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Biomedical subjects

M Sugimura

Publications and source records attributed to M Sugimura.

At least 55 records · Page 3Linked to original sources

Recycling of urea associated with the host plant urease in the silkworm larvae, Bombyx mori.

Urea concentration and urease activity in the midgut content were compared between larvae of the silkworm, Bombyx mori fed an artificial diet and those fed fresh mulberry leaves. A considerable amount of urea was found in the midgut content of the both larvae, however it was significantly lower in the larvae fed fresh mulberry leaves than in the larvae fed the artificial diet; average urea concentrations in the midgut content of the larvae fed fresh mulberry leaves and the artificial diet were 2.9 and 4.6 &mgr;mol/g, respectively. Urea in the midgut content seems to be secreted from the insect itself since the amount of urea in both diets were negligibly small. Urease activity was detected only in the midgut content of the larvae fed fresh mulberry leaves but not in other tissues of the larvae. On the other hand, no urease activity was detected in the midgut content of the larvae fed the artificial diet. Subsequently, to elucidate the role of mulberry leaf urease in the midgut lumen, larvae that had been reared on the artificial diet were switched to fresh mulberry leaves. The diet switch caused a rapid decrease in urea concentration in the midgut content and an increase in ammonia concentration in the midgut content, suggesting that secreted urea could be hydrolyzed to ammonia by mulberry leaf urease in the midgut lumen. Furthermore, to investigate the physiological significance of mulberry leaf urease on urea metabolism of the silkworm, (15)N-urea was injected into the hemocoel, and after 12 h the larvae were dissected for (15)N analysis. A considerable amount of (15)N was found to be incorporated into the silk-protein of the larvae fed fresh mulberry leaves, but there was little incorporation of (15)N into the silk-protein of the larvae fed the artificial diet. These data indicate that urea is converted into ammonia by the action of mulberry leaf urease in the midgut lumen and used as a nitrogen source in larvae fed mulberry leaves.

Journal Article↗

Induction of preeclampsia like phenomena by stimulation of sympathetic nerve with cold and fasting stress.

The purpose of this study was to examine the effect of cold-stress, fasting stress and cold plus fasting stress on the sympathetic nerve activity. Pregnant and nonpregnant rats were kept in cold environment (0 degrees C), or fasting condition (12 h), and cold plus fasting condition for 2 weeks. Their plasma corticotrophin releasing factor (CRF), catecholamines, insulin levels, and platelets were measured, and histological examinations were performed. In cold plus fasting stress rats, a significant increased CRF, epinephrine (E), norepinephrine (NE), and insulin levels with decreased platelet count (P<0.0001) were observed compared with control. Histological study revealed that diffused enlarged glomeruli with fibrin deposition in the kidney, hemostasis, ischemic necrosis and fibrin deposition in liver and swelling along with hemorrhagic necrosis in adrenal gland of cold plus fasting stress rats. The biochemical and histological changes in cold plus fasting, cold-stressed or fasting rats were similar to human preeclampsia. The findings observed in cold plus fasting stress rats were more pronounced either than cold-stressed or fasting group. These results demonstrate that cold plus fasting stress is an intense stimulator of sympathetic nervous system than either cold stress or fasting.

Adrenal Glands↗

Eruption speed and rate of angulation change of a cyst-associated mandibular second premolar after marsupialization of a dentigerous cyst.

The purpose of this study was to investigate the eruption speed and rate of angulation change of a cyst-associated mandibular second premolar after marsupialization of a dentigerous cyst in preadolescents. Premolars on the cyst and noncyst sides and size of the cyst were retrospectively examined with a total of 42 pairs of normalized panoramic radiographs in 20 patients who underwent neither extraction nor orthodontic traction of the cyst-associated mandibular second premolar after marsupialization. Sixteen premolars at the intraosseous eruption stage in a total of 9 preadolescents without cysts were also examined. The eruption speed and rate of angulation change of the cyst-associated mandibular second premolar were significantly faster than those of the premolars without cysts, and significantly correlated with the diminishing rate of the cyst size, which rapidly decreased for the first 3 months after marsupialization. In addition, the eruption speed of the cyst-associated mandibular second premolar correlated with that of the premolar on the noncyst side, and the rate of angulation change inversely correlated with the level of root formation. The results suggest that a cyst-associated permanent tooth erupts more rapidly regardless of the level of root formation and size and type of the cyst, and the abnormally tilted tooth axis improves more rapidly for the first three months after marsupialization of a dentigerous cyst in preadolescents.

Bicuspid↗

Preoperative concurrent chemoradiotherapy plus radical surgery for advanced squamous cell carcinoma of the oral cavity: an analysis of long-term results.

Locoregionally advanced squamous cell carcinomas of the head and neck continue to be a major clinical problem. We demonstrated in 1996 that preoperative concurrent cisplatin- or carboplatin-based chemotherapy and radiotherapy plus radical surgery in advanced oral cancer had minimal toxicity, had high clinical tumor response rates, was well tolerated and produced impressive complete response rates and a high 5-year survival rate. The purpose of the present study was the long-term follow-up of this treatment regimen for advanced oral carcinoma. Forty-eight patients with squamous cell carcinoma of the oral cavity (including soft palate) were treated preoperatively with cisplatin- or carboplatin-based chemotherapy in combination with simultaneous irradiation to a target volume of 40 Gy, and 2-6 weeks later underwent curative surgery. All patients with advanced Stage II (n=7), Stage III (n=22) and Stage IV (n=19) were treated and followed for an average of 7.2 years (range: 61-144 months). The overall actuarial survival of all patients was 81.3% at 5 years and also at 10 years. Progression-free survival at both 5 and 10 years was 84.8% for all patients, and 85.7% for Stage II, 90.0% for Stage III, and 78.9% for Stage IV patients. Progression-free survival rates according to the histopathologic regression grade of primary tumor following preoperative chemoradiotherapy at 10 years were 40. 0% for Grade IIa, 88.9% for Grade IIb, 100% for Grade III, and 87.5% for Grade IV. Patients who achieved good responses histopathologically (Grades IIb, III, IV) had superior survival rates in comparison to patients with extensive residual tumor (Grade IIa) in surgically resected specimens (p=0.0012). A better histologic regression grade was also associated with a higher survival rate even in the long-term analysis. This treatment regimen for advanced oral cancer produced high clinical and pathologic complete response and survival rates with an acceptable acute toxicity profile and lack of late therapeutic complications. The long-term follow-up showed gratifying results even for advanced oral cancers without a substantial increase in distant metastasis and second primary malignancy.

Adult↗

A new treatment of severe pre-eclampsia by long-term epidural anaesthesia.

We hypothesised that long term epidural anaesthesia suppresses sympathetic overactivity in pre-eclampsia. Two equal groups of severe pre-eclamptic patients were treated either with long-term epidural anaesthesia (epidural group) or bed rest, diet control, and an antihypertensive drug (control group). After 7 days of epidural block, mean arterial blood pressures decreased, platelet count and serum total protein increased in all cases while proteinuria decreased in four cases. All patients treated with a long-term epidural therapy continued their pregnancies for more than 3 weeks after admission. The infants in the epidural group had 1-min Apgar scores above 8, a body weight of 2240+/-310 g (mean +/- s.d.) and normal neonatal progress. In contrast, the pregnancies of eight patients in the control group were terminated within 2 weeks of admission due to severe pre-eclampsia or foetal distress, the birth weight of the infants was 1590+/-380 g (mean +/- s.d.) and four had neonatal distress. Progressive worsening in the mean arterial pressure, proteinuria, platelet count and serum total protein was found in these patients. Long-term epidural anaesthesia suppresses the sympathetic hyperactivity and thus improves pre-eclamptic condition which may open a new treatment in case of progressive severe pre-eclampsia.

Adult↗

Annexin V inhibits phosphatidylserine-induced intrauterine growth restriction in mice.

To investigate the role of phosphatidylserine (PS) derived from the activated platelets in placental circulation, we established an artificial PS-induced intrauterine growth restriction (IUGR) model in mice and examined whether annexin V, a PS-binding anticoagulant protein, could prevent the development of IUGR in the animal experiments. The ICR mice were injected in the tail vein on days 8, 11 and 14 of pregnancy with filtered PS/phosphatidylcholine (PC) microvesicles (<0.3 microm in maximal diameter). The microvesicles have a procoagulant activity which was inhibited by annexin V in a dose-dependent fashion. The mice were killed on day 18 of pregnancy and the placental and fetal weights were measured. The placental tissue specimens were examined microscopically. PS/PC vesicles induced significant reductions in fetal weights compared with PC vesicles alone. The placental tissue revealed severe congestion with fibrin depositions although the lung and kidney tissue specimens showed minimal histological changes. PS/PC microvesicles with recombinant annexin V showed no significant reductions in fetal weights in mice with PS/PC vesicles alone. These results suggest that PS from the activated platelets induces IUGR by enhancing the coagulation cascade in the placental circulation and that annexin V from the villous trophoblast prevents the development of IUGR.

Animals↗

Coagulation/fibrinolysis disorder in patients with severe preeclampsia.

We investigated coagulation/fibrinolysis parameters in 50 patients with severe preeclampsia. The coagulation and clinical indices in patients with severe preeclampsia were 1.595 and 1.414, respectively. These indices show a strong correlation between the clinical status and coagulation/fibrinolysis abnormalities. Among patients with severe preeclampsia, a significant decrease in antithrombin (AT) (p = 0.002) and a significant increase in plasmin inhibitor complex (PIC) (p = 0.002), D-dimer (p < 0.05), and thrombin-antithrombin complex (TAT) (p = 0.001) were observed in cases terminated by cesarean section compared with those cases of vaginal delivery. There was no significant difference in platelet count (Plt), however, deltaPlt (the difference between platelet counts in early gestation and before delivery) was significantly larger (p < 0.05) in cases that ended in cesarean section. Furthermore, among cases terminated by cesarean section, a significant increase in PIC (p < 0.01) was observed when pregnancies were terminated because of maternal factors compared with those terminated because of fetal factors. These results suggest that (1) even in patients with severe preeclampsia, vaginal deliveries can be successful when they display a less hypercoagulable state; (2) a decrease in Plt during pregnancy may be a predictive marker for the termination of pregnancy; and (3) an excessive hypercoagulable state in patients with severe preeclampsia may be associated with the termination of pregnancy, especially when there is an aggravation of maternal factors.

Adult↗

Detection of decreased response to activated protein C during pregnancy by an endogenous thrombin potential-based assay.

Pregnancy has been widely recognized as a predisposing risk factor for deep vein thrombosis (DVT). However, it still remains unclear why pregnant women without a history of familial thrombophilia or antiphospholipid syndrome (APS) have a higher incidence of DVT and pulmonary embolism (PE) during pregnancy and puerperium. We examined the activated protein C (APC) system in healthy pregnant women and in patients with the onset of DVT during puerperium. Sixty unselected Japanese pregnant women without a past or family history of thrombosis or APS and 3 Japanese women with DVT during puerperium were evaluated. Endogenous thrombin potential-ratio (ETP-r) was measured by determination of thrombin-alpha2-macroglobulin complexes in thromboplastin-activated patient plasma. APC sensitivity ratio (APC-sr) was calculated by the determination of ETP-r in patient plasma in the presence and absence of APC (final concentration [conc.] 5.9 nM) to evaluate the functional APC anticoagulant activity. Mean APC-sr was significantly increased at 30 weeks' gestation (2.35 +/- 0.72) and remained high during puerperium compared with the mean APC-sr in nonpregnant women (1.15 +/- 0.63). Mean APC-sr in patients with DVT at the onset was significantly higher (3.57 +/- 0.54) than mean APC-sr during puerperium was, indicating that the sensitivity to APC was reduced in the ETP-based assay. These data suggest a significant reduction in the functional sensitivity to APC associated with an increased risk of venous thrombosis during pregnancy.

Activated Protein C Resistance↗

Upregulation of thrombomodulin antigen levels in U937 cells by combined stimulation with estradiol-17beta and vitamin K2 (menaquinone 4).

The expression of thrombomodulin (TM) and tissue factor (TF) antigens by estradiol and vitamin K2 were studied in human leukemic cell lines including U937 (monoblastic leukemia), NB4 (acute promyelocytic leukemia), and HL60 (acute myeloblastic leukemia). Combined stimulation with estradiol-17beta and menaquinone 4 (MK4), homologue of vitamin K2, showed a remarkable increase of total TM antigen level only in U937 cells among these leukemic cell lines, whereas a single treatment of each agent showed a modest or a moderate increase. A synergistic effect of cotreatment with estradiol-17beta and MK4 was observed in an optimum concentration of 1.0 micromol of estradiol-17beta and 1.0 micromol of MK4. Estrogen receptors were detected only in U937 cells among these cell lines, and the competitive assay with an antiestrogenic agent showed a suppression on TM expression in a dose-dependent manner. In the mean time, concerning expression of TF antigens, if at all, only a very slight decrease was observed by costimulation with estradiol-17beta and MK4 in U937 and NB4 cells, whereas all-trans-retinoic acid (ATRA) showed a remarkable decrease in surface TF antigen levels in NB4 cells and also a modest decrease in U937 cells. These findings suggest that estradiol-17beta would up-regulate TM antigen expression via estrogen receptors and in cooperation with MK4, showing a different mechanism from ATRA.

Antigens↗

Propofol anaesthesia in mice is potentiated by muscimol and reversed by bicuculline.

We have examined the role of gamma-aminobutyric acid (GABA) neurones in propofol anaesthesia in mice using the righting reflex. Propofol i.p. increased the percentage of loss of the righting reflex in a dose-dependent manner with an ED50 value of 140 (95% confidence limits 123-160) mg kg-1 (n = 40; eight animals per dose, five doses per dose-response curve). The ED50 for propofol decreased significantly to 66 (58-75) mg kg-1 in the presence of the GABAA receptor agonist muscimol 1 mg kg-1 i.p. (n = 40) (P < 0.05). In contrast, the ED50 increased significantly to 240 (211-274) mg kg-1 in the presence of the antagonist bicuculline 5 mg kg-1 i.p. (n = 40) (P < 0.05). Our results suggest that propofol anaesthesia may be mediated, at least in part by GABA neurons.

Anesthetics, Local↗

Dehydroepiandrosterone sulphate promotes hyaluronic acid-induced cervical ripening in rabbits.

Hyaluronic acid (HA) stimulates the synthesis of interleukin (IL) 8, while dehydroepiandrosterone sulphate (DHEA-S) induces the expression of IL-8 and its receptor in the human cervical fibroblast. This has led us to investigate the effect of DHEA-S on HA-induced cervical ripening. Experiments were performed in pregnant rabbits using vaginal suppositories containing 1 mg HA, 30 mg DHEA-S, 30 mg DHEA-S + 0.1 mg HA, 30 mg DHEA-S + 1 mg HA, and 500 microl Witepsol-50 base (control). The effects were evaluated by measuring collagenase, gelatinase and elastase activities, water content, neutrophil infiltration, relative collagen concentration and histological assessment. The activities of collagenase, gelatinase and elastase were significantly increased in rabbits treated with DHEA-S + 1 mg HA compared with rabbits treated with DHEA-S + 0.1 mg HA (P < 0.009, P < 0.001, P < 0.009 respectively). Water content was markedly increased in rabbits treated with DHEA-S + 1 mg HA compared with DHEA-S + 0.1 mg HA treatment (P < 0.05). Neutrophil infiltration was markedly increased, while relative collagen concentration was significantly decreased with DHEA-S + 1 mg HA compared with the DHEA-S + 0.1 mg HA approach (P < 0.001, P < 0.002). The histology of cervices treated with DHEA-S + 1 mg HA showed the density of collagen to be markedly decreased, and collagen fibres irregularly separated. Increased vascularity with massive dilatation of blood vessels was also observed in these rabbits. We conclude that DHEA-S upregulates the HA-induced cervical ripening process.

Animals↗

Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas.

To investigate the contribution of the beta-catenin gene to the development of ovarian carcinomas, mutational analysis of exon 3 of the beta-catenin gene was conducted. We analyzed 61 primary ovarian carcinomas, consisting of 49 non-endometrioid-type and 12 endometrioid-type tumors, for genetic alteration of the beta-catenin gene. Five carcinomas showed beta-catenin mutations (S37C, T41I, T41A), including 4 (33%) of 12 endometrioid-type tumors and 1 (14%) of 7 mucinous-type tumors. All of these mutations altered at the serine/threonine residues that are potential sites of GSK3-beta phosphorylation. We detected no carcinomas with interstitial deletion involving exon 3 of beta-catenin. Furthermore, we immunohistochemically studied 27 of the 61 ovarian carcinomas. Both nuclear and cytoplasmic beta-catenin expressions were demonstrated in 4 of the 27 ovarian carcinomas for which tissue samples were available for examination. All 4 cases exhibited mutations in exon 3 of beta-catenin, including a mucinous carcinoma. Our results suggested that beta-catenin gene mutation at potential GSK3-beta phosphorylation sites results in accumulation of beta-catenin protein within the cells and its translocation to nuclei. Accumulated beta-catenin protein may be involved in the development of endometrioid-type ovarian carcinomas, and some mucinous-type ovarian carcinomas.

Adult↗

Mutational analysis of STK11 gene in ovarian carcinomas.

Recently STK11, the causative gene of Peutz-Jeghers syndrome (PJS) was identified on chromosome 19p13.3. PJS is often accompanied by several malignancies, including breast tumor, adenoma malignum of the uterine cervix, and ovarian tumor. To investigate the involvement of STK11 gene in the development of ovarian carcinomas, we analyzed 30 ovarian carcinomas for loss of heterozygosity (LOH) and STK11 gene mutations. We found one missense mutation (codon 281, Pro to Leu) with heterozygous and somatic status. This mutation occurred at codon 281, which lies within the mutational hot spot (codon 279-281) of STK11 gene previously reported in PJS. We also detected LOH in 2 (11%) of 19 informative ovarian carcinomas. Our results suggest that mutations of the STK11 gene may play a limited role in the development of ovarian carcinomas.

AMP-Activated Protein Kinase Kinases↗

A case of simultaneous presence of primary endometrial carcinoma and metastasis of a breast carcinoma to the ovary after 5 years of tamoxifen therapy.

We report a case of a 43-year-old woman with the simultaneous presence of a primary uterine endometrial cancer and metastasis of breast cancer to the ovary after 5 years of tamoxifen therapy. Tamoxifen therapy lengthens recurrence-free survival of the patient. However, the risk of endometrial cancer and the possibility of recurrence of breast cancer also must be considered.

Adult↗

DNA alterations in human oral squamous cell carcinomas detected by restriction landmark genomic scanning.

Genetic abnormalities in human oral squamous cell carcinomas (OSCC) were examined using restriction landmark genomic scanning (RLGS), a method of two-dimensional gel analysis allowing detection of amplifications and other aberrations in genomic DNA. DNAs from 11 oral tumours as well as from contiguous normal squamous epithelium, were cleaved with the restriction enzyme Not I, [32p] end-labeled and electrophoretically size-fractionated. Following a second digestion employing Hinf I, the further fragmented DNA was again electrophoretically separated. Five fragments/spots were found amplified in at least 64% (7/11) (chromosome nos. 4, 9-12 or 22) of carcinomas, with one of these spots amplified in 100% (chromosome no. 4) of tumour samples. In addition, six other spots were frequently reduced in at least 55% (chromosome nos. 15 or 9-12) of tumour tissues. Further characterization of these common changes is needed to determine if they represent important alterations in OSCC.

Carcinoma, Squamous Cell↗

Trends in oral cancer mortality in Japan: 1950-1993.

OBJECTIVES: To investigate trends in mortality rates of oral cancer patients in Japan between 1950 and 1993 by sex, age and cancer site, and compare the results with previous studies to determine whether there are any common characteristics of oral cancer patterns between Japan and European countries. MATERIAL AND METHODS: The mortality data obtained from the Japanese Vital Statistics were analyzed using the 5-year moving average method, and the mortality rates were adjusted to the 1990 world population by age and sex. Age-specific mortality rates were analyzed by birth cohort. RESULTS: The age-standardized mortality rates among the males increased from 1.14 per 100,000 person--years in 1952 to 1.84 in 1991, whereas the corresponding rate among females changed little over the same period. Cancer of the tongue was the most common cause of death in Japan among the five studied oral regions: lip, tongue, floor of the mouth, major salivary glands and oropharynx, males aged under 54 born in 1920 or later were found to have an increased risk of such disease. CONCLUSION: Further epidemiological investigations are necessary to clarify the etiology of oral cancer in Japan.

Adult↗

Time trends in the mortality rates for tobacco- and alcohol-related cancers within the oral cavity and pharynx in Japan, 1950-94.

Mortality data of oral cancer over 40 years in Japan were analyzed to investigate time trends of the disease site-specifically and discuss the relation between these trends and the changing patterns of consumption of tobacco and alcohol beverages. Mortality rates were adjusted to the world standard population. In the males, overall oral cancer (ICD-9: 141-149) mortality rates have increased consistently from the lowest value of 1.25 (per 100,000 per year) in 1956 to 2.40 in 1992. The rates for females were constantly lower than those for males, and formed a modest peak of 0.96 in 1979. Regarding site-specific mortality rates, tongue cancer (141) presented a decreasing trend, while oro/hypopharyngeal (146, 148) and mouth (143-145) cancers showed increasing patterns, particularly in males. When the changing patterns of male truncated rates for ages 35-64 were compared with those of the annual consumption of cigarette and alcohol per capita, the time trend of oro/hypopharyngeal cancer mortality was analogous to cigarette consumption rather than to alcohol consumption, mouth cancer vice versa, and tongue cancer was not related to tobacco or alcohol consumption. The present findings suggest that tobacco and alcohol have different site-specific effects on the development of cancers within the oral cavity and pharynx.

Adult↗