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Biomedical subjects

V Sundaram

Publications and source records attributed to V Sundaram.

27 records · Page 2Linked to original sources
PubMed1986

Carbonic anhydrase II deficiency: diagnosis and carrier detection using differential enzyme inhibition and inactivation.

Carbonic anhydrase (CA) I and II are soluble isozymes that represent the major nonhemoglobin proteins in the erythrocyte. We recently identified a deficiency of CA II as the enzymatic basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Virtual absence of the CA II peak on high-performance liquid chromatography, of CA II esterase activity, and of immunoprecipitable CA II were demonstrated on extracts of red cell lysates from all patients studied. Reduced levels of CA II were found in obligate heterozygotes. Here, we present evidence that CA II in red cell lysates can be quantitated by measuring CO2 hydratase activity in the presence of inhibitors that selectively inhibit the activity of CA I to a much greater extent than that of CA II. This was done with iodide (anion binding) and bromopyruvic acid (alkylation), and the respective assays evaluated as diagnostic tools for CA II deficiency in human red cells. These techniques greatly simplify the quantitation of CA II in hemolysates and should make genetic diagnosis and counseling for the newly described inborn error of metabolism due to CA II deficiency generally available. They also allow quantitation of CA I in red cell lysates.

Acidosis, Renal Tubular↗
PubMed1985

Carbonic anhydrase II deficiency in 12 families with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification.

Osteopetrosis with renal tubular acidosis and cerebral calcification was identified as a recessively inherited syndrome in 1972. In 1983, we reported a deficiency of carbonic anhydrase II, one of the isozymes of carbonic anhydrase, in three sisters with this disorder. We now describe our study of 18 similarly affected patients with this syndrome in 11 unrelated families of different geographic and ethnic origins. Virtual absence of the carbonic anhydrase II peak on high-performance liquid chromatography, of the esterase and carbon dioxide hydratase activities of carbonic anhydrase II, and of immunoprecipitable isozyme II was demonstrated on extracts of erythrocyte hemolysates from all patients studied. Reduced levels of isozyme II were found in obligate heterozygotes. These observations demonstrate the generality of the findings that we reported earlier in one family and provide further evidence that a deficiency of carbonic anhydrase II is the enzymatic basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. We also summarize the clinical findings in these families, propose mechanisms by which a deficiency of carbonic anhydrase II could produce this metabolic disorder of bone, kidney, and brain, and discuss the clinical evidence for genetic heterogeneity in patients from different kindreds with this inborn error of metabolism.

Acidosis, Renal Tubular↗
PubMed1985

Congenital absence of left pericardium in a family.

Characteristic radiographic findings of absence of the left pericardium were observed in two relatives who were related to two other individuals with different types of congenital heart defects. Familial occurrence of congenital absence of pericardium has not been reported previously. The strong male sex predilection in the previously reported patients, the segregation pattern of affected individuals in the pedigree presented here, and the presence of two other individuals with multifactorially determined congenital heart defects in the same pedigree suggest multifactorial determination of congenital absence of the left pericardium.

Adolescent↗
PubMed1985

Positive renal response to intravenous acetazolamide in patients with carbonic anhydrase II deficiency.

Carbonic anhydrase II (CA II) is the only soluble isozyme of CA which is known to be expressed in kidney. We recently identified a deficiency of this enzyme as the basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. In order to explore the physiological importance of CA II in the kidney, we studied the renal response to intravenously infused acetazolamide in two CA II-deficient patients and two control subjects. Following acetazolamide infusion, the CA II-deficient patients exhibited a prompt rise in urinary pH and HCO3- excretion similar to the response seen in control subjects. These findings indicate that CA II-deficient patients, who lack detectable CA II in their erythrocytes, still expressed an acetazolamide-inhibitable CA activity in their kidneys. These results can be explained in three ways: 1) the CA II deficiency which is profound in the erythrocytes of these patients may not be expressed in their kidney. 2) An acetazolamide-sensitive CA other than CA II, such as CA I and CA III, which is not normally expressed in kidney, is expressed in kidneys of CA II-deficient patients. 3) The CA II deficiency is expressed in kidney in these patients but the acetazolamide response is due to inhibition of the luminal, membrane-bound CA which is the product of a different gene and unaffected by the CA II deficiency mutation. We favor the third possibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1984

The origin of follicular dendritic cells in the mouse and the mechanism of trapping of immune complexes on them.

F1----parental bone marrow chimeras between CBA and B10 mice were used to show that even after 1 year follicular dendritic cells (FDC), also termed dendritic reticular cells, are not derived from bone marrow stem cells. However clusters of cells wrapped in the dendritic processes of FDC, isolated by enzyme digestion of the spleen contain B cells originating from donor marrow. This implies that evidence for the presence of antigens such as Ia-like detected by others (Gerdes, J. and Stein, H., Clin. Exp. Immunol. 1982. 48: 348) by immunohistology in or on FDC clusters should be interpreted with caution. Deposition of immune complexes on mouse spleen FDC depends upon the presence of a radio- and cyclophosphamide-sensitive population of cells, although FDC themselves are resistant to such treatments. After whole body irradiation the capacity to localize fluorescein isothiocyanate-labeled aggregated human gamma globulin can be restored by normal or T-deprived spleen cells, but restoration requires an interval of more than 1 though less than 5 days. These findings are compatible with the evidence of Gray et al., Eur. J. Immunol. 1984. 14: 47, that in the rat immune complexes are transported to FDC by a sessile population of marginal zone lymphocytes, as first suggested by Brown et al., Immunology 1973. 24: 955.

Animals↗
PubMedDate not supplied

Unusual manifestations of cushing's syndrome in a multiple endocrine neoplasia type I kindred.

OBJECTIVE: To describe two unusual cases of Cushing's syndrome in a kindred with multiple endocrine neoplasia type I (MEN I). METHODS: The clinical and laboratory data as well as follow-up course of the two patients are reviewed in detail. RESULTS: Our first patient with a history of MEN I had hypercortisolism and computed tomographic evidence of a right adrenal mass (8.5 by 11 cm) extending into the inferior vena cava as well as multiple pulmonary nodules. He was diagnosed with Cushing's syndrome attributable to metastatic adrenal cancer that progressed despite chemotherapy. He died 2 years later. His son, who was also diagnosed with MEN I, had adrenocorticotropic hormone-dependent Cushing's syndrome. The plasma corticotropin-releasing hormone (CRH) level was high; magnetic resonance imaging showed normal pituitary findings but an islet cell tumor of the pancreas. The islet cell tumor was resected, and the patient's urinary cortisol declined to upper limits of normal. CRH was detected in the tissue, and the patient was thought to have Cushing's syndrome as a result of a CRH-secreting islet cell tumor. One year later, however, his Cushing's syndrome recurred. Inferior petrosal sinus sampling suggested a pituitary source, and the patient underwent transsphenoidal hypophysectomy. Histopathologic examination did not reveal pituitary hyperplasia or microadenoma, but the patient was cured of his Cushing's syndrome. CONCLUSION: Cushing's syndrome is a rare initial manifestation of MEN I. We report two unusual causes of Cushing's syndrome in MEN I--that is, adrenal cancer and a probable CRH-secreting islet cell tumor. The natural history of Cushing's syndrome in MEN I is not known; further studies should be conducted.

Journal Article↗
PubMedDate not supplied

Induction of rifampicin metabolism during treatment of tuberculous patients with daily and fully intermittent regimens containing the drug.

Self-induction of rifampicin metabolism during daily and intermittent chemotherapy was studied by monitoring the changes in the serum half-life of the drug over a 4-week period in patients with pulmonary tuberculosis. Rifampicin 450 mg was administered to 8 patients who received treatment daily, 7 on thrice-weekly and 7 others on twice-weekly treatment. Serum half-life was computed from concentrations of the drug determined at 3, 4 1/2 and 6 hours after drug administration, on admission and at 1, 2 and 4 weeks after start of treatment. In the daily series, the mean serum half-life decreased from 4.9 hours on admission to 3.6 hours at 1 week (P = 0.02), and treatment beyond this had no further effect. In the thrice-weekly series, maximal induction was observed at the 2nd week, the mean values on admission and at 2 weeks being 5.8 and 3.7 hours, respectively (P less than 0.01). In the twice-weekly series, maximal induction was observed only at the 4th week, the mean values on admission and at 4 weeks being 4.9 and 3.7 hours, respectively (P less than 0.01). Serum activity of gamma glutamyl transferase was not found to be a suitable in vivo marker to monitor induction of the hepatic microsomal enzymes as no significant changes were observed in the activity of this enzyme in any of the 3 series during the 4-week period.

Drug Administration Schedule↗