p27, cyclin E, and CDK2 expression in normal and cancerous endometrium.

The objective was to investigate the immunohistochemical expression of p27, cyclin E, and CDK2 in normal and cancerous endometrium. Expression of p27 in premenopausal normal endometrium was significantly higher than that in postmenopausal normal endometrium (p=0.019). A significantly lower amount of p27 staining was observed in endometrial cancer tissues from premenopausal women than in normal premenopausal endometrium (p=0.015). Cyclin E expression in premenopausal normal endometrium was significantly higher than that in postmenopausal normal endometrium (p=0.003). A significantly higher amount of cyclin E staining was observed in endometrial cancer tissues from postmenopausal women than in normal postmenopausal endometrium (p=0.017). Regarding menopausal status, no significant difference in CDK2 staining was observed between cancerous and normal endometrium. There was a positive significant correlation between cyclin E and CDK2 expression levels in endometrial cancers (p<0.05). Western blot analysis confirmed elevated p27 protein levels in samples with positive p27 immunostaining. Considerable levels of p27 mRNA were detected in all normal and cancerous samples examined by semi-quantitative PCR. No significant relationship was found between telomerase activity and its association with p27 and cyclin E expression in endometrial cancers. These findings suggested that the decreased expression of p27 caused by post-translational mechanism might play an important role in endometrial cancer development in premenopausal women. In addition, increased cyclin E expression may play an important role in endometrial cancer development in postmenopausal women.

Topographic analysis of astigmatism induced by scleral shortening in pig eyes.

BACKGROUND: Corneal astigmatism is a severe postoperative problem in foveal translocation surgery. We evaluated the corneal astigmatism induced by scleral shortening in pig eyes in vitro. METHODS: We created three sizes of scleral shortening in pig eyes and examined the preoperative and postoperative corneal astigmatism. The three sizes of scleral shortening were; 6 mm x 12 mm, 9 mm x 12 mm, and 6 mm x 16 mm (radial x circumferential). The shortenings were created 11 mm from the limbus with 10 eyes in each group. Videokeratographic measurements were performed using the CAS System 2000, preoperatively and postoperatively, and the astigmatism caused by the scleral shortening was evaluated. RESULTS: The surgically-induced astigmatism was 2.1 +/- 1.2 diopters (D) in the 6 mm x 12 mm group, 5.2+/-1.5 D in the 9 mm x 12 mm group, and 3.7+/-1.0 D in the 6 mm x 16 mm group. Corneal astigmatism caused by scleral shortening depended on both the radial and circumferential shortening. Pre- and postoperative topographic corneal maps showed an irregular astigmatism pattern (lazy bowtie pattern). Because the central zone of the cornea showed a relatively regular astigmatism, the corneal astigmatism induced by scleral shortening did not affect the predicted corneal acuity. CONCLUSIONS: In foveal translocation surgery with scleral shortening, an excessive scleral resection in the radial direction can cause clinically intolerable regular and irregular astigmatism. Minimal scleral shortening that will satisfy the required translocated distance is recommended to reduce the risk/benefit ratio.

Are DNA ploidy and epidermal growth factor receptor prognostic factors for untreated ovarian cancer? A prospective study.

To identify prognostic factors for untreated ovarian cancer, DNA ploidy, proliferative index (P.I.) and epidermal growth factor receptor (EGFR) expression were analyzed in a prospective series of 40 patients with ovarian cancer and 7 patients with borderline malignant ovarian tumor followed up for 5 years or more (median, 77 months). The frequency of aneuploid cells was 53.8% (21/39) in ovarian cancer and 14.3% (1/7) in borderline malignancy. There was no significant association between DNA ploidy and the clinicopathologic findings, in which aneuploid ovarian cancer was more common among advanced tumors. The S-phase fraction and P.I. value were higher in the patients with aneuploid tumors (p = 0.076). EGFR expression was detected in 76.9% (30/39) of ovarian cancers and 42.9% (3/7) of borderline malignant ovarian tumors, and the mean EGFR level was 5.8 +/- 12.1 (range: 0-49.5) and 28.3 +/- 71.1 (range: 0-189.4) fmol/mg protein, respectively. There was no correlation between EGFR expression and DNA ploidy, P.I., and clinicopathologic findings analyzed. The 5-year survival rate in patients with aneuploid tumors was significantly worse in patients with ovarian cancer (p = 0.0165, log-rank test). No significant relationship was shown between P.I., EGFR expression, and 5-year survival. Cox multivariate analysis showed that DNA ploidy, P.I., and EGFR expression are not associated with the risk of death (p = 0.5917, p = 0.9924, and p = 0.6840, respectively), although clinical stage shows a significant relationship (p = 0.0027). Our data showed that DNA ploidy is significantly related to the prognosis by univariate analysis, but DNA ploidy, P.I., and EGFR expression were not independent prognostic factors for the untreated ovarian cancer.

Radiotherapy combined with transcatheter arterial infusion of cisplatin versus oral fluoropyrimidine anticancer agent for locally advanced carcinoma of the uterine cervix: a prospective follow-up study.

We randomized patients with locally advanced cervical cancer to receive radiotherapy combined with transcatheter arterial infusion (TAI) of cisplatin or oral fluoropyrimidine anticancer agents, and compared the prognosis by a prospective follow-up study. Sixty patients were studied who completed their planned radiation therapy with chemotherapy at the Department of Obstetrics and Gynecology of Hiroshima University Hospital between January 1991 and December 1998. Patients were randomly assigned to receive (A) radiotherapy with TAI of 120 mg/body cisplatin twice a month at the interval of 4 weeks or (B) radiotherapy with 200 mg/day oral 5-FU or UFT every day. In both groups, radiotherapy is routinely 50 Gy of external beam irradiation to the whole pelvis and 18-20 Gy (point A dose) of intracavitary irradiation using a remote after loading system (RALS). Serious adverse reactions interfering with treatment did not appear in either group. The effective histologic response was 28/32 (87.5%) in group A and 25/28 (89.3%) in group B. The median follow-up period were 28.3 months and 25.4 months in group A and B, respectively. There was no significant difference in the overall survival and disease-free survival rates for all patients, clinical stage III and squamous cell carcinoma. We could not conclude that radiotherapy with TAI of cisplatin achieved superior therapeutic efficacy in locally advanced cervical cancer. To improve the therapeutic effects, it is important to establish a new cisplatin-containing chemoradiotherapy regimen.

Expression of telomerase reverse transcriptase mRNA and its quantitative analysis in human endometrial cancer.

Three major components of telomerase, i.e., human telomerase RNA (hTERC), telomerase-associated protein (TEP1), and the human telomerase reverse transcriptase (hTERT), have been identified. Among them, TERT expression is very closely related to telomerase activity. The purpose of this study was to evaluate the implications of TERT expression and telomerase activity in endometrial cancer. Fresh surgical specimens of 36 endometrial carcinomas (CA group) and 9 samples of postmenopausal endometrial tissue without malignancy (NP group) were obtained at operation in our hospital. These specimens were analyzed for telomerase activity and TERT expression by TRAP assay and RT-PCR, respectively, and the detection and quantitative analysis were made. The results for endometrial cancer were compared with those for normal endometrium and with the clinical data. In the CA group, TERT expression was detected in 35/36 subjects (97.2%), whereas in 1/9 subject (11.1%) from the NP group. Relative TERT mRNA expression was 0.50 in the CA group, and this was significantly higher compared with the level of 0.10 in the NP group (p<0.05). Telomerase activity was detected in 34/36 subjects (94.4%) from the CA group and in 3/9 subjects (33.3%) from the NP group (p<0.05), while the RTA was 30.9 and 0.2, respectively (p<0.05). There was a significant correlation between the relative TERT expression and RTA (n=45, R=0.413, p<0.05). RTA was significantly higher at an advanced surgical stage (FIGO II, III or IV) than at an early stage (FIGO 0 or I) (52.4 vs. 20.4, p<0.05), but other clinical factors showed no relationship with TERT and RTA values. The detection and quantitative analysis of telomerase activity and TERT expression is helpful for distinguishing malignant from normal endometrium when the patient is postmenopausal, even if the tumor is very small or of low malignancy.

The relationship between photosensitive temporal lobe epilepsy and eye closure activity.

We describe a 16-year-old female patient affected by photo-induced temporal lobe epilepsy. During intermittent photic stimulation she showed a photoparoxysmal response in the EEG. This case was diagnosed from clinical symptoms, single photon emission computer tomography, and EEG data. The clinical symptoms were relieved by the administration of carbamazepine. As these photoparoxysmal responses were observed not only during photic stimulation, but also when patient was closing her eyes during an eye-opening test in complete darkness, we propose the existence of an alternative pathway such as from the extraocular muscles or orbicularis oculi, or activation of cortical activity due to the change of consciousness by closing eyes in inducing photosensitive epilepsy. We describe an additional case and discuss a novel aspect of photo-induced temporal lobe epilepsy.

Prospective analysis of DNA ploidy, proliferative index and epidermal growth factor receptor as prognostic factors for pretreated uterine cancer.

For the purpose of identifying prognostic factors for pretreated uterine cancer, DNA ploidy, proliferative index (P.I.) and epidermal growth factor receptor (EGFR) expression were analyzed in a large prospective series of 76 cervical cancer and 64 endometrial cancer patients observed for 5 years or more (median 76 months). The frequency of aneuploid cells was 62.0% (44/71) in cervical cancer and 16.7% (10/60) in endometrial cancer. There was no association between DNA ploidy and the clinicopathological findings without clinical stage, in which aneuploid cervical and endometrial cancers were significantly more common among advanced tumors (cervical: p<0. 05, endometrial: p<0.01). The P.I. was significantly higher in the patients with aneuploid tumors (cervical: p<0.05, endometrial p<0. 01). EGFR expression was detected in 56.6% (30/53) in cervical cancer and 59.6% (34/57) in endometrial cancer, and the mean EGFR level was 17.8+/-37.7 and 9.5+/-42.5 fmol/mg. protein, respectively. There was no correlation between EGFR expression and DNA ploidy, P.I. and clinicopathological findings analyzed. Five-year survival rate in patients with aneuploid tumors tended to have a worse outcome in cervical cancer cases (p=0.1003, log-rank test), and was significantly worse in endometrial cancer (p=0.0048, log-rank test). No significant relationship was noted between P.I., EGFR expression and 5-year survival. Cox multivariate analysis showed that DNA ploidy, P.I., and EGFR expression are not association with the risk of death. Our data showed neither DNA ploidy, P.I. nor EGFR expression were independent prognostic factors for pretreated uterine cancer.

Clinicocytopathological and immunohistochemical study of adenoma malignum of the uterine cervix.

Adenoma malignum is a rare type of very highly differentiated adenocarcinoma of the uterine cervix, and is quite difficult to diagnose because there are few findings definitely suggesting malignancy on cytologic or histologic examination. We recently encountered four patients with adenoma malignum and reviewed their clinicocytopathological and immunohistochemical findings. The most characteristic symptom was a watery discharge and an enlarged cervix was palpable, while multiple cystic lesions (MCL) were observed by transvaginal and abdominal ultrasonography, CT or MRI. On cytodiagnosis, the cervical gland cells formed large sheets or showed a palisading arrangement. Slightly enlarged nuclei and yellowish-orange staining of the cytoplasmic mucus were the characteristic findings. On histological examination, many cervical glands of different sizes were present and extended deep into the muscle layer, while branching or papillary growth into the lumen was also observed. On immunohistochemical study, HIK1083, a monoclonal antibody for gastric gland mucous cell mucin, was found to be positive in 3 of 4 cases, and this was fairly useful in the diagnosis of adenoma malignum.

[A case of uterine cervical cancer in which UFT was an effective preoperative treatment].

We report a case in which UFT was effective as a preoperative treatment for stage II b cervical cancer. The patient was a 66-year-old female whose chief complaint was brown vaginal discharge. Following cytological, histological and CT examinations, a diagnosis was made of papillary squamous cell carcinoma invading the vagina and left parametrium. We administered UFT (600 mg/day, for 5 days) as one course, and conducted two courses with an interval of 2 days. The tumor had shrunk 2 weeks later and a radical hysterectomy was performed after additional treatment with intraarterial cisplatin (120 mg/body) infusion. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD), which are enzymes in 5-FU metabolism, and the labeling index (ID) of DNA fragmentation in the tumor were estimated before and after UFT. The results showed that TS was 0.69 pmol/g tissue and DPD 39.98 pmol/mg/min before UFT, and that LI of DNA fragmentation was 21.8 +/- 5.0% before UFT and 37.9 +/- 16.2% after UFT. We suggest that preoperative UFT administration is an effective treatment for cervical cancer, and that TS, DPD and LI of DNA fragmentation might be useful biomarkers to estimate the sensitivity of UFT.

Semiquantitative analysis of telomerase activity in cervical cancer and precancerous lesions.

We investigated telomerase expression in cervical lesions and its diagnostic value for cervical cancer and the precancerous lesions. The subjects were 100 women who underwent cervical biopsy, comprising 16 normal cervix, 61 cervical intraepithelial neoplasia (CIN) and 23 invasive cervical cancer. Telomerase activity was detected by the telomerase repeat amplification protocol using a non-radioisotope system, and quantitated using a DNA image analyzing system. Telomerase was detected at 18.8% (3/16) in normal cervix, 32. 0% (8/25) in CIN I, 50.0% (3/6) in CIN II, 60.0% (18/30) in CIN III, and 91.3% (21/23) in invasive cervical cancer. Semiquantitation of telomerase activity was significantly higher in the subjects with invasive cancer than in those with CIN or a normal cervix (p<0.05). However, telomerase activity was not significantly different between the grades of CIN. Telomerase was detected in subjects with CIN, suggesting that telomerase expression is an early event in cervical carcinogenesis. Quantitation of telomerase activity may be helpful for the diagnosis of cervical cancer.

Microsatellite instability and hMSH2 gene mutation in a triple cancer (colon cancer, endometrial cancer, ovarian cancer) patient in hereditary non-polyposis colorectal cancer (HNPCC) kindred.

A patient who had triple cancer (colon cancer, endometrial cancer, and ovarian cancer) in HNPCC kindred is reported. Her family history revealed the occurrence of colon cancer in her paternal aunt and in two cousins, fulfilling the minimum HNPCC criteria. Microsatellite instability analysis revealed replication error (RER)+ in all cancer lesions at 2 microsatellite loci (D1S191, BAT 40). SSCP analysis suggested germline mutation in exon 2 of the hMSH2 gene. This case showed the importance of complete family-history investigations to identify HNPCC patients. In the near future, definitive diagnosis of HNPCC will be possible on the basis of DNA studies.

Delayed rupture of the spleen.

The concept of delayed splenic rupture is an evolving one. The cases reviewed have led us to reserve the term "delayed splenic rupture" for the situation in which early post-traumatic imaging of the spleen is normal and is followed by the diagnosis of splenic hemorrhage 48 or more hours after the initial insult. Post-traumatic splenic evaluation is indicated when the mechanism of injury is likely to injure the spleen, there is unexplained hypovolemia, or the patient complains of left upper quadrant pain or tenderness. Peritoneal lavage is indicated when hypovolemia is the main manifestation. Radionuclide study is used for screening isolated splenic or hepatic injury when the suspicion is low. Reduced availability of visceral angiogram has resulted in CT scan becoming the main diagnostic modality. When a patient presents with blunt abdominal trauma, awareness of the problem of splenic rupture and active diagnostic approach may help reduce the morbidity and mortality associated with splenic hemorrhage, either immediate or delayed.

Heterogeneity of free valine pools for protein synthesis on free and membrane-bound polysomes in rat liver.

When rat liver was pulse-labeled with [3H]valine in vivo, the nascent peptide on membrane-bound polysomes was found to be more highly labeled than that on free polysomes. Nascent peptides were purified from both classes of polysomes and, after hydrolysis, the amino acids were reacted with 14C-labeled 1-fluoro-2,4-dinitrobenzene. The specific activity of [3H]valine was determined from the [14C]-dinitrophenyl-[3H]valine after purification by two-dimensional thin layer chromatography. With this approach we found that the specific activity of [3H]valine in the nascent peptide of membrane-bound polysomes was more than twice that of free polysomes. Moreover, when rats were pretreated with a lysosomal protease inhibitor, the differences between the specific activities of valine in nascent peptides of the two classes of polysomes tended to decrease. Our results indicate the existence of two distinct pools for valine used for protein synthesis in liver cells; one serves as a precursor for the synthesis of secretory proteins on membrane-bound polysomes and the other as a precursor for the synthesis of intracellular proteins on free polysomes.