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Biomedical subjects

M Shiraki

Publications and source records attributed to M Shiraki.

At least 109 records · Page 6Linked to original sources

[Changes in bone mineral density and bone turnover within 12 months after oophorectomy: a prospective study compared with hysterectomized controls].

Nineteen patients (pts) with stage Ib to IIb uterine cervical cancer were studied for changes in bone mineral density and bone turnover within 12 months after radical hysterectomy and pelvic lymphadenectomy. Eleven out of 19 pts also underwent oophorectomy (OX), and the other 8 pts without OX were studied as controls. A significant increase in FSH and decrease in E2 (p less than 0.01) in OX pts indicated the completeness of oophorectomy, whereas no significant change in those levels showed retained ovarian function in the controls. In OX pts significantly increased serum alkaline phosphatase (p less than 0.01), urine-calcium/creatinine (p less than 0.05) and hydroxyproline/creatinine ratio (p less than 0.01) indicating high bone turnover after the oophorectomy were observed. However, a transient but significant (p less than 0.05) rise in these levels in the 3rd month in the controls was noted. In OX pts the spinal bone mineral density (BMD) measured by dual photon absorptiometry was significantly reduced to approximately 10% (p less than 0.05) within 12 months after oophorectomy, while in the controls loss of BMD was also observed up to 6 months, and it appeared to have returned towards baseline levels at 12 months after hysterectomy. These data suggest that a rapid and considerable loss of spinal BMD was mainly accelerated by the oophorectomy, but in part was contributed to by the stress or reduced physical activity for up to 6 months after radical hysterectomy.

Alkaline Phosphatase↗

[Changes in spinal and femoral bone mineral density due to pelvic irradiation following oophorectomy].

Since radiation therapy has been known to be a cause of bone atrophy (radiation osteopathy), it could be important whether postoperative radiotherapy in patients who have undergone oophorectomy further promotes bone mineral loss or not. Nineteen patients with stage Ib to IIb cervical cancer were studied. Eleven of the 19 patients received only surgical treatment and 8 received postoperative radiotherapy (50 grays to the pelvis and 40 grays to the lumber spine), because of the presence of advanced lesions or positive lymphnodes. A significant increase in FSH and decrease in E2 (p less than 0.01) compared to before treatment were observed in both groups. A significant increase in serum alkaline phosphatase activities (p less than 0.01), urine-calcium/creatinine ratio (p less than 0.05) and urine-hydroxyproline/creatinine ratio (p less than 0.01), which indicated high bone turnover, compared to before treatment in both groups also appeared. Although these chemical parameters in both groups changed coincidentally, the decline in spinal bone mineral density in the irradiated group was delayed at 12 months after the treatment. On the other hand, there was no difference in the changes in femoral bone mineral density in the two groups. These results suggest that radiotherapy might inhibit the bone mineral loss at the irradiated bone site even when there was an estrogen lack.

Adult↗

Randomized comparison of doxorubicin and vindesine to doxorubicin for patients with metastatic soft-tissue sarcomas.

Two treatment regimens for metastatic soft-tissue sarcomas were compared in a randomized trial in the cooperative group setting. Histopathologic diagnosis was affirmed by pathology reference panel review in 72% of the 347 patients. In 21% of patients, the reference panel affirmed the diagnosis of soft-tissue sarcoma but disagreed as to type; 7% of patients were ineligible based upon cell type. Of 298 patients evaluable, measurable tumor regression (partial or complete response) occurred in 17% of patients to doxorubicin (70 mg/m2 intravenously) and 18% of patients to doxorubicin (70 mg/m2 intravenously) and vindesine (3 mg/m2 intravenously), each given every 3 weeks. No difference existed in complete response (4% for doxorubicin, 6% for doxorubicin and vindesine) or median survival (9.4 months for doxorubicin, 9.9 months for doxorubicin and vindesine). Overall, 60% of those patients on doxorubicin and vindesine and 46% on doxorubicin experienced a severe or worse toxicity of treatment (P = 0.01). With greater toxicity and lack of any gains in efficacy, the results do not support use of the combination of doxorubicin and vindesine for metastatic soft-tissue sarcomas.

Adult↗

Phase II trial of 6-diazo-5-oxo-L-norleucine versus aclacinomycin-A in advanced sarcomas and mesotheliomas.

Ninety-eight patients with previously-treated advanced soft tissue sarcoma, bone sarcoma, or mesothelioma were randomly assigned to one of two intravenous single-agent treatment regimens, either 6-diazo-5-oxo-l-norleucine (DON; brief infusions of 50 mg/m2/day for 5 consecutive days every 4 weeks) or aclacinomycin-A (ACM-A, as 30-min infusions of 100 mg/m2 or 85 mg/m2, administered every 3 weeks). Of 43 patients who were evaluable for response, survival and toxicity, there were two responses (5%) produced by ACM-A; one in a male with mesothelioma, and one in a female with malignant fibrous histiocytoma. None of the 36 evaluable patients treated with DON developed an objective tumor response. Median survival was 4.8 months in the DON treatment arm, and 6.8 months in the ACM-A treatment arm. No patients on the DON arm experienced lethal or life-threatening toxicities, and severe toxicities resulting from this treatment included nausea and emesis (10%), stomatitis (2%), gastrointestinal toxicity (2%), and anemia (2%). Moderate toxicities included vomiting (24%), hematologic toxicity (24%), neurologic toxicity (7%), diarrhea (7%), mucositis (5%), fever (5%), palpitations (2%), hepatotoxicity (2%), bleeding (2%) and edema (2%). Fifteen percent experienced at least one severe reaction, and 63% experienced at least one moderate or greater toxicity. ACM-A was associated with four cases of life-threatening myelosuppression (7%); severe toxicities included myelosuppression (11%), neurologic toxicity (4%), diarrhea (2%), respiratory toxicity (2%), pain and muscle spasms (2%), edema (2%), and ulceration following extravasation (2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aclarubicin↗

Phase II trial of carboplatin in soft-tissue sarcoma.

As part of the Eastern Cooperative Oncology Group program for the assessment of new drugs in sarcomas, a Phase II trial of carboplatin was performed in patients who had received no more than one prior chemotherapy regimen. A total of 50 patients received either 400 mg/m2 or 320 mg/m2 depending on whether they had received prior radiotherapy. A response rate of 16% (95% confidence interval 6-32%) occurred in the 37 patients who had received doxorubicin as their only prior systemic therapy. Three of the six responses were complete and persisted for 7 to 34 months. In contrast none of the 13 patients who received carboplatin after initial progression on doxorubicin and subsequent progression on interferon alpha responded. The overall response rate was therefore 12% (95% confidence interval 5-24%). Toxicity was primarily hematologic, with 14 patients having Eastern Cooperative Oncology Group (ECOG) grade 3 toxicity and no grade 4 or 5 toxicities. In view of the number of complete responses, carboplatin should be studied further in untreated patients with advanced soft tissue sarcoma.

Adult↗

Prolactin inhibits plasminogen activator activity in the preovulatory follicles.

The present study was designed to determine the effects of PRL on changes in morphology and plasminogen activator (PA) activity in the preovulatory follicles. Rabbit ovaries were perfused with hCG alone or with hCG plus at 10, 10(2), or 10(3) ng/ml. PRL at 10(3) ng/ml directly inhibited the degeneration and decomposition of surface epithelial cells induced by hCG exposure. The subsurface connective tissue was visualized by treatment with sodium dodecyl sulfate, which removed surface epithelial cells from the ovary, thereby exposing collagen fibrils and the basal lamina. Sodium dodecyl sulfate treatment revealed inhibition of connective tissue disruption at the apex of the follicle wall in PRL-treated ovaries. PA activity in mature follicles in perfused rabbit ovaries exposed to hCG increased from 1.40 +/- 0.08 to 28.4 +/- 4.25 IU/g tissue after 4 h of perfusion. The addition of PRL to the perfusate inhibited the hCG-stimulated increase in intrafollicular PA activity in a dose-dependent fashion. Although at 7 h mature follicles treated by hCG alone showed greater intrafollicular PA activity than those treated with hCG plus PRL, this difference was not significant. These results suggest that PRL may act directly by interfering with mechanical events within the ovary that are required for the rupture of mature Graafian follicles, probably via the inhibition of intrafollicular tissue PA activity.

Animals↗

The effects of lipoxygenase products on progesterone and prostaglandin production by human corpora lutea.

The present study was undertaken to assess the effects of the products of the lipoxygenase pathway on steroidogenesis and the production of prostaglandins (PGs) by human corpora lutea in the midluteal phase. In the first experiment luteal cells were cultured with 5-hydroxyeicosatetraenoic acid (5-HETE) at 10, 100, 500, or 1000 ng/mL in the presence or absence of hCG at 100 ng/mL for 10 days. The addition of 5-HETE dose-dependently inhibited progesterone (P) production by the cultural luteal cells. P production stimulated by exposure to hCG was also reduced significantly in response to 5-HETE. However, 5-HETE had no effect on the production of 6-keto-PGF1 alpha, PGF2 alpha, or PGE2 by cultured luteal cells at any point during the culture period. In the second experiment the reaction products of soybean lipoxidase of arachidonic acid (AA-LIP) were added to cultured luteal cells. Treatment with either AA or LIP alone had no effect on basal P production. The addition of AA-LIP at all concentrations tested reduced P production by cultured luteal cells in the presence or absence of hCG. AA-LIP significantly reduced basal 6-keto-PGF1 alpha secretion in cultured luteal cells on day 2. Although the stimulatory effect of AA on luteal PGE2 production was maintained throughout the entire culture period, the lipoxygenase products of AA did not affect AA-stimulated PGE2 production by cultured luteal cell. These results suggest that the products of the lipoxygenase pathway may be important in the involution of human corpora lutea.

Adult↗

[Immunohistochemical localization of the chondroitin sulfate proteoglycan in demineralized rat periodontal tissue].

We investigated the immunohistochemical localization of the chondroitin sulfates (chondroitin-4 sulfate, -6 sulfate and dermatan sulfate) in demineralized rat periodontal tissue using monoclonal antibodies (2-B-6, 3-B-3). Also, fixative and demineralized methods were established using these monoclonal antibodies. The result showed that the most effective combination of fixative and demineralized methods was 2% glutaraldehyde 1% para-formaldehyde and 5% EDTA. Chondroitin-4 sulfate and dermatan sulfate were widespread in gingival connective tissue and periodontal membrane, with an especially strong response of dermatan sulfate shown along collagen fiber bundles. Chondroitin-6 sulfate was located in peripheral blood vessels. In alveolar bone, chondroitin-4 sulfate and dermatan sulfate were found inside Hareversion canals, Volkman's canals and lacunae. Chondroitin-6 sulfate was localized at peripheral blood in alveolar bone. In cementum, chondroitin-4 sulfate and dermatan sulfate were found at lacunae of cellular cementum and a part of embedding Sharpey's fiber.

Animals↗

[Effects of age and gender on serum levels of apolipoprotein A-I, A-II, B, C-II, C-III and E, measured by turbidimetric immunoassay, in normolipidemic Japanese elderly].

Accumulating evidence has suggested significant roles of apolipoproteins in lipoprotein metabolism. Therefore it is important to measure serum levels of apolipoproteins to understand the pathophysiology of lipid metabolism. The newly developed turbidimetric immunoassay (TIA) method for the determination of serum apolipoprotein concentration is the first method which can be employed with autoanalyzer, and is expected to be used widely. The standard values of serum concentrations of apolipoproteins measured by the TIA method for Japanese adults and children have been reported recently, but not yet for the elderly. Therefore, we investigated serum concentrations of apolipoproteins (A-I, A-II, B, C-II, C-III and E) in healthy normolipidemic elderly, aged 65-99 years, in order to obtain the standard values of apolipoproteins for the elderly. The subjects consisted of 84 males and 91 females. They had normal serum values for total cholesterol (TC) (120-220 mg/dl) and triglyceride (TG) (50-150 mg/dl). No one demonstrated clinical, biochemical or haematological evidence of cardiovascular, peripheral-vascular, cerebrovascular, hepatic, renal or endocrine disorders. Between-assay and intra-assay coefficient variations were approximately 5% and approximately 1.5%, respectively, in all apolipoproteins examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

[Effect of aging on bone mineral content. Part VII. The evaluation of osteoporosis treatment by the measurement of total body bone mineral content using dual photon absorptiometry].

In order to evaluate the degree of accuracy of measurement of total body bone mineral content (TBBMC) by dual photon absorptiometry (DPA), the TBBMC in four healthy male volunteers were measured serially for 3 to 12 months. In three to six determinations of TBBMC in various stage of radiation source (153-Gd), the coefficients of variation in four subjects were 1.59, 0.74, 1.25 and 1.27%. Thus, the mean CV was 1.22 +/- 0.35% (mean +/- SD). This indicates that the measurement of TBBMC using DPA is an accurate tool for long-term follow up of bone mineral content and up to 1.6% change of TBBMC might be considered to be a significant change in TBBMC. No apparent drift of TBBMC associated with source decay was noticed in the present study. Subsequently, fifteen females with osteoporosis were studied to evaluate the efficacy of certain therapeutic modes. The patients were divided into two groups. Group 1 (n = 10) given 10 to 40 U of elcatonin (eel calcitonin derivative) intramuscularly every week for 3 to 6 months. Group 2 (n = 5) were treated with 0.5 mu/day of oral 1-alpha-OHD3 for 3 to 6 months. The TBBMC of these fifteen patients were followed by DPA (Lunar DP-4). Seven patients out of ten treated with elcatonin (70%) showed significant (up to 1.6% change in TBBMC compared with baseline) increase in TBBMC after 3 to 6 months treatment. The mean percentage change in TBBMC in group 1 was 101.9 +/- 2.7% (mean +/- SD) when the initial TBBMC was taken as 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

[Diagnostic evaluation of plasma free gamma-carboxyglutamic acid in maintenance hemodialytic patients with renal osteodystrophy].

The levels of serum Bone Gla Protein (BGP) and plasma free gamma-carboxyglutamic acid (free gamma-Gla) were measured in 36 patients on maintenance hemodialysis and compared with conventional parameters of renal osteodystrophy (ROD), such as C-PTH, intact PTH, Al-PIII and hydroxyproline levels in serum, and sigma GS/D. Even though the values of BGP were significantly elevated in patients group, 64.5 +/- 1.74 ng/ml, but the low values within normal range could be found in 3 of 36 patients, also. On the other hand, plasma levels of free gamma-Gla were markedly elevated in all cases as high as 10.40 +/- 3.10 nmol/ml in average compared to 1.29 +/- 0.37 nmol/ml (n = 15) in healthy controls. Comparative analysis of BGP with other parameters showed exclusively significant correlation as follows, C-PTH: r = 0.833 (p less than 0.01), intact PTH: r = 0.702 (p less than 0.01), Al-PIII: r = 0.771 (p less than 0.01), hydroxyproline: r = 0.462 (p less than 0.01), sigma GS/D: r = -0.407 (p less than 0.05). Respective for its higher levels, comparative analysis of plasma levels of free gamma-Gla with other parameters failed to show a significant correlation except for correlation with C-PTH (r = 0.459, p less than 0.01). Based upon these results, we could confirm a marked elevation in plasma levels of free gamma-Gla in all patients, but couldn't point out its clinical value in ROD in this study.

1-Carboxyglutamic Acid↗

[Effects of 5-hydroxyeicosatetraenoic acid (5-HETE) on progesterone and prostaglandin production by human corpora lutea].

The present study was undertaken to assess the effects of 5-hydroxyeicosatetraenoic acid (5-HETE) on steroidogenesis and prostaglandin (PG) production in cultured luteal cells derived from human corpora lutea in the mid-luteal phase. The luteal cells were cultured with 5-HETE at 10, 100, 500, or 1,000 ng/ml in the absence or presence of hCG at 100 ng/ml for 10 days. The addition of 5-HETE to the culture media did not affect growth curves of cultured luteal cells. 5-HETE significantly inhibited progesterone (P) production by cultured luteal cells in a dose-related fashion on day 2. P production stimulated by exposure to hCG was also reduced significantly in response to 5-HETE. The addition of 5-HETE did not affect estradiol production by cultured luteal cells. The production of 6-keto-PGF1 alpha by cultured luteal cells in the presence of 5-HETE was slightly but not significantly less than that observed in the absence of 5-HETE. However, 5-HETE affects neither PGF2 alpha nor PGE2 production by cultured luteal cells throughout the culture period. The present study demonstrates that 5-HETE inhibits P production in cultured luteal cells by a mechanism(s) other than through PG production. These data suggest the involvement of a lipoxygenase pathway in the synthesis of P and 6-keto-PGF1 alpha of luteal cells.

Adult↗

Immunohistochemical study of chondroitin sulfate and dermatan sulfate proteoglycan in dental pulp and dentin.

We investigated the localization of chondroitin sulfate and dermatan sulfate proteoglycans in the dental pulp and dentin of rats, using a combination of an immunohistochemical technique coupled with specific enzymatic digestion. Chondroitin 4-sulfate and dermatan sulfate were found to be widespread in pulpal connective tissue, predentin and dentinal tubules. The response to predentin was found to be particularly strong. Chondroitin 6-sulfate was stretched in pulpal connective tissue and predentin, but showed only a weak response.

Animals↗

[Possible involvement of leukotriene B4 on human luteal function: special reference to determination of leukotriene B4 produced by cultured luteal cells].

The present study was undertaken to determine the production of leukotriene B4 (LTB4) by cultured human luteal cells in the mid-luteal phase using a reverse phase column (C8). The luteal cells were cultured with or without hCG at 100 ng/ml for 8 days. In the preliminary experiment, methods for extracting culture media samples were assessed prior to radioimmunoassay. Reverse phase column C8, but not C18, made possible the determination of LTB4 produced by human luteal cells. Progesterone (P) production by cultured luteal cells reached its maximum on day 4 following exposure to hCG, and then declined gradually. The concentrations of LTB4 produced by luteal cells varied from 100 to 500 pg/10(5) cells/2 days. However, exposure to hCG did not affect LTB4 production by cultured luteal cells. The level of LTB4 in culture medium (115.0 +/- 37.8 pg/10(5) cells/2 days) was reduced on day 4, but increased thereafter. LTB4 production appeared to decrease concomitantly with increased P production of cultured luteal cells. In conclusion, cultured luteal cells produced considerable amounts of LTB4 throughout the entire culture period. These results suggest that lipoxygenase activity of luteal cells may be closely related to steroidogenic potential.

Adult↗

Progesterone protects oocytes from premature degeneration within the follicle.

The present study was designed to determine the effects of gestrinone (R2323) in the process of follicle rupture and oocyte maturation and degeneration in an in vitro perfused rabbit ovary model. In the first experiment, R2323 at 10(2), 10(3), or 10(4) ng/ml was added to the perfusate of one ovary. The contralateral control ovary was perfused simultaneously with medium alone. Thirty minutes after the onset of perfusion, 50IU of human chorionic gonadotropin (hCG) was added to the perfusate of both ovaries. All ovaries exposed to R2323 plus hCG or hCG alone ovulated. The addition of R2323 to the perfusate did not affect the ovulatory efficiency of ovaries treated with hCG. No significant difference in the percentage of ovulated ova or follicular oocytes demonstrating germinal vesicle breakdown was seen with R2323 treatment. R2323 increased the degeneration rate of ovulated ova in a dose-dependent fashion. In the second experiment, in which experimental ovaries were perfused with R2323 (10(4) ng/ml) plus progesterone (10(3) ng/ml) and the control ovaries with R2323 (10(4) ng/ml) alone ovulation occurred in response to hCG. However, the addition of progesterone to the perfusate reduced the degeneration-inducing effect of R2323 on both ovulated ova and follicular oocytes. In conclusion, R2323 appears to act as an antiprogesterone, thereby promoting the degeneration of oocytes. The increased production of progesterone in the preovulatory follicle following the gonadotropin surge protects oocytes from premature degeneration within the follicles.

Animals↗

Involvement of plasminogen activator activity in the process of ovulation.

The present study was undertaken to determine the changes in follicular plasminogen activator (PA) activity during ovulation. In the first experiment, hCG (100 IU) administration in vivo enhanced PA activity in mature follicles within 1 hour. PA activity reached its maximum at 4 hours and then declined. A second peak occurred 8 hours after hCG administration. In the second experiment, the effects of an ovulatory dose (50 IU) of hCG on ovulatory efficiency and PA activity were assessed in mature and immature follicles with an in vitro perfused rabbit ovary preparation. Ovulatory efficiency in immature follicles was significantly less (p less than 0.01) (16.7 +/- 4.5%) than that in mature follicles (86.7 +/- 11.0%). During the perfusion, the growth of mature follicles was observed but not that of immature follicles. PA activity in mature follicles derived from unstimulated ovaries was 1.43 +/- 0.17 IU/g tissue. PA activity in mature follicles (28.4 +/- 4.2 IU/g tissue) 4 hours after in vitro exposure to hCG was significantly greater (p less than 0.01) than that found in immature follicles. In conclusion, exposure to gonadotropin stimulates PA activity in preovulatory follicles. Failure to increase PA activity in immature follicles impairs follicular development, resulting in reduced ovulatory efficiency. The increase in PA activity observed in ovulatory follicles implicates the plasmin-generating system in follicle rupture.

Animals↗

[The effect of 1,25(OH)2D3 on bone mineral content in senile osteoporosis--a dose-finding study].

In order to clarify the effect of 1,25(OH)2D3 on the bone mineral content in senile osteoporosis, we examined the radial mineral density in 41 female cases of senile osteoporosis treated with 1,25(OH)2D3. The diagnostic criteria of senile osteoporosis were as follows. 1) Radial mineral density at below 0.5 g/cm2 by SPA 2) Bone dystrophy score in vertebra at over I degree 3) Presence of vertebral fracture 4) Over 60 years of age The subjects were divided into 5 groups: a control group (n = 11), a 0.25 microgram of 1,25(OH)2D3 once-a-day group (n = 5), a 0.5 microgram of 1,25(OH)2D3 once-a-day group (n = 8), a 0.25 microgram of 1,25(OH)2D3 twice-a-day group (n = 8) and a 0.25 microgram of 1,25(OH)2D3 three times-a-day group (n = 9). There was no significant difference in background data among these groups except for serum Al-P activity. The radial mineral density was measured in these 5 groups before and every 3 months after, starting the treatment by single photon absorptiometry in 1/3 distal site of radius for 1 year. No significant difference was detected in the serum levels of Ca, Pi and Al-P activity after starting the treatment among the 5 groups. The area under curve (AUC) of the radial mineral content after the treatment was calculated in each group. There was a significant dose-related increase in the AUC (p less than 0.05). However, the urinary Ca/Cr ratio was increased in the group receiving 0.75 microgram/day of 1,25(OH)2D3 The final AUC in the group receiving 0.5 microgram/day of 1,25(OH)2D3 tended to be very high compared with that in the other groups. From the above, it was suggested that 1,25(OH)2D3 might be effective for the treatment of senile osteoporosis especially at the dose of 0.5 microgram/day.

Absorptiometry, Photon↗