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Biomedical subjects

R Chandra

Publications and source records attributed to R Chandra.

At least 19 recordsLinked to original sources

Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer.

We have developed methods to use anticyclin A, B, and E antibodies as reagents to specifically detect proliferating cells in specific phases of the cell cycle in formalin-fixed, paraffin-embedded sections of tissues and cells. Staining of 48 archival cases of breast cancer showed that these antibodies estimate the tumor proliferation fraction and therefore are potentially useful for the prediction of prognosis. A subset of cancers had a high frequency of tumor cells expressing cyclins A and E, out of proportion to other proliferation markers, suggesting that these tumors may have deregulated cyclin expression. In addition to recognizing authentic cyclin E in the nucleus of proliferating cells, anticyclin E antibody cross-reacted with a cytoplasmic protein in nonproliferating endothelial cells. This cross-reaction allows the simultaneous visualization and quantitation of microvessels in the tumors, measuring a second potential predictor of breast cancer prognosis, tumor angiogenesis.

Animals

Prenatal diagnosis of glomerulocystic kidney disease in short-rib polydactyly syndrome type II, Majewski type.

An 18-year-old gravida 1 para 0 female was presented at 35 weeks' gestation with severe oligohydramnios. Sonography revealed a fetus with hydrops, bilaterally enlarged echogenic kidneys, and short extremities. The infant died at birth and autopsy was compatible with short-rib polydactyly syndrome type II, Majewski type. Renal histology was consistent with glomerulocystic disease.

Adult

Cytotoxigenicity in Salmonella serovars.

Twenty two strains of Salmonella belonging to eight different serovars, namely S. enterica subsp. enterica serovar S. typhimurium, S. nchanga, S. newport, S. virchow, S. bovismorbificans, S. seftenberg, S. weltevreden and S. indiana, isolated from foods of animal origin, were tested for their cytotoxicity on MDBK and Vero cell-lines. Although all the strains were found to be cytotoxic for both the cell-lines, their cytotoxic activity varied greatly. A dose-related cytotoxic effect was observed. Polymyxin B sulphate @.25 mg/ml in PBS, pH 7.2), urea (8M in Tris-HCl buffer, pH 8.2) and cell-sonication were found to augment the release of cytotoxin.

Animals

Maternal psychiatric disorders in pediatric inflammatory bowel disease and cystic fibrosis.

The mothers of 72 children and adolescents with inflammatory bowel disease (IBD) and 44 mothers of children and adolescents with cystic fibrosis (CF) were given A-SADS interviews. Fifty-one percent of IBD mothers and 41% of cystic fibrosis mothers had a lifetime history of depression. More IBD than CF mothers had a history of suicide gestures or attempts, and were more likely to have a history of obsessive compulsive disorder. However, CF mothers were more likely to have experienced panic attacks.

Adolescent

Correlates of depression in new onset pediatric inflammatory bowel disease.

Of thirty six children with new-onset inflammatory bowel disease given a Kiddie-SADS interview, five children were depressed and ten had some depressive symptoms. Depressed children had less severe illness, and were more likely to have a maternal history of depression, more life events, and families characterized by less cohesion and more conflict.

Adolescent

Effects of a maternity waiting home on adverse maternal outcomes and the validity of antenatal risk screening.

OBJECTIVES: To evaluate the effect of a maternity waiting home (MWH) on adverse maternal outcomes and the validity of antenatal risk criteria in predicting dystocia. METHOD: A hospital-based cohort study was conducted at a district hospital in Zimbabwe. Information on the presence of antenatal risk factors, stay at an MWH, and mode and outcome of delivery was collected for each woman delivering at the hospital during 1989-1991. RESULTS: The risk of obstructed labor was 16 times higher for those not attending an MWH (n = 2915) than for those who did attend an MWH (n = 1573) (1 vs. 0.06%, P < 0.005). Among the non-users, 0.3% suffered a ruptured uterus compared with none of the MWH users. The presence of any one of the antenatal risk criteria used in Zimbabwe had a sensitivity of 78%, a specificity of 51% and positive predictive value of 25% for predicting dystocia. CONCLUSION: MWHs and antenatal risk screening are policy options for safe motherhood programs in settings where emergency obstetric services are not easily accessible.

Developing Countries

Quantitative analysis of viral burden in tissues from adults and children with symptomatic human immunodeficiency virus type 1 infection assessed by polymerase chain reaction.

The amount of human immunodeficiency virus type 1 (HIV-1) in various tissues was investigated by polymerase chain reaction (PCR) in 16 patients with end-stage HIV-1 infection and 7 patients with symptomatic but less advanced disease. During postmortem study of the 16 end-stage patients, HIV-1 DNA was found most often in lymph nodes and the spleen (both 100%), lung (93.8%), and colon (87.5%). Biopsied lymph nodes from the 7 symptomatic patients contained substantially higher copy numbers of HIV-1 RNA and DNA than did peripheral blood mononuclear cells (PBMC). Plasma viral RNA levels correlated significantly with the amount of HIV-1 RNA in PBMC (r2 = .86, P = .0025) but not with the level of viral RNA in lymph nodes in patients with symptomatic HIV-1 infection. These data suggest that although lymph nodes represent the main site for HIV-1 infection and replication, the level of circulating viral burden may not be solely determined by the magnitude of active HIV-1 replication in lymph nodes.

Acquired Immunodeficiency Syndrome

HIV-1 infection of subcortical astrocytes in the pediatric central nervous system.

Early reports of pediatric HIV-1-associated neuropathology described the presence of viral particles in some astrocytes, implicating direct infection of the immature nervous system as a contributing factor to the observed neuropathology. Several recent reports suggest that in those astrocytes infected with HIV-1, the level of antigenic expression of the proviral genome is below the sensitivity limits of conventional histochemical techniques. Identification of these astrocytes would instead require the use of a highly sensitive radiolabeled DNA or RNA probe for in situ hybridization to detect the persistent viral nucleic acids. To test this hypothesis, we examined autopsy tissue from 12 infants and children with AIDS-associated encephalopathy for the presence of HIV-1-infected astrocytes using combined isotopic in situ hybridization for the detection of viral-specific nucleic acids and immunohistochemistry for the identification of astrocytes. We detected HIV-1 nucleic acids in astrocytes in subcortical white matter from four pediatric patients with moderate to extensive leukoencephalitis. While gp41 was detectable only on macrophages and multinucleated giant cells, HIV-1 Nef protein was present in cells morphologically identified as astrocytes in two of these patients, further suggesting that HIV-1 establishes a persistent rather than a productive infection in astrocytes. Subcortical astrocytes may therefore be an unrecognized reservoir for HIV-1 in the developing nervous system of some children with AIDS-associated leukoencephalitis.

AIDS Dementia Complex

Mutants of the Drosophila ncd microtubule motor protein cause centrosomal and spindle pole defects in mitosis.

Nonclaret disjunctional (ncd) is a kinesin-related microtubule motor protein required for meiotic and early mitotic chromosome distribution in Drosophila. ncd translocates on microtubules with the opposite polarity to kinesin, toward microtubule minus ends, and is associated with spindles in chromosome/spindle preparations. Here we report a new mutant of ncd caused by partial deletion of the predicted coiled-coil central stalk. The mutant protein exhibits a velocity of translocation and ability to generate torque in motility assays comparable to near full-length ncd, but only partially rescues a null mutant for chromosome mis-segregation. Antibody staining experiments show that the partial loss-of-function and null mutants cause centrosomal and spindle pole defects, including centrosome splitting and loss of centrosomes from spindle poles, and localize ncd to centrosomes as well as spindles of wild-type embryos. Association of ncd with spindles and centrosomes is microtubule- and cell cycle-dependent: inhibition of microtubule assembly with colchicine abolishes ncd staining and centrosomal staining is observed in prometaphase, metaphase and anaphase, but diminishes in late anaphase/telophase. The cell cycle dependence of centrosomal staining and the defects of mutants provide clear evidence for activity of the ncd motor protein near or at the spindle poles in mitosis. The ncd motor may interact with centrosomal microtubules and spindle fibers to attach centrosomes to spindle poles, and mediate poleward translocation (flux) of kinetochore fibers, a process that may underlie poleward movement of chromosomes in mitosis. Together with previous work, our findings indicate that ncd is important in maintaining spindle poles in mitosis as well as in meiosis.

Animals

Bilateral beta 2-microglobulin amyloidomas of the buttocks in a long-term hemodialysis patient.

Only two cases of beta 2-microglobulin amyloid tumors involving the buttocks have been reported in the world literature. We report a case of bilateral buttock amyloid tumors with associated carpal tunnel syndrome and pathologic fracture involving the femoral head. This unusual local bilateral manifestation of the beta 2-microglobulin amyloidosis develops late in the course of hemodialysis and may be initiated by chronic trauma.

Amyloidosis

Structural and functional domains of the Drosophila ncd microtubule motor protein.

Nonclaret disjunctional (ncd) is a kinesin-related microtubule motor protein that is required for proper chromosome distribution in Drosophila. Despite its sequence similarity to kinesin heavy chain, ncd translocates with the opposite polarity as kinesin, toward microtubule minus ends. We have expressed different regions of the protein in bacteria and analyzed the proteins for function. Results indicate that ncd consists of three domains: a basic, proline-rich N-terminal "tail," a central alpha-helical coiled-coil stalk, and a C-terminal motor domain. The ncd N terminus proteins bundle microtubules in motility assays and show ATP-independent binding to microtubules in solution. Truncated proteins, lacking the tail but containing the predicted motor domain and differing lengths of the stalk, did not support microtubule gliding in in vitro assays but showed microtubule-stimulated MgATPase activity in solution. Addition of a nonspecific N terminus to two of the truncated proteins restored directional gliding and rotation of microtubules in motility assays, demonstrating that these properties map to the predicted mechanochemical domain of ncd. Physical properties of the C terminus proteins indicate that the stalk region is important for dimerization and that the ncd protein probably exists and functions as a dimer.

Adenosine Triphosphatases

Cranial fasciitis of childhood.

We present a child with a rapidly growing mass and lytic skull lesion that on pathologic evaluation was diagnosed as cranial fasciitis. This disease entity is not widely known by radiologists, and should be included in the differential diagnosis of lytic skull lesions.

Fasciitis

Prenatal diagnosis and management of congenital volvulus.

We present a case of a twin gestation in which one twin developed a complex abdominal mass and signs of small bowel obstruction. Following delivery, an exploratory laparotomy revealed a meconium pseudocyst and midgut volvulus. While the infant survived, a large portion of small bowel was atretic, resulting in short bowel syndrome. The prenatal diagnosis of volvulus is rare. When volvulus is present, the risk of bowel infarction is high, with variable perinatal outcome.

Adult

Brain tissue volume measurement from magnetic resonance imaging. A phantom study.

RATIONALE AND OBJECTIVES: The authors appraised the accuracy of a method for brain volume measurement from magnetic resonance images and evaluated the effects of the acquisition matrix, slice thickness, and tissue sampling on the measurement error. METHODS: The method uses two magnetic resonance imaging sequences to account explicitly for partial volume effects. The accuracy was measured with one-, two-, and three-compartmental phantoms that mimic the relaxation properties of brain tissues. The sensitivity of the method to section thickness was measured by repeated scans of human brain. RESULTS: Using a strongly T2-weighted sequence and two-compartmental phantoms, the average error was 5%, with 3% error for phantoms larger than 90 mL. In the three-compartmental phantoms the error varied from 2% to 7%. Varying the section thickness from 5 to 10 mm on three-compartmental phantoms and from 2.5 to 10 mm in the human brain did not significantly affect compartmental volumes. CONCLUSIONS: The experimental study validates the feasibility of monitoring localized volume changes in a three-compartmental model.

Brain