and were followed for at least 5 yr to examine the relationships between the initial findings and the subsequent development of retinopathy. RESULTS: A total of 49 of the subjects developed diabetic retinopathy during the follow-up period; of these, 4 patients progressed to preproliferative and 3 to proliferative retinopathy. Univariate analysis showed that the initial fasting plasma glucose levels, the HbA1 values, the 2-h postload plasma glucose levels, the estimated duration of diabetes, and the presence of persistent proteinuria were all associated with the development of diabetic retinopathy. However, age at the initial examination, estimated age at diabetes onset, sex, body mass index, type of therapy, and hypertension had little impact on the development of retinopathy. Stepwise multiple Cox regression analysis revealed that the initial HbA1 or fasting plasma glucose, the diabetes duration, and the presence of persistent proteinuria are significant independent predictors for the development of retinopathy. CONCLUSIONS: Initial fasting plasma glucose, diabetes duration, and proteinuria are important risk factors for the development of retinopathy in elderly patients with diabetes mellitus.

Age Factors↗

Ovarian serous borderline epithelial tumors with multiple retroperitoneal nodal involvement: metastasis or malignant transformation of epithelial glandular inclusions?

One of four patients who underwent lymph node excision at exploration for ovarian serous borderline epithelial tumor (OSBT) at Baystate Medical Center was found to have FIGO Stage III C lesion associated with extensive ovarian external (surface) papillary growth, peritoneal implants in the omentum and cul-de-sac, and involvement of multiple pelvic and periaortic lymph nodes by the tumor. Histologically, the lymph nodes showed an admixture of endosalpingeal glandular inclusions with neoplastic tissue identical to the ovarian tumor. The exact histogenesis and the prognostic significance of the nodal involvement by OSBT are still not fully understood. Although there is a small number of reported cases of lymph node involvement associated with OSBT, they are described as examples of nodal metastases or independent primary foci of malignant transformation. This paper presents an interesting association of OSBT with extensive pelvic and periaortic nodal involvement and reviews the relevant literature.

Adult↗

Phase II trials of interferons-alpha and -beta in advanced sarcomas.

Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha 2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c.t.i.w. In the second study, patients received IFN-beta ser 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta ser. Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha 2b and 17% of patients receiving IFN-beta ser. Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies.

Adult↗

Changes in bone mineral density and fracture prevalence in Japanese women after oophorectomy.

The bone changes after gynecological surgery during the early phase of recovery were examined. The subjects were randomly selected from women who had undergone bilateral oopho-hysterectomies (OOX, n = 98, 46.0 +/- 5.0 year-old) or hysterectomies (HX, n = 75, 43.6 +/- 4.6 year-old) within 4 years prior to entering the study. The ovarian functions in the HX group were presumed to be intact following the hysterectomies, judging from the cytological evaluation of the vaginal pap smears. The bone morphological changes in both groups were examined to measure the cortical thickness of the metacarpal bone (MCI) on hands X-ray film using microdensitometry, and the posterior/anterior height ratios (P/A ratio) of the entire vertebral bodies, on vertebral X-ray films using a digitizer. The changes in bone mineral densities in both groups were measured by dual energy X-ray absorptiometry at lumbar vertebrae (L2-4 BMD) and by microdensitometry at the metacarpal cortical bone; the bone densities of metacarpal bone were referenced by the density of aluminum step wedge on the same X-ray films. The prevalence of vertebral body fractures (P/A ratio greater than 1.4) in the OOX group (5.1%) was 3.9 times higher than that in the HX group (1.3%). There was a significant decrease in MCI in the OOX group compared with the HX group (p less than 0.01). L2-4 BMD in the OOX and HX group were 1.07 +/- 0.15 and 1.16 +/- 0.13 g/cm2, respectively (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sandwich immunoassay for intact human osteocalcin.

To overcome the problems of limited-region specificity associated with conventional radioimmunoassay (RIA), we developed a sandwich enzyme immunoassay (EIA) for intact human osteocalcin (hOC). For this EIA we used antibodies to the N- and C-terminal regions of hOC that were raised against an N-terminal 20-residue peptide and a C-terminal 7-residue peptide, both synthetic. Immunoassay profiles of tryptic digests of hOC and serum from patients with renal failure, fractionated by reversed-phase HPLC, facilitated direct demonstration of the region specificity of this method. A preliminary study of serum osteocalcin concentrations in patients with renal failure further confirmed this specificity, showing lower positive rates obtained by this method than by conventional RIA. The cross-reactivity data of hOC with bovine and rat osteocalcins by the sandwich method indicated its species specificity. These studies demonstrate the superior specificity of this sandwich EIA compared with conventional RIA and thus confirm its potential diagnostic superiority.

Adult↗

[Time course changes in bone mineral density and calcium metabolism after oophorectomy].

Time course changes in bone mineral density and calcium metabolism after oophorectomy were investigated in comparison with those in hysterectomized and pre-operated women, retrospectively. A total of 191 women who had a regular menstrual period for 1 year prior to entering the study or to the operation, were divided into 3 groups; group 1 consisted of 33 women who were admitted to receive a gynecological operation (pre-OP group), group 2 consisted of 57 women who received hysterectomy within 5 years prior to entering the study (HX group) and group 3 consisted of 101 women who received hysto-oophorectomy (bilateral) at the same timing as the HX group (OOX group). All the subjects had their bone mineral density measured at the lumbar vertebrae (L2-4BMD) by means of dual energy X-ray absorptiometry (DXA) and at the metacarpal bone by the microdensitometrical (MD) method. Serum and urinary parameters related to bone and calcium metabolism were also evaluated. After dividing the subjects in accordance with the length of time after the operation, the time course changes in each parameter were calculated. In the 2 years after OOX, the L2-4BMD decreased significantly and rapidly, and the change in L2-4BMD in the subsequent period was quiescent. In the HX group, there was no significant change in L2-4BMD. When the period after the OOX was divided into 2 subcategories in accordance with the speed of decline in lumbar BMD as the rapid and the slow phases, the time course changes in blood and urine parameters showed different trends.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

[The effect of estrogen and, sex-steroids and thyroid hormone preparation on bone mineral density in senile osteoporosis--a comparative study of the effect of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) on senile osteoporosis].

In order to assess the effect of sex steroids on bone mineral density in Japanese with senile osteoporosis, the bone mineral density in 1/3 distal site of radius was measured serially before and after treatment for 2 years using single photon absorptiometry. Sixty seven old females with senile osteoporosis were divided into 4 groups, Group 1 (n = 28, mean age; 74.4 +/- 1.3 y.o., mean +/- SEM) was the control group, Group 2 (n = 14, mean age; 73.7 +/- 1.7 y.o.) was treated with 0.5-1.0 micrograms/day of 1 alpha -OHD3, Group 3 (n = 12, mean age; 75.4 +/- 2.9 y.o.) was treated with conjugated estrogen (Premarin) in a dose of 0.3125 mg/day (3 approximately 4 weeks administration followed by 1 week rest) and Group 4 (n = 13, mean age; 76.4 +/- 1.8 y.o.) was treated with sex-steroids (pregnenolone : androstenedione : androstenediol : testosterone : estrone = 1.0 mg : 1.0 mg : 0.5 mg : 0.1 mg : 5 micrograms/tablet) and thyroid hormone (thyroid-sicca 7.5 mg/tablet) preparation in a dose of 2 tablets/day. When the radial bone mineral density (RMD) before the treatment was taken as 100%, RMDs of each group at 6, 12, 18 and 24 months were 96.4 +/- 3.1%, 97.3 +/- 2.0%, 93.7 +/- 2.1% and 96.1 +/- 1.8% in Group 1, 100.8 +/- 2.8%, 106.4 +/- 2.1%, 101.3 +/- 3.4% and 108.8 +/- 2.9% in Group 2, 103.0 +/- 2.8%, 106.2 +/- 3.5%, 105.9 +/- 4.3% and 100.2 +/- 4.7% in Group 3, 105.3 +/- 2.2%, 104.7 +/- 2.3%, 112.6 +/- 6.4% and 112.1 +/- 6.7% in Group 4, respectively. Therefore, significant increases in RMD were observed in Groups 2, 3 (transient) and 4 when compared with Group 1. In Group 3, serum level of parathyroid hormone (PTH) was significantly (p less than 0.05) increased from 0.28 +/- 0.03 ng/ml before the treatment to 0.55 +/- 0.15 ng/ml at 24 months after the treatment. In Group 2, transient (6 months after the treatment) but significant (p less than 0.01) increase in urinary Ca/Creatinine ratio from 0.15 +/- 0.04 to 0.20 +/- 0.03 was found. Serum A1-P activities in Group 4 was shown to increase transiently from 131 +/- 10 IU to 151 +/- 12 IU (p less than 0.05) at 6 months and to 158 +/- 13 IU (p less than 0.01) at 12 months followed by subsequent decrease to 135 +/- 6 IU at 18 months and 133 +/- 10 IU at 24 months after the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Vitamin E and the susceptibility of erythrocytes and reconstituted liposomes to oxidative stress in aged diabetics.

A remarkable increase in the permeability of erythrocyte ghosts and liposomal membranes composed of erythrocyte lipids from aged diabetics was revealed by measuring [14C]glucose leakage. There were no significant differences in the contents of free cholesterol or phospholipids, or in the cholesterol/phospholipid ratio between diabetic and normal erythrocyte membranes, but significantly higher amounts of unsaturated fatty acids, arachidonic acid and docosahexaenoic acid were observed in the erythrocyte membranes of diabetics. Reconstituted liposomes prepared from aged diabetic erythrocyte lipids were highly susceptible to superoxide-induced oxidative stress. Vitamin E was highly effective in suppressing the peroxidative lysis of liposomes composed of diabetic erythrocyte lipids. The effect of superoxide dismutase (SOD) on the inhibition of peroxidation of unsaturated lipids within liposomal membranes was less than that of vitamin E.

Aged↗

Calcium requirement in elderly Japanese women.

In order to evaluate calcium requirements (RC) in Japanese elderly women, a calcium balance study was carried out in 9 osteoporotics (73.9 +/- 2.7 years old, mean +/- SE) and 9 normal elderly women (67.0 +/- 2.5 years old). Diet containing 700 mg/day of calcium were given for at least 1 week. Then, diets containing approximately 700 mg/day (722.5 +/- 91.9 mg/day) of calcium in the 1st week and 1,474 mg/day of calcium in the 2nd week were served. The amount of calcium intake to maintain zero balance, defined as daily RC, was 550.4 +/- 50.0 and 648.8 +/- 44.7 mg/day in normal and osteoporotic subjects, respectively. There was no statistically significant difference between these two groups. Although the recommended daily allowance (RDA) for the adult Japanese is 600 mg/day, our study suggests that RDA in the elderly Japanese should be 847 mg.

Aged↗

Involvement of leukotriene B4 in ovulation in the rabbit.

The present study was undertaken to assess the effects of lipoxygenase products on ovulation, oocyte maturation, and steroid production in the perfused rabbit ovary preparation. Ovulatory efficiency was significantly reduced when rabbit ovaries were perfused with human CG (hCG) plus nordihydroguaiaretic acid (NDGA) at 10(-5) or 10(-6) M, as compared to contralateral hCG-treated controls. The addition of NDGA to the perfusate inhibited hCG-induced ovulation in a dose-related manner. The percentage of ovulated ova and follicular oocytes achieving germinal vesicle breakdown did not differ significantly between NDGA-treated ovaries and contralateral controls. Leukotriene B4 (LTB4) production by the perfused rabbit ovaries reached its maximum 6 h after exposure to hCG and then declined. The addition of NDGA at 10(-5) M significantly inhibited hCG-stimulated LTB4 production by rabbit ovaries throughout the entire perfusion periods. The ovulatory efficiency in ovaries treated with hCG alone or with hCG plus NDGA correlated significantly with LTB4 production by perfused rabbit ovaries 6 h after exposure to hCG (alpha = 0.8893, P less than 0.01). Furthermore, the addition of LTB4 at 100 ng/ml to the perfusate reversed the inhibitory effects of NDGA on hCG-induced ovulation. However, exposure to NDGA affected neither progesterone nor estradiol production elicited by hCG administration. These results suggest that NDGA may block hCG-induced ovulation in vitro, probably via the inhibition of LTB4 production by rabbit ovaries.

Animals↗

Relation between body size and bone mineral density with special reference to sex hormones and calcium regulating hormones in elderly females.

We studied the relation between body size and bone mineral density in elderly females. The study included a total of 93 ambulatory females aged over 60 years. They were divided into 3 groups according to their body mass index (BMI; kg/m2): slender group with BMI less than 20 (n = 28), normal group with BMI of 20 to 24.9 (n = 43) and obese group with BMI greater than or equal to 25 (n = 22). Fracture incidence, bone mineral density, calcium regulating hormones and steroid hormones were studied in an intergroup comparative manner. The incidence of vertebral fracture was found to be negatively correlated with BMI (the incidences of vertebral fracture in slender, normal and obese were 78.6, 48.8 and 22.7%, respectively) and bone mineral density was also BMI-related (0.390 +/- 0.016, 0.456 +/- 0.015 and 0.493 +/- 0.018 g/cm2, respectively: p less than 0.01 in ANOVA; mean +/- SE). The number of years after menopause was shorter in patients with a higher BMI. There was no intergroup difference in serum levels of PTH, vitamin D and estrogens. On the other hand, serum levels of calcitonin, DHEA, DHEAS, delta-4 androstenedione and testosterone were found to be higher in subjects with a higher BMI. From the present results, it seems that bone mineral density is supported not only by weight-bearing stress upon bone, but also by serum levels of calcitonin and androgens in obese females.

Age Factors↗

[The characteristics of metabolic acidosis in aged patients with chronic renal failure].

The present study was designed to clarify the characteristics of metabolic acidosis in aged patients with chronic renal failure. The subjects consisted of ambulatory cooperative patients (19 males and 18 females). Their values of creatinine clearance (Ccr) varied from 6.8 to 107.5 ml/min/1.73 m2. The relationship of Ccr to acid-base and electrolyte disturbances was investigated. The estimations of normal values in acid-base and electrolyte composition were based on the method of Hoffmann. The results are summarized as follows: 1. A high incidence of metabolic acidosis was demonstrated in patients whose Ccr values were below 20 ml/min/1.73 m2. 2. A significant positive correlation of Ccr values and plasma levels of bicarbonate (p less than 0.001) and a significant inverse correlation of Ccr values and serum levels of chloride (p less than 0.01) were observed. 3. The values of the anion gap did not change, irrespective of Ccr values. 4. Serum concentrations of potassium were inversely correlated with plasma levels of bicarbonate (p less than 0.01). Hyperchloremic normal anion gap acidosis with hyperpotassemia was the characteristic feature of metabolic acidosis in aged patients with chronic renal failure. The normal anion gap could be explained by normophosphatemia or mild hyperphosphatemia, even in the patients with advanced renal failure.

Acid-Base Equilibrium↗