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Biomedical subjects

R S Markin

Publications and source records attributed to R S Markin.

At least 109 records · Page 6Linked to original sources
PubMed1987

Hepatitis in fatal infectious mononucleosis.

A detailed clinicopathologic analysis of 30 patients with sporadic fatal infectious mononucleosis and 31 males with fatal infectious mononucleosis and the X-linked lymphoproliferative syndrome was performed to determine the extent of hepatic dysfunction in these cases. At death, the median age of patients with sporadic infectious mononucleosis was 10.7 yr vs. 2.4 yr for X-linked lymphoproliferative syndrome. The median survival time was 8 wk for sporadic infectious mononucleosis and only 4 wk for X-linked lymphoproliferative syndrome. The male to female ratio was 3:2 in sporadic infectious mononucleosis; all patients with X-linked lymphoproliferative syndrome were males. Fever, sore throat, lymphadenopathy, hepatomegaly, and splenomegaly were prominent findings. Hepatic dysfunction was uniformly present and caused death in 13 of 30 sporadic infectious mononucleosis cases and 18 of 31 X-linked lymphoproliferative syndrome cases. Diagnosis of infectious mononucleosis was confirmed by heterophile antibody titers or Monospot, Epstein-Barr virus antibody studies, viral culture, molecular hybridization studies, clinical and histologic findings, and pedigree analysis.

Child↗
PubMed1987

Thymic lesions in fatal infectious mononucleosis.

Thymic lesions were studied in 35 patients with fatal infectious mononucleosis (FIM) including 21 males with the X-linked lymphoproliferative syndrome (XLP) and 14 non-XLP patients. Six patterns based on the lymphocyte content and status of Hassall's bodies were observed: massive lymphoproliferation effaced the architecture and Hassall's bodies (HB) in 6 cases. Epstein-Barr virus (EBV)-laden B cells surrounded by cytotoxic T cells and natural killer cells were found in one of these cases. Only 5 of the 35 thymuses contained normal-appearing HB. Seven showed a moderate reduction in HB. Rarely, multinucleated giant cells and hyaline globules were seen where one might expect HB to reside. Plasma cells and macrophages were generally abundant. Eight displayed a marked depletion of HB. In 7, no HB were recognized. Massive necrosis was seen in one of these cases. Stress involution was encountered in only two patients, both of whom had sporadic fatal IM. Thymic lesions and alterations were similar but less extensive in sporadic FIM. These morphological studies, taken in context with clinical and experimental reports, suggest that destruction of thymic epithelium may contribute to the progression of immune defects seen in XLP following EBV infection. The destruction of HB that we observed was similar in appearance to lesions in several other immune deficiency disorders.

Age Factors↗
PubMed1987

Mesenchymal chondrosarcoma: a case report.

Mesenchymal chondrosarcoma is a rare tumor distinctly different from the more common chondrosarcoma. It shows a predilection for the head and neck in both osseous and extraosseous forms. The prognosis for cure is poor, with a high incidence of local recurrence as well as regional and distant metastasis. Treatment is based on radical surgical excision, although combination chemo-therapy has recently shown promise. Additional experience with this tumor is required to define the most efficacious form of treatment.

Adult↗
PubMed1987

Effect of pH and ions on the electronic structure of saccharin.

The sodium salt of saccharin is biologically more active as a urothelial cell mitogen in vivo, when fed to male rats, than are the potassium or calcium salts or the acid form, despite similar concentrations of saccharin excreted in the urine. The differences in bladder-mitogenic activity between sodium saccharin and the other salts of saccharin may be the result of known differences in the ionic composition of the urine of rats receiving these various forms of saccharin. These changes in the rat urine following administration of the different salts of saccharin could be responsible for the observed mitogenic responses to oral saccharin; alternatively the differences in the ionic composition of the urine could result in changes in the electronic structure of the saccharin molecule itself, allowing it to be more active in certain ionic environments. Since the pKa of saccharin is 1.8, essentially all of the saccharin in urine (pH greater than 5) will exist in the ionized form. We have used 17O, 15N, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy to explore the electronic structure of the saccharin molecule in aqueous solution. By observing the NMR spectra of the saccharinate ion in the presence of varying concentrations of hydrogen, potassium, sodium, calcium, magnesium, bicarbonate and urate, we have demonstrated that at physiological levels none of these ions significantly alters the electronic structure of the saccharin molecule. Hence the differences in the mitogenic response to the different saccharin salts cannot be explained by alterations in the structure of the saccharin molecule.

Carbon Isotopes↗
PubMed1987

Hypothalamic hamartoma: a report of 2 cases.

Two patients with hypothalamic hamartoma presented with isosexual precocious puberty. LHRH challenge showed a pubertal LH response in both cases. Serum FSH responses to LHRH were pubertal in case 1, but prepubertal for case 2. Computed tomography revealed isodense noncontrast-enhancing retrosellar mass lesions in both cases. The tumors were composed of mature neurons and neuroglial tissue. Electron microscopy of the lesions failed to demonstrate dense core (neurosecretory) granules in either case. Subtotal removal of the harmartomas resulted in decreased LH responsiveness to LHRH in both cases. Serum FSH responsiveness to LHRH was not significantly suppressed postoperatively in case 1, and FSH responsiveness to LHRH in case 2 showed exaggerated levels, more typical of very young prepubertal girls. Postoperative magnetic resonance imaging (MRI) scans of both patients are also presented.

Child, Preschool↗
PubMed1985

Abnormal erythrocyte pyrimidine nucleotides in uremic subjects.

Uremia causes major increases in the erythrocyte (RBC) purine nucleotides, presumably secondary to phosphate retention, but no previous study has been made of the pyrimidine nucleotides, normally absent from RBC. This investigation was prompted by demonstration of the abnormal presence of RBC pyrimidine nucleotides, primarily cytidine triphosphate (CTP) plus cytidine diphosphate-choline (CDP-C) and cytidine diphosphate-ethanolamine (CDP-E), in two types of congenital hemolytic anemia as well as in lead poisoning. These observations suggested an analogy to the RBC membrane dysfunction of uremia. This is a report of the identification of CDP-C and CDP-E as the predominant abnormal pyrimidine nucleotides in the RBC hemolysates of uremic subjects. High-performance liquid chromatography of hemolysates from uremic adults showed a 50% increase in purine nucleotides and the abnormal presence of pyrimidine nucleotides and diesters at approximately 10% of the concentration of the purine nucleotides. By means of UV spectra and 31P nuclear magnetic resonance, these were identified as CDP-C and CDP-E. The increased purine and abnormal pyrimidine nucleotides of uremic RBC were unrelated to the pre- or posthemodialysis state, allopurinol, levels of blood lead, copper and zinc, or RBC pyrimidine 5'-nucleotidase, the cytosolic enzyme that specifically dephosphorylates the pyrimidine nucleotides. Although the accumulation of CTP, CDP-C and CDP-E may be an epiphenomenon of phosphate retention, it also suggests a common pathway to the accelerated hemolysis of chronic renal insufficiency.

5'-Nucleotidase↗
PubMed1985

Immunohistochemical characterization of lymphocytes in uninflamed ventricular myocardium. Implications for myocarditis.

Evaluation of endomyocardial biopsy specimens for lymphocytic myocarditis requires accurate identification of lymphocytes, a task at times difficult considering that other myocardial interstitial cells mimic lymphocyte morphology. To wit, the number of mononuclear cells present in normal (uninflamed) myocardium has remained in doubt. We studied the myocardium from hearts that were obtained at autopsy and transvenous endomyocardial biopsy specimens with monoclonal antibodies and immunohistochemical stains to determine the normal numbers and distribution of lymphocytes in uninflamed hearts. In the ventricular myocardium of hearts obtained at autopsy, total immunohistochemically marked lymphocytes averaged 3.6/sq mm, with most being T-cell marker-positive. The ratio of T-helper to T-suppressor-cytotoxic (OKT-4:OKT-8) cells was 1.44. The number of myocardial lymphocytes demonstrated by immunohistochemical staining correlated well with, but was consistently less than, the number obtained by quantitative light microscopic studies on unmarked samples. Thus, the immunohistochemical technique allows for objective enumeration of cells and provides avenues for quantitation of lymphocyte subpopulations in inflamed hearts.

Adolescent↗
PubMed1984

The effects of dietary amino acids on hepatic L-asparagine synthetase.

Rats were fed Roger's synthetic amino acid diets, complete or without asparagine, aspartate, or glutamate, for 2 weeks. Hepatic and serum amino acid content and hepatic asparagine synthetase were assayed before and after the test diets were administered. Special attention was paid to the multiple forms of asparagine synthetase present. Rats fed the test diet without asparagine exhibited high molecular weight (110,000) alpha-form and intermediate molecular weight (57,000) beta-form of asparagine synthetase. Rats fed the complete test diet and the test diet without asparatate exhibited only the beta-form of the enzyme. Rats fed the test diet without glutamate exhibited no enzyme activity. These data are related to the hepatic amino acid levels and to the role of asparagine and asparagine synthetase in amino acid homeostasis.

Amino Acids↗
PubMed1984

Spinal cord compression secondary to Gaucher's disease.

A case of compression of the spinal cord and cauda equina secondary to collapse of the T-12 and L-3 vertebral bodies in a patient with type 1 Gaucher's disease is presented. Decompressive laminectomies were done at both the T-12 and L-3 levels with moderate improvement of the patient's neurologic findings. Histologic examinations confirmed the presence of Gaucher's cells in the bone. Review of the literature revealed only one previous report.

Cauda Equina↗
PubMed1984

Identification of cytidine diphosphodiesters in erythrocytes from a patient with pyrimidine nucleotidase deficiency.

Pyrimidine 5'-nucleotidase deficient (PND) erythrocytes contain elevated levels of pyrimidine nucleotides and relatively normal purine nucleotide levels. The composition of this nucleotide pool has been examined by others, but not all of the abnormal red cell metabolites in this disorder were identified. We have isolated and positively confirmed the identity of cytidine diphosphate (CDP)-choline and CDP-ethanolamine from PND red cells using methods including proton FT-NMR, spectroscopy, and comparative mass spectrometry. The concentrations of these and other pyrimidine nucleotidase-deficient erythrocyte nucleotides were determined using anion-exchange high performance liquid chromatography and ultraviolet (u.v.) detection. The pyrimidine diphosphodiesters appear to be the most prominent abnormal pyrimidine nucleotides in PND red cells, accounting for 55% of the total red cell pyrimidine nucleotides in this disorder. It is proposed that these abnormal phosphodiesters may be related to the accelerated hemolysis in PND.

5'-Nucleotidase↗
PubMed1983

31P NMR study of erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency.

The composition of phosphate metabolites and the intracellular pH in erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency were examined using 31P NMR spectroscopy. Several resonances were identified in spectra from intact cells and from extracts. The 2,3-bisphosphoglycerate line intensities were normal but the NTP resonances were about twice normal due to the presence of millimolar quantities of pyrimidine phosphates. Several intense resonances were also observed in the diphosphodiester region of the spectrum. One compound contributing to these lines has been identified as cytidine diphosphocholine. The resonances of NTPs were in a position indicating that the additional triphosphates were also bound by Mg2+. Direct measurement shows that there is a nearly proportional increase in total cell Mg2+ in the patient's cells, in agreement with the interpretation of the spectra. The intracellular pH was about 0.2 unit lower in the patient's erythrocytes. This lower pH is due to the elevation in intracellular fixed negative charges and the shift in permeable anions consequent to the Donnan equilibrium. We suggest that the lower intracellular pH may explain the lower oxygen affinity of these cells in the presence of otherwise normal 2,3-bisphosphoglycerate levels and the increased Mg2+ triphosphates level, because the Mg2+ form of NTPs is known not to alter the oxygen affinity of hemoglobin under physiologic conditions. Furthermore, the lower intracellular pH can also explain the abnormalities in glycolytic intermediates observed for these cells.

5'-Nucleotidase↗
PubMed1983

Partial purification and zinc dependence of human red cell pyrimidine-5'-nucleotidase.

Human red cell pyrimidine-5'-nucleotidase (EC 3.1.3.5) was partially purified from the blood of normal subjects by ion-exchange and affinity chromatography. Red cells were lysed in 50 mmol/l Tris-Cl buffer at pH 7.5 containing 1.0 mmol/l dithiothreitol and 0.5 mmol/l EDTA. The lysate was centrifuged and introduced onto a column of Sephadex A-50. After washing, the pyrimidine-5'-nucleotidase activity was eluted from the column with a NaCl gradient from 0 to 200 mmol/l in Tris buffer at pH 7.5. The pyrimidine-5'-nucleotidase was then desalted on Sephadex G-25 and introduced onto a UDP agarose column with a Tris buffer at pH 6.5 containing 150 mmol/l NaCl. This partial purification resulted in an approximately 80,000-fold increase in enzyme concentration. The Km for the partially purified enzyme was 0.32 mmol/l for UMP, 0.16 mmol/l for CMP and 0.11 mmol/l for OMP with a pH maximum of 7.5. This partially purified pyrimidine-5'-nucleotidase was then dialyzed in 50 mmol/l Tris-Cl buffer at pH 7.5 with 0.01 mmol/l CaCl2 and NaCl against 2 X 10(-3) mol/l 1,10-phenanthroline for 24 h at 4 degrees C. This incubation resulted in 73% decrease in enzyme activity which could be restored by the addition of zinc into the mixture, but not by the addition of other divalent metal ions.

5'-Nucleotidase↗
PubMed1981

Kinetic mechanism of beef pancreatic L-asparagine synthetase.

The kinetic mechanism of bovine pancreatic asparagine synthetase was deduced from initial velocity studies and product inhibition studies of both the glutamine-dependent and ammonia-dependent reactions. For the glutamine-dependent pathway, parallel lines were observed in the double reciprocal plot of 1/V vs. 1/[glutamine] at varied aspartate concentrations, and in the plot of 1/V vs. 1/[ATP] at varied aspartate concentrations. Intersecting lines were found for the plot of 1/V vs. 1/[ATP] at varied glutamine concentrations. Product inhibition patterns, including dual inhibitor studies for measuring the synergistic effects of multiproduct inhibition, were used to support an ordered bi-uni-uni-ter ping-pong mechanism. Glutamine and ATP sequentially bind, followed by the release of glutamate and the addition of aspartate. Pyrophosphate, AMP, and asparagine are then sequentially released. When the ammonia-dependent reaction was studied, it was found that the mechanism was significantly different. NH3 bound first followed by a random addition of ATP and aspartate. Pyrophosphate, AMP, and asparagine were then sequentially released as in the glutamine-utilizing mechanism. From these studies, a comprehensive mechanism has been proposed through which either glutamine or NH3 can provide nitrogen for asparagine production from aspartate.

Adenosine Triphosphate↗
PubMed1979

Regulation of carbohydrate metabolism in mouse liver. Effect of glucagon on gluconeogenic/glycolytic flux in isolated perfused livers.

1. Glucagon stimulated gluconeogenesis from both [U-14C]lactate and [14C]xylitol in isolated perfused mouse liver. 2. Addition of cyclic AMP also stimulated gluconeogenesis from [U-14C]lactate. 3. Glucagon caused a rapid (2.5 min) 12-fold increase in hepatic cyclic AMP but not cyclic GMP concentration. 4. Glucagon caused a rapid and stable decrease in hepatic fructose 1,6-diphosphatase activity measured in vitro. 5. The results are interpreted to indicate that glucagon stimulates hepatic gluconeogenesis in mice via cyclic AMP by two different mechanisms: (a) increased substrate uptake (i.e. utilization) and (b) increased gluconeogenic efficiency (i.e. inhibition of alternate substrate fates).

Animals↗