Lack of Carcinogenicity of Quercetin in F344/DuCrj Rats

Quercetin was administered at dietary levels of 0(control), 1.25 and 5.0% to groups of 50 male and 50 female rats for 104 weeks, and then all animals were maintained without quercetin supplement for a further 8 weeks. At 5.0% quercetin, both sexes showed growth retardation throughout the study. There were no treatment-ascribed effects regarding clinical signs, mortality, urinalyses or hematology. Although serum glucose in 5.0% quercetin-treated males was significantly decreased and some relative organ weights in 5.0% groups showed statistically significant increases, these latter changes seemed to be related to the growth retardation. An increased incidence of non-neoplastic hyperplastic polyps in the cecum was noted in the 5.0% males. The incidences of cystic changes and fibroadenomas of the mammary gland, and foci (areas) of hepatocellular alteration in the 5.0% females, and liver bile duct proliferations in the 5.0% males were significantly decreased. No proliferative lesions of the urinary bladder related to treatment with quercetin were found in any rats. The incidences of several other nonneoplastic and neoplastic lesions which demonstrated statistically significant changes appeared to be related to the growth retardation or to be within the normal range, and therefore none was considered to be significant biologically. Thus, the investigation did not demonstrate any clear carcinogenic effect of quercetin on F344 rats at dietary levels of up to 5.0%.     

A Relationship between Clomipramine Brain Concentration and Its Effect on Serotonin Metabolism

Abstract: The relationship between clomipramine (CMP) brain concentration and its inhibitory effect on serotonin (5HT) turnover was investigated in rats treated with a single dose and multiple doses of CMP. CMP reduced the 5-hydroxyindole acetic acid (5HIAA) brain levels in two groups of rats. Concerning the 5HT turnover measured by the probenecid (PBC) technique, there were significant correlations between the CMP brain level (x) and 5HIAA brain level (y) after PBC injections in both acute and chronic experiments. The regression lines for the respective groups were y = 764 - 117 log x (r = 0.84, P < 0.001) and y - 770 - 97.7 log x (r - 0.68, P < 0.001). The regression coefficient for the acute experiment was greater than that for the chronic one (p < 0.001), indicating a less dose-response in the latter. From these findings, the acute dosing with CMP seemed to reduce the 5HT turnover without reference to the dose but a prolonged administration seemed to vary in its effect. This may be due to a compensatory mechanism in the 5HT system induced by chronic CMP-treatment.     

Production and characterization of a monoclonal antibody to the v-mos oncogene protein.

Valuable information about proto-oncogenes and their physiological functions has been obtained by studying their expression in normal cells. However, the protein product of the c-mos gene, the cellular homologue of the transforming gene (v-mos) of Moloney murine sarcoma virus, has not been detected in normal mouse cells or tissues. Here, we have constructed a v-mos expression vector, pRI-delta mos, which directs the synthesis of a truncated v-mos gene product, a protein A fusion protein. Using the truncated v-mos oncoprotein produced in Escherichia coli as immunogen, we prepared anti-v-mos monoclonal antibodies (MAbs). In immunoblotting assays, the MAb was reactive with v-mos oncoprotein and detected bands at 43 KDa or 39 kDa in the tissue extract of mouse testes or ovaries, respectively, in which the c-mos protooncogene mRNA is expressed. These results demonstrate that the v-mos MAb obtained is suitable for elucidating the physiological functions of v-mos gene product and may also be utilized to detect c-mos gene product at the cellular level.     

Acoustic neurinoma presenting with repeated intratumoral hemorrhage. Case report

A case of acoustic neurinoma with multiple intratumoral hemorrhages is reported. A 56-year-old male noted sudden hearing reduction in his left ear in October of 1985. The diagnosis of a local physician was sudden deafness. About 10 months later, he had two episodes of severe headache without nausea or vomiting. The patient was hospitalized in October of 1986. Neurological examination cerebellar ataxia. cerebellar ataxia. Plain and enhanced computed tomography revealed only an unremarkable low-density area at the left cerebellopontine angle. In contrast, magnetic resonance imaging (MRI) clearly demonstrated a large (3 x 4 x 5 cm), multicystic tumor in the site. On exposure of the tumor at surgery, most of the cysts were found to be filled with a dark red or xanthochromic fluid. The tumor was completely removed following numerous cyst punctures to decrease its volume. There was no evidence of subarachnoid hemorrhage. Histological examination showed a typical acoustic neurinoma. The cyst wall contained numerous telangiectasia-like lesions. The initial symptom of this patient was sudden hearing loss, which is an atypical manifestation of acoustic neurinoma. The massive intratumoral hemorrhage was thought to be caused by telangiectatic lesions in the cyst wall. MRI clearly demonstrated the hemorrhagic cysts within the tumor, especially in the posterior fossa.     

MRP2基因单核苷酸多态性对晚期卵巢癌铂类化疗敏感性的影响

目的 :探讨MRP2基因单核苷酸多态性与晚期卵巢癌对铂类化疗敏感性的关系。方法 :本研究包括 89例晚期卵巢癌患者 ,其中Ⅲ期 77例 ,Ⅳ期 12例。所有患者均行肿瘤细胞减灭术 ,术后常规化疗 6～ 8疗程 ,均用顺铂加紫杉醇及其他药物化疗。 89例患者中 ,完全缓解 (CR)或部分缓解 (PR) 6 2例 ,肿瘤无变化 (NC)或进展 (PD) 2 7例。采用单核苷酸延伸技术 ,检测肿瘤组织中MRP2基因促进子 (C 2 4T)、第 10外显子 (G12 4 9A)及第 2 8外显子 (C3972T)的单核苷酸多态性。观察其对铂类化疗敏感性的影响。结果 :MRP2基因促进子及第 2 8外显子单核苷酸多态性对卵巢癌患者对铂类化疗反应无明显影响 ,而MRP2基因第 10外显子突变型与铂类化疗敏感性密切相关 (P <0 0 5 )。结论 :MRP2基因第 10外显子单核苷酸多态性影响晚期卵巢癌患者对铂类化疗的敏感性     

Usefulness and limitations of ECG-gated myocardial single-photon emission computed tomography with 99mTc-methoxy-isobutyl-isonitrile (MIBI) in patients with prior myocardial infarction]

To evaluate the relationship between regional wall motion and 99mTc-methoxy-isobutyl-isonitrile (MIBI) uptake, ECG-gated single-photon emission computed tomography (SPECT) with 99mTc-MIBI was performed in 20 patients with prior myocardial infarction. The left ventricular images at end-diastole (ED) and end-systole (ES) were divided into 39 segments, respectively. Based on circumferential profile analysis, relative uptake (%EDc, %ESc), percent count increase (% delta C), and normalized percent count increase (% delta Cn) were analyzed in each segment and compared with regional wall motion indices assessed by echocardiography and left ventriculography. ECG-gated SPECT with 99mTc-MIBI provided high contrast tomograms of the left ventricular myocardium. %EDc and %ESc showed good correlations with regional wall motion indices. % delta C and % delta Cn, however, showed lower correlations compared with %EDc and %ESc. In conclusion, high-quality left ventricular images were obtained with 99mTc-MIBI ECG-gated SPECT, but quantitative analysis based on only percent count increase (% delta C) have limitations for evaluation of regional wall motion.     

Localized amyloidosis of urinary bladder: a case report

A case of localized amyloidosis of the urinary bladder is reported. A 82-year-old woman visited our hospital with the chief complaint of miction pain and residual urine sensation. Cystoscopic examination revealed a broad-based and nonpapillary tumor without bleeding on the right lateral wall. A transurethral biopsy of this tumor was performed. A histopathological examination with H.E. and Congo red stains demonstrated amyloid deposition in the submucosal layers of the vesical wall. Rectal biopsy and other findings suggested no deposition of amyloid in other organs. On the basis of these findings, we made a diagnosis of localized amyloidosis of the urinary bladder. To the best of our knowledge, the present case is the 23rd of localized amyloidosis of urinary bladder in Japan. The patient was asymptomatic after biopsy. We discuss the clinical features and management of this disease.     

The usefulness of prolonged high dose delayed contrast computed tomography for the diagnosis of intracranial angiographically occult vascular malformations

It is difficult to diagnose angiographically occult vascular malformations. When conventional CT (plain & contrast enhancement) can not demonstrate the lesions, it was impossible to diagnose in the past. We developed a new technique which enabled us to diagnose them. Materials and methods; Seven cases of spontaneous intracerebral hemorrhage, in which no abnormality was detected by repeated magnified serial angiography with subtraction technique and prolonged injection technique, were examined. In each case, conventional CT (plain & enhancement using 100 ml of 60% meglumine iothalamate) was performed first, which was immediately followed by the administration of 220 ml of 30% meglumine iothalamate for one hour. CT is taken at the end of the infusion. It, we call, is prolonged high dose delayed contrast CT: PHDD-CT. Total dose of iodine used in this technique was 59.22 gI (1.0 gI/kg body weight: BW). Results; Contrast enhancement effect of PHDD-CT was much better than that of conventional CT in all the cases. In three cases, the lesions were more clearly delineated in PHDD-CT. In four cases, only PHDD-CT could demonstrate the lesions. No side effect was observed. Comments; Several techniques for better enhancement have been reported, however they used large volume of contrast medium such as 1.5 or 2.0 gI/kg BW. Our technique can be performed with more security. Based on our good results, we recommend to use this PHDD-CT technique for the diagnosis of angiographically occult vascular malformations.     

Clinical study on heterogeneity of chronic myelomonocytic leukemia

We examined fourteen patients with chronic myelomonocytic leukemia (CMMoL) according to the following staging criteria at diagnosis; Group A: bone marrow (BM) blast less than 5% (eight cases), Group B; BM blast more than 5% and less than 30% (five cases), Group C; BM blast more than 30% (one case). Compared with Group A, Group B patients have much more peripheral blood leukocyte, granulocyte and monocyte counts, LDH level, and serum and urine lysozyme levels. Two of the five Group B cases transformed to acute leukemia (BC) within one and a half year, and other three patients died of infection and hemorrhage within a year. On the contrary, three of the eight Group A patients survived four years, and transformation to acute leukemia occurred in only one case after four years. Autopsy revealed multiple organ infiltration of monocytoid granulocytes on the patients with advanced stage and more bone marrow blasts. Two cases have coexistence of myeloproliferative disorders, one with essential thrombocythemia, and another with myelofibrosis, which, later, transformed to acute leukemia. And a Group C patient transformed to chronic phase with chemotherapy, and maintained the state for six years, but at the end stage, mature monocytes increased and pancytopenia developed. These findings indicate the heterogeneity of CMMoL in respect of the disease stage and the coexistence of other myeloproliferative disorders.