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Biomedical subjects

M Witt

Publications and source records attributed to M Witt.

At least 91 records · Page 5Linked to original sources
PubMed1991

Correlation of phenotypic and genetic heterogeneity in cystic fibrosis: variability in sweat electrolyte levels contributes to heterogeneity and is increased with the XV-2c/KM19 B haplotype.

We have reinvestigated a classification of clinical heterogeneity among cystic fibrosis (CF) patients that we previously reported and investigated the possible relationship of the identified CF subgroups to haplotypes around the CF gene and to HLA-DR haplotypes. Age-corrected values for sweat electrolytes, rate of progression of lung disease as assessed by Brasfield chest x-ray scores, and severity of pancreatic insufficiency as assessed by daily supplemented enzyme dosage were obtained for 55, 59, and 59 patients, respectively. XV-2c and KM19 RFLPs were determined by hybridization to TaqI and PstI digests of human genomic DNA, respectively, and analysis of mutations by PCR amplification followed by allele-specific oligo-deoxynucleotide hybridization was performed for 29 patients. HLA-DR restriction fragment length polymorphisms (RFLPs) were determined by hybridization of cDNA beta 1 and genomic DQ alpha probes to TaqI digests of human genomic DNA. The results show that the previous subdivision on the basis of age-corrected levels of sweat electrolytes, as well as measures of severity of lung disease and pancreatic disease, is valid. In addition, the C and D haplotypes are associated with lower age-corrected sweat sodium level. No significant relationship between CF haplotypes and the other two disease variables or between HLA-DR haplotypes and any of the clinical variables was found.

Child↗
PubMed1991

Effect of dietary iron deficiency or excess on the induction of mammary carcinogenesis by 1-methyl-1-nitrosourea.

The hypothesis that low body iron stores are protective against cancer whereas high body stores promote tumor occurrence was examined in the 1-methyl-1-nitrosourea (MNU)-induced experimental model for breast cancer. Twenty-one-day-old female Sprague-Dawley rats were randomized into one of three experimental groups and fed a formulation of AIN-76A diet modified to be low in iron (2 p.p.m.), or the same diet supplemented with an adequate (120 p.p.m.) or excess (1200 p.p.m.) amount of iron provided as FeSO4.7H2O. Rats were maintained on their respective diets throughout the experiment which was terminated 32 weeks post carcinogen administration. Rats were injected i.p. with either 25 mg MNU/kg body wt or the saline-solvent in which MNU was dissolved at 50 days of age. In the first 14 weeks, dietary iron deficiency resulted in a low hematocrit and a decrease in weight gain. The appearance of mammary tumors was markedly suppressed in this group compared to those given an adequate or excess level of iron. It has been reported in the literature that reduction in weight gain due to food restriction at a period immediately after carcinogen administration severely inhibits the subsequent development of tumors. Thus the low tumor incidence in the iron-deficient rats during this time frame could be attributed to the combined effects of low hematocrit and depressed weight gain. For the period between week 14 and week 32, the hematocrit in the iron-deficient animals was maintained at a normal level, and the body wt of these rats was comparable to that of the controls given an adequate level of iron. The rate of tumor appearance in the iron-deficient group during the second half of the experiment was similar to that of the iron-adequate group in the first half of the experiment. In other words, it appeared that once hematocrit and body wt gain were restored to normal in the iron-deficient animals, tumor incidence was only minimally affected by low dietary iron. In the second half of the experiment, the tumor incidence in the adequate iron group seemed to have plateaued, whereas it continued to rise in the excess iron group. Thus excess iron appears to be more prominent than iron deficiency in modification of mammary carcinogenesis, especially when the confounding effects of low hematocrit and reduced weight gain are taken into consideration in the latter case.

Animals↗
PubMed1991

Polymerase chain reactions with alphoid-repeat primers in combination with Alu or LINEs primers, generate chromosome-specific DNA fragments.

Y alphoid primers in combination with Alu and LINEs primers generated new DNA fragments in polymerase chain reactions (PCR) on DNA from a Y-only somatic cell hybrid but not from X-only, 3-only, or 21-only hybrids. X alphoid primers used in a similar manner generated new DNA fragments from the X-only hybrid, and 1 of the primers (X2) also generated new DNA fragments on 3-only and 21-only hybrids when used in conjunction with Alu or LINEs primers. In all but one case, consensus alphoid primers generated new chromosome-specific fragments in PCR reactions with the Alu or LINEs primers. A search for cryptic Alu- or alphoid-alone PCR products as the source for one Alu-alphoid band (chosen at random) was negative. Partial sequencing of products demonstrated that alphoid and Alu sequences were indeed contiguous in some newly synthesized DNA fragments. While Alu or LINEs primers generate smears of DNA fragments on total human DNA, the alphoid-non-alphoid repeat combinations generated electrophoretically distinguishable bands of DNA when the template was total DNA. While these were distinguishable with different chromosome-specific alphoid primers, the DNA fragments were not of the same sizes as those generated with the chromosome-only hybrids.

Animals↗
PubMed1991

Functional role of mucoid exopolysaccharide (alginate) in antibiotic-induced and polymorphonuclear leukocyte-mediated killing of Pseudomonas aeruginosa.

We evaluated in vitro the functional role of mucoid exopolysaccharide (MEP) of Pseudomonas aeruginosa in blocking antibiotic-induced and polymorphonuclear leukocyte (PMN)-mediated pseudomonal killing. The serum-resistant P. aeruginosa isolates used were mucoid strain 144MR and its nonmucoid revertant, strain 144NM. By timed kill curves, early bacterial effects of amikacin against mucoid strain 144MR were substantially less than those observed with nonmucoid strain 144NM; this effect was reversible with enzymatic hydrolysis of MEP of strain 144MR by alginase. Also, early tobramycin uptake (15 to 30 min) by mucoid 144MR cells was less than that seen with nonmucoid strain 144NM; pretreatment of 144MR cells with alginase substantially enhanced early tobramycin uptake compared with untreated 144MR cells (P = 0.08). In strain 144NM (but not in strain 114MR) there was a notable postantibiotic leukocidal enhancement effect manifested by increased nonopsonic killing following brief exposure of these cells to supra-MIC amikacin; pretreatment of strain 144MR with alginase rendered these cells more susceptible to amikacin-induced postantibiotic leukocidal enhancement. Similarly, direct PMN-mediated nonopsonic killing of mucoid strain 144MR was significantly less than that observed with strain 144NM (P less than 0.05); pretreatment of 144MR cells with alginase rendered this strain equal to strain 144NM in susceptibility to nonopsonic killing. In addition, exogenous sodium alginate or extracted MEP of strain 144MR interfered with effective nonopsonic killing of strain 144NM by PMNs. Studies also indicated that mucoid strain 144MR was phagocytosed significantly less well than its nonmucoid mate (P less than 0.00001), an effect reversed by pretreatment of the mucoid cells with alginase. These data confirm that P. aeruginosa MEPs functionally decrease the uptake and early bactericidal effect of aminoglycosides in vitro and interfere with effective PMN-mediated nonopsonic phagocytosis and killing of mucoid strains.

Alginates↗
PubMed1990

Electron microscopic demonstration of lectin binding sites in the taste buds of the European catfish Silurus glanis (Teleostei).

Taste buds in the European catfish Silurus glanis were examined with electron microscopic lectin histochemistry. For detection of carbohydrate residues in sensory cells and adjacent epithelial cells, gold-, ferritin- and biotin-labeled lectins were used. A post-embedding procedure carried out on tissue sections embedded in LR-White was applied to differentiate between the sensory cells: The lectins from Helix pomatia (HPA) and Triticum vulgare (WGA) bound to N-acetyl-galactosamine and to N-acetylglucosamine residues occurring especially in vesicles of dark sensory cells. This indicates a secretory function of these cells. Most light sensory cells--with some exceptions, probably immature cells--, are HPA-negative. The mucus of the receptor field and at the top of the adjacent epithelial cells was strongly HPA-positive. Pre-embedding studies were performed in order to obtain information about the reaction of the mucus with lectins under supravital conditions. The mucus of the taste bud receptor field exhibited intensive binding to WGA, but not to the other lectins tested. Most lectins bound predominantly to the surface mucus of the nonsensory epithelium and to the marginal cells close to the receptor field. The strong lectin binding to mucins and the relatively weak lectin binding to cell surface membranes in pre-embedding studies suggest that the mucus possibly serves as a barrier which is passed selectively only by a small amount of lectins or lectin-carbohydrate complexes. Lectin-carbohydrate interactions may play a role in recognition phenomena on the plasmalemmata of the taste bud sensory cells. Recognition processes directed to bacteria or viruses should be considered as well.

Animals↗
PubMed1990

[Lateral tilt of the tibia following valgus correcting tibial head osteotomy].

In varus deformity of the knee describes the lateral tilt of the shank the disturbed weight bearing situation more completely than the well known femorotibial angle. The results of a retrospective study concerning 66 high tibial osteotomies showed at the follow up-status a bigger influence of the tibial tilt in comparison to a smaller one of the femorotibial angle. The postoperative lateral tibial tilt should range from 4 to 6 degrees. It seems useful to consider the tilt of the shank to indicate high tibial osteotomy.

Biomechanical Phenomena↗
PubMed1989

A rapid method for detection of Y-chromosomal DNA from dried blood specimens by the polymerase chain reaction.

The alphoid satellite family is the only repetitive DNA family showing chromosome specificity. We have developed a simple, rapid, and reliable test for sex diagnosis based on detection of these sequences in undigested genomic DNA using the polymerase chain reaction. In our test, dried blood specimens were the source of DNA. When female DNA was used as a template for the reaction, only the expected 130-bp X-chromosome-specific fragment was detected, while with male DNA both the expected 170-bp Y-chromosome-specific and X-chromosome-specific fragments were detected. The Y-chromosome-specific fragment was further characterized by restriction enzyme analysis. The Y fragment was detectable when DNA obtained from an equivalent of 10 microliters of spotted blood was used in the reaction, whereas detection of the X fragment was possible with DNA from an equivalent of 5 microliters of blood. Our test may find various applications in newborn screening and in forensic science.

Blood↗
PubMed1989

Lectin binding sites in normal and phenobarbitale/halothane treated rat liver. A histochemical study.

The content of carbohydrate residues of both normal and phenobarbitale-halothane-hypoxia exposed rat liver has been examined by means of lectin histochemistry. Eight biotinylated lectins specific to galactose, N-acetyl-galactosamine, N-acetyl-glucosamine, fucose and mannose were applied to paraffin sections of rat liver at light microscopic level. The most distinct binding was observed at the structures of the "perisinusoidal functional unit": Kupffer cells are bound by S-WGA, SBA and PNA. Bile canaliculi display binding sites for RCA I and WGA. Cytoplasm of hepatocytes appears lectin-negative, except for PSA. The enhanced reaction of S-WGA, PNA and SBA after the preincubation of the sections with neuraminidase indicates the occurrence of sialic acid in Kupffer cells. The phenobarbitale-halothane-hypoxia exposed rat liver shows centrolobular degeneration of hepatocytes with a diminished amount of hepatocyte and Kupffer cells as well. The lectin binding pattern of sinusoidal walls, membranes of hepatocytes and bile canaliculi remains the same compared to that of normal rat liver. This finding suggests that at least the carbohydrate content of membranes in the liver resists severe destruction under phenobarbitale-halothane-hypoxia. It is assumed that there exists a connection between intact carbohydrate residues and the regeneration of liver parenchyma.

Animals↗
PubMed1989

Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment.

The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.

Androgen Antagonists↗
PubMed1988

Lectin histochemistry on mucous substances of the taste buds and adjacent epithelia of different vertebrates.

In the present study carbohydrate residues in taste buds (TBs) and adjacent epithelial formations of a teleostean fish, a frog and the rabbit were detected by means of lectin histochemistry. Biotinylated lectins from Pisum sativum (PSA), Arachis hypogaea (PNA), Dolichos biflorus (DBA), Triticum vulgaris (WGA and succinylated WGA), Glycine max (SBA) and Ulex europaeus (UEA I) have been applied. The lectins were bound to an avidin-biotin-peroxidase-complex (ABC) and visualized by diaminobenzidine/H2O2. Most intensive reactivity was observed at the taste disc cells of the frog with DBA, S-WGA and SBA. PNA did not bind to the TBs of any of the animals tested. As shown in SBA preparations, sialic acid is present in a nonacylated and an acylated form in the mucosa of the frog's tongue. The TBs of the fish possess all the sugars we looked for except for the disaccharide D-galactose-(1-3)-beta-D-N-acetyl-galactosamine (Gal/GalNAc) and sialic acid. The TBs of the rabbit contain GalNAc, as detected with DBA, but not with SBA; and fucose (Fuc), mannose (Man) and N-acetyl-glucosamine (GlcNAc). As revealed by preincubation of the tissue sections with neuraminidase in TB cells of the rabbit, sialic acid masks Gal/GalNAc and GalNAc. These lectin-binding characteristics show that in the TBs of some selected representatives which belong to different vertebrate classes exist different mucous substances. These substances possess different binding characteristics to specific sugars, and this is possibly of particular interest to chemoreception phenomena.

Animals↗
PubMed1987

Lectinhistochemical demonstration of galactose- and N-acetyl-D-galactosamine residues in cells of the rat anterior pituitary.

Lectins are a useful tool for identification of differently glycosylated hypophyseal hormones, prohormones and glycoconjugates without hormone function. Beta-D-galactose and beta-N-acetyl-D-galactosamine (GalNAc) containing glycoconjugates were identified by light microscopy with biotinylated lectins in immunocytochemically localized cells of the anterior pituitary of the rat. Galactose, histochemically detectable by the peanut lectin (PNA), was found at penultimate position of the carbohydrate chain after removal of sialic acid. Galactose containing cells correspond to gonadotrophs and thyrotrophs located mainly in medioanterior regions of the pituitary. The lectins from the soybean (SBA) and horse gram (DBA) both specific for GalNAc residues, are bound to round and also polygonal cells corresponding again to gonadotrophs and thyrotrophs.

Acetylgalactosamine↗