Lack of association between a polymorphism in the promoter region of the dopamine D2 receptor and personality traits.

Disturbances of the dopaminergic neurotransmitter system have been associated with a personality trait that involves novelty seeking. A functional polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) has been reported to be associated with schizophrenia. We examined the association between this polymorphism in the DRD2 promoter region and personality traits, as assessed with the Tridimensional Personality Questionnaire. No significant association emerged between the polymorphism in the DRD2 promoter region and personality traits. Entering sex and age as covariates in an analysis of covariance did not change the results. These data fail to confirm an association between a polymorphism in the promoter region of the DRD2 and personality traits.

Overexpression of CDK2 is a prognostic indicator of oral cancer progression.

Cyclins and cyclin-dependent kinases (CDKs) play key roles in cell cycle regulation, a process of which dysregulation can lead to uncontrolled cell growth and hence to cancer. We have already reported the alteration of CDK4 and cyclin D1 expression in oral cancer. In this study, we examined by immunohistochemistry the expression of CDK2, and cyclins A and E in 20 normal oral mucosa, 42 dysplastic epithelia, and 103 oral squamous cell carcinomas (SCCs). The expressions of CDK2, and cyclins A and E were not detected in the normal epithelium and significantly altered from epithelial dysplasia to SCC. While there were no significant correlations between the expression of cyclins A, E and the patients' survival, CDK2 expression was significantly correlated with lymph node involvement (P = 0.025), tumor differentiation (P = 0.032), mode of tumor invasion (P = 0.017), and shorter survival period (P = 0.0173). These results suggest that the elevated expression of CDK2 is a critical factor in oral cancer progression and can be used as a negative predictive marker of the patients' prognosis.

The influence of blood arterial oxygen condition on the tumor response to preoperative radiation therapy in oral cancer patients.

The relationship between clinicopathological factors and response of radiation therapy in oral squamous cell carcinoma has been studied. It has been suggested that factors such as tumor site, extent and tumor differentiation determine the response to radiation therapy. It is known that oxygenation is related to the therapeutic effects of radiation therapy. However, there are few reports on the relationship between oxygen condition and the response to radiation therapy. The present study was carried out to assess whether any clinicopathological factors, including an evaluation of the oxygen condition can be used to predict the effects of preoperative radiation therapy in oral squamous cell carcinomas. Forty-seven patients with oral cancer treated with external radiation therapy preoperatively were evaluated. There were no significant differences in response to the radiation with respect to age, sex, tumor site, stage, macroscopic shape of tumors, and the histological factors. The hemoglobin (Hb) and arterial oxygen content (CaO(2)) levels of favorable cases (Hb: 14.4 g/dl, CaO(2) 19.1 ml/dl) were significantly higher than those of unfavorable cases (Hb: 11.0 g/dl, CaO(2): 16.1 ml/dl). These findings suggest that oxygen conditions of oral cancer patients predict tumor response to preoperative radiation therapy.

Suppression of conditioned fear by administration of CCKB receptor antisense oligodeoxynucleotide into the lateral ventricle.

We investigated the role of CCK in the development of anxiety by determining whether CCKB receptor antisense suppressed intracellular Ca(2+) concentration in vitro or suppressed conditioned fear stress in vivo. First, for the in vitro studies, we used rat pituitary tumor GH3 cells since these cells have CCKB receptors. GH3 cells were stimulated by 10 microM CCK-4; intracellular Ca(2+) concentration was measured. The CCKB receptor antisense at 1 or 10 microM reduced the subsequent response to 10 microM CCK-4 in a time-dependent manner. Second, for the in vivo studies, the CCKB receptor antisense, sense, random sense, or saline was infused at a constant rate for 6 days into rat lateral ventricles via mini-osmotic pumps. Individual rats were then subjected to 30 min of inescapable electric footshock in a chamber with a grid floor. Twenty-four hours later, the rat was again placed in the chamber and observed for 5 min without shocks. This study showed that CCKB receptor antisense significantly suppressed intracellular Ca(2+) concentration in GH3 cells and significantly reduced freezing behavior in rats, indicating that the CCKB receptor plays an important role in anxiety.

Alterations of Rb, p16(INK4A) and cyclin D1 in the tumorigenesis of oral squamous cell carcinomas.

Immunohistochemical analysis of Rb, p16(INK4A) and cyclin D1 expression was performed on 78 oral squamous cell carcinoma (SCC), 46 leukoplakia, and 20 normal mucosa. Rb and p16(INK4A) expression were observed in all normal mucosa and most of leukoplakia. Lack of Rb and p16(INK4A) was observed in 56.4 and 67.9% of SCC, respectively. The overexpression of cyclin D1 was not observed in normal mucosa and was observed in 35.9% of SCC. A strong reciprocal relationship between Rb and p16(INK4A) expression was observed in oral SCC, and all these SCC cases have at least one of the alterations in the Rb pathway.

Expression of a truncated epidermal growth factor receptor in oral squamous cell carcinomas.

Epidermal growth factor receptor (EGFR) frequently overexpresses in cancers, including oral squamous cell carcinomas (OSCC). We previously identified a truncated EGFR (tEGFR) in human oral keratinocytes. In this study, we evaluated the prognostic value of tEGFR in 45 cases of OSCC. tEGFR expression inversely correlated with EGFR expression (r=-0.83, P<0.01), decreased with T-stage progression and lymph-node metastasis (P<0.05). The EGFR/tEGFR ratio correlated with the lymph-node metastasis (P<0.05) and survival outcome (hazard ratio =3.601; P<0.05). These results suggest that tEGFR may play an important roles in oral carcinogenesis and that the EGFR/tEGFR ratio may be a prognostic factor for OSCC.

Association of preoperative radiation effect with tumor angiogenesis and vascular endothelial growth factor in oral squamous cell carcinoma.

This study examined the relationship between tumor angiogenesis and the radiation-induced response, evaluated based on pathological changes, in oral squamous cell carcinoma patients treated with preoperative radiation therapy. Forty-one cases of squamous cell carcinoma treated with preoperative radiation therapy were investigated. Tumor angiogenesis was assessed by scoring the intratumor microvessel density (IMVD). Expression of vascular endothelial growth factor (VEGF) was also evaluated before and after preoperative radiotherapy. There was no correlation between IMVD in the specimens before therapy and the pathological response to radiation therapy. However, radiation therapy decreased IMVD in the specimens after therapy. A significant association was observed between VEGF expression and resistance to radiation therapy: only 4 of the 21 patients whose tumors exhibited a high level (2 + or 3 + ) of VEGF staining experienced a major (3 + or 4 + ) pathological response to radiation therapy. Furthermore, an increasing level of VEGF expression after radiation therapy was observed in non-effective (0 to 2 + ) response cases. These results suggest that VEGF expression and the induction of this protein are related to radiosensitivity and could be used to predict the effects of preoperative radiation therapy on oral squamous cell carcinoma.

Infrequent alternations of RB pathway (Rb-p16INK4A-cyclinD1) in adenoid cystic carcinoma of salivary glands.

Retinoblastoma (Rb) tumor suppressor genes' products and of the proteins regulating its phosphorylation and function in G1 arrest, p16INK4A and cyclin D1, play important roles in the regulation of the cell cycle. Rb gene inactivation, reflected by the absence of Rb protein expression, has been reported in oral squamous cell carcinomas. p16INK4A is frequently deleted, methylated, or mutated, and cyclin D1 gene amplification in many malignancies including oral squamous cell carcinomas (SCC). These findings suggested that Rb pathway of G1 arrest are the most commonly affected genes in Oral SCC. However, alternation of Rb pathway in salivary gland tumors was not clear. In this study, the expressions of Rb, p16INK4A, and cyclin D1 alternations were analyzed by immunohistochemical assay in 5 specimens of normal salivary glands and twenty-two cases of adenoid cystic carcinomas (ACC). Proliferating cell nuclear antigen (PCNA) labelling index (P.I.) was used for the evaluation of cell proliferation. Rb was consistently expressed in normal salivary glands and ACC. Loss of p16INK4A expression was observed in three cases (13.6%) of ACC. And overexpression of cyclin D1 was observed in four cases (18.2%). The three p16INK4A absent cases were the tumors with predominantly solid pattern and those cases were overexpressed cyclin D1. The cell proliferation activities of p16INK4A absent tumors (P.I. = 24.2 +/- 2.1%) were significantly higher than those of p16INK4A present tumors (P.I. = 10.4 +/- 3.5%) (P < 0.05). Cyclin D1 expression was also related to cell proliferation (P.I. of cyclin D1 negative cases vs. cyclin D1 positive: 10.1 +/- 3.0% vs. 22.6 +/- 3.4%) (P < 0.05). These findings suggested, however, alternations of Rb pathway were infrequent events in ACC of salivary glands and inactivation of p16INK4A, cyclin D1 overexpression may be related to the high cell proliferating activity of ACC.

Apoptosis and p53 are associated with effect of preoperative radiation in oral squamous cell carcinomas.

This study was carried out to elucidate whether apoptosis and p53 can be used to stratify oral cancer patients into groups with a favorable or unfavorable response to preoperative radiation therapy. Thirty-two patients were evaluated. The apoptosis index was 1.7+/-0. 9% in the ineffective cases, and it was significantly lower than effective cases (3.2+/-1.2%). While 14 of 16 effective cases (86.7%) did not express p53, 13 of 16 ineffective cases (81.3%) overexpressed p53. These results suggest that mutated p53 in tumors is associated with a poor response to radiation which may be related to evasion of apoptosis in oral cancer.

Increased anxiety behavior in OLETF rats without cholecystokinin-A receptor.

Cholecystokinin (CCK) may have a role in the mediation of human panic disorder and anxiogenic (anxiolytic)-like activity in an animal model of anxiety. Otsuka Long Evans Tokushima Fatty (OLETF) rats lacked CCK A receptors (CCKAR) because of a genetic abnormality. In order to elucidate the involvement of CCKAR in the regulation of anxiety, we investigated the exploratory behavior on elevated plus-maze test, the black and white box test, and open field test with OLETF rats in comparison with normal [Long-Evans Tokushima Otsuka (LETO)] rats. And OLETF rats increased the number of stretched attend postures and decreased open arm entry and the % time of open arm in an elevated plus-maze test. Time spent in the white box decreased significantly in OLETF rats than LETO rats. The total line crossing decreased significantly in OLETF rats compared to LETO rats. The missing CCKAR had a significant anxiogenic-like effect. These data support the involvement of the CCKAR in the neurobiological mechanism of anxiety.

Nucleotide sequence of vitellogenin mRNA in the bean bug, Riptortus clavatus: analysis of processing in the fat body and ovary.

The bean bug, Riptortus clavatus, has immunologically distinct yolk proteins, vitellin (Vn)-1 and-2 and their precursors, vitellogenin (Vg)-1 and-2. We have cloned the full nucleotide sequence of Vg-1 cDNA. The deduced amino acid sequence has some similarities to other insect Vgs. It contains two polyserine regions, which are characteristic of other Vgs. Vg-1 mRNA appeared after treatment with the juvenile hormone analogue, methoprene, implying transcriptional regulation. We found four enzymatic cleavage sites in the Vg molecule. Two of them match the consensus for dibasic processing endoprotease, which is also conserved in processing sites for other insect Vgs. We showed that the processing at each site was incomplete, and this resulted in production of more than the five polypeptides which would be expected from four processing sites in the molecule. The physiological significance of multiple polypeptides in insect Vgs is still unclear.

[A case of endometrioid carcinoma of the prostate].

A case of endometrioid carcinoma of the prostate is reported. A 64-year-old man was admitted to our department with initial macrohematuria and dysuria. The transrectal ultrasonogram showed remarkable prostatic hypertrophy and the serum level of both prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP) ranged within normal limits. Urethrocystographical and cystoscopical findings indicated prostatic hypertrophy with elongation of prostatic urethra and mild trabeculation of bladder wall. During transurethral resection of the prostate, papillary tumor was accidentally found in the left lobe near the vermontanum. Histopathological examination revealed adenocarcinoma of the prostatic urethra and the tumor displayed no immunoreactivity for PSA or PAP. Under diagnosis of prostatic urethral cancer total cystoprostatectomy and urethrectomy were performed and ileal conduit was constructed for urinary diversion. As intraductal papillae and complex ramifying glands were histopathologically confirmed in the specimen and the immunohistochemical staining showed positivity of PSA and PAP, the tumor was diagnosed as endometrioid carcinoma of the prostate.

[A case of retroperitoneal fibrosarcoma: usefulness of magnetic resonance imaging].

A 62-year-old man with dyspnea was admitted to our hospital. Computed tomography showed a large right renal mass. Results of T1- and T2- weighted magnetic resonance imaging showed a very low-intensity region suggestive of retroperitoneal fibrosarcoma. On March 13, 1996, complete tumor resection and lymphadenectomy were done. The histopathological diagnosis was of fibrosarcoma. After the operation, the patient was treated twice with a combination chemotherapy regimen consisting of cyclophosphamide, vincristine, adriamycin and dacarbazine. At the most recent follow-up, 1-year postoperatively, the patient was well with no local recurrence or distant metastases.

Fractional clearances of low molecular weight proteins in lead workers.

Urinary alpha 1-microglobulin (alpha 1-m) and beta 2-microglobulin (beta 2-m) can be used as early indicators of renal tubular dysfunction. However, low levels of lead exposure cause an increase in urinary alpha 1-m, but not in urinary beta 2-m. In order to clarify the level of tubular dysfunction in early lead nephropathy, fractional clearances of alpha 1-m (FC-alpha 1-m) and beta 2-m (FC-beta 2-m), i.e., the ratios of these clearances to the creatinine clearance, were measured in 99 male lead workers. Blood urea nitrogen, serum creatinine, uric acid, and urinary creatinine and N-acetyl-beta-D-glucosaminidase activity were also measured to diagnose the presence of other renal dysfunction. The median of FC-alpha 1-m was 0.13% in the control group. The FC-alpha 1-m increased in lead workers with blood lead (B-Pb) levels above 20 micrograms/dl. The correlation of FC-alpha 1-m with urinary alpha 1-m was highly significant, but there was no correlation with serum alpha 1-m. The median of FC-beta 2-m was 0.065% in the control group. There was a correlation of FC-beta 2-m with FC-alpha 1-m, but there was no correlation with B-Pb, or with serum beta 2-m. These results suggest the following: There was a very low excretion rate of alpha 1-m and beta 2-m in both the control group and the lead exposed groups. The excretion rate of alpha 1-m was higher than that of beta 2-m.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum immunoglobulin and complement C3 levels in workers exposed to lead.

Serum immunoglobulin and complement C3 levels were measured in workers exposed to lead at a secondary lead refinery and a solder factory. In the first survey, significant correlations were found between blood lead and IgA with a correlation coefficient of 0.296, and between blood lead and IgE with a correlation coefficient of 0.314. No other significant correlations were found among the indicators of lead exposure and humoral immunity. In the second survey, no significant correlations were found between blood lead and IgG and IgA. A significantly higher number of subjects with IgE of more than 400 IU/ml was found in the group with blood lead of more than 60 micrograms/100 g.

[Hyperthermic treatment in patients with benign prostatic hypertrophy].

Hyperthermic treatment was performed in 31 patients with benign prostatic hypertrophy (BPH). Eight patients of them had a urethral catheter because of urinary retention. The prostate was heated trans-rectally to 43-45 degrees C. The treatment consisted of 10 sessions of 60 min. each. To evaluate this treatment, the following parameters were determined before, during and one week after the last hyperthermia session: subjective symptoms score, and residual urine volume, uroflowmetry and transrectal ultrasound of the prostate as objective data. Symptoms score improve in all patients. Of 8 patients with a catheter, the catheter could be removed from 4 patients. There was no significant change in prostate volume, but significant decreases of residual urine volume, and increases of maximum flow rate and mean flow rate were observed. No adverse reactions were seen. Judging from the above results, this treatment is considered to be useful for patients with BPH.

[Total anomalous pulmonary venous connection in adult: report of a case].

Total anomalous pulmonary venous connection (TAPVC) is a cardiac disorder that seldom permits survival into adulthood without surgical correction in infancy. We reported a successful total correction in a 47-year-old man with TAPVC. Cardiovascular angiography demonstrated the features of Darling I a type TAPVC. Cardiac catheterization showed Qp/Qs: 5.8, Pp/Ps: 0.31, Rp/Rs: 0.06 and mild pulmonary hypertension. On operation, the posterior wall of left atrium anastomosed to the common pulmonary vein over 4 cm length, ASD (5.0x3.8 cm) was closed with patch, and the communicating vein was ligated. The patient made uneventful postoperative recovery and is well 3 months following surgery.