Phenytoin-induced gingival overgrowth caused by death receptor pathway malfunction.

OBJECTIVE: In this study, we investigated the role of phenytoin (PHT) in death receptor-induced apoptosis of gingival fibroblasts to clarify the mechanism of PHT-induced gingival overgrowth. METHODS: Human gingival fibroblasts were cultured to semiconfluence and treated with PHT (0.025, 0.1, 0.25, and 1.0 µM) for 48 h, and then, the apoptotic cell numbers were relatively determined by absorptiometry. After 24 h of 0.25 µM PHT treatment, caspase activity was measured by absorptiometry, apoptotic and cell cycle phase distribution was analyzed by flow cytometry, expression levels of apoptotic genes were quantified by real-time qPCR, and expression of apoptotic proteins was detected by Western blot analysis. After 48 h of 0.25 µM PHT treatment, appearance of apoptotic cells was detected by TUNEL assay. RESULTS: PHT treatment decreased the proportion of apoptotic cells in gingival fibroblasts compared to a serum-free control culture in response to the protein changes as follows: PHT upregulated c-FLIP and, in turn, downregulated FADD, caspase-8, and caspase-3; PHT upregulated c-IAP2 and downregulated TRAF2; PHT downregulated caspase-9 and caspase-3 via decreased RIPK1 activity and increased Bcl-2 activity. CONCLUSION: PHT-induced gingival overgrowth may result from the above-mentioned mechanisms involving apoptosis inhibition in gingival fibroblasts.

[Sedative premedication is necessary for infants in anesthetic induction under the presence of mother].

We examined the necessity of sedative premedication for elective operation of childhood when induction was performed beside the mother. One hundred and nine patients (aged from 2 to 8 years) were assigned randomly to two groups; midazolam (0.5 mg.kg-1, orally, n = 56) was administered 45 min before induction in Group M, and vehicle was administered (n = 53) in Group C. The differences between the two groups about their calmness and behavior were investigated using double blind method, and analyzed according to their ages, as infants (2 to 4 years), kindergarteners (5 to 6 years) and school children (7 to 8 years). The significantly higher incidences of agitation or alertness were observed in infants of Group C (P < 0.05) and all other patients were calm and well sedated. We conclude that sedative premedication is necessary in infants even if induction is performed beside patient's mothers.

Validity of cadmium concentration in rice as the "dose" of the dose-response relationship between cadmium intake and renal dysfunction.

It is well known that cadmium (Cd) causes renal dysfunction such as increase of beta(2)-microglobulin excretion into urine. Although Cd in rice seems to be one of the largest sources of total Cd intake in Japan, there are very few studies that have epidemiologically clarified the relationship between Cd concentration in rice (Cd-R) and renal dysfunction, because such studies are basically ecological studies, in which confounding factors are difficult to take into consideration. To derive safety levels for foodstuff from Cd-R, it is essential to evaluate the effect of confounding factors. Thus, we investigated the dose-response relationship between renal dysfunction and not only Cd-R but also confounding factors, and we tried to determine whether Cd-R is an adequate indicator of "dose" in the dose-response relationship between Cd intake and renal dysfunction. In 1971, Cd-R data were obtained from rice samples collected by the Environment Agency, Government of Japan in the Fuchu area of Toyama Prefecture, which is known as a place where many itai-itai disease patients were found, and medical data were collected during 1979-1984 by Toyama Prefecture. First, the dose-response relationship between Cd-R and renal dysfunction was analyzed using the data from the Fuchu area. Second, to investigate the effect of confounding factors, analysis using the data from both the Fuchu area and an unpolluted area with environmental factors different from those of the Fuchu area was performed. The results showed that the cause of renal dysfunction could not be explained by Cd-R alone, and confounding factors were not negligible. Although it is difficult to clarify precisely the confounding factors from the available data, it is concluded that deriving a safety level for foodstuffs using only the Cd-R level as a reference is not appropriate.

[Prevalence of problem drinkers among dental students].

In 1997 and 1998 we statistically studied fourth-year dental students for their drinking and smoking habits. The subjects numbered 103 (65 males, 38 females) in 1997 and 127 (79 males, 48 females) in 1998, totaling 230. The questionnaire included the Kurihama Alcoholism Screening Test (KAST), the Adolescent Alcohol Involvement Scale (AAIS), and the Fagerström Tolerance Questionnaire (FTQ). Problem drinkers as defined by KAST, scoring at least 2 points, represented 12.6% of the total in 1997 and 13.4% in 1998, exceeding 10% in both years. Alcoholic misusers, with at least 42 point on the AAIS, stood at 19.4% in 1997 and 17.3% in 1998. The incidence of students assessed as having 6 points on the Quantity-Frequency Scale (QF Scale) stood at 18.4% in 1997 and 10.2% in 1998. Compared between two sexes, KAST detected no significant difference between the two groups: 13.9% for males and 11.6% for females. Alcoholic abusers on the AAIS, however, were estimated at 22.9% in males and 9.3% in females, the ratio for males being more than twice as high as that for females. It was also found that 47.9% of the male students and 33.7% of their female counterparts drank every weekend and that 31.3% of the males and 5.8% of the females kept drinking until they were drunk. Female students thus appeared to drink more frequently, though they consumed smaller amounts of alcohol at a time. The smoking rate was lower than the average in the Japanese for both groups; nicotine dependence was also lower in dental students. It was demonstrated that dental students drink more alcohol more frequently, with a higher incidence of problem drinkers.

Masticatory ability in relation to oral status and general health on aging.

In recent years in the field of clinical dentistry, and particularly in gerodontics, there has been a growing awareness of the importance of nutrition. Because a lack of masticatory ability leads to an impaired nutritional status, the dentist must be abreast of current knowledge on masticatory ability. Although there are many approaches to the measurement of masticatory ability with natural or functional teeth, there is no ideal method for this measurement in the elderly. This is because the elderly are usually missing more than half of their teeth, and thus have various dentitions. For example, the dentition of 70-years old subjects varies from no missing teeth to no remaining teeth. Moreover, the prosthetic appliances used vary from partial dentures to complete dentures. The present study was performed to establish a method for the objective assessment of masticatory ability which could be applied to the elderly, with their various dentitions. We demonstrated a useful jelly of varying hardness (G-1 jelly) for this assessment. In addition, we examined the correlation between masticatory ability, oral status and general health of the elderly, using this new assessment method.

Endocervical glandular atypia and adenocarcinoma: a correlation of cytology and histology.

Of the 34,384 cervical smears sampled by cervical scraping and Cytobrush, reactive glandular atypia was found in 1.7%, low-grade glandular atypia in 0.08%, and high-grade glandular atypia/adenocarcinoma in 0.05%. Cells of reactive glandular atypia and low-grade atypia could be distinguished from those of high-grade atypia/adenocarcinoma by the architecture of the cellular aggregates, nuclear morphology, and nuclear-cytoplasmic ratios. Further histologic studies found that most reactive and low-grade atypias were associated with condyloma, squamous dysplasia, carcinoma in situ, and cervicitis. Eighty-two percent of women with cellular evidence of high-grade atypia/adenocarcinoma were confirmed to have in situ or invasive adenocarcinoma of the cervix. Although Cytobrush samples seem to improve the detection of early-stage glandular neoplasms, many minor atypias unrelated to cervical carcinogenesis are also detected.

[A study on the ability of leukocytes in the cervical mucus of pregnant women to produce superoxide anions using the histochemical nitroblue tetrazolium reduction test].

We performed the histochemical nitroblue tetrazolium (NBT) reduction test for leukocytes in cervical mucus and peripheral blood in women in pregnancy to investigate the leukocyte functions in the uterine cervix during pregnancy. The results were as follows. (1) With regard to leukocytes in cervical mucus, the proportion of NBT positive leukocytes was significantly highest in women in the third trimester and was higher in pregnant women than in non-pregnant women. (2) With regard to leukocytes in peripheral blood, the ability of leukocytes to reduce NBT in pregnant women was significantly greater than that of leukocytes in non-pregnant women. These results suggest that the bactericidal activity of leukocytes in cervical mucus during pregnancy is probably more accelerated than that of leukocytes during non-pregnancy.

[Quantitative nitroblue tetrazolium reduction test of peripheral blood polymorphonuclear leukocytes in women in pregnancy and labor].

We performed the quantitative nitroblue tetrazolium (NBT) test for normal peripheral blood polymorphonuclear leukocytes (PMNs) to investigate the functions of PMNs during pregnancy and labor. The results were as follows. With regard to the spontaneous NBT test, the ability of PMNs to reduce NBT in pregnant and parturient women was significantly greater than to reduce NBT in non-pregnant women. The greatest ability was observed in PMNs in parturient women. With regard to the PMA-stimulated NBT test, the ability of PMNs to reduce NBT in pregnant and parturient women was significantly greater than to reduce NBT in non-pregnant women. Stimulation of NBT reduction was observed when PMNs were exposed to kallikrein. These results suggest that PMNs are so much affected by pregnancy that their functions are accelerated in pregnancy and labor, and that PMNs may have favorable effects on pregnancy and labor not only in the aspect of defense mechanisms but also in the aspect of the ripening of the uterine cervix, and that PMNs may be affected by kallikrein during labor.

[The present status of mass population screening for cancer of the uterine cervix and the therapeutic results in the detected cases in Miyagi Prefecture].

The mass screening for cervical cancer in the population of Miyagi Prefecture has covered the total 1,078,999 women by March 1981. Invasive cancer of the uterine cervix was discovered in 1032 women, carcinoma in situ in 829. 2) By methods of the examination, the institutional examination was on 72.5% of the examined in 1980. 3) With regards to the rates of examinees by age and the detection rate of the cancer of uterine cervix in 1980, the low detection rate in the age range of 30-50 years whose examination rate was over 20% compares against the high detection rate in the high age range, whose examination rate was low. 4) CAI in years 1965, 1970, 1975 and 1980 were 60.0, 116.7, 193.2 and 229.8 respectively. 5) The 302 cases of invasive cancer detected and treated before the end of 1974 were classified in clinical stages and investigated the results of treatment. The detection in Stage I was in 84.1%, this high percentage being a main factor to make the total treatment results of uterine cervical cancer pushed up to the high figure.

[Mechanical properties of microfilled composite resins (author's transl)].

The various mechanical properties of seven microfilled composite resins were evaluated, comparing with two conventional composite resins. The following results were obtained. 1) Though microfilled composite resins were more excellent than conventional ones on surface roughness after polishing or brushing, but they were inferior to conventional ones on the resistance to brushing abrasion. 2) Tensile, compressive and bending strength were dependent on inorganic filler content and properties of matrix resin. Particularly, their mechanical properties in the wet condition were strongly influenced by whether matrix resin was hydrophilic or hydrophobic. Compared with conventional composite resins, microfilled ones contained 30 to 40 wt% of filler had lower values of tensile and bending strength, and near values of compressive strength. While, microfilled ones contained 50 to 60 wt% of filler had higher values of compressive strength, and near values of tensile and bending strength, compared to conventional ones. 3) Modulus of elasticity and hardness were mainly dependent on inorganic filler content. Moduli of elasticity of microfilled composite resins were about 25 to 33% of them of conventional ones, and hardnesses of microfilled ones were approximately 50% of them of conventional ones except some materials. Hardnesses of microfilled composite resins with 50 to 60 wt% of filler were similar to them of conventional ones.

[Dimensional stabilities of microfilled composite resins (author's transl)].

Thermal expansion, expansion by water sorption, water sorption and solubility to water, which will influence to the marginal closure of cavities restored, were evaluated in seven microfilled composite resins, comparing with two conventional composite resins. The following results were obtained. 1) Coefficients of linear thermal expansion of microfilled composite resins were 41 to 84 x 10(-6)/degrees C in the dry condition and 57 to 93 x 10(-6)/degrees C in the wet condition. Those values were about 2 to 3 times those of conventional composite resin, and about 6 to 8 times that of teeth. 2) Linear expansion by water sorption was highly correlated to water sorption. Microfilled composite resins had higher values of liner expansion by water sorption compared to conventional ones. 3) Generally, water sorption of microfilled composite resins were higher than those of conventional ones. After 7 days, they were about 0.4 to 1.9 mg/cm2. Values of microfilled ones which contained larger amount of filler or was composed of more hydrophobic matrix resin, however, were lower than others. 4) Solubilities to water of microfilled composite resins also were higher than those of conventional ones. Particularly, microfilled ones which were used organic composite filler and UDMA monomer as base material and photopolymerized had relatively higher values.

Clinical and histopathological study of carcinoma of the corpus uteri.

Clinical and histopathological investigations were carried out in 71 cases of carcinoma of the corpus uteri treated at the Department of Obstetrics and Gynecology, Tohoku University Hospital over the 10 year period from 1968 through 1977. The ratio of cases of the corpus uteri to those of the cervix was 6.5/100. The average age of the former group was 58 years and 30% of them were nulligravida. The rates of accompanying hyprtension and obesity were 21% and 20%, respectively. With regard to clinical stages, 75% were Stage I, 13% were Stage II, 10% were Stage III and 1% were Stage IV. The histological grade was G1 in 61%, G2 in 26%, and G3 in 13%. In Stage I, 80% of the cases had myometrial invasion into less than 1/3 of the uterine wall, but in Stage II invasion was limited to 1/3 in less than 25%. Metastasis to pelvic lymph nodes was found in 3 of 34 cases (9%): 1 of 24 cases of Stage I (4%) and 2 of 9 (cases of Stage II (22%). All three of these cases had myometrial invasion reaching deeper than 1/3 of the uterine wall. Those with deep myometrial invasion showed a diffuse invasive pattern, as did those of G2 or G3 lesions. Cases of G1 lesions showed a relatively shallow myometrial invasion, whereas there was a tendency for cases of G2 or G3 lesions to have deep myometrial invasion. The over-all 5 year relative survival rate was 83%, while that for the Stage I patients was 98%. All 12 of the patients who died of recurrence of carcinoma of the corpus uteri died within 2 years of treatment.

A facile and regiospecific preparation of 6-alkyluridines.

2',3'-O-Isopropylideneuridine, upon lithiation and subsequent alkylation, was transformed to 6-alkyl derivatives in a regiospecific manner. After acidic treatment of the acetonides, 6-alkyluridines (methyl, ethyl, propyl, isopropyl, butyl, secbutyl, and hexan-3-yl) were obtained. 5'-Deoxy-6-alkyluridines (methyl, ethyl, and isopropyl) were also prepared by the same route from 5'-deoxy-2',3'-O-isopropylideneuridine.

Cytological diagnosis in dysplasia of the uterine cervix.

Cytologic specimens presenting primarily superficial or intermediate dysplastic cells in the smear obtained by scraping the uterine cervix were defined as mild dysplasia, and those presenting primarily parabasal (or deep layer) dysplastic cells were defined as severe dysplasia. The rate of agreement of the above cytologic diagnosis to the histological diagnosis by target biopsy using the colposcope was 50% and 51% in mild and severe dysplasia, respectively. Specimens containing a few atypical cells which were strongly suspected to be malignant were classified as IIIb. From this group, malignant lesions were found in 48% and severe dysplasia in 35%.