Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.     

谷氨酸脱氢酶,胆碱氧化酶和葡萄糖-6-磷酸酶对溶酶体中~(67)Ga积累的影响(英文)

目的:比较正常肝组织与肝癌AH 109A,吉田肉瘤中谷氨酸脱氢酶,胆碱氧化酶和葡萄糖-6-磷酸酶的活力对~(67)Ga摄取与积累的影响;方法:制备~(67)Ga枸橼酸溶液给大鼠静注后处死大鼠,制备亚细胞悬液,液闪计数器测定放射活度.结果:~(67)Ga的放射活性在正常肝组织溶酶体中(55％积聚)显著高于肝癌AH109A(32％积聚)和吉田肉瘤(18％)积聚.谷氨酸脱氢酶的活力在正常肝组织,肝癌和吉田肉瘤分别是1830±s 320 U·L~(-1),23±s 6 U·L~(-1)和7±s 2 U·L~(-1);胆碱氧化酶的活力分别是46±s 10 U·L~(-1),25.0±s 0.4 U·L~(-1),2.0±0.4 U·L~(-1);葡萄糖-6-磷酸酶活力分别是2550±s 180 U·L~(-1),84±s 14 U·L~(-1),78±s13 U·L~(-1).结论:正常肝组织中溶酶体酶活力很强,对~(67)Ga的积累起较大作用.癌变组织酶活力降低而作用减弱.吉田肉瘤细胞无肝细胞特点,其溶酶体对~(67)Ga积累作用不大.     

Cytokines as an adjuvant to tumor vaccines: Efficacy of local methods of delivery

Background: We examined alternative methods of delivering cytokines as an adjunct for priming lymph node (LN) cells draining sites of vaccine inoculation for the purpose of generating immune cells for adoptive immunotherapy. Methods: Using syngeneic murine tumors we examined the ability of IL-2, IL-4, or GM-CSF delivered locally to a site of tumor inoculum to induce antitumor reactive draining LN cells. Mice were inoculated subcutaneously with tumor cells transduced to secrete cytokine; tumor cells admixed with fibroblasts transduced to secrete cytokine; or intralesional inoculation of cytokine in established tumor to induce sensitized LN cells capable of mediating tumor regression in adoptive transfer. Results: Both IL-4 and GM-CSF cytokines were effective in enhancing the antitumor reactivity of vaccine-primed LN cells compared to IL-2, which was ineffective. The local delivery of GM-CSF by autocrine or paracrine secretion of genetically engineered cells, as well as direct intratumoral delivery was capable of upregulating LN sensitization compared to systemic administration, which did not. Conclusions: The local delivery of GM-CSF as an adjuvant for tumor vaccination can be accomplished by various methods, including direct injection, which avoids the need for gene transfer.     

Olfactory dysfunction in Parkinson's disease

Journal of Neurology - Olfactory dysfunction in Parkinson's disease (PD) has been described for more than thirty years and known as one of the commonest non-motor symptoms in PD. Recently, it...     

A case of orbital apex syndrome caused by localized invasive aspergillosis successfully treated with voriconazole]

A 71-year-old man with left periorbital pain and diplopia was hospitalized for evaluation and treatment. He had a past history of untreated diabetes mellitus. Shortly after admission, the patient experienced rapid onset of visual loss in the left eye. MRI and CT showed a lesion expanding from the left orbital apex to the left pterygopalatine fossa. Invasive aspergillosis was diagnosed by open biopsy of intrasinus mucosa via the left maxillary sinus. The patient was treated with voriconazole, an antifungal agent, and marked improvements in left periorbital pain and eye movement were subsequently obtained, although visual acuity was not recovered. This is the first report documenting the clinical utility of voriconazole for sino-orbital invasive aspergillosis.     

Urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats.

BACKGROUND: Otsuka Long-Evans Tokushima Fatty (OLETF) rats genetically develop diabetes which is associated with hypertension. In preliminary studies, urinary excretions of L-PGDS (lipocaline-type prostaglandin D synthase) increase before diabetic nephropathy obviously develops, and this may predict progression of renal injury following diabetes. In the present study, we attempted to define whether urinary excretions of L-PGDS behave as the predictor of development of diabetic nephropathy in OLETF rats. METHODS: We investigated alterations of urinary L-PGDS excretions during the establishment of diabetes and assessed the relationship between the L-PGDS excretions and renal function in OLETF rats. Furthermore, we treated OLETF rats with troglitazone and analysed the effects on L-PGDS metabolisms. Urinary L-PGDS was measured by immunoenzyme assay and the occurrence of L-PGDS and its mRNA in the kidney was assessed by immunohistochemistry and a PCR method. RESULTS: Urinary excretions of L-PGDS were significantly higher in OLETF rats than non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. The excretions age-dependently increased in OLETF and this increase appeared to be due to increased glomerular permeability to L-PGDS. Messenger RNA and antigenicity of L-PGDS were demonstrated in renal tissue; however, the de novo synthesis of L-PGDS mRNA seemingly contributed to urinary L-PGDS excretions much less than glomerular filtration. Multiple regression analysis revealed that urinary L-PGDS was determined by urinary protein excretions, and not by high blood pressure per se. Conversely, urinary proteinuria in the established diabetic nephropathy was predicted by urinary L-PGDS excretions in the early stage of diabetes. CONCLUSIONS: Urinary excretions of L-PGDS are likely to reflect the underlying increase in glomerular permeability. This property may be useful to predict forthcoming glomerular damage following diabetes in OLETF rats.     

A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions.

Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.     

Anti-Candida albicans activity of essential oils including Lemongrass (Cymbopogon citratus) oil and its component, citral]

The effects of 12 essential oils, popularly used as antifungal treatments in aromatherapy, on growth of Candida albicans were investigated. Mycelial growth of C. albicans, which is known to give the fungus the capacity to invade mucosal tissues, was inhibited in the medium containing 100 micro g/ml of the oils: lemongrass (Cymbopogon citratus), thyme (Thymus vulgaris), patchouli (Pogostemon cablin) and cedarwood (Cedrus atlantica). Not only lemongrass oil but also citral, a major component of lemongrass oil (80%), in the range of 25 and 200 micro g/ml inhibited the mycelial growth but allowed yeast-form growth. More than 200 micro g/ml of citral clearly inhibited both mycelial and yeast-form growth of C. albicans. These results provide experimental evidence suggesting the potential value of lemongrass oil for the treatment of oral or vaginal candidiasis.     

在免眼中进行经瞳孔阈值下温热疗法的组织学效应和蛋白表达

目的：研究阈值下经瞳孔温热疗法（TTT）对视网膜组织学的效应。方法：对正常视网膜色素的兔眼进行TTT，通过1个810nm激光二极管产生直径为1．2mm能量为50mW的光斑，持续时间为15、30和60秒。4周后进行荧光血管造影并摘除眼球，通过电子显微镜和免疫组化染色来检查。     

Lack of rapid initiating, promoting or sequential syncarcinogenic effects of di(2-ethylhexyl)phthalate in rat liver carcinogenesis

The effect of prolonged dietary administration of the peroxisomeproliferating plasticizer di(2-ethylhexy1)phthalate (DEHP wasstudied on liver carcinogenesis initiated by N-2- fltuorenylmxhmide(FAA) and with that of the neoplasm-promoter phenobarbital (PB).Also, DEHP was studied as an initiator by giving it in placeof FAA before PB. Male rats were fed FAA for 7 weeks to inducebepatocellular altered foci, and were subsequently given nochemical, 12 000 p.p.m. DEHP or 500 p.p.m. PB for 24 weeks inthe diet. In the rats fed DEHP, substantial hepatomegaly andperoxisome proliferation were induced. No evidence of indudionof hepatacellular altered foci or hepatic neoplasms was foundeither when DEHP was given alone for 24 weeks or for 7 weeksfollowed by PB. Also, DEHP fed for 24 weeks had no promotingeffect on liver altered foci that were induced by FAA and producedlittle or no enhancement of the occurrence of FAA-induced liverneoplasms. In contrast, PB exerted a marked enhancing effecton foci and substantially increased the incidence and multiplicityof liver neoplasms. Thus, the findings demonstrate that DEHPdid not have either a rapid initiating activity, a significantsequential syncarcinogenic activity, or a promoting effect onliver carcinogenesis under conditions in which numerous agentswith such activities have been identified.