Molecular cloning and regional distribution of rat brain cyclophilin.

Cyclosporine A (CsA) is a potent immunosuppressive drug that has widespread clinical uses in organ transplantation and the treatment of autoimmune disorders. However, the drug's clinical applications are on an empiric basis with a poor understanding of the basic mechanism(s) of action. CsA may exert some of its effects by binding to a cellular receptor protein--the cyclosporine receptor (also called cyclophilin). Cyclophilin (CyP) is an ubiquitous, soluble, cytoplasmic 17 kDa protein which has recently been shown to be a peptide-prolyl isomerase. CsA specifically binds to this protein and inhibits its isomerase activity. A rat cyclophilin cDNA clone was isolated from a rat brain lambda gt11 cDNA library. Northern blot analysis shows a single 1 kb messenger RNA in rat brain. In order to determine the regional distribution of the Cyp mRNA in situ hybridization was performed. The Cyp mRNA appeared to be expressed throughout the brain but there were particularly high levels in the cerebral cortex and hippocampus compared to the relatively low levels in white matter areas and tracts. At the cellular level, the Cyp mRNA is expressed at much higher levels in neurons than in glia. The high levels of Cyp in cortical (neuronal) areas may, in part, explain the global encephalopathic symptoms clinically observed in CsA neurotoxicity.     

Transcanalicular laser-assisted dacryocystorhinostomy with diode laser

This article compares the efficacy of transcanalicular laser assisted dacryocystorhinostomy (TL DCR) with conventional external dacryocystorhinostomy (Ex DCR). All patients were randomly divided into two groups – Group A included patients who underwent TL DCR and Group B included patients who underwent Ex DCR. 168 operations were done in a total of 163 patients; 79 patients in group A and 84 patients in group B. The overall success rate was 90.12% in group A and 95.40% in group B. The mean total surgical time was 17.41 min in group A and 49.49 min in group B. The duration of stay in hospital was about 3 hours for group A and about 48 hours for group B. Intra and post operative complications were more in group B than in group A. TL DCR can offer a minimally invasive technique with comparable results and better patient satisfaction than Ex DCR.     

TRMA syndrome (thiamine-responsive megaloblastic anaemia): An example of rare monogenic diabetes: is thiamine a magic pill for anaemia and diabetes?

Thiamine-responsive megaloblastic anaemia (TRMA) is a rare syndrome presenting with early onset non-autoimmune diabetes mellitus, megaloblastic anaemia and sensorineural deafness. We report a 16-month-old male, a youngest case of genetically confirmed TRMA syndrome in Indian phenotype, born to consanguineous parents. We found a homozygous pathogenic variant in exon 2 of the SLC19A2 gene, c.314G>A (p.Gly105Glu). The anaemia showed a good response to daily thiamine doses and was able to avoid unwanted blood transfusion. There was no benefit with regard to insulin requirement. Early detection of hearing impairment and referral to audiological treatment was possible. The report indicates that TRMA should be considered as a differential diagnosis for patients presenting with suggestive clinical symptoms which would have tremendous impact on patient management if identified early.     

Behavioural battery testing: Evaluation and behavioural outcomes in 8 inbred mouse strains

The use of large scale behavioural batteries for the discovery of novel genes underlying behavioural variation has considerable potential. Building a broad behavioural profile serves to better understand the complex interplay of overlapping genetic factors contributing to various paradigms, underpinning a systems biology approach. We devised a battery of tests to dissect and characterise the genetic bases of behavioural phenotypes, but firstly undertook to evaluate several aspects considered potentially confounding for mapping quantitative traits. These included investigating: individual versus sibling housing; testing at different times during the day; battery versus non-battery testing; and initial placement within the light-dark box. Furthermore, we assessed how behavioural profiles differed in our battery across 8 inbred strains. Overall, we found the behavioural battery was most sensitive to paired-housing effects, where weight and some measures in the open field, elevated plus maze and light-dark box differed significantly between sibling housed and singly housed mice. Few large effects were found for testing at different times of day and battery versus non-battery testing. Placement in the light-dark box influenced activity and duration measures, which profoundly affected the analysis outcome. Behavioural profiles across eight inbred strains (C57BL/6J, 129S1/SvImJ, A/J, BALB/cByJ, C3H/HeJ, DBA/2J, FVB/NJ, and SJL/J) demonstrated some robust strain ranking differences for measures in the open field and light-dark tests in our battery. However, some tests such as the elevated plus maze produced incongruous strain ranking effects across measures. The findings reported herein bear out the promise of behavioural batteries for mapping naturally occurring variation in mouse reference populations.     

Choroid plexus papilloma of the posterior third ventricle during infancy & childhood: report of two cases with management morbidities

We report two cases of posterior third ventricular choroid plexus papilloma, one in an 8-month-old infant and another in a two-year-old child. These cases presented with features of obstructive hydrocephalus. Both these patients underwent a ventriculo-peritoneal (VP) shunt surgery prior to the tumor excision. Following the VP shunt surgery both patients developed ascitis requiring exteriorization of the abdominal end of the shunt. There was a clear proof of CSF overproduction: 1400-1500 ml/day in the eight-month-old infant and 900-1200 ml/day in the two-year-old child. In the former it was transient and could be treated with revision of the VP shunt whereas in the second case a ventriculo-arterial shunt had to be done. In the second case a staged reduction cranioplasty was also performed for an enormously enlarged head (head circumference--74 cm). Interesting clinical and radiological findings and useful management strategies are described.     

The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases

To evaluate the proficiency of phosphatases as catalysts, the rate of the uncatalyzed hydrolysis of simple phosphate monoester dianions was estimated by extrapolating rates measured over a range of high temperatures. The rate of spontaneous hydrolysis of phenyl phosphate dianion indicates that a linear free energy relationship reported earlier is reliable for leaving groups whose conjugate acids have pKa values up to at least 10. Using Teflon reaction vessels, it proved possible to follow the hydrolysis of methyl phosphate and 3-(4-carboxy)-2,2-dimethylpropyl phosphate in strong alkali. Even in 1 M KOH, the reaction was found to be specific acid catalyzed. These results establish an upper limit for dianion reactivity, which had been overestimated earlier as a result of the leaching by alkali of silicic acid from quartz reaction vessels. The present findings indicate that the half-time for attack by water on alkyl phosphate dianions is 1.1 x 10(12) years (k = 2 x 10(-20) s) at 25 degrees C and that phosphatases involved in cell signaling and regulation produce the largest rate enhancements that have been identified thus far. Protein phosphatase-1 and inositol 1-phosphatase exceed all other known enzymes in their affinities for the altered substrates in the transition state.     

No effect of transfusion transmitted virus viremia on the distribution and activation of peripheral lymphocytes in hemodialyzed patients

AIM: We aimed to examine the distribution and activation of peripheral T cells in TTV positive (n = 32) and negative (n = 17) hemodialyzed patients. The control group (n = 20) consisted of healthy blood donors. METHOD: TTV-DNA was detected by seminested PCR. CD3, CD4, CD8, CD19, CD56, CD3/HLA-DR, CD3/CD69 and the Th1/Th2 ratio of T cells were analyzed by flow cytometry. Circulating IFN-gamma, IL-2, IL-4, IL-6, IL-10, IL-13, TNF-alpha, TGF-beta levels were measured by ELISA in the sera. RESULTS: There was no difference between the CD3, CD4, CD8 and CD19 values of HD subjects. In addition, the expression of both activation markers, HLA-DR and CD69, was significantly elevated in the TTV-positive and -negative HD groups compared to the controls, but not showing any difference from each other. The measurements of intracellular cytokines showed the enhanced occurrence of INF-gamma + CD4 T cells, and decreased appearance of IL-4 + CD4 lymphocytes in the HD groups without any significant difference between the TTV virus positive and negative patients. In addition, HD also elevated the expression of IL-10 in CD4 and CD8 (Th2) cells. There were only two significant changes in the levels of circulating cytokines: (a) IL-2 increased; (b) IL-13 decreased in both groups of HD patients compared to the controls, independently of TTV positivity or negativity. CONCLUSIONS: We assume that transfusion-transmitted virus does not cause any specific change in the distribution and activation of lymphocytes in the peripheral blood of hemodialyzed patients. Hemodialysis itself, however, results in a significant activation of peripheral T cells with the domination of increased production of Th1 type cytokines, IFN-gamma, IL-2, in contrast to the decreased synthesis of Th2 type cytokines, IL-4 and IL-13. Furthermore, the increased expression of IL-10 in the CD4 and CD8 cells of HD patients can be the sign of a contraregulatory Th2 activation as an answer on the Th1 effect.     

Gluteal neuralgia - unusual presentation in an adult with intrasacral meningocele: a case report and review of literature

A nineteen year old man with intrasacral meningocele is reported, who presented with long standing episodic gluteal pain and progressive muscle wasting. Magnetic resonance imaging established the diagnosis. Surgical excision relieved the pain but muscle wasting persisted. Pertinent literature is reviewed.