The pineal gland is not essential for circadian expression of rat period homologue (rper2) mRNA in the suprachiasmatic nucleus and peripheral tissues

To investigate the functional involvement of the pineal gland in circadian expression of the rat period homolog gene (rPer2) in the suprachiasmatic nucleus (SCN) and peripheral tissues, we performed Northern blot analysis in tissues from pinealectomized rats. The ectomy did not have any significant effects on rPer2 mRNA expression patterns both in a daily light-dark condition and in a constant darkness. These results suggest that the rhythmic secretion of pineal melatonin is not essential for the circadian expression of clock genes in the SCN and other peripheral tissues of rats.     

Spontaneous closure of ventricular septal defects followed up from <3 months of age

BACKGROUND: This study evaluates the incidence and timing of spontaneous closure (SC) of ventricular septal defect (VSD) using Doppler color flow mapping. METHODS: A total of 225 infants (mean age 30 days) were diagnosed with uncomplicated VSD: 31 (14%) subpulmonary VSD, 159 (70%) perimembranous, and 35 (16%) muscular. The patients were divided into two groups according to the presence or absence of congestive heart failure (CHF). SC was confirmed with color Doppler. RESULTS: Surgical closure was performed in 59 patients (26%). SC occurred in 107 patients (48%); three (10%) of 31 with subpulmonary VSD, 75 (47%) of 159 with perimembranous VSD, and 29 (83%) of 35 with a muscular VSD. Average age at SC was 19 months. In three SC patients with a subpulmonary VSD, there was no aortic valve prolapse and no aortic regurgitation. SC occurred in 96% of SC patients with a perimembranous VSD by the age of 6 years, and in 93% of those with a muscular VSD by the age of 3 years. In patients without CHF, the rate of SC was 72%; 23% in subpulmonary VSD, 74% in perimembranous, and 85% in muscular. SC occurred in only 23% of patients with a perimembranous VSD with CHF. Mean age at the final examination was 6.9 years in 59 patients with a VSD remaining open, and 63% of patients with a perimembranous VSD remaining open had an aneurysm of the ventricular membranous septum. CONCLUSIONS: The SC rate of VSD by mean age of 6.9 years was 48%, but it was 72% in patients without CHF. In patients with CHF, SC was seen only in patients with a perimembranous VSD. The rate of SC was 10% in subpulmonary VSD. The authors contend that SC probably occurred by growth of muscular septum surrounding VSD. Muscular VSD spontaneously closed earlier than perimembranous VSD.     

Life-table analysis of artificial insemination pregnancy rates for couples with male factor and idiopathic infertility

Background :  In the summer of 2002, standard guidelines for the application of assisted reproductive technology were reported by a research group of the Ministry of Health, Labor and Welfare. The present study aimed to examine the relationship between the number of cycles of artificial insemination and the cumulative pregnancy rates according to the cause of infertility.
Methods :  Patients who experienced their first cycle of artificial insemination during the period of January 1999–December 2002 were included in the study and were divided into a male factor infertility group and an idiopathic infertility group. Cumulative pregnancy rates resulting from artificial insemination with the husband's semen were calculated by the life-table approach.
Results :  During the study period, 139 couples entered the assisted reproduction program and underwent 581 cycles. Significant differences were observed in cumulative pregnancy rates between the two groups.
Conclusion :  It is recommended that couples with male factor infertility and who fail to conceive within six or seven cycles of intrauterine insemination, consider a modification of treatment strategy such as in vitro fertilization, because cumulative pregnancy rates of this group were reached at a plateau within six or seven cycles. In contrast, patients with idiopathic infertility, the cumulative pregnancy rates appeared to increase constantly with each subsequent cycle. It is important to consider modifications of treatment strategy in the light of the cause of infertility. (Reprod Med Biol 2004; 3 : 27–31)     

Diagnostic and prognostic role of urinary collagens in primary human bladder cancer

Collagen type 4 alpha 1 (COL4A1) and collagen type 13 alpha 1 (COL13A1) produced by urothelial cancer cells support the vital oncogenic property of tumor invasion. We investigated the diagnostic and prognostic capability of COL4A1 and COL13A1 in voided urine and compared the observed values with those of fragments of cytokeratin‐19 (CYFRA21‐1), nuclear matrix protein 22 (NMP‐22), and voided urine cytology in bladder cancer (BCa). We collected voided urine samples from 154 patients newly diagnosed with BCa, before surgery and from 61 control subjects. Protein levels of COL4A1, COL13A1, CYFRA21‐1, and NMP‐22 in urine supernatants were measured using enzyme‐linked immunosorbent assays. Diagnostic performance and optimal cut‐off values were determined by receiver operating characteristic analysis. Urine levels of COL4A1, COL13A1, the combined values of COL4A1 and COL13A1 (COL4A1 + COL13A1), and CYFRA21‐1 were significantly elevated in urine from patients with BCa compared to the controls. Among these biomarkers, the optimal cut‐off value of COL4A1 + COL13A1 at 1.33 ng/mL resulted in 57.4%, 83.7%, 56.1%, 80.7%, and 91.7% sensitivity for low‐grade tumors, high‐grade tumors, Ta, T1, and muscle invasive disease, respectively. We evaluated the prognostic value of preoperative urine levels in 130 non‐muscle invasive BCa samples after the initial transurethral surgery. A high urinary COL4A1 + COL13A1 was found to be an independent risk factor for intravesical recurrence. Although these data need to be externally validated, urinary COL4A1 and COL13A1 could be a potential diagnostic and prognostic biomarker for BCa. This easy‐to‐use urinary signature identifies a subgroup of patients with a high probability of recurrence and progression in non‐muscle invasive and muscle invasive BCa.     

CXCL12/CXCR4 activation by cancer‐associated fibroblasts promotes integrin β1 clustering and invasiveness in gastric cancer

Cancer‐associated fibroblasts (CAFs) are reportedly involved in invasion and metastasis in several types of cancer, including gastric cancer (GC), through the stimulation of CXCL12/CXCR4 signaling. However, the mechanisms underlying these tumor‐promoting effects are not well understood, which limits the potential to develop therapeutic targets against CAF‐mediated CXCL12/CXCR4 signaling. CXCL12 expression was analyzed in resected GC tissues from 110 patients by immunohistochemistry (IHC). We established primary cultures of normal fibroblasts (NFs) and CAFs from the GC tissues and examined the functional differences between these primary fibroblasts using co‐culture assays with GC cell lines. We evaluated the efficacy of a CXCR4 antagonist (AMD3100) and a FAK inhibitor (PF‐573,228) on the invasive ability of GC cells. High CXCL12 expression levels were significantly associated with larger tumor size, increased tumor depth, lymphatic invasion and poor prognosis in GC. CXCL12/CXCR4 activation by CAFs mediated integrin β1 clustering at the cell surface and promoted the invasive ability of GC cells. Notably, AMD3100 was more efficient than PF‐573,228 at inhibiting GC cell invasion through the suppression of integrin β1/FAK signaling. These results suggest that CXCL12 derived from CAFs promotes GC cell invasion by enhancing the clustering of integrin β1 in GC cells, resulting in GC progression. Taken together, the inhibition of CXCL12/CXCR4 signaling in GC cells may be a promising therapeutic strategy against GC cell invasion.     

Unilateral Autoimmune Pulmonary Alveolar Proteinosis with Polymyositis-related Interstitial Lung Disease

A 61-year-old patient with cystic bronchiectasis and bronchial artery hyperplasia in the left lung was diagnosed with polymyositis-related interstitial lung disease. After nine months of immunosuppressive therapy, he developed unilateral autoimmune pulmonary alveolar proteinosis (APAP) in the right lung with respiratory failure. After bronchial artery embolization to prevent massive hemoptysis, whole-lung lavage was performed using veno-venous extracorporeal membrane oxygenation. His respiratory condition improved, and he was discharged from the hospital with supplemental oxygen. Three reported cases of APAP with polymyositis-related interstitial lung disease, including the present case, were all positive for anti-glycyl tRNA synthetase antibody and were under immunosuppressive treatment.     

Selectivity of cerebral vasodilators on basilar arteries

Ca-antagonistic activities of cerebral vasodilators, nicardipine and 1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100) were tested on basilar and renal arteries, thoracic aorta and portal vein of rabbit, and rat vas deferens. Both the cerebral vasodilators used herein had a selectivity to basilar arteries. The selectivity to the basilar arteries is considered to be one of the factors in deciding the pharmacological property of the cerebral vasodilators.     

Association between maternal gestational diabetes mellitus and high‐sensitivity C‐reactive protein levels in 8‐year‐old children: The Yamanashi Adjunct Study of the Japan Environment and Children’s Study (JECS)

Gestational diabetes mellitus (GDM) is one of the most common pregnancy‐related complications; it is associated with adverse pregnancy outcomes and metabolic disorders in offspring, consistent with the concept of the developmental origins of health and disease. This cohort study of women without diabetes (n = 761), who were part of the Yamanashi Adjunct Study of the Japan Environment and Children’s Study, aimed to explore the associations between maternal GDM and their offspring’s level of high‐sensitivity C‐reactive protein (hsCRP), a biomarker of inflammatory and cardiovascular diseases. We analyzed the associations between GDM and the offspring’s hsCRP levels using a multiple logistic regression model. A mother with GDM significantly increased the risk for high hsCRP level by 4.07‐fold (≥2.0 mg/L) in the child. As such, maternal GDM was significantly associated with increased serum hsCRP levels in 8‐year‐old children.     

The relationship between intraocular pressure and refractive error adjusting for age and central corneal thickness

PURPOSE: To investigate the relationship between intraocular pressure (IOP) and refractive errors after adjusting for age, central corneal thickness (CCT), and other related factors. METHODS: IOP, CCT and refractive errors were measured in the right eyes of 1855 subjects, aged 40-82 years, in a cross-sectional study design. Subjects were divided into groups by refractive status: hyperopia, emmetropia, mild myopia, moderate myopia, or high myopia. With adjustments for age, CCT, blood pressure, obesity, education, hypertension, diabetes, and smoking status, IOP was estimated for each refractive status using a general linear model. RESULTS: IOP increased with advancing degrees of myopia, even after adjustment for age, CCT, and other related factors (p = 0.011). Estimated IOP of moderate myopia was significantly higher than that of emmetropia (p = 0.022). CONCLUSIONS: Our results confirm the positive association between IOP and increasing degrees of myopia. This finding would support the hypothesis that the relationship between glaucoma and myopia might be pressure mediated.