Reduction of oocyte lipid droplets and meiotic failure due to biotin deficiency was not rescued by restoring the biotin nutritional status

BACKGROUND/OBJECTIVESOocyte lipid droplets play a crucial role in meiosis and embryo development. Biotin is associated with fatty acid synthesis and is the coenzyme for acetyl-CoA carboxylase (ACC). The effects of a biotin deficiency on the oocyte lipid metabolism remain unknown. This study examined the effects of a biotin deficiency and its replenishment on murine 1) oocyte lipid droplet levels, 2) ovary lipid metabolism, and 3) oocyte meiosis.MATERIALS/METHODSMice were divided into 3 groups: control, biotin deficient (BD), and recovery groups. The control and BD groups were fed a control diet or BD diet (0.004 or 0 g biotin/kg), respectively. The recovery group mice were fed a BD diet until day 21, and were then fed the control diet from days 22 to 64. This study then quantified the oocyte lipid droplet levels, assessed the oocyte mitochondrial function, and examined the ability of oocytes to undergo meiosis. Ovarian phosphorylated ACC (p-ACC), lipogenesis, β-oxidation, and ATP production-related genes were evaluated.RESULTSThe BD group showed a decrease in lipid droplets and mitochondrial membrane potential and increased p-ACC levels. In the recovery group, the hepatic biotin concentration, ovarian p-ACC levels, and mitochondrial membrane potential were restored to the control group levels. On the other hand, the quantity of lipid droplets in the recovery group was not restored to the control levels. Furthermore, the percentage of oocytes with meiotic abnormalities was higher in the recovery group than in the control group.CONCLUSIONSA biotin deficiency reduced the oocyte lipid droplet levels by downregulating lipogenesis. The decreased lipid droplets and increased oocyte meiosis failure were not fully restored, even though the biotin nutrition status and gene expression of lipid metabolism was resumed. These results suggest that a biotin deficiency remains robust and can be long-lasting. Biotin might play a crucial role in maintaining the oocyte quality.     

Mucinous cystadenocarcinoma of the retroperitoneum: a light and electron microscopic study

A large, ovarian-type, retroperitoneal cystic tumor existing in the presence of normal ovaries was studied morphologically by light and electron microscopy. The cyst was monolocular, having several papillary nodules which measured 0.2-2.0 cm in diameter, and protruded into the lumen. Histologically, most of the tumor wall was covered by mesothelium-like cells which showed signs of differentiation into either a benign endocervical type mucinous epithelium or a mucinous epithelium of borderline malignancy, particularly around the nodules. The papillary nodules themselves had the histological features of a well-differentiated mucinous adenocarcinoma. These light and electron microscopic features resembled those of ovarian mucinous tumors. Histogenetically, the tumor appeared to be derived from a mesothelial inclusion cyst; some of the mesothelium being transformed by metaplastic change into the endocervical type mucinous epithelium and undergoing further transformation into either the mucinous epithelium of borderline malignancy or the well-differentiated mucinous adenocarcinoma by some unknown factors.     

Peritoneal tuberculosis with elevated serum CA 125 levels: A case report

Laparotomy in a 62-year-old woman with elevated serum CA 125 antigen levels with the provisional diagnosis of ovarian carcinoma revealed peritoneal tuberculosis. After treatment with the bacteriocidal chemotherapeutic agents, the antigen level returned to the normal, and she has been well for 24 months postoperatively.     

Medical visits of childhood cancer survivors in Japan: A cross‐sectional survey

Background: Although more children with cancer continue to be cured, these survivors experience various late effects. Details of the medical visit behaviors of childhood cancer survivors (CCS) in adulthood remain to be elucidated. Methods: In order to examine medical visits in the past and future of CCS, we performed a cross‐sectional survey with self‐rating questionnaires on medical visits of CCS compared with control groups (their siblings and the general population). Results: Questionnaires were completed by 185 CCS, 72 of their siblings and 1000 subjects from the general population and the results were analyzed. Mean ages at this survey and the duration after therapy completions of CCS were 23 and 12 years, respectively. We found that the previous treatment hospitals (where CCS were treated for their cancer) were the most commonly visited medical facilities for the CCS group (74% for female patients and 64% for male patients) and more than half of the CCS preferred to continue visiting the previous treatment hospital with enough satisfaction in Japan. The multivariate analysis showed that female sex and relapse were significantly associated with the past visits to the previous treatment hospital and that the CCS with brain tumors or bone/soft tissue sarcomas and CCS with any late effects tended to continue the relationships with the hospital. In addition female sex was also significantly associated with desired future visits to the previous treatment hospital. On the other hand, the married CCS tended to be disinclined to visit the hospital it in the future. Conclusions: In order to optimize risk‐based care and promote health for CCS after adulthood, we should discuss the medical transition with CCS and their parents.     

A case of recurrent gastric cancer successfully treated with TS-1

A patient with recurrent gastric cancer which infiltrated the pelvic muscle after the treatment of paraaortic lymph node and ovarian metastases was successfully managed by a novel oral anticancer drug, TS-1. TS-1 was administered at a dose of 80 mg/day. One course consisted of two repetitions of consecutive administration of TS-1 for 14 days and withdrawal of TS-1 for 14 days. Adverse reactions were mild and the patient did not request hospitalization after two courses had been completed. Subjective symptoms such as difficulty in walking improved after one week and a partial response was obtained after 2 weeks of treatment. At the end of 4 courses we could remove an indwelling pyelocatheter for the ureter stricture. As of 14 months after the beginning of administration of TS-1, the patient is being treated as an outpatient and has attained a better QOL than before.     

Dependence of the thymidylate synthase inhibition rate on the interval after the last administration of tegafur in sigmoid colon cancer patients

The thymidylate synthase (TS) inhibition rate was measured after tegafur (FT) administration (1.5 g/day, at least 10 days) in 7 sigmoid colon cancer patients. The TS inhibition rate decreased as the interval between the time of the last administration and the time of the tumor resection increased longer. This study provides basic data for considering methods of drug administration and assessment of modification, for example, by leucovorin. © 1993 Wiley-Liss, Inc.     

Screening for Nicotine Dependence among Smoking-related Cancer Patients

To identify lung and head-and-neck cancer patients who will have difficulty stopping smoking it is necessary to measure the severity of their nicotine dependence. In this study, we compiled a Japanese version of the Fagerström test for nicotine dependence (FTND) and examined its reliability and validity. One hundred and fifty-one cancer patients participated in this study and took our Japanese version of the FTND. Socio-demographic and medical data and information about smoking habits were obtained from a semi-structured interview, and the patients' nicotine dependence was evaluated according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Ed., Rev. (DSM–III–R). The mean FTND scores±SD of the group with nicotine dependence and the group without nicotine dependence were 6.85±2.00 and 3.70±2.13 respectively, and the difference was significant ( P < 0.001, Mann-Whitney's U-test). The test-retest correlation was 0.75. Cronbach's a of the FTND was 0.66. The FTND score correlated significantly with the number of satisfied criteria of nicotine dependence ( r =0.70; P <0.001, Pearson's correlation). By using a receiver-operating-characteristic curve, we determined a score of 5/6 as a suitable cut-off point for nicotine dependence; this point gave high sensitivity and specificity (0.75 and 0.80, respectively). These results suggest that our Japanese version of FTND is a reliable and valid measure of nicotine dependence in patients with smoking-related cancers.     

O6-Methylguanine-DNA Methyltransferase (MGMT) as a Determinant of Resistance to Camptothecin Derivatives

The precise mechanisms of resistance to camptothecin (CPT)-derived DNA topoisomerase (topo I) inhibitors and the determinants remain unclear. We found that a DNA repair protein, O⁶-methylguanine-DNA methyltransferase(MGMT), participated in resistance to irinotecan hydrochloride (CPT-11), its active metabolite SN-38, and a novel CPT derivative, DX-8951f. In 17 human cancer cell lines, MGMT gene expression level closely correlated with sensitivity to the CPT derivatives, and inhibition of MGMT activity by nontoxic 5 μM O⁶-benzylguanine augmented the drug activity in relation to the MGMT expression levels in 8 cell lines examined. Transfection of pCR/MGMT-sense into U-251MG and pCR/MGMT-antisense into T98G and HEC-46 cells revealed that increased MGMT expression decreased the sensitivity to CPT-11, SN-38, and DX-8951f, whereas repressed MGMT expression sensitized cells to the drugs. Western analysis revealed that treatment of MGMT -expressing T98G cells with the drugs caused a decrease of both MGMT and topo I in a dose-dependent manner. Although, in the transfectants, MGMT expression did not so closely correlate with the sensitivity to drugs as to nimustine hydrochloride (ACNU), MGMT is probably an important resistance determinant to CPT derivatives, and may play some role in the topo I-mediated DNA damage and/or the repair process.     

Neurogenic vasoconstriction as affected by cholinergic and nitroxidergic nerves in dog ciliary and ophthalmic arteries.

PURPOSE: To determine the involvement of noradrenergic and other vasoconstrictor nerves in the contraction of ocular arteries and the modification by cholinergic and nitroxidergic nerves of vasoconstrictor nerve function. METHODS: Changes in isometric tension were recorded in helical strips of the canine posterior ciliary and external ophthalmic arteries denuded of the endothelium, which were stimulated by transmurally applied electrical pulses (5 Hz). Vasoconstrictor mediators were analyzed by pharmacological antagonists, such as prazosin, alpha,beta-methylene ATP, a P2alpha-purinoceptor antagonist, and BIBP3226, a neuropeptide Y receptor antagonist. RESULTS: Transmural electrical stimulation produced contractions that were potentiated by N(G)-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The contraction was partially inhibited by prazosin and abolished by combined treatment with alpha,beta-methylene ATP but was not influenced by BIBP3226. Stimulation-induced contraction was attenuated by physostigmine and potentiated by atropine. Contractions induced by exogenous ATP were reversed to relaxations by alpha,beta-methylene ATP. In the strips treated with L-NA, prazosin, and alpha,beta-methylene ATP, the addition of L-arginine elicited relaxations by nerve stimulation. The ATP-induced relaxation was attenuated by aminophylline, whereas neurogenic relaxation was unaffected. CONCLUSIONS: Ciliary and ophthalmic arterial contractions by nerve stimulation are mediated by norepinephrine and ATP, which stimulate alpha1-adrenoceptor and P2X purinoceptor, respectively. ATP from the nerve is unlikely involved in vasodilatation. Acetylcholine derived from the nerve impairs the neurogenic contraction, possibly by interfering with the release of vasoconstrictor transmitters, and neurogenic NO also inhibits the contraction postjunctionally by physiological antagonism.