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Biomedical subjects

I Furuta

Publications and source records attributed to I Furuta.

At least 19 recordsLinked to original sources

Correlations of bcl-2 and p53 expression with the clinicopathological features in tongue squamous cell carcinomas.

bcl-2 oncogene prolongs cell survival by inhibition of apoptosis. p53 tumor suppressor gene participates not only in cell proliferation control but also in induction of apoptosis. The expression of both bcl-2 and p53 proteins in 52 primary tongue squamous cell carcinomas (SCCs) was immunohistochemically explored in correlations with clinico-pathological features, patient's prognosis and apoptosis index (AI) of this tumor type. bcl-2 and p53 expression were identified in 26/52 (50%) cases and 31/52 (60%) cases, respectively. The frequency of bcl-2 expression was associated with tumor histologic grade (P = 0.0128) and marginally with mode of tumor invasion (P = 0.0671) but not with lymph nodal involvement. The frequency of p53 expression was associated with mode of tumor invasion (P = 0.0458) and pN status (P = 0.0224) but not with tumor histologic grade. Moreover, the three combined bcl-2/p53 staining patterns of bcl-2-/p53-, bcl-2+/p53- and bcl-2-/p53+, and bcl-2+/p53+ were significantly correlated with tumor histologic grade (P = 0.0299), mode of tumor invasion (P = 0.0022) and pN status (P = 0.0024). In addition, the frequent appearance of bcl-2 protein expression was associated with a decrease in AI (P = 0.0290). Our results suggest that the combined investigation on the two biological markers may have value in assessment of tumor aggressiveness, and that the suppressing mechanism of bcl-2 oncogene in regulation of apoptosis preserves in tongue SCC.

Apoptosis

Evaluation of argyrophilic nucleolar organizer regions in tongue squamous cell carcinomas.

Using a silver staining technique, argyrophilic nucleolar organizer regions (AgNORs) were studied on the biopsy specimens taken from 67 tongue squamous cell carcinomas (SCCs), and the relations of the results of AgNORs to the clinicopathological findings, to the labelling indices of proliferating cell nuclear antigen (PCNA LI), and to the outcomes of the disease were investigated. The mean numbers of AgNORs per cell were 1.67 +/- 0.19 (n = 27) in the control squamous epithelia and 3.58 +/- 1.15 (n = 67) in the tongue SCCs, respectively, and a significant difference was found between the two groups (P < 0.0001). Concerning the clinicopathological findings, the mean numbers of AgNORs in the progressive cases (T3, T4), in the factor N-positive groups (N1, N2), and in the advanced stages (stages III, IV) were statistically higher than those in T1, T2, N0, and earlier stage (stages I, II) tumours, respectively. Similarly, a higher value of the AgNOR count was present in the histological grade III or diffuse invasive tumour. There was also a directly significant correlation between the AgNOR counts and the labelling indices of PCNA (r = 0.53, P < 0.0001). Concerning the outcome of the disease, the mean numbers of AgNORs were higher in the group with local recurrence or with lymph-node metastasis. A lower rate of 5 years' survival was found in the high value group (63.5%) of AgNORs compared with that of the low value group (86.0%), with a significant difference between the two groups (P < 0.05). The results suggest that AgNORs may reflect the degree of malignancy and cellular proliferation in tongue SCCs.

Adult

Studies on Methicillin-Resistant Staphylococcus aureus Bacteremia Due to Laboratory Medical Analysis.

We encountered 64 patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia between April 1993 and March 1994. Mean patient age was 54 years. There were 46 males and 18 females. Underlying diseases mainly consisted of traffic accident (10 patients), valvular heart disease (5 patients), chronic renal failure (5 patients), leukemia (5 patients), pneumonia (3 patients), and malignant lymphoma (3 patients). The common clinical laboratory findings of MRSA bacteremia included decreses in total protein, albumin and hemoglobin as well as increases in white blood cells (neutrophils) and C reactive protein. In particular, an increase in C reactive protein by 10 mg/dl or more may be useful for diagnosing bacteremia. Laboratory findings were compared between surviving and non-surviving patients. There were significant differences in albumin, cholesterol, bilirubin, creatinine, and CRP. In 18 patients (28.1%), bacteremia was caused by infection due to contamination of central venous catheters. Since medical treatment with intra-vascular devices may cause bacteremia, sufficient caution is needed.

Journal Article

Gestational transient hyperthyroxinaemia (GTH): screening for thyroid function in 23,163 pregnant women using dried blood spots.

OBJECTIVE: Transient elevation of serum free T4 (gestational transient hyperthyroxinaemia; GTH) occurs occasionally during normal pregnancy, especially in early gestation. However, the frequency of GTH and its clinical features remain unclear to date. The aim of this study was to determine the occurrence rate of GTH and the relation between serum levels of hCG, free T4 (fT4), and TSH in a large number of pregnant women. DESIGN: The four criteria of GTH were as follows: (1) no past history of thyroid disease, (2) negative tests for MCHA and TGHA, (3) no multiple pregnancies or trophoblastic disease and (4) transient hyperthyroxinaemia at less than 16 weeks of gestation. Thyroid function and hCG levels in 23,163 pregnant women were evaluated by mass sreening. If individual fT4 levels were more than the upper limit, blood re-sampling and the clinical and laboratory analysis of thyroid function were performed to exclude women with thyroid disease. The concentrations of hCG, fT4, and TSH in women with GTH and normal pregnant controls (n = 218) were compared. Regression analysis was performed for the comparison between hCG, fT4, and TSH levels in women with GTH. MEASUREMENTS: Blood samples were obtained using dried blood spots. Blood levels of fT4 was measured by radioimmunoassay, TSH and hCG were measured by fluoroimmunoassay. Anti-microsome antibody (MCHA) and anti-thyroglobulin antibody (TGHA) were measured by indirect agglutination reaction. RESULTS: GTH was observed in 66 of 23,163 women. The overall occurrence rate of GTH was 0.285%. In 22 of the 66 GTH women, serum TSH was undetectable. Using regression analyses, the concentration of fT4 was correlated with hCG levels in women with GTH (P < 0.05, r = 0.269), whereas the concentration of TSH was not correlated with hCG or fT4 level. The concentrations (M +/- SD) of fT4, TSH, and hCG in women with GTH were 42.5 +/- 12.3 pmol/l, 0.20 +/- 0.31 mU/l and 190.2 +/- 98.8 x 10(3) IU/l, whereas those of controls were 14.6 +/- 3.8 pmol/l, 1.43 +/- 1.25 mU/l and 60.1 +/- 45.1 x 10(3) IU/l. The concentrations of fT4 and hCG were significantly (P < 0.0001) higher than those of normal controls, and TSH was significantly (P < 0.0001) lower than those of normal controls. CONCLUSION: The occurrence rate of gestational transient hyperthyroxinaemia was 0.285%, and could possibly be attributed to increased levels of circulating hCG. Based on the data obtained from a large number of pregnant women, we propose gestational transient hyperthyroxinaemia as a definite clinical entity.

Blood Specimen Collection

Hematopoietic cytokine levels and in vitro colony formation assay in fetal anemia.

Fetal anemia causes hydrops fetalis and fetal ascites/hydrothorax, and in severe cases the prognosis is poor. Little other than alloimmunity and viral infections are known as mechanisms causing fetal anemia. The aim of this study was to elucidate any pathogenesis in fetal anemia due to otherwise idiopathic etiology. The levels of three hematopoietic cytokines, IL-3, erythropoietin (EPO), and granulocyte colony-stimulating factor (G-CSF) were measured in blood samples obtained by cordocentesis from six fetuses with anemia (Hb <10.0 g/dl) and 34 fetuses without anemia. Cordocentesis was performed prior to the onset of labor or uterine contractions in all pregnant women. The concentration of IL-3 in fetuses with anemia [M+/-(SD), 8.3 (10.1) pg/ml] was significantly lower than that in fetuses without anemia [59.9 (71.0) pg/ml]. EPO and G-CSF levels were not different between the two groups. In addition, through in vitro colony formation assay, using blood stem cells from two fetuses with severe anemia and three fetuses without anemia, it was found that colony forming unit-erythroid, burst forming unit-erythroid and granulocyte macrophage-colony forming unit were significantly suppressed in blood stem cells from the two fetuses with severe anemia. Thus, the malfunction of differentiation and proliferation of blood stem cells and the decrease of hematopoietic cytokine levels in the fetal circulation may be responsible for the occurrence of fetal anemia.

Colony-Forming Units Assay

In vitro production of progesterone and estradiol by rat granulosa cells regulated by cabergoline and prolactin.

Cabergoline (CG), a dopamine agonist, and prolactin (PRL) added in vitro to isolated granulosa cells from immature rats cultured in serum-free medium inhibited FSH-stimulated production of progesterone. The lowest effective concentrations of CG and PRL were 10(-8)M and 1 ng/mL, respectively. In combination, the inhibitory activities were additive. CG at 10(-8) M also suppressed estradiol production by isolated rat granulosa cells; whereas PRL did not. In conclusion, CG inhibits FSH-stimulated progesterone and estradiol production by rat granulosa cells.

Animals

[Antifungal susceptibility of clinically isolated Candida albicans by broth microdilution method].

In this study we investigated the antifungal susceptibility of 285 strains of Candida albicans isolates at Kinki University Hospital from March 1995 to December 1996. The antifungal agents tested were fluconazole, miconazole, intraconazole, amphotericin B and flucytosine. The susceptibility testing were performed according to the broth microdilution method standardized by National Committee for Clinical Laboratory Standards (M27-T). Most isolates of C. albicans showed relatively a low MIC value and the MIC90S were calculated at 1 microgram/ml; fluconazole, 0.125 microgram/mg; miconazole, 0.06 microgram/ml; itraconazole, 1 microgram/ml; amphotericin B, 0.25 microgram/ml; flucytosine. There was only one strain that showed high resistance against fluconazole and it showed cross-resistance against miconazole and itraconazole. There were two flucytosine resistant strains. The MICs of amphotericin B were tightly clustered and resistant strain were not observed.

Amphotericin B

Low in vitro thyrotropic activity of a human chorionic gonadotropin molecule in the first trimester during pregnancy.

Rat thyroid cell strain FRTL-5 is widely used to analyze thyroid stimulators, and responds to purified hCG with increased cyclic AMP production. The aim of this study was to determine the in vitro thyrotropic activity of an immunological hCG molecule according to gestational age during normal pregnancy using the FRTL-5 cell culture system. Sera were collected from 7 normal nonpregnant control and a total of 72 normal pregnant women. Seventy-two pregnant women consisted of 40 women in the first trimester (7-14 weeks' gestational age (GW) (group I)), 16 women in the second trimester (15-28 GW, group II), and 16 women in the third trimester (29-40 GW, group III). Concentrations of serum hCG and FT4 of group I were higher than those of groups II and III (p < 0.001). In the in vitro assay, the supernatants were subjected to radioimmunoassay for cAMP. In order to analyze in vitro thyrotropic activity of an immunological hCG molecule, cAMP accumulation rate expressed as cAMP accumulation (nM) divided by maternal serum concentration of hCG (IU/ml) was determined in all three groups. By regression analyses, a statistically significant positive correlation was observed between serum hCG concentration and cAMP accumulation in group I (r = 0.399; p < 0.05), group II (r = 0.915; p < 0.0001) and group III (r = 0.671; p < 0.01). cAMP accumulation rate in group I (0.355 +/- 0.022, mean +/- SE) was significantly low when compared with group II (0.508 +/- 0.051) (p < 0.01) and group III (0.556 +/- 0.063) (p < 0.001). Thus, it was found for the first time that the in vitro thyrotropic activity of an immunological hCG molecule in the first trimester was lower than those of the second and the third trimesters. In terms of the in vitro thyrotropic activity, an immunological hCG molecule in the first trimester differs from that of the later trimesters.

Animals

Immunocytochemical localization of salivary peptide P-C in human submandibular gland.

Human saliva contains a proline-rich polypeptide, salivary peptide P-C, which potentiates insulin release and reduces glucagon release from perfused rat pancreas to decrease blood glucose level. To elucidate the process of secretion into humoral fluid of this peptide morphologically, we investigated ultrastructural localization of P-C in human submandibular gland by immunogold technique with anti-peptide P-C whose specificity to P-C was confirmed by immunoblotting. The labeling with gold particles which represents the distribution of P-C-like-immunoreactivity (P-C-LI) was detected in the secretory granules and rough endoplasmic reticula of the acinar serous cells and in few mucosa cells. P-C-LI was also observed in the lumen of striated duct but not intracellularly in the ductal cells themselves, indicating that P-C is not probably reabsorbed there. These results suggest that salivary peptide P-C is present in acinar serous cells, is secreted into the oral cavity, and may be reabsorbed through the digestive tract to modulate the blood glucose level after feeding.

Aged

Erythropoietin, granulocyte-colony stimulating factor, interleukin-1 beta and interleukin-6 during the normal menstrual cycle.

OBJECTIVE: Menstruation and ovulation are the main events during the menstrual cycle. Menstruation may influence the complete blood count because of its blood loss. Since ovulation is an inflammatory-like phenomenon, white blood cell count may change during ovulation. For these reasons, we have investigated the complete blood count and peripheral serum concentrations of associated cytokines during the normal menstrual cycle. MATERIALS AND METHODS: Normal healthy female volunteers (N = 9; age, 21-33 years) with menstrual cycles of 25-33 days recorded basal body temperature every day and venous blood samples were collected three times per week. Complete blood count was performed and erythropoietin, granulocyte-colony, stimulating factor, interleukin-1 beta, interleukin-1 beta, interleukin-6 and hormones (FSH, LH, estradiol and progesterone) were measured. RESULTS: The red blood cell, total white blood cell, granulocyte and platelet counts showed no statistically significant changes during the menstrual cycle when using analysis of variance with the Scheffe F-test. No changes in erythropoietin, interleukin-1 beta and interleukin-6 were seen throughout the menstrual cycle. In contrast, serum granulocyte-colony stimulating factor concentrations increased significantly to 28.0 +/- 3.1 pg/ml (mean +/- S.E.M.) during the ovulatory phase, compared to 10.7 +/- 0.6 pg/ml in other phases. CONCLUSION: These results indicate that menstrual blood loss does not affect the complete blood count and suggest that granulocyte-colony stimulating factor plays and important role in the mechanism of ovulation.

Adult

Cytokines concentrations in the cervical mucus of pregnant women.

OBJECTIVE: Interleukin-1 alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in specimens of cervical mucus were assayed to assess defense mechanisms against infection in the cervical canal during pregnancy. METHODS: Two hundred and thirty-nine pregnant women who attended the obstetrics outpatient clinic in our hospital were included as subjects. Cervical mucus was collected with a newly developed collection swab, and cytokines and granulocyte elastase in the samples of cervical mucus were quantified using enzyme immunoassay kits. The 1-factor ANOVA, the Kruskal-Wallis test, and scheffé's F were used for statistical analysis. RESULTS: Interleukin-1 alpha, interleukin-1 beta and interleukin-8 levels rose significantly as the concentrations of granulocyte elastase increased. High concentrations of interleukin-1 alpha (75.36 +/- 19.93 pg/ml), interleukin-1 beta (1005.29 +/- 238.75 pg/ml) and interleukin-8 (4822.4 +/- 633.2 pg/ml) were found in the specimens from the group of high granulocyte elastase levels. CONCLUSIONS: These cytokines might be involved in defense mechanisms against ascending infection from the vagina.

Adolescent

[A case of leiomyomatosis in pelvic lymph nodes].

We report a rare case of leiomyomatosis in iliac lymph nodes, which was found in a woman operated with a diagnosis as keratinizing epidermoid carcinoma of the cervix. A 39-year-old Japanese female, married, who had received hormonal therapy in her past history, visited the Department of Obstetrics and Gynecology at Kinki University Hospital, with a chief complaint of bloody discharge. Colposcopy and biopsy suggested a diagnosis of keratinizing epidermoid carcinoma of the cervix. A radical hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph nodes dissection was performed. Histopathological examination showed a keratinizing epidermoid carcinoma of the cervix. An intramural leiomyoma nodule (0.5cm in diameter) was detected in the fundus of the uterus. Histopathologically, this was a typical benign leiomyoma. The lymph nodes were free of neoplasms. But bilateral iliac lymph nodes were enlarged up to soybean size. Microscopically, the iliac lymph nodes contained a large amount of well differentiated smooth muscle tissue (11/30). Immunohistochemical investigation showed a positive reaction for smooth muscle actin and desmins in the spindle cells proliferated in the lymph nodes; no cytokeratin positivity was detected. Leiomyomatosis of lymph node may rise through metaplasia of intranodal decidua or endometriosis by myofibroblasts or smooth muscle cells, reflecting the multipotentiality of the pelvic subcoelomic mesenchyme that can be found in the peripheral sinus of lymph nodes.

Adenocarcinoma, Papillary

[Future prospects of emergency laboratory tests--problems of immunoserologic tests].

Regarding problems in emergency and urgent immunoserologic tests, I mainly focused on infectious diseases and CPR and discussed the correspondence of dangerous needle stick injuries, and the significance of emergency CRP measurement in various body fluids using highly sensitive determination methods. The actual conditions and correspondence of infections due to dangerous needle stick injuries (accidental pricking with used needles) such as hepatitis, syphilis, acquired immunodeficiency syndrome (AIDS), adult T-cell leukemia (ATL), herpes simplex, falciparum malaria, tuberculosis, Rocky mountain spotted fever, and human colonic adenocarcinoma are discussed. With regard to emergency CRP measurement, application of highly sensitive determination methods and the significance of CRP measurement of various body fluids (healthy adult blood, cord blood, cerebrospinal fluid, urine and puncture fluid) are described. The reference values for CRP concentrations in various body fluids were established at 15 to 3,063 ng/ml for serum (male; 26 to 3.992 ng/ml, female; 11 to 1,672 ng/ml), 9 to 73 ng/ml for cord blood, 2 to 10 ng/ml for cerebrospinal fluid and less than 2 ng/ml for urine.

Accidents, Occupational

Serum concentration of endogenous G-CSF in women during the menstrual cycle and pregnancy.

Although granulocyte-colony stimulating factor (G-CSF) is commonly used in the field of supportive therapy for cancer treatment, the serum concentration of endogenous G-CSF in healthy women is still obscure due to the low sensitivity (30 pg mL-1) of the usual enzyme immunoassay. With the development of a highly sensitive (1.0 pg mL-1) chemiluminescent immunoassay by Kiriyama et al., we have clarified the changes of serum G-CSF levels in healthy women during the menstrual cycle and pregnancy. The G-CSF concentration showed a peak value of 27.3 +/- 2.5 pg mL-1 (mean +/- SEM) at the ovulatory phase during the menstrual cycle, which is significantly higher than in all other phases (P < 0.0001, unpaired t-test). A significantly higher value compared to the menstrual cycle, except during the ovulatory phase, was also revealed throughout pregnancy (P < 0.0001, unpaired t-test). These results suggest that G-CSF plays an important role in ovulation and the maintenance of pregnancy.

Adult

Apoptosis in testis germ cells: developmental changes in gonadotropin dependence and localization to selective tubule stages.

Recent studies have demonstrated apoptotic DNA fragmentation in the testis of immature rats deprived of gonadotropins. However, the exact cell type undergoing apoptosis during testis development and the age differences of gonadotropin dependence of testis cell apoptosis are unclear. The present study used gel fractionation and in situ methods to quantitate developmental changes of testis cell DNA fragmentation and to localize the specific cell type affected in developing rats with and without treatment with a GnRH antagonist. Apoptotic DNA fragmentation in whole testis was measured in rats between 8-70 days of age. A gradual increase (1.8- to 2.0-fold) in testis apoptotic DNA fragmentation was seen in rats between 16-28 days of age, compared with 8-day-old animals, followed by a decrease in adult animals. To study gonadotropin dependence of testicular apoptosis, serum FSH and, to a lesser extent, LH were suppressed by treatment with a long-acting GnRH antagonist (azaline-B, 250 micrograms/kg body wt, two injections at 2-day intervals). Pretreatment with the GnRH antagonist increased apoptotic DNA fragmentation in rats between 16-32 days of age but not in younger and adult animals demonstrating an age-related change in gonadotropin dependence. To identify the exact testis cell type undergoing apoptosis, in situ analysis of DNA fragmentation was performed. In rats at 16-24 days of age, spermatocytes in selected tubules were found to have increased DNA fragmentation. In contrast, neither Leydig cells nor Sertoli cells were affected. In 32-day-old and adult animals, increased DNA fragmentation was seen in early primary spermatocytes of some tubules. Treatment with GnRH antagonist increased the number of cells with DNA fragmentation as well as percentage of tubules affected. In animals between 16-32 days of age, meiotic spermatocytes were labeled, whereas early spermatids were also labeled in 24- and 32-day-old animals. In adult animals, the level of apoptotic DNA fragmentation was not affected by GnRH antagonist treatment. However, DNA isolated from specific stages of the seminiferous tubules of adult animals showed stage-specific changes of apoptotic DNA fragmentation with 2-fold higher levels found in stages I and XII-XIV compared with stage VIII. In situ analysis of adult testis demonstrated that spermatocytes were the major cell type affected. In conclusion, the present study demonstrated that at least three factors determine the onset of apoptosis of the male germ cells: 1) the developmental stage of the animal; 2) serum levels of gonadotropins, especially FSH; and 3) specific stage of the seminiferous epithelial cycle. The present approach provides the basis for future analysis of the role of gonadotropins and other factors in the regulation of testis cell degeneration in normal and pathological states.

Animals