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.     

Purification and some properties of a Vero toxin from a human strain of Escherichia coli that is immunologically related to Shiga-like toxin II (VT2)

A cytotoxin to Vero cells (Vero toxin), which was immunologically related to Shiga-like toxin II (SLT-II) (or VT2), was purified from a stain of Escherichia coli isolated from a patient with hemolytic uremic syndrome. The toxin was active on Vero cells but much less active on HeLa cells, a property similar to that of the recently identified SLT-II variant from E. coli strains that caused edema disease of swine. Thus the toxin purified in this report was tentatively named Shiga-like toxin II variant (Vero toxin 2 variant). The purification procedures consisted of ammonium sulfate fractionation, DEAE-Sepharose CL-6B column chromatography, chromatofocusing column chromatography, and repeated high performance liquid chromatography (HPLC) on TSK-gel G-2000SW column and on TSK-gel DEAE-5PW columns. About 90 micrograms of purified toxin was obtained from 451 of the culture supernatant with a yield of about 16%. The purified toxin consisted of A and B subunits of molecular sizes similar to those of SLT-II (VT2). The isoelectric point of the purified toxin was 6.1, which was different from that of SLT-II (VT2) (pI = 4.1). In an Ouchterlony double gel diffusion test, purified toxin and SLT-II (VT2) formed precipitin lines with spur formation against anti-purified toxin and anti-SLT-II (anti-VT2), respectively. The purified toxin was cytotoxic to Vero cells, about 6 pg of the toxin killing 50% of the Vero cells, and showed lethal toxicity to mice when injected intraperitoneally, the LD50 being about 2.7 ng per mouse.     

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.     

Follicle structure-dependency of thyroglobulin and thyroxin staining in the thyroid glands of Graves' disease

H.E. morphology of the thyroid glands from 170 patients with Graves' disease was studied, and the thyroid follicles were classified into two main groups: (1) F pattern, in which the follicles show circle/ellipse on cut sections; (2) P pattern, in which the follicular epithelium protrudes into the lumen or a follicle, is accompanied by proliferation of tubular or microfollicular structures. Studies on three serial sections of 88 thyroid glands stained with hematoxylin and eosin, thyroglobulin (TG), and thyroxin (T4), respectively, revealed the followings: (i) TG/T4 staining is dependent on the follicle structure (i.e., F or P); while the epithelium and colloid including scalloped vesicles in F follicles generally exhibited a direct relationship between TG and T4 staining, those in P follicles often showed an intense TG, but negative T4 staining. (ii) The results of morphological and immunohistochemical studies of P follicles among the cases are consistent with the view that P follicles are in the process of proliferation of immature daughter follicles from a main follicle and of their maturation. (iii) P follicles of Graves' thyroid glands were evaluated as possible non-neoplastic counterparts of well-differentiated follicular and papillary tumors.     

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.     

Alexia with agraphia produced by localized infarction in the inferior posterior region of the left temporal lobe

There have been several reports on alexia with agraphia due to hemorrhage or trauma in the inferior posterior region of the left temporal lobe since Yamadori (1982) first reported a case of cerebral hemorrhage. We presented the first case of alexia with agraphia due to a circumscribed infarct in the inferior posterior region of the left temporal lobe. A 65-year-old right-handed man had an acute onset of inability to read Japanese "kana" letters and to write any letters. He had no difficulty in speaking or understanding. Neurological examination on admission was normal except for homonymous quadrantanopia in the right upper field. Neuropsychological findings: Spontaneous speech was fluent without dysprosody. There were no disturbances in auditory understanding or in repetition. He could read Japanese "kanji" characters correctly, however, he could not read any "kana" letters. Writing was also disturbed severely even as to his address, name or telephone number. Calculation was also difficult. There were no disturbances in naming colors, no ideomotor or constructional apraxia nor visual agnosia. X-ray computed tomography (CT) scan showed a faint low density area with ring enhancement suggesting a cerebral infarct in the inferior posterior region of the left temporal lobe. Patient's hospital course was characterized by a marked improvement of alexia, especially of "kana" letters as compared with that of "kanji" characters. Dissociative improvement of alexia compared with agraphia in this case could be explained by the fact that the lesion was in close contact with the occipital lobe and that he also had pure alexia in the early stage.     

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.