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Biomedical subjects

S Suresh

Publications and source records attributed to S Suresh.

At least 73 records · Page 4Linked to original sources

25-Hydroxycholesterol induces reorganization of lysosomes in normal but not Niemann-Pick disease type C astrocytes.

25-hydroxycholesterol (25-OHC), an oxysterol that potently regulates cellular cholesterol metabolism, induced formation of novel fibrillar structures in normal mouse astrocytes as observed by fluorescence microscopy with the cholesterol probe, filipin. These fibrils were identified as lysosomes by their immunoreactivity for the lysosome associated membrane glycoprotein (LAMP). In contrast, astrocytes derived from the Niemann-Pick disease type C (NPC) mutant mouse were resistant to this oxysterol-induced lysosomal reorganization. NPC astrocytes have abnormal intracellular cholesterol storage as observed by brightly positive filipin staining of their lysosomes. These results show that lysosomal cholesterol storage in NPC astrocytes is associated with a block in oxysterol-mediated fibrillar reorganization of lysosomes.

Animals↗

X-ray studies on crystalline complexes involving amino acids and peptides. XXVII. Effect of chirality, specific interactions and characteristic aggregation patterns in the structures of arginine and its complexes with formic acid.

The crystal structures of DL-arginine dihydrate, DL-arginine formate dihydrate and L-arginine formate have been determined and refined using X-ray crystallographic techniques. The three structures, along with other related ones, demonstrate the conformational variability of arginine. The amino acid molecules aggregate essentially in a similar manner in DL-arginine dihydrate and in the known structure of L-arginine dihydrate; the effects arising out of the reversal of the chirality of half the amino acid molecules are absorbed by small local adjustments. However, such a reversal leads to profound differences in aggregation in DL-arginine and L-arginine formates, in contrast to the situation in the corresponding acetates. Thus the effect of chirality on biomolecular aggregation cannot be easily predicted or even rationalized. Arginine-carboxylate interactions in the complexes primarily involve the guanidyl groups and contain specific interactions. Indeed the primary mode of arginine-carboxylic acid aggregation is substantially invariant in the arginine complexes of succinic, acetic and formic acids.

Acetates↗

X-ray studies on crystalline complexes involving amino acids and peptides. XXVI. Crystal structures of two forms of L-histidine acetate and a comparative study of the amino acid complexes of acetic acid.

L-Histidine acetate crystallizes in two forms: (I) orthorhombic; P2(1)2(1)2(1); a = 5.027, b = 11.126, c = 17.473 A; Z = 4; (II) monoclinic; C2; a = 15.649, b = 9.276, c = 8.566 A; beta = 94.65 degrees; Z = 4. The structures were solved by direct methods and refined to R-values of 0.056 and 0.089 for 1131 and 1330 observed reflections, respectively. The conformations of the histidine molecule in the two forms are different. However, both are such that they facilitate the occurrence of a specific interaction of the histidine molecule with a carboxylate group. The basic elements of aggregation are hydrogen-bonded histidine ribbons, but they are of different types in the two structures. The ribbons are interconnected by acetate ions to form the crystals. The structures contain two characteristic interaction patterns involving amino and carboxylate groups, one of which is observed for the first time. The two water molecules in form II and their symmetry equivalents form an uninterrupted hydrogen-bonded chain running through the crystal. They also present an interesting case of disorder in hydrogen bonds. A comparative study involving amino acid complexes of acetic acid shows that the presence of acetate ion could lead to new aggregation patterns, specific interactions and characteristic interaction patterns with varying degrees of similarity with those observed in other structures containing amino acids.

Acetates↗

The genetic predisposition to fibrocalculous pancreatic diabetes.

Fibrocalculous pancreatic diabetes (previously known as tropical pancreatic diabetes) is a rare cause of diabetes confined to countries within the tropical belt. The aetiology of fibrocalculous pancreatic diabetes is thought to be environmental although the agent(s) is unknown. We have investigated a possible genetic basis of this disease by looking for restriction fragment length polymorphisms of genes implicated in the aetiology of diabetes mellitus. Seventy-six Dravidian patients with fibrocalculous pancreatic diabetes were studied, and the restriction fragment length polymorphisms obtained compared to racially matched control subjects (n = 94), patients with Type 2 (non-insulin-dependent) diabetes (n = 87) and Type 1 (insulin-dependent) diabetes (n = 58). No association of fibrocalculous pancreatic diabetes was found with restriction fragment length polymorphisms of the insulin receptor gene. Although no association of fibrocalculous pancreatic diabetes was found with polymorphism of the HLA DR alpha/DQ alpha/DX alpha genes, an association was found with the Taq 1 restriction fragment length polymorphisms of the DQ beta gene (DQ beta T2/T6 present in 39% of patients with fibrocalculous pancreatic diabetes compared to 19% in control subjects; p = 0.01; corrected p value = 0.04) which is similar to that found in Type 1 but not Type 2 diabetes. An association of fibrocalculous pancreatic diabetes was also found with the hypervariable region in the 5-prime flanking region of the insulin gene; 40% of patients possessed the class 3 allele compared to 9.5% of control subjects p = 0.0001; corrected p value = 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Familial aggregation in tropical fibrocalculous pancreatic diabetes.

There is very little information on the genetic factors associated with fibrocalculous pancreatic diabetes (FCPD). Ninety-eight first-degree relatives of FCPD patients were subjected to detailed studies, which included glucose tolerance tests, x-ray films of the abdomen, ultrasonography, and studies of exocrine pancreatic function. The study shows that there is a familial aggregation of FCPD with evidence of vertical transmission of the disease from parent to offspring in some families. Routine screening of families of FCPD probands helped to pick up cases in the stage of impaired glucose tolerance. There is heterogeneity in FCPD with respect to familial factors. Some families show marked familial aggregation of FCPD while in others the disease occurs either sporadically or in association with other family members who have abnormal glucose handling.

Adolescent↗

Fibrocalculous pancreatic diabetes in the elderly.

Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes seen in tropical countries. It is secondary to chronic, calcific, non-alcoholic pancreatitis. FCPD is usually a disease of youth. This paper reports on two elderly onset cases of FCPD. Macrovascular complications are usually rare in FCPD patients. These two patients had evidence of macrovascular diseases probably due to the older age group of the patients.

Calcinosis↗

Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant.

Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture.

Animals↗

Effect of insulin on low-density-lipoprotein metabolism in human lymphocytes in vitro.

The metabolism of low-density lipoproteins (LDL) in vitro in the presence of insulin was studied in freshly isolated human peripheral-blood lymphocytes. Insulin appeared to decrease the binding affinity of 125I-LDL to its cell-surface receptor, without any change in apparent Vmax or in the number of LDL receptors. As a consequence, the absolute amounts of 125I-LDL internalized and degraded were lower in the presence of insulin than in its abscence, although the fraction of internalized 125I-LDL degraded in either instance was quite similar. 3-Hydroxy-3-methylglutaryl-CoA reductase activity, and hence cholesterol synthesis, were stimulated by insulin. This effect of insulin was independent of the inhibitory effect of LDL on cholesterol synthesis. At the same time, acid cholesterol esterase and acyl-CoA: cholesterol O-acetyltransferase activities were lower in cells incubated with insulin than in controls. The net effect of these metabolic alterations seems to be that cells accumulate greater quantities of free and esterified cholesterol when treated with insulin.

AMP-Activated Protein Kinases↗

Real-time ultrasonography in neuromuscular problems in children.

Ultrasound imaging of 20 cases of progressive muscular dystrophy and 10 cases of suspected infantile spinal muscular atrophy in children was performed by us, as a double-blind plot study matched against 25 controls. Open muscle biopsy was restricted to the muscular dystrophy group. The ultrasonographic findings were correlated with parameters such as functional disability of muscle and muscle biopsy features in the dystrophy group. It was interesting to observe that the muscle echogram was abnormal in both types of neuromuscular problems, the controls giving a normal muscle echogram. Ultrasonography was helpful in detection of unequivocal changes in our cases with mild clinical disability. It had a close correlation with changes in gross muscle architecture, as seen on muscle biopsy.

Adolescent↗

Plasma lipoprotein cholesterol in India in healthy persons and those with coronary heart disease.

The plasma total cholesterol and lipoprotein cholesterol levels are presented for 186 healthy Indian subjects and 213 patients with coronary heart disease (CHD). Plasma lipid and lipoprotein concentrations vary with age. Higher total cholesterol and LDL cholesterol were noted in men compared with women. HDL cholesterol is highest in women in the age group 20-49 years. HDL cholesterol levels (negatively associated with CHD) are significantly higher in India compared with western countries. It is suggested that the high level of HDL cholesterol may be responsible for the relatively low incidence of CHD in India.

Adult↗

Latex allergy in children: diagnosis and management.

Latex allergy is an increasingly common condition, in both children and health care workers who provide care for them. Subpopulations at particular risk include children with spina bifida, children undergoing multiple surgical procedures, and health care workers in the operating theatre. Chemical additives in latex gloves can cause an irritant or allergic contact dermatitis. Latex proteins are responsible for most of the immediate IgE-mediated hypersensitivity allergic reactions. Symptoms range from rhinitis, conjunctivitis and urticaria to anaphylaxis and death. A latex-directed history is the primary method of identifying latex sensitivity, although both skin and serum testing is available and increasingly accurate. (Latex avoidance should be used in all individuals with a positive skin or blood test or a positive history). The most important preventive measure for patients with or at risk for latex allergy is minimizing direct patient exposure to latex products, most notably latex gloves. Recent operating room studies indicate simple preventive measures can dramatically reduce intraoperative reactions. Preoperative prophylaxis with antihistamines and steroids have not been shown to be necessary or effective. Treatment of an allergic reaction begins with immediate removal of any identified source of latex in direct patient contact. Treatment is similar to anaphylaxis from other causes, and may require the use of epinephrine. Everyone caring for the patient at risk for latex allergy must be involved in making their medical environment safe.

Child↗