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Biomedical subjects

S Majumdar

Publications and source records attributed to S Majumdar.

At least 217 records · Page 12Linked to original sources

Fractal geometry and vertebral compression fractures.

Cancellous bone in postmenopausal osteoporosis is characterized by widely spaced and disconnected trabeculae. These architectural changes may disproportionately increase bone fragility compared with the decrease in bone mass alone. To determine whether there is an independent architectural contribution to fracture risk, we applied fractal geometry to the cancellous bone in osteoporosis. Fractal objects have recurrent, branching patterns that are quantified by a fractal dimension D, that describes how the object fills space. Photomicrographs of transiliac bone biopsy specimens were digitized, and D was calculated from the negative of the straight portion of the slope of the log of the number of pixels containing boundary points versus the log of the pixel size over a range of pixel sizes. The results were compared with the cancellous bone histomorphometry in 31 individuals, aged 19-80 years, who were healthy before sudden death. D was inversely related to age (r = -0.72, p < 0.0001) and trabecular spacing (r = -0.87; p < 0.0001) and directly related to bone area (r = 0.86, p < 0.0001) and trabecular number (r = 0.83, p < 0.0001). We then examined 12 healthy volunteers and 12 patients with vertebral compression fractures as a result of osteoporosis who were matched for age and cancellous bone area. The patients with fractures had a 7.9% lower mean value for D (1.224 +/- 0.085 SD versus 1.329 +/- 0.125, p < 0.026). Other markers of the cancellous architecture, such as trabecular width, separation, and number, were not different between the matched groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phantom studies simulating the impact of trabecular structure on marrow relaxation time, T2'.

Phantom studies were conducted to investigate the impact of trabecular structure on the T2' signal measured by MRI. For a separation of density from structural effects, several phantoms were built. They consisted of parallel polyethylene strings arranged in a variety of different patterns to simulate a) a constant uniform trabecular distribution with increasing trabecular thickness and b) different structures with identical overall trabecular density. An asymmetric spin echo sequence was used to determine the apparent relaxation time T2'. Changes in T2' are induced by susceptibility differences between the polyethylene strings simulating trabeculae and Gd-DTPA doped saline simulating bone marrow. The results showed an increasing T2' decay rate with a) decreasing spacing while the string density was constant and b) with increasing string density while the string arrangement was constant. The results demonstrate that the T2' signal is affected not only by density but also by spatial distribution. However, the results also indicate that a separation of the two effects is not possible from a T2' measurement alone, but that e.g., a matching CT slice that would provide purely density information is additionally needed. Theoretical simulations confirmed these results.

Bone Marrow↗

Insulin stimulates glycolysis and pentose cycle activity in bovine microvascular endothelial cells.

Glucose metabolism via the pentose cycle, glycolysis and the Krebs cycle was quantified in bovine microvascular endothelial cells. The major measured end-product of glucose was L-lactate, with relatively small amounts of glucose carbons converted to CO2 and pyruvate. The pentose cycle accounted for less than 4% of the glucose utilized. About 60-70% of the metabolized glucose carbons could not be accounted for by lactate, pyruvate and CO2. Insulin stimulated glycolysis and pentose cycle activity, but had no effect on glucose oxidation via the Krebs cycle. As the pentose cycle is a major source of NADPH which is required for the synthesis of nitric oxide (the endothelium relaxing factor), insulin may play a role in regulating NO generation in endothelial cells by modulating the pentose cycle activity.

Animals↗

Effect of Escherichia coli enterotoxins on macromolecular absorption.

Macromolecular absorption of gliadin, a wheat protein and alpha lactalbumin, a milk protein was evaluated in control and Escherichia coli enterotoxin (heat-stable, heat-labile, and both heat-stable and heat-labile enterotoxin) treated mice. The peak concentration of gliadin and lactalbumin was two hours and three hours after their ingestion, respectively. There was also a significant increase (p < 0.01) in the absorption of both the proteins in all the three toxin treated groups compared with the control group. These results suggest that intestinal permeability and macromolecular absorption changes after E coli infection.

Animals↗

MR imaging of the arthritic knee: improved discrimination of cartilage, synovium, and effusion with pulsed saturation transfer and fat-suppressed T1-weighted sequences.

PURPOSE: To assess the applicability of three-dimensional (3D) magnetic resonance (MR) imaging with pulsed saturation transfer (ST) or fat saturation in depicting articular structures in arthritic knees. MATERIALS AND METHODS: Eleven patients underwent MR imaging with T1-weighted spin-echo (SE); unenhanced and contrast material-enhanced T2*-weighted 3D gradient-echo with and without on-resonance pulsed ST; and T1-weighted, fat-presaturated 3D gradient-echo techniques. Images with ST were subtracted from those without ST. RESULTS: Both fat-suppressed imaging and ST-subtraction (STS) techniques generated a high contrast-to-noise ratio among cartilage, synovium, effusion, bone, and adipose tissue. Both techniques depicted hypertrophic synovial tissue on unenhanced images; contrast material was necessary to differentiate between synovium and cartilage on STS images. CONCLUSION: 3D MR imaging with fat-suppressed or STS techniques provides good discrimination among articular structures in arthritic knees. Fat-suppressed imaging is faster than STS imaging and offers better contrast between cartilage and synovium. These techniques may improve monitoring of arthritic disease progression and therapeutic response.

Arthritis, Rheumatoid↗

Quantification of articular cartilage in the knee with pulsed saturation transfer subtraction and fat-suppressed MR imaging: optimization and validation.

PURPOSE: To assess the reproducibility and accuracy of volumetric quantifications of articular cartilage in the knee determined with three-dimensional (3D) magnetic resonance (MR) imaging combined with pulsed saturation transfer subtraction (STS) or T1-weighted fat suppression (FS) imaging. MATERIALS AND METHODS: Eight osteoarthritic knees were imaged repeatedly with optimized STS and FS sequences. Cartilage volumes were determined from 3D reconstructions of FS and STS images and by means of water displacement of surgically retrieved tissue. RESULTS: Mean over- or underestimation of cartilage volume at STS and FS imaging was 0.40 mL +/- 0.11 (standard deviation) (8.2%) and 0.31 mL +/- 0.08 (5.9%), respectively. Intraobserver reproducibility error was 0.20-0.65 mL (3.6%-6.4%) for STS and 0.21-0.58 mL (4.2%-6.4%) for FS imaging. Interobserver error was less than 0.62 mL and 7.8%. CONCLUSION: Three-dimensional data analysis of MR images acquired with STS or FS allows accurate and reproducible volumetric quantification of articular cartilage in the knee.

Aged↗

Postheparin lipolytic activity in acute and chronic renal failure.

Lipid profile and postheparin lipolytic activity (PHLA) were investigated in 21 patients with acute renal failure (ARF), 24 with chronic renal failure (CRF), and 23 healthy volunteers. Plasma triglycerides were significantly elevated in ARF (155.19 +/- 72.39 mg/dL) as well as CRF (166.79 +/- 72.36 mg/dL), as compared to controls (89.91 +/- 23.41 mg/dL, p < .001). PHLA was determined at 5, 10, 30, and 60 min after intravenous heparin (100 U/kg) and was observed to be reduced in ARF (7.82 +/- 1.41 mumol FFA/mL/h) as well as CRF (8.44 +/- 1.68 mumol FFA/mL/h) at 10 min, as compared to the values in the control subjects (12.03 +/- 2.43 mumol FFA/mL/h, p < .01). No correlation was found between PHLA and plasma triglycerides in ARF or CRF. In 15 patients in each group, PHLA subfractions, hepatic triglyceride lipase (HTGL), and lipoprotein lipase (LPL) were determined at similar time intervals after heparin. Both fractions were found to be reduced significantly (p < .01) in ARF as well as in CRF versus controls. These findings indicate that the lipid alterations in acute and chronic renal failure share common features including hypertriglyceridemia and reduced PHLA and its subfractions HTGL and LPL.

Acute Kidney Injury↗

Isolation & chemical composition of lung surfactant from human amniotic fluid.

Lung surfactant was isolated from human amniotic fluid collected at term and studied with reference to the material isolated from human and rabbit lung lavage. The isolated material showed 58 per cent lipid by dry weight, 29 per cent protein and relatively smaller amounts of nucleic acids, sialic acid and hexose. Phosphatidyl choline was the predominant phospholipid species and accounted for 46 per cent of the total lipid by weight, followed by phosphatidyl glycerol (7%) and phosphatidyl ethanolamine (5%). Cholesterol was the major neutral lipid fraction present (10%) and was almost entirely in the free form. Other lipid fractions present in minor quantity were triglycerides, esterified cholesterol, phosphatidyl serine, phosphatidyl inositol and sphingomyelin. The material contained a very high degree of alkaline phosphatase activity, while other enzymes such as acid phosphatase, glucose-6-phosphatase, ATPases, 5'-nucleotidase and beta-N-acetyl glucosaminidase were also present.

Amniotic Fluid↗

Protein kinase C isotypes and signal-transduction in human neutrophils: selective substrate specificity of calcium-dependent beta-PKC and novel calcium-independent nPKC.

Neutrophils possess at least two phospholipid-dependent forms of protein kinase C, a classical Ca/PS/DG-dependent beta-isotype of protein kinase C and a Ca-independent but PS/DG-dependent novel protein kinase C (nPKC) which we now demonstrate to have different substrate specificities. Activation of human neutrophils triggers assembly of an NADPH oxidase in the membrane and generation of O2-. A role for the major Ca-dependent isotype beta-PKC in neutrophils is proposed in stimulus-induced phosphorylation and association of a cytosolic 47 kDa protein (p47-phox) with the membrane NADPH oxidase. In this study we demonstrate that purified beta-PKC and nPKC have very different substrate specificities; beta-PKC but not nPKC phosphorylated both endogenous and recombinant p47-phox. In addition, beta-PKC but not nPKC phosphorylated [ser25]PKC(19-31), the substrate peptide based on a sequence in the Ca-dependent alpha, beta and gamma-isotypes. Pseudosubstrate(19-36), derived from the C-terminus of Ca-dependent PKC isotypes, inhibited beta-PKC but not nPKC activity using either Histone IIIS or peptide(19-31) as substrate. Pseudosubstrate(19-36) also inhibited beta-PKC catalyzed phosphorylation of endogenous and recombinant p47-phox. Pseudosubstrate(19-36) also inhibited the O2- generation triggered by GTP gamma S in electroporated neutrophils by 50%. 32P-Labelled neutrophils electroporated in the presence of GTP gamma S showed phosphorylation of multiple cytosolic proteins including a 47 kDa band, and phosphorylation of membrane-associated 34 kDa, 47 kDa and 54 kDa proteins. Pseudosubstrate(19-36) inhibited phosphorylation of p47-phox in the membrane but not in the cytosol. These findings suggest translocatable, Ca-dependent isotypes of PKC such as beta-PKC may play a role in the phosphorylation of membrane associated p47-phox and the assembly or maintenance of an active NADPH oxidase.

Calcium↗

Hematopoietic bone marrow in the adult knee: spin-echo and opposed-phase gradient-echo MR imaging.

Hematopoietic bone marrow in the distal femur of the adult may be mistaken for a pathologic marrow process in magnetic resonance imaging of the knee. We investigated the incidence of hematopoietic marrow in the distal femur in a series of 51 adult patients and compared spin-echo (TR/TE in ms: 500/35, 2000/80) and opposed-phase gradient-echo (0.35 T, TR/TE in ms: 1000/30, theta = 75 degrees) magnetic resonance images. Zones with intermediate to low signal intensity on T1-weighted spin-echo and opposed-phase gradient-echo sequences representing hematopoietic marrow within high signal intensity fatty marrow were observed in 18 of the 51 patients. Five patterns of marrow signal reduction were identified; type 0: uniform high signal, i.e., no signal change; type I, focal signal loss; type II, multifocal signal loss without confluence; type III, confluent signal loss; and type IV, complete homogeneous reduction in marrow signal. Opposed-phase gradient-echo sequences demonstrated markedly greater red-yellow marrow contrast than conventional spin-echo sequences. Follow-up studies in three patients using a gradient-echo sequence with TE varying from 10 to 21 ms at 1-ms increments showed a cyclic increase and decrease in red and yellow marrow signal intensity depending on the TE. The contribution of intravoxel chemical shift effects on red-yellow marrow contrast in opposed-phase gradient-echo images was verified by almost complete cancellation of the TE-dependent marrow signal oscillation with use of a chemically selective pulse presaturating the water protons. Hematopoietic marrow in the adult distal femur in the absence of hematologic abnormalities is found primarily in women of menstruating age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cerebral perfusion in children: detection with dynamic contrast-enhanced T2*-weighted MR images.

Cerebral perfusion dynamics were assessed with dynamic contrast material-enhanced T2*-weighted magnetic resonance (MR) imaging in 33 subjects aged 3-20 years. Group A (n = 20) had sickle cell anemia without clinical evidence of cerebrovascular disease. Group B (n = 13) consisted of 12 patients with cerebrovascular disease and homozygous sickle cell anemia and one patient without that anemia. All subjects underwent conventional MR imaging and a dynamic study in which a spoiled gradient-echo pulse sequence was used to generate images (acquisition time, 2.5 seconds) during injection of a compact bolus of gadopentetate dimeglumine (0.1 mmol/kg). For qualitative analysis, the dynamic images were displayed in cine mode. Group A demonstrated symmetric sequential region patterns of loss of signal intensity within 10 seconds of injection. Group B exhibited signal loss asymmetries that corresponded to cerebrovascular lesions on conventional MR images. Quantitative analysis enabled estimation of hemodynamic parameters, including relative cerebral blood volume, relative cerebral blood flow, and mean transit time. This method of assessment of cerebral perfusion dynamics complements conventional MR imaging.

Adolescent↗

Phage psi 92: a new choleraphage infecting Vibrio cholerae cells belonging to serovars 01 and non-01.

A new choleraphage, psi 92, with an icosahedral head and no tail structure has been described. This phage has a wide host range. It infects and lyses strains belonging to different serovars and biotypes of Vibrio cholerae. The phage utilises host DNA degradation products for its own DNA synthesis. psi 92 contains a linear double-stranded DNA of 56 kbp. A physical map of the phage genome has been constructed using the restriction enzyme KpnI. Intracellular development of phage psi 92 following infection was examined by thin-section electron microscopy.

Bacteriophages↗

Renal function in SFD and AFD preterm babies.

Maturation of neonatal glomerular function as evidenced by serum creatinine and creatinine clearance was assessed in 15 preterm small for dates infants (Group I) and compared with values obtained in 15 preterm appropriate for date babies (Group II), on 3rd, 7th and 14th postnatal days. The mean gestational ages were 34.2 and 32.5 weeks and birth weights 1436 +/- 302g and 1752 +/- 422 g, respectively. The mean serum creatinine values in Group I were 1.40 +/- 0.28, 1.18 +/- 0.22 and 0.92 +/- 0.11 mg/dl and for Group II, 1.22 +/- 0.22, 1.01 +/- 0.24 and 0.82 +/- 0.17 mg/dl on days 3, 7 and 14, respectively. Glomerular filtration rates as evidenced by creatinine clearance were 16.08 +/- 3.53, 21.25 +/- 4.79 and 36.96 +/- 6.44 ml/min/1.73 m2 for Group I as compared to 21.38 +/- 6.65, 35.96 +/- 11.47 and 57.61 +/- 21.61 ml/min/1.73 m2 for Group II on these days, showing statistically significant (p < 0.001) increase in renal function in both the groups from days 3 to 14. Even though the serum creatinine values in the two groups were comparable at identical postnatal ages, creatinine clearance was shown to be statistically less (p < 0.05 on day 3, p < 0.001 on day 7 and p < 0.01 on day 14, respectively) in Group I as compared to Group II, thereby implying slower renal maturation in small for dates preterm babies.

Creatinine↗

Alpha-1-antichymotrypsin inhibits the NADPH oxidase-enzyme complex in phorbol ester-stimulated neutrophil membranes.

The generation of superoxide anion and release of granule contents are essential to the bactericidal function of neutrophils, but may also contribute to host tissue damage during inflammation. In previous studies (J. Immunol. 146:2388), we have demonstrated that the acute phase reactant alpha-1-antichymotrypsin (ACT), a potent inhibitor of the serine protease cathepsin G, also suppresses superoxide anion generation. The inhibitory effect of ACT was not directly linked to its antiproteolytic activity and may reflect interaction at a site other than its reactive loop. To further characterize the mechanism of inhibition, we investigated the direct effects of ACT on the NADPH oxidase enzyme complex and the signaling pathways that regulate motivation of the respiratory burst. We present evidence that ACT does not intefer with agonist-stimulated calcium mobilization or translocation and activity of protein kinase C. ACT was an effective inhibitor of superoxide anion generation in membrane preparations isolated from PMA-activated cells. These results support the notion that ACT is acting on a component of the active assembled NADPH oxidase complex. Thus, ACT may have an important role in regulation of specific aspects of the inflammatory processes and the modulation of toxic oxygen-based host tissue damage.

Arachidonic Acid↗

Genes for beta-thromboglobulin and platelet factor 4 are closely linked and form part of a cluster of related genes on chromosome 4.

The small inducible gene (SIG) family encodes related proteins that are involved in the overlapping processes of coagulation, inflammation, immune response, and wound repair. This family contains two branches, termed CXC and CC, which are distinguished by whether or not the first two of four conserved cysteine residues are separated by an additional amino acid residue. All of the CXC SIGs map to chromosome 4, including those encoding beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), both of which are expressed by megakaryocytes in a tissue-specific fashion. Both of these latter two genes have been previously reported to be duplicated, there being a PF4 and a PF4alt gene, and a beta TG1 and beta TG2 gene. We now show by pulse-field gel electrophoresis (PFGE) that the beta TG genes are closely linked to the PF4 genes and to other previously mapped CXC SIGs, namely IL8 (encoding interleukin-8), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and two related genes GRO2 and GRO3, on a single 700-kb Sfil fragment localized to chromosome bands 4q12-q13. The only CXC SIG not linked to this cluster is that encoding gamma-interferon-induced 10-Kd protein (INP10), which has been previously localized to 4q21. Analysis of lambda genomic clones demonstrate that the beta TG1 and PF4 genes are separated by less than 7 kb, and the beta TG2 and PF4alt genes by approximately 5 kb. Within each beta TG/PF4 duplication, the beta TG-like gene is upstream of its linked PF4-like gene. Thus, the beta TG/PF4 genes appear to form a close-linked complex expressed in a megakaryocyte-specific fashion. Further genomic studies may provide additional insights into the regulation of the tissue-specific expression of the beta TG/PF4 gene complex, while further analysis of the linked CXC SIG cytokine family may provide further understanding of their evolutionary history.

Autoradiography↗