R353Q polymorphism, activated factor VII, and risk of premature myocardial infarction in Japanese men.

BACKGROUND: The association between myocardial infarction (MI) and the R353Q polymorphism of the Factor VII (FVII) gene, which reportedly influences FVII concentrations, activated Factor VII (FVIIa), or FVII antigen (FVIIag), remains controversial. METHODS AND RESULTS: The present case - control study in 127 Japanese men with their first MI at or before 45 years of age and 150 matched healthy controls was designed to clarify this association in premature MI. R353Q polymorphism was determined by polymerase chain reaction, and plasma concentrations of FVIIa and FVIIag were assayed. The distribution of the RR, RQ, and QQ genotypes with respect to R353Q polymorphism was 117, 10, and 0 in the patients, and 131, 17, and 2 in the controls. The Q allele was negatively associated with premature MI (odds ratio =0.41, p=0.038). The plasma concentration of FVIIa was slightly higher in patients (55.1+/-40.9 U/L) than in controls (44.8+/-20.2 U/L), but not significantly (p=0.078); the plasma concentration of FVIIag did not differ between patients (88.7+/-15.7%) and controls (87.0+/-9.0%) (p=0.557). Plasma FVIIa concentrations were influenced by R353Q polymorphism (p<0.001). CONCLUSIONS: The Q allele may be protective against premature MI.     

Endocarditis caused by Candida parapsilosis.

The authors report a case of endocarditis caused by Candida parapsilosis. To the best of our knowledge, a case has not been described previously in Japan in the English literature. A battery of 8 peroxidase-labeled lectins was tested on sections of paraffin-embedded tissue to determine which lectin could be used in the microscopic diagnosis of C. parapsilosis. One lectin, from Archis hypoaea (PNA) was found to react with C. parapsilosis. On the other hand, C. albicans, Aspergillus, Mucor, and Cryptococcus did not react with A. hypoaea (PNA). On fluorescence microscopic study, C. parapsilosis was not fluorescent, but other fungi were fluorescent when exposed to ultraviolet illumination. Therefore, we propose new procedures for identification of C. parapsilosis in tissue sections using lectin histochemistry and fluorescence microscopy.     

Effects of 17beta-estradiol, nonylphenol, and bisphenol-A on developing Xenopus laevis embryos

Many chemicals released into the environment have the capacity to disrupt the normal development of aquatic animals. We investigated the influence of nonylphenol (NP), bisphenol-A (BPA), and 17beta-estradiol (E2) on developing Xenopus laevis embryos, as a model animal in the aquatic environment. Embryos were exposed to eight different concentrations of NP, BPA or E2 between 3 and 96 h post-fertilization (p.f.). Short body length, microcephaly, flexure, edema, and abnormal gut coiling were induced by 20 microM NP, BPA or 10 microM E2 by 96 h p.f. To clarify sensitive stages to these compounds, embryos were exposed to chemicals for 45 or 48 h starting at different developmental stages and experiments were terminated 96 h p.f. BPA and NP induced abnormalities in developing X. laevis, though the sensitive stages of embryos to these chemicals are different, BPA affecting earlier stages and NP affecting at later stages. To analyze the functional mechanisms of BPA and NP in induction of morphological changes, we adapted a DNA array technology and identified 6 X. laevis genes, XIRG, alpha skeletal tropomyosin, cyclin G1, HGF, troponin C2, and ribosomal protein L9. These findings may provide important clues to elucidate common mechanisms underlying teratogenic effects of these chemicals.     

Intraperitoneal administration of the biological response modifier OK-432 and peritoneal recurrence following gastrectomy

In patients with gastric cancer invading the serosa, there is often peritoneal dissemination. In an attempt to control such peritoneal recurrences, OK-432, a compound composed of penicillin G-treated, attenuated Streptococcus pyogens of human origin, was administered intraperitoneally at the time of gastrectomy. The non-specific antitumor activity of the peritoneal macrophages was investigated for its cytostatic activity against the cultured human lung cancer cell line, QG-90. OK-432 given intraperitoneally significantly increased the number of the peritoneal macrophages (p less than 0.05), and also enhanced the cytostatic activity (p less than 0.01). On the basis of these findings, OK-432 IP after gastrectomy was given to 13 of 68 patients with gastric cancer invading the serosa and who underwent curative resection. The five-year survival rate of patients given the drug was 63.5%, while the rate was 52.9% in those not given the drug. OK-432 IP seemed to be effective when lymph node involvement was nil or limited to around the area of the stomach. The peritoneal recurrence rate was, however, not affected by OK-432 IP. Elevation of body temperature and some dehydration were the only observed side effects of OK-432. In attempts to control peritoneal recurrences in patients with gastric cancer invading the serosa, randomized controlled trials on OK-432 IP are now being designed.     

Electrophysiologic properties of atrial muscle in paroxysmal atrial fibrillation

The electrophysiologic properties of atrial muscle were studied by programmed atrial stimulation in 42 patients with paroxysmal atrial fibrillation (PAF) and in 53 control patients without PAF. Single premature atrial stimulation was given at the right atrial appendage following 8 basic stimuli with a basic cycle length of 500 ms. Repetitive atrial firing (RAF) was defined as the occurrence of 2 or more successive premature atrial activations following single premature atrial stimulation. Fragmented atrial activity (FAA) was defined as an increase by more than 75% of the duration of the atrial electrogram in response to a single premature stimulation. Interatrial conduction delay was defined as an increase of the conduction time by more than 50 ms in response to a single premature stimulation. RAF was induced in 26 of 42 patients (61.9%) with PAF and in 14 of 53 control patients (26A%). FAA and interatrial conduction delay were elicited in 69.0 and 80.9% of patients with PAF and in 34.0 and 56.6% of control patients, respectively. In 16 patients with PAF in whom RAF was not induced, FAA developed in 11 patients (68.8%). In 88.1% of 42 patients with PAF and in 41.5% of 53 controls, RAF or FAA, or both, were elicited by atrial premature stimulation. It is concluded that the incidence of RAF and FAA were significantly higher in patients with PAF than in the control group, and the induction of RAF or FAA, or both, was closely related to the vulnerability of the atrial muscle to atrial fibrillation.     

Predictive factors for tumor response to chemotherapy in patients with pancreatic cancer

BACKGROUND/AIMS: Systemic chemotherapy for pancreatic adenocarcinoma, at present, has been of limited value in clinical practice and only a small portion of patients obtains meaningful palliation. METHODOLOGY: We retrospectively examined 96 patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy to determine factors predictive of tumor response. None of the patients had received any prior anti-cancer treatment except for pancreatectomy. RESULTS: Of these 96 patients, 5 patients (5.2%) showed partial response but none showed complete response. There was no responder with a performance status of 2 or 3, serum albumin level less than 3.5 g/dL, serum total bilirubin level equal to or more than 2.0 mg/dL, or peritoneal dissemination. Response rates tended to be higher in the subgroups of female patients, those with serum albumin level > or = 3.5 g/dL and those with serum carcinoembryonic antigen level < 10 ng/mL, although there were no significant differences. CONCLUSIONS: Patients with a poor performance status, hypoalbuminemia, jaundice, or peritoneal dissemination might be inappropriate candidates for systemic chemotherapy and might be treated with other experimental approaches or supportive care.     

Detailed kinetic analysis of adrenocorticotropin secretion by dispersed rat anterior pituitary cells in a microperifusion system: effects of ovine corticotropin-releasing factor and arginine vasopressin

We have developed a microperifusion system in which we have examined the ACTH secretory responses of acutely dispersed normal rat anterior pituitary cells to ovine CRF (oCRF) and arginine vasopressin (AVP), alone and in combination. The system approached square-wave stimulus hydrodynamics. ACTH secretion was observed within 5 sec of exposure to either secretagogue and reached a maximum within 20-40 sec. ACTH secretion remained constant for as long as oCRF was perifused and then fell gradually toward the basal level. Persistent ACTH release after oCRF perifusion was stopped could not be explained by persistence of oCRF in the perifusion chamber. In contrast to the response to oCRF, ACTH secretion fell progressively toward basal despite continued AVP perifusion. AVP had a synergistic effect with oCRF only if it was perifused simultaneously with oCRF or within 30 sec after oCRF was stopped; it had no synergistic effect if perifused immediately before oCRF. Simultaneous perifusion of oCRF and AVP resulted in an oCRF-like response of greater magnitude, whereas sequential perifusion of oCRF followed by AVP resulted in the usual plateau response to oCRF followed by the initial spike response characteristic of very high concentrations of AVP alone and a subsequent rapid decrease in secretion despite continued perifusion of AVP. The different kinetic response profiles suggest that oCRF and AVP act via different intracellular signal transduction pathways, and the time and sequence dependency of their synergism suggests that the factors that mediate their interactions have different intracellular half-lives. The microperifusion system appears to be uniquely suited to detailed kinetic analysis of anterior pituitary hormone secretion and the intracellular pathways through which secretagogues act and interact.