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Biomedical subjects

J Kania

Publications and source records attributed to J Kania.

At least 19 recordsLinked to original sources

Occupational obstructive disorders: nonspecific airways obstruction and occupational asthma.

Airways obstruction as a result of occupational exposure may be divided into two categories on the basis of whether or not occupational asthma is present. The first category, nonspecific airways obstruction, takes place in the absence of occupational asthma, and demonstrates only modest changes in airways responsiveness. The second category, occupational asthma, usually has a causal relationship to exposure, and demonstrates marked changes in airways responsiveness. These distinctions are of use in diagnosis, treatment, and disability assessment.

Asthma

The value of a zero power intraocular lens.

An intraocular lens with a reversed optic and with haptics angulated forward presses the posterior capsule more posteriorly than other types of lenses. This position is thought to be important even in eyes that do not need intraocular lenses for optical reasons, such as eyes with high axial myopia (because of their increased tendency to postoperative retinal detachment) and eyes with postoperative capsular fibrosis. "Zero lenses" were implanted in seven eyes. The lenses had a convex posterior surface and a concave anterior surface which were parallel. The position of the posterior capsule, measured with ultrasound, was 4.9 mm to 5.8 mm (mean 5.5 mm) behind the anterior corneal surface. In two fellow eyes without a lens (after planned extracapsular cataract extraction), the posterior capsule was 4.1 mm and 4.3 mm behind the anterior corneal surface.

Humans

Outpatient treatment of patients with substance abuse and coexisting psychiatric disorders.

Thirty-two patients with coexisting substance abuse and other psychiatric disorders were treated in a unique outpatient pilot program that used techniques drawn from both psychiatric and substance abuse treatment. Eleven patients remained in treatment for 3 or more months, and seven completed a year or more of treatment. Severity of associated psychiatric illness did not affect retention in treatment. Drug-abusing patients and those with personality disorders dropped out quickly; patients with a history of reliable outpatient treatment involvement tended to remain in treatment. Treatment retention was associated with reduced hospital utilization. The authors suggest guidelines for management of patients with coexisting substance abuse and other psychiatric disorders.

Adult

[Insulin secretion and utilization of insulin in piglets after insulin, arginine and glucose loads].

The insulin secretion and utilization dynamics have been investigated in 35 six weeks old healthy piglets in order to find the connection with spontaneous hypoglycemia. The trial to load piglets with insulin showed an average time t1/2 = 4.93 minutes accepted as normal in 10 piglets with the mean increase in body weight equal to 0.19 kg/day, prolonged time t1/2 = 7.56 minutes in 7 piglets with the decreased gain of body weight to 0.108 kg/day, and short time t1/2 = 2.78 minutes with the poor gain of body weight in 6 piglets at the age of 6 weeks. In 10 weeks old piglets the noted time t1/2 was 14.7 minutes. The trial to load piglets with L-arginine--HC1 showed a high insulin secretion amounting to 105.5 microU/ml of plasma in 3 piglets only, assumed as correct, and a low insulin secretion amounting to an average of 20.5 microU/ml of plasma in 10 piglets corresponding, according to the criteria of diagnostics, to the subclinical form of human diabetes mellitus. The glucose tolerance test enabled to distinguish 7 strongly reacting piglets (over 100 microU/ml of plasma), 10 moderately responding piglets (from 20 to 100 microU/ml), and 2 piglets not responding (16 microU/ml) by means of increase in insulin concentration. The differentiated results with the individuals deviations to subclinical values observed in healthy piglets, point to serious difficulties in the maintenance of the equilibrium between insulin secretion and utilization. Excessive secretion lasting over 2 hrs and very fast utilization of insulin as well as the level of glucose not compensated by gluconeogenesis, can be the cause of hypoglycemia.

Animals

Drug use by alcoholics in outpatient treatment.

Although increasing attention has been paid to the problems of combined and sequential alcohol and drug abuse, data about drug use by alcoholics during the course of outpatient treatment are not available. Urine testing for commonly abused drugs was obtained on 112 alcoholic outpatients during a 2-week period. Ten urine samples were positive for abuseable drugs. Patients' age, length of treatment involvement, and history of drug use prior to treatment appeared to affect drug use during treatment. At 4 month follow-up of the 10 patients with positive urine tests, five were drug free, three had discontinued but then returned to drug use, and two had been discharged. Given the limitations of such a cross-sectional study, the incidence of drug use by alcoholics during outpatient treatment seems high enough to warrant further study.

Adult

Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs.

In six conscious dogs with esophageal, gastric, and pancreatic fistulas, the effects of intravenous infusion of neurotensin and intraduodenal instillation of sodium oleate on gastric and pancreatic secretion were determined under basal conditions and after exogenous (secretin and cholecystokinin octapeptides) or endogenous stimulants (feeding and duodenal acidification). Neurotensin given intravenously in graded doses (1.5-200 pmol . kg-1 . min-1) to fasted dogs produced a dose-dependent stimulation of pancreatic bicarbonate and protein secretion reaching, respectively, about 18 and 100% of maximal responses to secretin and cholecystokinin octapeptide (CCK). Duodenal oleate in graded doses (0.5-16 mmol/h) resulted in a similar pattern of bicarbonate and protein secretion but increased plasma neurotensin only to about 10% of that achieved with infusion of exogenous neurotensin producing an equal rate of pancreatic secretion. Neurotensin, like oleate, potentiated the action of secretin and CCK on pancreatic bicarbonate and had additive effects on protein response to these secretagogues. Both neurotensin and oleate increased pancreatic response to liver extract meal kept in the stomach at constant pH (5.5) and the response to sham feeding but decreased the response to ordinary feeding, probably due to the inhibition of gastric acid secretion and reduction of duodenal acidification. Neurotensin given intra-arterially directly to the pancreas or to isolated intestinal segment increased dose dependently the blood flow and oxygen consumption without affecting general circulation. We conclude that 1) neurotensin mimics the pancreatic secretory effects of intestinal fat, 2) neurotensin may contribute in part to fat-induced stimulation of the pancreatic secretion, and 3) the secretory effects of neurotensin are accompanied by a marked stimulation of intestinal and pancreatic circulation and metabolism.

Animals

Prostaglandins and alkaline secretion from oxyntic, antral, and duodenal mucosa of the dog.

Alkaline secretion (AS) measured under basal conditions in oxyntic and antral pouches of conscious dogs averaged about 20 mumol/30 min and was about three times lower than that from the duodenal pouch. Natural prostaglandin E2 and prostaglandin F2 alpha, but not prostaglandin I2, were effective stimulants of AS, mainly when given topically. Stable analogues such as 16,16-dimethyl prostaglandin E2 and prostaglandin I2 were relatively more potent stimulants than their parent prostaglandins (PGs), particularly when applied topically. The highest alkaline response of the oxyntic pouch to PG was about 5% of the maximal acid response of this pouch to histamine. Indomethacin reduced markedly AS from the duodenal but not from the oxyntic or antral pouch. AS from the duodenal pouch was relatively more sensitive than that from gastric pouches to the stimulation by PGs, which were effective also after pretreatment with indomethacin. This study shows that the oxyntic, antral, and duodenal mucosa of conscious dogs is capable of secreting bicarbonate, and this secretion, particularly from the duodenal mucosa, is highly sensitive to the stimulation with certain PGs, mainly of the E and F type and their analogues, and to suppression by indomethacin, a potent inhibitor of PG biosynthesis, suggesting that endogenous PGs are involved in the mechanism of AS.

Animals

Isolation, characterization and implications of anti-TF (Thomsen-Friedenreich) agglutinins from different sources.

Anti-TF agglutinins from peanut (Arachis hypogaea) and from vertebrate sera of different species have been successfully isolated by affinity chromatography on acid-activated Sepharose 4 B. The proteins were characterized by immunoelectrophoresis, polyacrylamide gel electrophoresis in the presence of SDS and with respect to their carbohydrate binding specificities. Anti-TF substances from sera showed one precipitin arc in immunoelectrophoresis, but quantitative immunoprecipitation revealed our human anti-TF to be a mixture of the three Ig-classes IgG, IgA and IgM. This finding was confirmed on SDS gel electrophoresis, where high molecular weight aggregates were found before reduction. Hemagglutination inhibition revealed that all isolated anti-TF compounds exhibit an exceptionally high affinity for the immunodominant group of the TF-antigen, namely the beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosamine disaccharide. On examination of formalin-fixed and neuraminidase treated tissue sections (kidney, mammary gland), fluorescein-labelled anti-TF from horse serum showed a virtually identical pattern when compared with fluorescein labelled peanut lectin. Likewise isolated IgA-class myeloma J 539, which shows specificity against beta-(1 leads to 6)-galactans, only bound to the appropriate Gal-beta-(1 leads to 6)-Gal structures, such as those found on bovine lung or the albumin gland of Helix pomatia. Rabbit anti-VCN (Vibrio cholerae neuraminidase) activity could be selectively abolished by beta-galactosyl-containing inhibitors, whereas papain F(ab) fragments from rabbit anti-VCN immunoglobulin did not compete with anti-TF for binding sites on VCN-treated human red cells. Anti-TF, on the other hand, did not compete with anti-VCN for active VCN.

Agglutinins

beta-Galactosidase chimeras: primary structure of a lac repressor-beta-galactosidase protein.

A protein possessing both lac repressor and beta-galactosidase activities in a single polypeptide of about 155,000 daltons was purified from a deletion mutant of Escherichia coli in which the lacI and Z genes are fused. A 77-residue cyanogen bromide peptide containing the fusion joint was isolated. A radioimmunoassay with an antibody prepared against CNBr2 (residues 3-92) of beta-galactosidase was used to monitor its purification. The sequence of the joining peptide was determined by analysis of tryptic peptides and by automatic sequencer analysis. The site of joining is from residue 355 of lac repressor to residue 24 of beta-galactosidase (or 356 to 25), indicating that the last 4 residues at the carboxyl terminus of lac repressor and the first 23 residues at the amino terminus of beta-galactosidase are not essential for the activities of these two proteins. The exact site of the fusion is not known because lac repressor residue 356 and beta-galactosidase residue 24 are both leucine residues. Examination of the nucleotide sequences around the two end points of the deletion revealed a homology of 9 identities in a stretch of 11 base pairs.

Amino Acid Sequence

Construction, isolation and implications of repressor-galactosidase - beta-galactosidase hybrid molecules.

Escherichia coli heterogenotes, which produce hybrid molecules between the chimaeric protein repressor-galactosidase and the enzyme beta-galactosidase, were constructed. Repressor-galactosidase in which fully active lac repressor is covalently linked to active beta-galactosidase, is an aggregate with a core structure of four beta-galactosidase parts and two peripheral lac repressor dimers. The lac repressor dimers, which are separated by tetrameric beta-galactosidase, retain all the biological activities of tetrameric lac repressor. Substitution of repressor-galactosidase subunits with beta-galactosidase subunits leads to hybrid molecules with y beta-galactosidase subunits aggregated with (4-y) repressor-galactosidase subunits (where y = 1, 2 or 3). A 2:2 hybrid, i.e. a tetrameric beta-galactosidase core with one lac repressor dimer grafted to it, binds at least 100 times less strongly to 32P-labelled lambdaplac DNA than pure lac repressor or repressor-galactosidase. The data suggest a model in which lac repressor binds with two subunits to lac operator and with the other two subunits elsewhere on the DNA, possibly on sequences like the lac operator.

Bacterial Proteins

Use of a sequence-specific DNA-binding ligand to probe the environments of EcoRI restriction endonuclease cleavage sites.

The DNAs of bacteriophage lambda and adenovirus were incubated with the sequence-specific DNA-binding ligand 6,4'-diamidino-2-phenylindole. Digestion of the ligand-DNA complexes with EcoRI nuclease and subsequent agarose gel electrophoresis demonstrated that the ligand inhibited nuclease activity at some sites, but not at others. The results suggest that diamidino-2-phynylindole can be used to probe the immediate environments of the EcoRI cleavage sites.

Adenoviridae

The functional repressor parts of a tetrameric lac repressor-beta-galactosidase chimaera are organized as dimers.

The chimaeric protein repressor-galactosidase, in which fully active lac repressor is covalently linked to the active enzyme beta-galactosidase, was used as a system for probing the quaternary structure of lac repressor. Electron micrographs revealed repressor-galactosidase to be a tetrameric aggregate. When lac repressor, alone, was crosslinked with dimethyl suberimidate, dimers, trimers, tetramers, and oligomers of the protein subunit were produced, whereas crosslinking of the tetrameric repressor-galactosidase resulted in the production of only dimers of the chimaera. Treatment of lac repressor with iodine resulted in the formation of protein dimers; the same result was obtained with repressor-galactosidase. After limited proteolysis of lac repressor, no crosslinking was obtained after treatment with dimethyl suberimidate, whereas iodine still produced a covalent linkage. These results are interpreted as evidence that the lac repressor parts of the tetrameric repressor-galactosidase-chimaera are organized as dimers on the tetrameric-beta-galactosidase core. Because this chimaera has been previously shown to have normal repressor activity [B. Müller-Hill and J. Kania (1974) Nature, 249,561-563], we conclude that lac repressor still is biologically active as a dimeric aggregate.

Bacterial Proteins