Cerivastatin inhibits fetal calf serunvinduced DNA synthesis in cultured rat mesangial cells

SUMMARY: Inhibition of mevalonate synthesis by several statins has been shown to suppress DNA synthesis in glomerular mesangial cells. In the present study, we investigated the effect of a new statin, cerivastatin, on fetal calf serum (FCS)-induced DNA synthesis of cultured rat mesangial cells. Cultured rat mesangial cells were stimulated by 10% FCS in the presence or absence of cerivastatin and mevalonate. 5-bromo-2-deoxyuridine (BrdU) incorporation was used to assess DNA synthesis. the present study showed that 10% FCS caused marked stimulation of DNA synthesis in the mesangial cells. Cerivastatin inhibited FCS-stimulated BrdU incorporation in a dose-dependent manner. IC₅₀ was approximately 1 umol/L. Exogenous mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented the inhibitory effect of cerivastatin on DNA replication. It appears that cerivastatin, by inhibiting the synthesis of mevalonate, may suppress DNA synthesis in the mesangial cells.     

Successful treatment for squamous cell carcinoma of the female urethra with combined radio- and chemotherapy

We report on two cases of women with locally advanced squamous cell carcinoma of the urethra. Patient 1 also displayed regional lymph node metastasis. Treatment comprised combined radiotherapy to 60 Gy and chemotherapy with 5-fluorouracil and cisplatin. Complete response was obtained in both patients, including the inguinal lymph nodes of Patient 1. Patient 1 experienced recurrent inguinal lymph node metastasis on the contralateral side at 42 months after initial treatment, and the same treatment was performed followed by surgical excision. Both patients remain alive with no evidence of disease, at 12 months after recurrence in Patient 1, and at 27 months after treatment in Patient 2.     

Long-term survival after bilateral adrenalectomy for metachronous adrenocortical cancer

We report the case of a female patient with bilateral metachronous adrenocortical cancer who survived long-term after adrenalectomy. In 1991, the patient underwent left adrenalectomy to remove a huge adrenal mass (10 x 9 cm) displaying no hormonal abnormality. Histological diagnosis was adrenocortical cancer. A right adrenal mass (7 x 6 cm) was found 4 years after left adrenalectomy. Right adrenalectomy was performed, and histological diagnosis was again adrenocortical cancer. The patient remains alive with no evidence of disease 8 years after last surgery.     

Inhibition of Lipid Peroxidation by Sesquiterpenoid in Heterotheca inuloides

A sesquiterpenoid, 7-hydroxy-3,4-dihydrocadalin, isolated from a Mexican medicinal plant Heterotheca inuloides was evaluated as an antioxidant. This sesquiterpenoid inhibited mitochondrial and microsomal lipid peroxidation induced by Fe(III)-ADP/NADH or Fe(III)-ADP/NADPH. Furthermore, 7-hydroxy-3,4-dihydrocadalin protected red cells against oxidative haemolysis. This sesquiterpene was thus shown to be effective in protecting biological systems against oxidative stresses.     

A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β-2-Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

PROBLEM : To determine if patients with unexplained recurrent miscarriage have a deficiency of decidual immunosuppressor cells that produce transforming growth factor β type 2, as has been found in mice with abortion due to rejection and/or trophoblast failure. METHODS : Decidual biopsy specimens were taken as near to the placental attachment site as possible under ultrasound guidance from first trimester legal termination (control) patients with recurrent miscarriage and non-viable pregnancy, and from patients with sporadic missed abortion. The tissue was tested for TGFβ-2⁺ suppressor cells by in situ hybridization, immunohistochemistry, and analysis of supernatants. RESULTS : TGFβ-2-related suppressor molecules similar but not identical to those identified in pregnant mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent miscarriage patients showed a lack of suppressor cells and 59% were subnormal in comparison to 20 controls and 5 sporadic miscarriage patients, where 80–85% of the patients had detectable suppressor cells. CONCLUSIONS : Suppressor cell deficiency is compatible with a role for rejection and/or trophoblast failure in some patients with recurrent miscarriage. Presence of suppressor cells in most patients with missed abortion (4/5) is compatible with an alternative cause of fetal death, similar to findings reported in genetic fetal death mice.     

Bacterial invasion into the colonic mucosa in ulcerative colitis

Abstract This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.     

The Effect of Cimetidine on Natural Killer Activity of Peripheral Blood Lymphocytes of Patients with Ovarian Carcinoma

The effect of cimetidine on the natural killer (NK) activityof peripheral blood lymphocytes (PBL) of 32 patients with ovariancarcinoma was studied before and after surgery or chemotherapy.There was no significant difference in the NK activity betweennormal healthy women and patients who had been disease-freefor more than a year after initial surgery, while those in patientswith a large residual tumor after surgery were profoundly suppressed.Cimetidine stimulated the NK activity in the disease-free patientsin vivo or in Vitro. In addition, cimetidine augmented the responseto phytohemagglutinin of PBL from the disease-free patients.The NK activity of PBL of patients with a large residual tumorunder chemotherapy consisting of cisplatinum, adriamycin andcyclophosphamide, "CAP," was about half of that before initiationof chemotherapy. The inhibition of the NK activity by chemotherapywas abrogated by in vitro exposure of the PBL to cimetidine.     

A Case of Pneumocytoma (So-Called Sclerosing Hemangioma) With Lymph Node Metastasis

A case of "sclerosing hemangionia" (pneumocytoma) of the lungwith lymph node metastasis is reported. A 22-year-old Japaneseman was found to have a well-defined round lesion in the rightlung (S⁷), which increased in size slightly during a 2-yearfollow-up period. He underwent right lower lobectomy with a preoperative diagnosisof a benign lung tumor. The pulmonary tumor revealed histologicalfeatures characteristic of "sclerosing hemangioma" of the lung,in addition to which there were many large polygonal foamy cells,forming tubular or papillary structures. These cells were foundby electron microscopy to contain numerous cytoplasmic lamellarbodies and showed a positive reaction with anti-surfactant apoproteinantibody immunohistochemically. Therefore, they were consideredto be cells differentiating toward type II pneumocytes. Reviewof 21 typical "sclerosing hemangionia" disclosed a few or somesuch foamy cells in 10 cases. A single hilar lymph node wasthe site of microscopic metastases, which consisted of "largeclear foamy cells" and smaller polygonal or round cells withslightly eosinophilic cytoplasm, both of which were componentsof the pulmonary "sclerosing hemangioma" This case supportsthe theory that "sclerosing hemangioma" is a neoplasm of typeII pneumocyte lineage. Although it is said to be benign, rarecases apparently show metastatic potential.     

Serum hyaluronic acid reflects the effect of interferon treatment on hepatic fibrosis in patients with chronic hepatitis C

Changes in serum hyaluronic acid (HA) in 35 patients treated with interferon (IFN) were studied and the histological change in fibrosis was analysed. Serum HA levels and hepatitis C virus (HCV) RNA were followed from the start of therapy to 12 months after completion of treatment. Histological changes in pre- and post-treatment liver biopsies were assessed using a modified Knodell's scoring system. The serum levels of HA (r = 0.79; P<0.0001) correlated with the degree of fibrosis more closely than with that of amino terminal peptides of type III procollagen (PIIIP; r = 0.45; P<0.05) or type IV collagen (IV-C; r = 0.42; P<0.05). Only complete responders (CR) had a significant decrease in serum levels of HA and IV-C (P<0.05), in parallel with histological improvement (P<0.01). Neither partial responders (PR) nor non-responders (NR) had significant changes in histological scores and in serum levels of fibrotic markers. Significant differences were observed between CR and NR, both in HA levels (P<0.01) and PIIIP levels (P<0.05) 12 months after the cessation of treatment. These results suggest that serum HA is an indicator of the extent of fibrosis in chronic hepatitis C. Serial determinations of serum HA levels may be of use for monitoring the histological response of hepatic fibrosis to IFN treatment in chronic hepatitis C.     

Adrenoleukodystrophy indicated by abnormal electroencephalography

An 8 year old boy with adrenoleukodystrophy and his asymptomatic brother, both with abnormal electro-encephalography as the initial sign of adrenoleukodystrophy, are reported. After suffering from aseptic meningitis caused by Echo virus 30, the first case was suspected of having a complication of meningitis because of persistent abnormal electro-encephalography (i.e. slow wave bursts in the occipital region). This patient was finally diagnosed as having adrenoleukodystrophy because of the increased level of very long chain saturated fatty acids, and typical occipital lesions demonstrated by magnetic resonance imaging and computed tomography. Dietary therapy was tried, but the course was progressive. The brother's electroencephalography was also abnormal and so was diagnosed as having asymptomatic adrenoleukodystrophy because of an increased level of very long chain saturated fatty acids, although brain magnetic resonance imaging was normal. Abnormal electro-encephalography can therefore be an initial sign of adrenoleukodystrophy even if magnetic resonance imaging shows no abnormality in the brain.