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A A Keshgegian

Publications and source records attributed to A A Keshgegian.

51 records · Page 3Linked to original sources

Anion gap and immunoglobulin concentration.

The serum anion gap is often decreased in patients who have multiple myeloma or monoclonal gammopathy, presumably owing to the unmeasured contribution of cations by the paraprotein. In 83 patients who had moderate-to-severe diffuse (polyclonal) elevations in immunoglobulin concentration (> 3 g/dl), the mean serum anion gap was significantly lower than in patients who had normal concentrations of immunoglobulin. In the subgroup with immunoglobulin levels greater than 4 g/dl, the mean anion gap was 8.7 mEq/l, compared with 11.9 for the control group (P < 0.001). Known causes of decreased anion gap, such as hyperkalemia or hypercalcemia, were absent. The albumin concentration had a minimal effect on the anion gap. The mean anion gap was independent of the patient's diagnosis and the relative contribution of each immunoglobulin class to the total immunoglobulin. Thus, patients who have diffusely elevated immunoglobulin concentrations, as well as those who have monoclonal elevations, have a significantly lower mean anion gap. This low anion gap should be considered in the evaluation of the acid-base status of these patients.

Acid-Base Equilibrium↗

(University of Pennsylvania Case Conference): oligoclonal immunoglobulins in cerebrospinal fluid in multiple sclerosis.

In the normal state, immunoglobulins are polyclonal. They migrate as a broad band on electrophoresis, reflecting the diversity of immunoglobulin species secreted by the many clones of immunoglobulin-producing cells. In lymphoproliferative disorders, monoclonal immunoglobulins are often found, migrating as electrophoretically homogeneous bands, reflecting the large amount of a single immunoglobulin being secreted by the single proliferating neoplastic clone. In certain neurological diseases, such as multiple sclerosis, the cerebrospinal fluid (CSF)2 often exhibits an oligoclonal immunoglobulin pattern consisting of several electrophoretically homogeneous bands in the gamma-globulin regin (Figure 1). We present two cases of neurological disease with an oligoclonal immunoglobulin pattern in the CSF electropherogram. In the discussion we consider the definition, etiology, and pathogenesis of multiple sclerosis, and laboratory tests that are useful in multiple sclerosis, emphasizing methods for the demonstration and interpretation of an oligoclonal immunoglobulin pattern.

Adult↗

Enzymic polyadenylation of 5S ribosomal ribonucleic acid and synthesis of a complementary deoxyribonucleic acid.

The 5S ribosomal RNA has been isolated, pure and intact, from rat liver (5 mg of 5S RNA from 150g of liver). The 5S RNA serves as a primer for calf thymus poly(A) polymerase with 20% of the efficiency of (Ap)3A. Bacterial 5S RNA and transfer RNA also serve as primers; rat liver 18S and 28S ribosomal RNAs support poly(A) synthesis poorly. Neither the 5S RNA primer nor the appended poly(A) tract is nicked or degraded by poly(A) polymerase, and initiation of poly(A) tracts on 5S RNA primers continues throughout the reaction period. The rate of initiation is dependent on the enzyme concentration; the ATP concentration affects the rate of elongation. The polyadenylated material increases in size over time, with the largest material reaching a size of 6.8 S in 5 h, corresponding to an appended poly(A) tract of 140 nucleotides. Using polyadenylated 5S RNA, oliog(dTY as primer, and avian myeloblastosis virus reverse transcriptase, we synthesized DNA complementary to 5S RNA. The complementary DNA has an apparent molecular weight (in alkaline sucrose gradients) of 4.3 X 10(4). Base composition analysis and nearest-neighbor analysis of the DNA are as expected for a complement of 5S RNA, indicating that the entire 5S sequence is copied. The complementary DNA hybridizes to 5S RNA with a R0t1/2 of 8.9 X 10(-4) mol.s.L-1. No hybrid is formed with Escherichia coli 16S and 23S ribosomal RNA, E. coli 5S ribosomal RNA, yeast transfer RNA, rat liver transfer RNA, or rat liver 18S and 28S RIBOSOMAL RNA. The Tm of the 5S RNA:5S DNA hybrid in 15 mM NaCl containing 1.5 mM sodium citrate is 74 degrees C, 2.5 degrees C below the theoretical melting temperature of a DNA duplex of 60% G + C. Analysis of the hybrid in buoyant density gradients also indicates that hybridization is both specific and precise. The complementary DNA anneals to calf thymus, rat liver, and salmon sperm DNAs but not to E. coli DNA. Annealing of 5S cDNA to calf thymus DNA with a C0t1/2 of 2.1 suggests that there are several thousand 5S RNA genes in the calf thymus genome (haploid). At least that number of 5S RNA genes is present in the salmon sperm genome.

Animals↗

Waldenström's macroglobulinemia associated with a mixed cryoglobulin. Report of a case with partial precipitation in vitro at 37 degrees C.

A 68-year-old man had Waldenström's macroglobulinemia associated with a mixed cryoglobulin (monoclonal IgM kappa and polyclonal IgG, 0.96 g/dL) manifested by purpura, weight loss, hepatosplenomegaly, and proteinuria. On cooling of serum warmed to 50 degrees C, the cryoglobulin begins to precipitate above 40 degrees C, with substantial precipitation at body temperature. Incubation at 37 degrees C (after equilibration at 50 degrees C) causes approximately two thirds of the cryoglobulin to precipitate in 30 to 60 minutes; the precipitate dissolves on rewarming the serum to 50 degrees C. The ability of this cryoglobulin to precipitate at 37 degrees C in vitro indicates that the temperature spectrum of cyroglobulin precipitation can extend to body temperature or above it, and suggests that some serum samples that contain cryoglubulins must be separated quickly at a temperature of 37 degrees C or higher.

Aged↗

Nodular renal blastema in trisomy 13.

The autopsy records and material of 14 cases of karyotype-proved trisomy 13 were reviewed. There were one or more foci of nodular renal blastema in six cases. Patients with nodular renal blastema had lived up to five days; patients in whom foci were not found at autopsy had lived six to 37 days. The presence of nodular renal blastema did not substantially correlate with other renal anomalies or the number or severity of extrarenal anomalies. The presence of nodular renal blastema in trisomy 13 expands the spectrum of syndromes associated with nodular renal blastema and supports its relationship with disorders of growth regulation. The presence of the lesions only in very young infants suggests that most, or all, foci of nodular renal blastema regress with age.

Abnormalities, Multiple↗

Inhibition of mammalian polyadenylate polymerase by 2-aza-1,N6-etheno-adenosine triphosphate.

2-Aza-1,N6-etheno-adenosine triphosphate (aza-epsilonATP), a fluorescent analog of adenosine triphosphate, significantly inhibits polyadenylate [poly(A)] polymerase of bovine lymphosarcoma and calf thymus, with 50% inhibition at 200 muM (in the presence of an equal concentration of adenosine triphosphate). Calf thymus RNA polymerases II and III are inhibited 32 and 20%, respectively, by a 3.8-fold excess of aza-epsilonATP; DNA polymerase alpha is not inhibited. The inhibition of poly(A) polymerase by aza-epsilonATP appears to be competitive with adenosine triphosphate; incorporation of aza-epsilonATP is not observed. Polymers of 2-aza 1,N6-etheno-adenosine monophosphate are used as primers, but pootly. 1,N-Etheno-adenosine triphosphate and 9-beta-D-arabinofuranosyladenine triphosphate are poor inhibitors of poly(A) polymerase; adenosine diphosphate is ineffective. Deoxyadenosine triphosphate inhibits to the same extent as aza-epsilonATP, while other naturally occurring nucleotides inhibit poly(A) polymerase to varying degrees, with deoxynucleoside triphosphates more potent than ribonucleoside triphosphates. Inhibition of poly(A) polymerase by naturally occurring nucleoside triphosphates suggests that nucleotides may regulate the enzyme in vivo; inhibition by the fluorescent analog aza-epsilonATP suggests that this compound may be useful in elucidating poly(A) metabolism in both normal and neoplastic cells.

Adenosine Triphosphate↗

RNA polymerase isolated from bovine lymphosarcoma by sequential low- and high-salt extraction.

Bovine lymphosarcoma tissue has been extracted with low- and high-salt buffers [0.05 M Tris-C1 plus or minus 0.3 M (NH4) 2S04]. Diethylaminoethyl-Sephadex chromatography of both the high-salt and low-salt extracts yields RNA polymerases I and II, although low-salt extraction releases only one-third as much activity. Extraction by high salt of the residue from the low-salt extract, followed by diethylaminoethyl-Sephadex chromatography, yields additional enzyme activity with properties of Form II. Purification of the low-salt extract by protamine precipitation, elution with sodium succinate, and phosphocellulose chromatography yields a preparation of RNA polymerase (RNAP) with hybrid properties, combining the salt optimum of Form I, diethylaminoethyl-Sephadex elution pattern of form II, and alpha-amanitin sensitivity of Form III. RNAP. transcribes native D,A and chromatin efficiently. More RNAPL is recovered from lymphosarcoma tissue than from calf thymus.

Amanitins↗

Poly (A) polymerase of bovine lymphosarcoma.

Poly(A) polymerase has been extensively purified from low-salt extracts of bovine lymphosarcoma. The enzyme is Mn2+ dependent, requires an oligonucleotide or RNA primer, incorporates only adenosine triphosphate, and is inhibited by other ribonucleotides or deoxynucleotides. Oligoadenylate and ribosomal RNA are good primers for the enzyme; transfer RNA and poly(A) are poor. RNA transcribed in vitro by homologous RNA polymerase is an efficient primer. The properties of the enzyme are similar to the properties of the Mn2+ -activated poly(A) polymerase of calf thymus. Approximately the same amount of enzyme appears to be present in lymphosarcoma and calf thymus.

Adenine Nucleotides↗

Gardner's syndrome with duodenal adenomas, gastric adenomyoma and thyroid papillary--follicular adenocarcinoma.

A case of a woman with Gardner's syndrome, originally manifested by multiple adenomatous polyps of the colon, is presented. She underwent subtotal colectomy at 14 years of age. Over the next 15 years she had a composite odontoma, an impacted supernumerary tooth, two epidermal inclusion cysts, multicentric paillary-follicular adenocarcinoma of the thyroid, two tubulovillous adenomas of the duodenum in which argyrophilic cells were a prominent feature, and an adenomyoma of the gastric antrum. The presence of all of these lesions in one patient expands the spectrum of lesions seen with Gardner's syndrome and supports the concept of a generalized abnormality of growth regulation as the cause of the syndrome.

Adenocarcinoma↗