NADPH oxidase drives cytokine and neurotoxin release from microglia and macrophages in response to HIV-Tat

Previous reports have shown that the human immunodeficiency virus (HIV) regulatory protein Tat has both pro-oxidant and pro-inflammatory properties, suggesting that Tat might contribute to the neurological complications of HIV. However, the intracellular mechanisms whereby Tat triggers free radical production and inflammation, and the relationship between Tat-induced free radicals and inflammatory reactions, are still subject to debate. The present study was undertaken to evaluate the specific effects of Tat on NADPH oxidase in microglia and macrophages, and to determine the specific role of NADPH oxidase in Tat-induced cytokine/chemokine release and neurotoxicity. Application of Tat to microglia or macrophages caused dose- and time-dependent increases in superoxide formation that were prevented by both pharmacologic NADPH oxidase inhibitors and by specific decoy peptides (gp91ds). Furthermore, inhibition of NADPH oxidase attenuated Tat-induced release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF), and monocyte chemoattractant protein 1 (MCP-1), and decreased microglial-mediated neurotoxicity. Finally, macrophages derived from NADPH oxidase-deficient mice displayed reduced superoxide production, released lower levels of cytokines/chemokines, and induced less neurotoxicity in response to Tat compared to wild-type macrophages. Together, these data describe a specific and biologically significant signaling component of the macrophage/microglial response to Tat, and suggest the neuropathology associated with HIV infection might originate in part with Tat-induced activation of NADPH oxidase.     

Study on the anatomical dimensions of the human sigmoid colon

Although the sigmoid colon is commonly afflicted with disease, studies on its anatomical dimensions are scarce. It is suspected that dimensions of the sigmoid colon change with age. This study documents data on the anatomical measurements of the sigmoid colon in 70 Indian subjects (51 live and 19 cadavers). Seven parameters of sigmoid colon anatomy measured included length and width of the sigmoid colon and mesocolon at specific points. Three mesocolic indices (width to length ratios) were calculated. Comparisons of measurements in the live and cadaver subjects and in the two sexes were made. The relationship of change in parameters with age was assessed. Appropriate statistical methods were used and the differences were considered significant at P < or = 0.05. The study showed wide ranging variations in the values of various measured parameters of the sigmoid colon. Seven patterns of the shape of the sigmoid loop were identified. In the commonest pattern the sigmoid mesocolon was vertically longer than wide (dolichomesocolic), the sigmoid loop having its maximum convexity located just a little proximal to the apex. Patterns where the width of the mesocolon was greater than the vertical length (brachymesocolic) were also observed. The gender analysis showed that the sigmoid mesocolon of the female was brachymesocolic (wider than long), whereas that of the male was dolichomesocolic (longer than wide). This might explain the higher incidence of sigmoid volvulus in the male. This study also showed that the measurements of the sigmoid colon and its mesocolon do not change significantly within the age range of 16-60 years in the two sexes. Also noteworthy is the observation that in the cadaver the sigmoid colon shows considerable shrinkage, particularly of its mesocolon; consequently the data from cadaver subjects, though valuable for anthropometric use, have limitations when used for clinical applications.     

Immune reactions associated with silicone-based ventriculo-peritoneal shunt malfunctions in children

The implantation of ventriculo-peritoneal (VP) shunting systems is the most commonly performed neurological procedure in children with hydrocephalus. Although the overall complication risk is low, the cumulative risk of shunt failure is high and unfortunately results in a high prevalence of revision surgeries. In this study, we explored the concept that some pediatric patients may develop an immune response to either the proteins attached to the silicone implant surface or to the biomaterial itself, and that this reaction may contribute to VP shunt failure in some individuals. The data displays that the sterile shunt malfunction group had a higher rate of protein deposition and increased levels of autoantibodies to the extracted surface proteins as compared to individuals with functioning shunting systems. The precise nature of the shunt-bound proteins that serve as antigens in this experiment have not yet been determined. The data also indicated that some individuals develop antibodies to polymeric substances that cross-react with partially polymerized acrylamide. The detection of significant amounts of shunt-bound protein, antibody responses to these proteins and to polymeric substances suggest that an immunological response to these proteins may play a role in the mechanism behind sterile shunt malfunctions.     

Comparison of two culture media and three sampling techniques for sensitive and rapid screening of vaginal colonization by group B streptococcus in pregnant women

The Centers for Disease Control and Prevention (CDC) recommend universal screening of all pregnant women between 35 and 37 weeks of gestation for group B streptococci (GBS) by use of a selective broth medium. Recent reports suggest that Granada medium can be used for rapid and direct visual identification of GBS colonies. However, studies comparing the Granada medium method to the selective broth method are few, and while some report comparable sensitivities, others have found significant differences in detection rates between the two methods. This prospective study compared a method using Granada agar to a Todd-Hewitt broth method with subculture to blood agar in order to determine which GBS detection method is more sensitive and less labor-intensive and has a more rapid turnaround time. Detection rates for three sampling techniques (rectovaginal, vaginal only, and cervical only) were also compared. Consecutive specimens for GBS screening received over a 6-month period from 1,635 pregnant women were included. Overall, GBS was detected in 390 (23.8%) women. The Granada medium gave positive results for 348 of these women, and the selective broth gave positive results for 385, indicating sensitivities of 89.2% for the Granada medium and 98.7% for the selective broth. These findings show that the Granada medium method is less sensitive than the selective broth method and should not replace it as the only method for screening pregnant women for GBS. However, the Granada medium method reduced detection time to 1 day and also reduced the use of ancillary tests in approximately 90% of positive cases. Additionally, no significant differences were noted in the detection rates with rectovaginal, vaginal, and cervical specimens.     

Cytologic features of central giant-cell granuloma of the jaw

In this present series, we studied in detail the cytologic features of five histopathologically verified cases of central giant-cell granuloma (CGCG). All the patients in this series were female, with an age range of 11-60 years. There were three cases with involvement of the lower jaw and two cases had upper jaw involvement. Cytology smears showed dispersed single cells in the background. Nuclei of the individual cells were round to ovoid with fine chromatin and inconspicuous nucleoli. The cytoplasm of these cells was moderate in amount with indistinct cell borders. Many randomly scattered multinucleated giant cells with 10-20 nuclei were present in the background. Combination of clinical features, radiologic pictures, and cytologic features may be helpful for diagnosis of CGCG on fine-needle aspiration cytology.     

Inherited prothrombotic defects in Budd-Chiari syndrome and portal vein thrombosis: a study from North India

We studied 57 patients with Budd-Chiari syndrome (BCS) and 48 with portal vein thrombosis (PVT) for underlying inherited prothrombotic defects such as protein C, protein S, and antithrombin III deficiencies. Genetic mutations for factor V Leiden, prothrombin gene 20210A, and methyltetrahydrofolate reductase (MTHFR) C677T were studied in 29 patients in each group. Inherited prothrombotic defects were detected in 16 (28%) of 57 patients with BCS and 7 (15%) of 48 patients with PVT. Factor V Leiden mutation was the most common prothrombotic defect in BCS (5/29 [17%]) followed by protein C deficiency (7/57 [12%]) and protein S deficiency (4/57 [7%]), whereas in PVT, protein C deficiency was the most common inherited prothrombotic defect (4/48 [8%]) followed by protein S deficiency (2/48 [4%]). The factor V Leiden mutation was detected in only 1 (3%) of 29 cases of PVT. The heterozygous MTHFR C677T mutation was detected in 7 (24%) of 29 patients with BCS and 6 (21%) of 29 patients with PVT. Antithrombin III deficiency, homozygous MTHFR C677T mutation, and prothrombin G20210A mutation were not detected in any patients.     

Recurrent diffuse lipomatosis of the neck--a case report

Diffuse lipomatosis is a rare disorder of adipose tissue occurring in young people . It has a predilection for trunk and proximal extremities where it presents as poorly circumscribed overgrowth of fatty tissue. Definite diagnosis is established by histological examination of tumor. Though it attains extensive size and has a high tendency to recur, the clinical course is benign.     

Corpus callosum morphometry: comparison of fresh brain,preserved brain and magnetic resonance imaging values

In recent years interest in the anatomy of corpus callosum (CC) has led to a number of studies on morphometric analysis of CC, either in vivo on magnetic resonance imaging (MRI) or on preserved (formalin-fixed) cadaveric brain specimens. There are very few reports comparing the values obtained by both these methodologies, and to the authors' knowledge no study of CC morphometry in fresh (unfixed) autopsy brains has been done. Morphometric measurements of the CC were done on fresh autopsy brains ( n  = 15), preserved cadaveric brains ( n  = 44) and MRI scans ( n  = 30) in adults (age range: 20–60 years) of both sexes without any intracranial brain pathology, in north-west Indian subjects. Most of the CC measurements were found to be more in the fresh autopsy brain group as compared to the preserved cadaveric brain and MRI group. The distance between the splenium and superior colliculus in the fresh autopsy brain group was almost twice that in the other two groups. In addition, there was a similarity between the preserved cadaveric brain and MRI values for most of the parameters, but the distances between the genu and fornix and between the genu and anterior commissure were larger in the MRI group as compared to the other two groups. The present data may be of value in studying deviations from the normal in various disease processes as well in surgical planning of intraventricular and callosal pathologies.