HTL V-I from Iranian Mashhadi Jews in Israel is phylogenetically related to that of Japan,India, and South America rather than to that of Africa and Melanesia

A new endemic focus of human T-lymphotropic virus type I (HTL V-I) was recently reported among Mashhadi Jews, a group of immigrants from northeastern Iran to Israel. We extracted DNAs from fresh peripheral blood mononuclear cells (PBMCs) and/or gargle mouthwash from 10 HTL V-I carriers, who consisted of members of one family, and HTL V-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL) patients. Long terminal repeat (LTR) regions of proviral DNAs were sequenced and analyzed phylogenetically. In a phylogenetic tree, all the Mashhadi HTL V-I isolates belonged to subtype A, one of the three subtypes of the cosmopolitan type of HTL V-I, and made a tight cluster distinct from the other isolates of subtype A from Japan, India, the Caribbean Basin, and South America. Although a few nucleotide substitutions were observed among the clones sequenced, no characteristic sequence variation was found in different disease manifestations, even in one family or different sources of DNA preparation.     

Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats

In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammutory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4g/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutroph il infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact ruts. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.     

Cannabinoid-induced presynaptic inhibition at the primary afferent trigeminal synapse of juvenile rat brainstem slices

Systemic or intraventricular administration of cannabinoids causes analgesic effects, but relatively little is known for their cellular mechanism. Using brainstem slices with the mandibular nerve attached, we examined the effect of cannabinoids on glutamatergic transmission in superficial trigeminal caudal nucleus of juvenile rats. The exogenous cannabinoid receptor agonist WIN 55,212-2 (WIN), as well as the endogenous agonist anandamide, hyperpolarized trigeminal caudal neurones and depressed the amplitude of excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) monosynaptically evoked by stimulating mandibular nerves in a concentration-dependent manner. The inhibitory action of WIN was blocked or fully reversed by the CB₁ receptor antagonist SR 141716A. WIN had no effect on the amplitude of miniature excitatory postsynaptic currents (mEPSCs) recorded in the presence of tetrodotoxin or cadmium. The inhibitory effect of WIN on EPSCs was greater for those with longer synaptic latency, suggesting that cannabinoids have a stronger effect on C-fibre EPSPs than on Aδ-fibre EPSPs. Ba²⁺ (100 μ m ) blocked the hyperpolarizing effect of cannabinoids, but did not affect their inhibitory effect on EPSPs. The N-type Ca²⁺ channel blocker ω-conotoxin GVIA (ω-CgTX) occluded the WIN-mediated presynaptic inhibition, whereas the P/Q-type Ca²⁺ channel blocker ω-agatoxin TK (ω-Aga) had no effect. These results suggest that cannabinoids preferentially activate CB₁ receptors at the nerve terminal of small-diameter primary afferent fibres. Upon activation, CB₁ receptors may selectively inhibit presynaptic N-type Ca²⁺ channels and exocytotic release machinery, thereby attenuating the transmitter release at the trigeminal nociceptive synapses.     

Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients

A few studies have reported a correlation between magnesium and co-morbidity and mortality in end-stage renal disease. We investigated the prognostic value of serum magnesium concentration for mortality in 515 patients on maintenance hemodialysis (60 +/- 12 years, 306 males and 209 females; 24% diabetics). The patients underwent follow-up for 51 +/- 17 (mean +/- SD) months, and the relationship between the baseline magnesium concentration (mean of four months) and outcomes was analyzed statistically. During the follow-up period, there were 103 all-cause deaths, including 63 non-cardiovascular deaths. Kaplan-Meier analysis revealed that mortality was significantly higher in the lower magnesium group (< 2.77 mg/dL, i.e. < 1.14 mmol/L, n = 261), compared to that in the higher magnesium group (> or = 2.77 mg/dL, n = 254) (p < 0.001). Multivariate Cox proportional hazard analysis demonstrated that serum magnesium was a significant predictor for mortality (HR [per 1 mg/dL increase], 0.485 [95% CI, 0.241-0.975], p = 0.0424), particularly for non-cardiovascular mortality (HR 0.318 [95% CI, 0.132 to 0.769], p = 0.0110), after adjustment for other confounders, such as age, gender, hemodialysis duration, and the presence of diabetes. In conclusion, it is demonstrated that lower serum magnesium level is a significant predictor for mortality in hemodialysis patients, particularly for non-cardiovascular mortality, although the mechanisms remain to be explored in future studies. Factors affecting serum magnesium concentrations should be investigated in terms of better survival, including dietary magnesium intake. Further extensive studies may be also needed for possible reconsideration of the current dialysate magnesium concentration (1.0 mEq/L, i.e. 0.50 mmol/L used in most countries), one of the strong contributors to the serum magnesium concentrations of dialysis patients.     

The effects of prostaglandin E1 on the pepsin activities in gastric mucosa and juice.

Prostaglandin E1 elevated pepsin activity in gastric mucosa but lowered pepsin activity in the gastric juice of rats treated by pylorus ligation and intragastric administration of hydrochloric acid. In these animals zymogen granules with low electron density were numerous in the gastric chief cells following prostaglandin E1 treatment. The prostaglandin E1-induced increase in mucosal pepsin activity was slightly inhibited by actinomycin D and there was no apparent increase in 3H-thymidine incorporation into gastric mucosa following treatment with prostaglandin E1. It is suggested that prostaglandin E1 causes an elevation of pepsin activity in the gastric mucosa by stimulating pepsin synthesis and perhaps also by facilitating pepsin release from zymogen granules. However, it also appears to inhibit pepsin release from the mucosa into the gastric cavity judging by the decrease of pepsin activity in gastric juice. The reduced pepsin activity in gastric juice may account, in part, for the reported anti-ulcerative action of prostaglandin.     

MARKED EPITHELIAL HYPERPLASIA OF THE RAT GLANDULAR STOMACH INDUCED BY LONG-TERM ADMINISTRATION OF IODOACETAMIDE

Iodoacetamide (IAA), an ulcerogenic compound, was continuously given to male Wistar rats for up to 74 weeks. No carcinomas developed but marked glandular hyperplasias were frequently observed accompanied by chronic ulcer or erosion in the fundic region. They showed pseudo-invasive growth into the submucosa, the granulomatous tissue and even into the muscle layer, but no cellular and nuclear atypia was observed in their glands. Characteristically the mucosal damage caused by chronic IAA treatment was restricted to the fundic mucosa along the limiting ridge. Abnormally regenerated mucosa in the damaged area showed pyloric gland type metaplasia, demonstrated histo-chemically by paradoxical concanavalin A-staining and high-iron diamine-Alcian blue staining for mucin. No intestinal metaplasia was observed in these mucosa.     

VDE-initiated intein homing in Saccharomyces cerevisiae proceeds in a meiotic recombination-like manner

BACKGROUND: Inteins and group I introns found in prokaryotic and eukaryotic organisms occasionally behave as mobile genetic elements. During meiosis of the yeast Saccharomyces cerevisiae, the site-specific endonuclease encoded by VMA1 intein, VDE, triggers a single double-strand break (DSB) at an inteinless allele, leading to VMA1 intein homing. Besides the accumulating information on the in vitro activity of VDE, very little has been known about the molecular mechanism of intein homing in yeast nucleus. RESULTS: We developed an assay to detect the product of VMA1 intein homing in yeast genome. We analysed mutant phenotypes of RecA homologs, Rad51p and Dmc1p, and their interacting proteins, Rad54p and Tid1p, and found that they all play critical roles in intein inheritance. The absence of DSB end processing proteins, Sae2p and those in the Mre11-Rad50-Xrs2 complex, also causes partial reduction in homing efficiency. As with meiotic recombination, crossover events are frequently observed during intein homing. We also observed that the absence of premeiotic DNA replication caused by hydroxyurea (HU) or clb5delta clb6delta mutation reduces VDE-mediated DSBs. CONCLUSION: The repairing system working in intein homing shares molecular machinery with meiotic recombination induced by Spo11p. Moreover, like Spo11p-induced DNA cleavage, premeiotic DNA replication is a prerequisite for a VDE-induced DSB. VMA1 intein thus utilizes several host factors involved in meiotic and recombinational processes to spread its genetic information and guarantee its progeny through establishment of a parasitic relationship with the organism.     

Antiinflammatory actions of ephedrines in acute inflammations1

Ephedrine (EP), pseudoephedrine (PEP), ephedroxane (EX) and pseudoephedroxane (PEX) inhibited carrageenin-induced hind-paw edema in sham-operated mice as well as adrenalectomized mice. Hind-paw edema induced by histamine, serotonin, bradykinin and prostaglandin E (1) was suppressed by these alkaloids, showing that they exert the antiinflammatory activity at the early exudative stage of inflammation. Although tolazoline and propranolol had no effects on the inhibitory activity of EX and PEX, treatment with tolazoline decreased the antiinflammatory activity of EP and PEP on carrageenin-induced hind-paw edema. Antiinflammatory activity of PEP was reduced by previous treatment with reserpine, indicating the antiinflammatory activity of EP and PEP to be partly concerned with the sympathetic nervous system. Although these alkaloids injected I.C.V. elicited no antiinflammatory actions on carrageenin-induced hind-paw edema and the inhibitory activity of morphine on carrageenin-induced hind-paw edema was potentiated by the concurrent administration of PEP and EX, demonstrating that the mechanism of antiinflammatory activity does not involve the central nervous system. Further, these alkaloids inhibited prostaglandin E (2) biosynthesis.     

Tumor-associated glycoprotein (TAG-72) detected in adenocarcinomas and benign lesions of the stomach

Murine monoclonal antibody (MAb) B72.3, prepared against a membrane-enriched extract of metastatic carcinoma and reactive with a high-molecular-weight determinant, designated tumor-associated glycoprotein (TAG)-72, was shown to be reactive immunohistochemically with 97% of a variety of primary adenocarcinomas of the stomach (n = 40). All "early" gastric carcinomas were reactive with MAb B72.3, although the average percentage cellular reactivity was lower than in "advanced" carcinomas. TAG-72 antigen was detected in benign lesions (i.e. adenomatous polyps and hyperplastic polyps) with intestinal metaplasia. Dysplastic lesions characterized by cellular atypia, abnormal differentiation, and disorganized mucosal architecture demonstrated higher TAG-72 expression than non-dysplastic epithelia. In contrast, normal gastric mucosa was generally non-reactive with MAb B72.3. Assays using serial sections of normal, benign and malignant gastric tissues with two MAbs (B1.1 and COL-6) directed against distinct epitopes of carcinoembryonic antigen (CEA) demonstrated differential reactivity, confirming that TAG-72 and CEA are distinct, non-coordinately expressed antigens. Our results suggest that TAG-72 antigen may be expressed in malignant and dysplastic epithelial cells, as well as in intestinalized epithelium of the stomach which has been closely related to subsequent carcinoma development. Hence, MAb B72.3 may be a useful immunohistochemical adjunct for detecting early foci of adenocarcinomas and premalignant lesions of the stomach.     

Correction to: Efficient photodynamic therapy against drug-resistant prostate cancer using replication-deficient virus particles and talaporfin sodium

Lasers in Medical Science - After publication of this paper, the authors determined an error in Fig.&nbsp;1.