Search PubMed⌕ Search

Biomedical subjects

A Rapoport

Publications and source records attributed to A Rapoport.

At least 73 records · Page 4Linked to original sources
PubMed1987

Human preproparathyroid hormone synthesized in Escherichia coli is transported to the surface of the bacterial inner membrane but not processed to the mature hormone.

cDNA encoding human preproPTH (hpreproPTH) was expressed in Escherichia coli to study the processing of the precursor to hPTH and its secretion by the bacterial secretory apparatus. We first constructed hybrid genes that differed randomly in the distance between the E. coli lac promoter's ribosomal binding site and DNA encoding a fusion protein with beta-galactosidase activity and the prepro sequence of hpreproPTH on the aminoterminus. Starting with clones identified as efficient producers of beta-galactosidase on indicator agar plates, the coding sequence for hpreproPTH was reconstituted intact. In a different construction we placed the hpreproPTH coding sequence downstream from the lac promoter at a distance of 12 base pairs from the ribosomal binding site. PTH immunoreactive proteins from multiple clones were identified by protein gel electrophoresis and by protein microsequencing. PTH-related proteins encoded by different plasmids were shown to be hpreproPTH with amino-terminal extensions of either two or four amino acids and as authentic hpreproPTH. Two hPTH fragments, hPTH(3-84) and hPTH(8-84), were also observed. The trypsin accessibility of hpreproPTH and of the two hPTH fragments in pulse-chase, cell-fractionation experiments using intact and lysed spheroplasts lets us conclude that the mammalian signal sequence directs hpreproPTH to the surface of the spheroplast membrane but is not appropriately cleaved by the signal peptidase.

Animals↗
PubMed1987

Consequences of amino-terminal deletions of preproparathyroid hormone signal sequence.

PTH is initially synthesized as a larger precursor, containing a 25 amino acid signal sequence. Modification of cDNA encoding the hormone precursor resulted in the synthesis of proteins whose signal sequences were shortened at their amino termini. The effects of these mutations were analyzed using a cell-free translation system and rat pituitary GH4 cells in culture. Removal of the first six amino acids of the signal sequence had no effect on the efficiency or kinetics of protein processing as measured in the two assay systems. Mutants lacking 10 or 13 amino acids were not processed efficiently in the cells, nor were they translocated across microsomes in the cell-free translation system. These studies suggest that a modest change in the hydrophobic domain of the signal sequence, which might not have been predicted to alter function, led to a dramatic decline in signal activity.

Amino Acid Sequence↗
PubMed1985

Therapeutic association for nasopharyngeal cancer.

The authors studied retrospectively 16 cases of malignant epithelial nasopharyngeal tumors which were treated at the Head and Neck Service of the Heliópolis Hospital, São Paulo, Brasil, from December 1977 to December 1983. The treatment was intra-arterial chemotherapy (IAC) followed by radiotherapy. The chemotherapeutic schedules were: methotrexate and vincristine, methotrexate, bleomycin and vincristine (2 different schedules) and methotrexate, bleomycin, vincristine and cisplatinum. Objective responses to IAC were observed in 18.6% of the cases. Only 3 patients are alive at 26, 37 and 53 months; 2 of them had exhibited response to IAC. The authors analyze the results and suggest randomized trials in order to determine the exact effects of this method of treatment.

Adult↗
PubMed1985

Routine preoperative exercise testing in patients undergoing major noncardiac surgery.

A prospective study of preoperative exercise testing was carried out in 200 patients older than 40 years scheduled for elective major noncardiac surgery under general anesthesia. The exercise test response was electrocardiographically positive in 32 patients (16%) (2 patients had a markedly positive test), equivocal in 11 patients (5.5%) and negative in 157 patients (78.5%). The patients were followed with serial pre- and postoperative electrocardiograms (ECGs) and determinations of serum creatine kinase (CK) and CK-MB. Six patients (3%) had primary endpoints: 3 (1.5%) died postoperatively and 3 (1.5%) had definite postoperative myocardial infarction. Secondary endpoints of suspected postoperative myocardial ischemia/injury diagnosed by ECG or elevation in CK-MB levels occurred in 27 patients (14%). Endpoint events were more common in patients aged 70 years or older. Endpoint events were also more common in patients with an abnormal (positive or equivocal) preoperative exercise test response than in those with a negative response (27% vs 14%); however, preoperative exercise results were not statistically significant independent predictors of cardiac risk. Using multivariate analysis, the only statistically significant independent predictor of risk was the preoperative ECG. Endpoint events were more common in patients with an abnormal than in those with a normal ECG (23% vs 7%, p less than 0.002). Because the results of exercise testing do not appear to add substantially to the risk separation provided by the ECG at rest, exercise testing is not recommended as a routine preoperative method for assessing perioperative risk in older patients who are being evaluated before major elective noncardiac surgery under general anesthesia.

Adult↗
PubMed1985

Structural analysis of both products of a reciprocal translocation between c-myc and immunoglobulin loci in Burkitt lymphoma.

The balanced translocations that occur between the c-myc and immunoglobulin loci in Burkitt lymphoma provide an unusual opportunity to analyze both products of a reciprocal recombination. Accordingly, we have determined the structure of the two reciprocal products of a translocation that joins the 5' portion of the c-myc gene on chromosome 8 to the immunoglobulin mu switch recombination signal on chromosome 14. By determining the nucleotide sequences at the translocation crossover points of both product chromosomes, we precisely locate these points with respect to nearby genes. This determination allows us to conclude that translocation involves nonhomologous recombination, is highly conservative of c-myc sequences (deleting only 16 bp at the crossover point), but deletes over 2 Kb of immunoglobulin sequences from the mu switch signal. The mu constant and c-myc genes are joined head-to-head about 3 Kb apart, while the IgH enhancer and an aberrantly rearranged D/J region are linked to sequences 5' of c-myc on the reciprocal product.

Burkitt Lymphoma↗
PubMed1985

Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes.

Autosomal dominant familial hypocalciuric hypercalcemia was found in a kindred with neonatal severe primary hyperparathyroidism, previously judged to be an autosomal recessive trait. Mild hypercalcemia was documented in eight members representing three generations. Mild hypercalcemia was documented at an age as early as one week. In seven adults presumed to be heterozygotes, urinary calcium levels were in the same range as for familial hypocalciuric hypercalcemia. An additional adult member (who previously underwent parathyroidectomy for neonatal severe primary hyperparathyroidism) showed an abnormality in renal clearance of calcium and sodium characteristic of combined familial hypocalciuric hypercalcemia and surgical hypoparathyroidism. Parathyroidectomy in three hypercalcemic members did not cause normocalcemia. Unlike other kindreds with familial hypocalciuric hypercalcemia in whom hypercalcemia is consistent over time and moderate in heterozygotes, this kindred was characterized by heterozygotes showing hypercalcemia that was intermittent and mild. The consanguineous parents of the two previously described severely affected neonates were judged to be heterozygotes for familial hypocalciuric hypercalcemia. In conclusion, (1) a gene presenting as familial hypocalciuric hypercalcemia can be expressed as hypercalcemia that is intermittent and very mild in heterozygotes; (2) such a gene can cause neonatal severe primary hyperparathyroidism in homozygotes.

Adolescent↗
PubMed1985

Quantitative radionuclide scanning in metabolic bone disease.

A simple method of quantifying skeletal uptake of 99Tcm-methylene diphosphonate, using a rectilinear scanner and a simultaneously image standard, is described. The pattern of quantified uptake in ten regions of the skeleton, the sacro-iliac joints and kidneys in 57 controls and 54 patients with various metabolic bone disease is presented. This method distinguishes patients with primary hyperparathyroidism and osteomalacia from controls with a sensitivity adequate for clinical purposes. In primary hyperparathyroidism the increased skull uptake of tracer correlated well with levels of serum alkaline phosphatase, plasma parathyroid hormone, urinary hydroxyproline excretion and the degree of intracortical resorption in the metacarpal bones. The skull uptake in oestoporosis was normal or moderately elevated and correlated well with bone mass density measurements of the radius. Patients with osteomalacia also showed the greatest increase in tracer uptake in the skull. Patients with thyrotoxicosis differed from most other patients by showing moderately increased uptake in shafts of long bones. We propose our method of quantitative bone uptake as a useful noninvasive test to detect metabolic bone disease and to monitor responses to therapy of bone disease.

Adolescent↗
PubMed1979

Role of dialysis in the treatment of severe hypercalcemia: report of two cases successfully treated with hemodialysis and review of the literature.

The role of dialysis in the treatment of patients with severe hypercalcemia is uncertain. The fourteen previously reported cases of hypercalcemia treated with either peritoneal or hemodialysis have been reviewed. Two additional patients treated with hemodialysis are described in this report. Because the use of large volumes of intravenous fluids was contraindicated, each of the patients received a low calcium bath (0-1 mEq calcium per liter) hemodialysis for three and a half hours. After dialysis, the serum calcium fell to normal in both and remained normal thereafter with treatment of the underlying disease (multiple myeloma in one and vitamin D intoxication in the other). Hemodialysis can clear up to 682 mg of calcium per hour as compared to 124 mg per hour for peritoneal dialysis and 82 mg per hour with forced saline diuresis. Low calcium bath hemodialysis is indicated when the presence of renal and/or cardiac failure prevents the administration of large volumes of intravenous fluids to hypercalcemic patients.

Aged↗
PubMed1978

Unusual fractures associated with osteoporosis in premenopausal women.

Two premenopausal women (aged 40 and 34 years) and multiple undisplaced, often asymptomatic fractures of the femurs, ribs, metatarsals and other bones. The fractures, which appeared on roentgenograms as transverse radiolucent zones with variable callus formation, healed slowly or not at all despite treatment with calcium and vitamin D. They resembled pseudofractures (Looser's transformation zones) radiologically, but the biochemical and histologic findings were those of idiopathic osteoporosis rather than osteomalacia. Since neither patient had been subjected to unusual stress it was concluded that the fractures had resulted from normal activity in abnormal bone.

Adult↗
PubMed1978

Visceral calcification and the CaXP product.

The authors studied the presence of visceral calcification as evidenced by the visceral uptake of bone-seeking radionuclides during the course of a bone scan among 22 patients with terminal renal failure maintained on dialysis, nine patients with hypercalcemia secondary to malignancy, and nine patients with primary hyperparathyroidism. Uptake by the lungs or stomach was observed in 11 renal failure patients (50%) and in four of those with malignancy and hypercalcemia (44%). None of the patients with primary hyperparathyroidism had evidence of visceral calcification. The serum CaXP product was significantly higher among those with visceral calcification than those without. The results of this study indicate that a CaXP product of 60 represents the saturation product of calcium phosphate in serum above which spontaneous precipitation of this salt may occur in such viscera as stomach and lungs.

Adult↗
PubMed1978

Studies in inhibitors of calcification and levels of urine saturation with calcium salts in recurrent stone patients.

Studies have been done on patients with recurrent renal calculous disease, measuring in addition to the usual serum and urine constituents the inhibiting capacity of the urine and the activity products of calcium oxalate, octocalcium phosphate and brushite. Studies on the 24-hour urine calcium, phosphorus and uric acid and serum calcium indicate no essential differences between patients with calcium oxalate, mixed or uric acid stones and normal individuals. We were unable to demonstrate a difference in the inhibiting capacity of the urine between normal individuals and patients with calcium oxalate calculi, and levels of saturation of urine with calcium oxalate were identical in the calcium oxalate stone patients and normal individuals. The degree of saturation of urine with calcium phosphate is significantly greater in stone patients.

Calcification, Physiologic↗
PubMed1978

Influence of exchange volume and dialysate flow rate on solute clearance in peritoneal dialysis.

To find the ideal dialysate flow rate and exchange volume for use in long-term peritoneal dialysis, 10 patients were studied over a period of 1.5 yr. Exchange volumes of 1 or 2 liters and dialysate flow rates of 1, 2, 3, 4, and 6 liters/hr were tested. Dextrose concentration remained constant at 1.5 g/100 ml. Peritoneal clearances for BUN, creatinine, and uric acid were calculated at 2, 5, 10, 15, and 20 hr during dialysis making a total of 120 clearances for each patient. All patients used a reverse osmosis automatic machine. The clearance of all three solutes tended to be higher with exchange volumes of 2 liters than they did with 1 liter; this trend was significant for BUN (P less than 0.025) and uric acid (P less than 0.025) but not for creatinine. There was a significant rise in clearance with increasing flow rates per hour for all solutes as shown in the following table. (Formula: see text), Since patients could not tolerate a flow rate of 6 liters/hr, we conclude that flow rate of 4 liters/hr with a 2-liter exchange will give maximum efficiency.

Blood Glucose↗