Higher melatonin secretion is associated with lower leukocyte and platelet counts in the general elderly population: the HEIJO‐KYO cohort

Circulating white blood cell (WBC) and platelet (PLT) counts are widely available and inexpensive cellular biomarkers of systemic inflammation and have been associated with a risk of cardiovascular disease, cancer, and mortality. Melatonin may reduce systemic inflammation through its direct and indirect antioxidative effect; however, the associations of melatonin secretion with systemic inflammation remain unclear. In this cross‐sectional study on 1088 elderly individuals (mean age, 71.8 years), we measured overnight urinary 6‐sulfatoxymelatonin excretion (UME) and WBC and PLT counts as indices of melatonin secretion and systemic inflammation, respectively. UME was naturally log‐transformed for linear regression models because of skewed distribution (median, 6.8 μg; interquartile range, 4.1–10.6 μg). Univariate models revealed that higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (P = 0.046 and 0.018). After adjusting for potential confounding factors significantly associated with WBC or PLT counts, higher log‐transformed UME levels were significantly associated with lower WBC and PLT counts (WBC: β, ?0.143; 95% confidence interval, ?0.267 to ?0.020; P = 0.023; PLT: β, ?6.786; 95% confidence interval, ?12.047 to ?1.525; P = 0.012). Furthermore, the adjusted mean differences in WBC and PLT counts between the lowest and highest UME tertile groups were 0.225 × 10⁹/L and 9.480 × 10⁹/L, respectively. In conclusion, melatonin secretion was significantly and inversely associated with WBC and PLT counts in the general elderly population. The associations were independent of several major causes of systemic inflammation, including aging, obesity, smoking, hypertension, diabetes, and physical inactivity.     

Fractal dimensions of ductal patterns in the parotid glands of normal subjects and patients with Sj?gren syndrome.

RATIONALE AND OBJECTIVES. The sialographic ductal patterns of the parotid glands in patients with Sj?gren syndrome were compared with those of normal patients by measuring the fractal dimensions. METHODS. Fractal dimensions were estimated using the modified pixel dilation method. RESULTS. The mean fractal dimension was 1.64 +/- 0.06 for the normal glands and 1.39 +/- 0.10 for the glands with Sj?gren syndrome (P < .005). No correlation between the age or sex and fractal dimension was observed for both groups. In Sj?gren syndrome, a significant difference in the fractal dimension was observed between the subgroup having punctuate fillings with a diameter less than 1 mm and the subgroup from 1 to 2 mm (P < .001). CONCLUSION. The fractal dimension is useful as a numeric grading of the complexity of the ductal pattern and the progression of parotid disease.     

Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents enhanced by β-adrenergic stimulation

 To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type Ca²⁺ currents (I _Ca,L) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I _Ca,L was recorded by a step-pulse protocol after eliminating K⁺ conductances (internal Cs⁺ plus tetraethylammonium chloride and K⁺-free extracellular solution). A-II (100 nM) did not affect basal I _Ca,L, but inhibited I _Ca,L that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I _Ca,L was completely blocked by A-II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT₁) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A-II also inhibited the I _Ca,L enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I _Ca,L enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT₁ receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent accentuated antagonism of inotropy.     

Genetic contribution of tumor necrosis factor (TNF)-alpha gene promoter (-1031, -863 and -857) and TNF receptor 2 gene polymorphisms in endometriosis susceptibility

PROBLEM: Tumor necrosis factor (TNF)-alpha is a major cytokine involved in inflammatory and immune function. The aim of this study was to investigate whether polymorphisms at positions -1031, -863 and -857 in the TNF gene promoter region (TNFA) and TNF receptor type 2 gene (TNFR2) are responsible in part for genetic susceptibility to endometriosis. METHODS OF STUDY: TNFA and TNFR2 polymorphisms were determined in 123 patients with endometriosis and 165 fertile healthy women by the polymerase chain reaction (PCR) - preferential homoduplex formation assay and PCR-restriction fragment length polymorphism, respectively. RESULTS: The frequency of the TNFA-U01 haplotype was increased significantly in patients with endometriosis compared with controls (P = 0.045, OR = 1.45). The TNFA-U01 haplotype was strongly associated with HLA-B*0702. No difference was found in TNFR2 polymorphism between patients and controls. CONCLUSION: Our results indicated that TNFA promoter polymorphism was associated with susceptibility to endometriosis. However, this association was not independent of HLA-class I polymorphisms.     

Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues

Immunohistochemical studies were performed to clarify the significance of the expression or overexpression of epidermal growth factor (EGF), EGF-receptor (EGFR), p53, v- erb B, ras p21 in 23 cases each of tubular adenoma and adenocarcinoma. The expression of EGF, EGFR, p53, v- erb B, and ras p21 in paraffin-embedded tissues, from 46 patients with colorectal tumors (adenoma: 23 cases; 14 mild dysplasia, six moderate dysplasia, three severe dysplasia, adenocarcinoma: 23 cases; 17 well differentiated, two moderately differentiated, three poorly differentiated, one mucinous carcinoma was analyzed immunohistochemically using anti-EGF, EGFR, p53, v- erb B and ras p21 antibodies. The EGF and ras p21 tended to express more strongly in carcinoma cases than in the adenoma cases, and in severe and moderate dysplasia than in mild dysplasia (EGF: stained positive in five adenomas [21.74%] and 17 adenocarcinomas [73.91%]; ras p21: stained positive in six adenomas [26.09%] and 14 adenocarcinomas [60.87%]. The EGFR stained positive in two adenomas (8.70%) and two adenocarcinomas (8.70%). The p53 and v- erb B showed positive staining only in the carcinoma cases (p53: stained positive in four cases [17.39%]; v- erb B: stained positive in eight cases [34.78%]). This study suggests that these factors seem to have some role in the progression of colon neoplasms. It suggests that genetic alteration is not always equal to the overexpression of protein products, but that it reflects them well, and that the staining makes some contribution to differential diagnosis in colorectal neoplasms.     

Parosteal fasciitis of the clavicle

A rare case of parosteal fasciitis arising from the periosteum of the left clavicle in a 27-year-old woman is reported. Magnetic resonance imaging demonstrated the lesion surrounding the periosteum of the clavicle. The lesion was iso-intense with muscle on T(1)-weighted images and hyperintense on T(2)-weighted images. At surgery, the lesion was discovered to be densely adherent with the periosteum, and excised along with the periosteum. Histopathological examination revealed the proliferation of myofibroblasts in a vague storiform or short fascicular pattern. A large amount of extravasated erythrocytes, and a few lymphocytes were present in the matrix. There were some foci of abundant myxoid materials. Immunohistochemical study showed the cells to be positive for vimentin, alpha-smooth muscle actin and HHF35, but negative for desmin. There was no local recurrence at a 6 months postoperative follow up.     

Familial amyloidotic polyneuropathy (ATTR Ser50Ile): the first autopsy case report

We report an autopsy case of a pedigree of familial amyloidotic polyneuropathy (FAP) with a mutation of isoleucine-50 transthyretin (ATTR Ser50Ile). A 47-year-old man started developing severe diarrhea and weight loss at age 41 years, followed by urinary incontinence, autonomic-nervous-system abnormalities and serious heart failure; the diagnosis of FAP (ATTR Ser50Ile) was made on the basis of genetic, histochemical and immunohistochemical analysis. Six years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, perforation of the sigmoid colon and marked systemic amyloid deposition. The total amount of amyloid deposited in the heart was greatly increased and was much lower in the thyroid gland and kidneys compared with amyloid deposits in ordinary FAP (ATTR Val30Met). Amyloid deposition in peripheral vessel walls was prominent, particularly in lymphatics and veins. His elder sister, 54 years old, started to develop orthostatic hypotension at age 49 years, followed by dysesthesia, diarrhea and severe congestive heart failure. Endomyocardial biopsy revealed severe TTR–amyloid deposition; ultrastructural examination demonstrated that amyloid fibrils were deposited disproportionately and extended radially around microvessels. These characteristic patterns of systemic amyloid deposition and distinct clinical manifestations, especially in the cardiovascular system, are considered to be a characteristic feature of ATTR Ser50Ile amyloidosis. Received: 31 August 1999 / Accepted: 19 October 1999     

Mapping-guided focal cryoablation and endoaneurysmorrhaphy for a case of ischemic ventricular tachycardia with left ventricular aneurysm

A 74-year-old woman admitted with exertional dyspnea. Echocardiography revealed the giant left ventricular aneurysm. In the hospital course, she fell into sustained monomorphic ventricular tachycardia. Coronary angiogram showed complete obstruction of the LAD. Left ventricular ejection fraction was 20%. The origin of tachycardia seems to be at infero-apicallateral area of LV by electrophysiology study. Because of the failure of RF energy ablation, we planned mapping-guided cryoablation, CABG and endoaneurysmorrhaphy. To prevent air embolism and myocardial ischemic damage for long aortic cross clamp, intraoperative endocardial mapping was carried out on beating heart due to continuous normothermic coronary blood perfusion (300 ml/min) from the aortic root cannula under aortic clamping. Cold crystalloid cardioplegia changed into the root cannula after EPS, focal cryoablation (-100 degrees C) was performed 3 times on cardiac arrest. Sustained VT was not inducible in the following study. CABG and endoaneurysmorrhaphy was performed on repeated cardiac arrest during single aortic clamp. Postoperative course was uneventful, and she discharged 8 weeks after the operation.     

Molecular epidemiological study on tetracycline resistance R plasmids in enterohaemorrhagic Escherichia coli O157:H7.

Restriction patterns obtained with EcoRI and Southern hybridization were used for the differentiation of tetracycline-resistant (Tet(r)) R plasmids in enterobaemorrhagic Escherichia coli (EHEC) O157:H7 isolates from a mass outbreak at a kindergarten in Obihiro-City, Hokkaido, Japan, 1996. Two kinds of Tet(r) R plasmids of 50 and 95 kb were detected. The 50-kb plasmids were identical to each other, while the 93-kb plasmids were of three types that were very similar to each other. The tet genes of both 50- and 95-kb R plasmids were 100% identical to the tet gene of pSC101 and all plasmids hybridized to a probe for tet. Because food-origin O157 strains were sensitive to tetracycline, we concluded that such Tet(r) R-plasmids might transfer to drug-sensitive O157 strains in the infected individuals.