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Biomedical subjects

A Brown

Publications and source records attributed to A Brown.

At least 379 records · Page 21Linked to original sources

Cardiac lymphoma associated with superior vena caval syndrome and cardiac tamponade: case history.

A sixty-three-year-old patient with malignant histiocytic lymphoma of the heart presented with both superior vena cava syndrome and cardiac tamponade. A two-dimensional echocardiogram showed a large tumor mass in the right atrium and pericardial effusion with right ventricular compression. Superior and inferior vena cavagrams disclosed a lobulated tumor located in the right atrium that extended into and obstructed the superior vena cava. After the pericardial effusion was drained and the diagnosis was established, the patient was irradiated and given chemotherapy with resolution of the tamponade and superior vena cava obstruction.

Cardiac Tamponade↗

Inhibitory effect of galanin on basal and pentagastrin-stimulated gastric acid secretion in rats.

The dose-dependent effects of galanin on basal and pentagastrin-stimulated gastric acid secretion in pentobarbital-anesthetized rats were examined. Intravenous infusion of galanin at doses of 0.31, 0.62, 1.25, 1.87, 3.11, and 6.22 nmol/kg-1/h-1 into pentagastrin-stimulated rats produced a diminution in gastric acid secretion which was maximal (54.7%) at the level of the 1.87 nmol/kg-1/h-1 dose. Furthermore, the effect was biphasic, since both lower and higher doses of peptide were less effective. At the optimum concentration of 1.87 nmol/kg-1/h-1 galanin also inhibited basal gastric acid secretion. We conclude that endogenous galanin might be involved in the physiologic regulation of gastric acid secretion.

Animals↗

GM2-gangliosidosis B1 variant: analysis of beta-hexosaminidase alpha gene abnormalities in seven patients.

A single nucleotide transition within exon 5 of the beta-hexosaminidase alpha chain gene was identified in a Puerto Rican patient with GM2-gangliosidosis B1 variant as the mutation responsible for the unusual enzymological characteristics of this variant (G533----A; Arg178----His) (the DN-allele). A total of seven patients with enzymological characteristics of B1 variant have since been studied. They were Puerto Rican (DN), Italian, French, Spanish, two patients of mixed ethnic origin (English/Italian/Hungarian and English/French/Azores), and a Czechoslovakian. In confirmation of our earlier finding based on screening with allele-specific probes, all patients except the one from Czechoslovakia carried the same DN-allele. A new point mutation found in this patient changed the same codon affected in the DN-allele (C532----T; Arg178----Cys). An asymptomatic Japanese individual included as a control also carried one allele with the DN-mutation. Site-directed mutagenesis and expression studies in COS I cells demonstrated that either of the two point mutations abolishes the catalytic activity of the alpha subunit. The Spanish patient was homozygous for the DN-allele, but others were all compound heterozygotes. The Puerto Rican patient was a compound heterozygote with the DN-mutation in one allele and with the four-base insertion in exon 11, one of the two mutations found in the classical Ashkenazi Jewish Tay-Sachs disease, in the other allele. Abnormalities of the other allele were not identified in all other compound heterozygous patients. In these patients, the level of mRNA derived from the other allele was variable, ranging from being undetectable to being much lower than normal. This series of studies uncovered a new B1 variant mutation, confirmed our preliminary finding that the DN-allele has a surprisingly wide geographic and ethnic distribution, and pointed out the highly complex nature of the molecular genetics of this rare disorder. They also support our working hypothesis that mutations responsible for the unique enzymological characteristics of the B1 variant should be located in or near exon 5 of the gene and that this region of the enzyme protein is critical for its catalytic function.

Alleles↗

Extrarenal production of calcitriol.

Under normal circumstances extrarenal sources of calcitriol probably constitutes a microendocrine system involved in cell differentiation and local intercellular communication with no influence on systemic calcium homeostasis. Under pathological conditions such as chronic renal failure, extrarenal sources have the potential to normalize serum calcitriol after adequate stimulation (such as, 25(OH)D administration). Extrarenal 1,25-(OH)2D3 synthesis is controlled by physiological levels of calcitriol. However, in sarcoidosis and other granulomatous diseases, 1,25-(OH)2D3 production by macrophages is deregulated, causing severe alterations in systemic calcium homeostasis.

Animals↗

[A case of entomophthoromycosis caused by Conidiobolus coronatus].

The authors report a case of entomophthoromicosis caused by Conidiobolus coronatus, a saprophytic fungus that belongs to the class Zygomycetes (Phycomycetes in the past). Our patient was from a rural area. The paranasal sinuses had been drained surgically and a polyp was removed from his nasal cavity. He had a deformity in the face and nasal obstruction. His general condition and immunological status were normal except for epistaxis since childhood. The diagnosis was made clinically by the appearance of the lesion and confirmed by the mycological and histopathological findings. The therapeutic response was slow but with total resolution of the lesion.

Adult↗

Aging changes of the rhesus monkey optic nerve.

The authors counted axons in one optic nerve from each of 28 juvenile and aged rhesus monkeys using an automated image analysis system. All nerves were fixed immediately after death and treated identically. Animals ranged in age from 1 1/2 to 29 yr, which correlates with a human age range of 4 1/2-87 yr. Mean axonal number for all specimens was 1,117,859. Large variations in axonal numbers were found, even within a subgroup of ten animals aged 1 1/2-2 yr. Although young nerves had generally more fibers than those from old animals, this difference was not quite statistically significant, translating into a yearly loss of 4319 fibers (0.45% of the total). Age did not have any significant effect on mean axonal diameter.

Aging↗

Allan-Herndon syndrome. II. Linkage to DNA markers in Xq21.

The original family with the Allan-Herndon type of X-linked mental retardation has been investigated for linkage by using DNA probes spanning the length of the X chromosome. Available for study, over 3 generations, were 13 affected males, three obligate carriers, and three normal sons of the obligate carriers. Initial disease-to-marker analysis suggested linkage to three markers (DXYS2 [7b], DXS250 [GMGX22], and DXS3 [p19-2]) located in Xq21. All three exhibited the same maximum lod score of 2.3 at a maximum theta of .05. Multipoint analysis using LINKMAP and a set of four DNA markers (DXYS1-DXYS2-DXS3-DXS94) gave a multipoint lod score of 3.58 for a location of the Allan-Herndon syndrome near locus DXYS1 (pDP34). Therefore, our data indicate that the gene for the Allan-Herndon syndrome is likely located in Xq21.

Abnormalities, Multiple↗

Monoclonal antibodies that cross-react with the E1 glycoprotein of different alphavirus serogroups: characterization including passive protection in vivo.

A panel of four monoclonal antibodies (mAb) were produced that cross-react with representatives of two different togavirus serogroups, namely sindbis (SIN) and Semliki Forest (SF) viruses, by ELISA and ADCMC assays. Three of these mAb, IgG2a and IgG2b isotypes, passively protected C3H/Hej mice against 10 and 100 LD50 of SF challenge and one, IgM, did not protect against either challenge dose, or even at 1 LD50. All these mAb were cross-reactive with the E1 glycoprotein of the viruses by immunoblotting in which three different patterns of reactivity were evident, suggesting that three epitopes were involved. The patterns depended upon whether the mAb recognized E1 extracted from purified virions or infected cells and whether SDS-PAGE and immunoblotting were done in the presence or absence of beta-mercaptoethanol. One mAb (IgM) reacted with nonreduced or reduced E1 from either virions or cells suggesting recognition of a linear epitope. The other three mAb reacted with nonreduced but not reduced E1 from virions suggesting that recognition depends upon conformational epitopes. These three mAb reacted also with nonreduced E1 extracted from SF-infected cells whereas only one reacted with nonreduced E1 extracted from SIN-infected cells.

Animals↗

The antibody response to salmonellae in mice and humans studied by immunoblots and ELISA.

The antibody response to salmonellae in mice and humans was studied by immunoblots and ELISA. Sera from mice infected with attenuated salmonellae (including an aroA live vaccine strain) recognized up to 45 different bands on immunoblots at the height of the response, including lipoprotein, OmpA protein, porins, a putative heat-shock protein and flagella. Adsorption of antisera with intact or sonicated smooth or rough salmonellae prior to immunoblotting showed that antibodies were directed against exposed, masked and intracellular antigens. Sera from H-2 congenic B10 mice which vary in their ability to clear salmonellae from the reticuloendothelial system (RES) showed a progressive increase in the intensity of the antibody response, which persisted longer in animals which failed to clear bacteria from the RES. The LPS response was much stronger in susceptible mice. Sera from 18 confirmed cases of human typhoid recognized similar antigens to mouse typhoid sera, with individual variations; there was no correlation between the immunoblot pattern and the titres of other serological tests for typhoid fever.

Animals↗

Metabolic clearance rate and production rate of calcitriol in uremia.

We have previously demonstrated that while both normal humans and dogs tightly control serum calcitriol levels after 25(OH)D administration, anephric humans and 5/6 nephrectomized dogs significantly increase circulating 1,25(OH)2D when supraphysiological concentrations of 25(OH)D are reached in serum. Plasma 1,25(OH)2D level is determined not only by its rate of production but also by its rate of degradation. To further characterize the mechanisms involved in the responses to 25(OH)D therapy in normal circumstances and in chronic uremia, we measured metabolic clearance rate (MCR) and production rate (PR) of 1,25(OH)2D in normal dogs and in dogs with moderate and severe renal failure, at normal and supraphysiological serum concentrations of 25(OH)D. Basal MCR in uremic dogs, either with moderate or with severe renal failure, did not differ significantly from normals (6.7 +/- 0.7, 6.8 +/- 0.4 and 6.8 +/- 0.3 ml/min, respectively). Oral 25(OH)D administration for two weeks did not affect MCR either in normal animals or in both groups of uremic dogs. 25(OH)D treatment did not affect production rates in normal dogs and in animals with moderate renal failure (with normal basal values of 1,25(OH)2D), but significantly increased 1,25(OH)2D production from 0.13 +/- 0.01 to 0.25 +/- 0.04 micrograms/day (P less than 0.05) in dogs with severe renal insufficiency. These data suggest that it is the basal level of 1,25(OH)2D which regulates the synthesis of 1,25(OH)2D in response to 25(OH)D administration in normal and uremic animals.

Animals↗

The pharmacokinetics and dose proportionality of cilazapril.

1. The pharmacokinetics and dose proportionality of cilazapril, an orally active angiotensin-converting enzyme (ACE) inhibitor, were investigated in a four-way randomized crossover study in 24 volunteers, over the 0.5 to 5 mg dose range intended for therapeutic use. 2. Plasma concentrations of cilazapril and of the active metabolite cilazaprilat together with plasma ACE activity were determined by radio-enzymatic assay. 3. Plasma concentrations of both cilazapril and cilazaprilat increased in proportion to dose over the range studied. All doses produced substantial inhibition of ACE. Higher doses were associated with earlier onset and longer duration of maximal effect.

Administration, Oral↗