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Biomedical subjects

J Handler

Publications and source records attributed to J Handler.

At least 19 recordsLinked to original sources

[Plasma concentrations of folic acid, vitamin B12 and progesterone of cyclic bitches, bitches during pregnancy and induced abortion and bitches with pyometra].

The aim of this study was to investigate the plasma concentrations of folic acid, vitamin B12 and progesterone at different stages of the sexual cycle and pregnancy, during induced abortion and in bitches with pyometra. Bitches (n = 97) were assigned to groups as follows: a) oestrous cycle (n = 42) b) pregnancy (n = 25) c) induction of abortion (n = 10 and d) pyometra (n = 20). Oestrous cycle stages were determined by vaginal inspection and cytology. Pregnancies were estimated by ultrasound (5.0 Mhz; linear transducer; Schimadzu) at days 15-25, 35-45 and 46-63 of pregnancy. Treatments for the induction of abortion were started between days 25 and 35 after mating (5 microg/kg cabergoline daily, Galastop; 5-10 microg/kg Alfaprostol every other day, Gabbrostim). Diagnosis of pyometra was confirmed by ultrasound and vaginoscopy. Folic acid and vitamin B12 concentrations did not differ among different stages of the oestrous cycle. The mean concentration of folic acid during early pregnancy (days 15-25) exceeded levels of later stages (days 46-63): 9.4 +/- 3.7 microg/ml and 4.7 +/- 1.8 microg/ml, respectively (p < 0.01). A positive correlation between folic acid and vitamin B12 was determined in pregnant dogs ( r = 0.925; p < 0.02). Before the induction of abortion, the concentration of folic acid was 9.6 +/- 5.2 microg/ml; during abortion it decreased to 5.0 +/- 3.2 microg/ml (p < 0.01). A significant correlation (r = 0.925; p < 0.02) between progesterone and folic acid was obtained in bitches with abortion. The mean concentration of folic acid in bitches with pyometra significantly differed from that of bitches at different stages of the oestrous cycle (p < 0.05). The mean concentration of folic acid was significantly lower in metoestrous bitches when compared to bitches with pyometra (p < 0.05). The decrease of serum concentrations of folic acid during pregnancy and induced abortion show that fetal growth and abortion caused higher consumption of folic acid. Concerning bitches did not show any deficiency symptoms, which is why it can be concluded that this decrease is physiological.

Abortion, Veterinary↗

Matrix metalloproteinase 2 (MMP-2) and tissue transglutaminase (TG 2) are expressed in periglandular fibrosis in horse mares with endometrosis.

Periglandular arrangement of myofibroblasts, associated with the deposition of extracellular matrix (ECM), is a cardinal feature of endometrosis in mares. We hypothesized that a disturbance in the expression of matrix degrading enzymes such as matrix metalloproteinases (MMP's) and matrix cross-linking proteins might lead to an imbalance in deposition and degradation of extracellular matrix components and thereby accentuate degeneration. Therefore, distributions of MMP-2, capable of collagen IV and laminin degradation, and tissue transglutaminase (TG2), a cross-linker of extracellular matrix proteins, were investigated by means of immunohistochemistry on uterine biopsies of healthy mares and animals with endometrosis. It was illustrated that both proteins were present in fibrotic regions of affected endometria, and that they were in most cases colocalized. Periglandular MMP-2 expression was significantly associated with dilated and fibrotic uterine glands. Furthermore, MMP-2 and TG 2 were demonstrated in the stratum compactum of healthy and endometrotic endometria. Gelatin zymography proved that active and inactive pro-form of MMP-2 were present in all examined samples with significantly higher amounts of total and active MMP-2 in affected endometria. TG 2-activity, determined by an in situ assay, was found in cases of severe periglandular fibrosis. We suggest that both enzymes play a major role in changes that occur in ECM homeostasis in endometrial fibrotic regions.

Animals↗

Mineralised deposits in the uterine glands of mares with chronic endometrial degeneration.

Chronic degenerative disease of the mare's endometrium is characterised by changes in the uterine glands, including cystic dilation, hyperplasia and periglandular fibrosis. Endometrial biopsies were taken from 23 mares with different grades of endometrial degeneration. Solid structures were identified within the lumina of the uterine glands and shown to be calcified by histochemical staining. Most of them were not homogenous but composed of a mixture of mineral and organic substances. Further examinations of these mineralised structures by immunohistochemical methods revealed the presence of the non-collagenous matrix proteins osteopontin, osteonectin and bone sialoprotein, which are known to be involved in calcification processes such as urolithiosis. Osteopontin and bone sialoprotein were identified within the calculi, frequently arranged in concentric layers. Osteonectin was the only matrix protein that was also present in the glandular epithelium. Osteocalcin was not found in either the calculi or the glandular epithelial cells.

Animals↗

[Suitability of sonographic evaluation of ovarian dynamics and uterine involution for prediction of postpartum fertility in the cow].

To investigate the suitability of sonography for prediction of puerperal fertility, we used 34 cows with normal puerperium. For this purpose, the animals were examined gynecologically and by transrectal sonography at 10-day intervals between day 15 and day 45 p.p. as well as at oestrus, when they were inseminated. We judged uterine involution by diameter and sonographic structure of the uterine cross-section and ovarian activity by the presence of follicles and corpora lutea. Cows, which became pregnant after first insemination p.p., were assigned to group G1 (n = 16) and animals, which failed to conceive, to group G2 (n = 18). The cows of G1 obtained significantly better results concerning both uterine involution and ovarian activity than cows of G2. Thus, diameter of the uterine horn decreased faster and sonographic structure of the uterine cross section returned markedly earlier to the nonpregnant appearance in G1 than in G2. Group G1 also showed a significantly higher percentage of dominant follicles at all examinations. The results of the study show a distinct relationship between uterine involution and ovarian activity and puerperal fertility. But it has also to be resumed that the prediction of fertility for individuals will always be restricted by other reasons causing failure of conception.

Animals↗

Lectin binding patterns of uterine glands in mares with chronic endometrial degeneration.

OBJECTIVE: To evaluate changes of glycoconjugate in uterine glands of endometrial tissues obtained from mares. ANIMALS: adult mares. PROCEDURE: Uterine biopsy samples were collected during the breeding season and analyzed histologically for signs of chronic endometrial degeneration. Stage of the estrous cycle was established, using clinical examination and determination of hormonal status. Uterine tissue samples were analyzed, using lectin histochemical and immunohistochemical techniques (estrogen and progesterone receptors). Connective tissues were stained to determine alterations of ground substance in periglandular fibrosis. RESULTS: Of 50 mares, 30 (60%) were classified as normal or having modest alterations, and 20 (40%) were classified as having moderate or severe endometrial degeneration. In normal equine endometrium, several lectins (Helix pomatia agglutinin, Lotus tetragonolobus agglutinin, Ricinus communis I agglutinin, Ulex europaeus agglutinin, and wheat germ agglutinin) bound to glycoconjugates of the luminal epithelium and openings of uterine glands. Lectin binding patterns of cystic dilated glands or fibrotic glands in endometrial samples were remarkably strong, whereas normal surrounding cells remained unstained. Lotus tetragonolobus lectin was not suitable for detecting endometrial alterations. Connective tissues stained with Alcian blue and results of Hale colloidal-iron binding revealed acidic ground substance in periglandular fibrosis. Estrogen and progesterone receptors were evenly distributed in healthy and affected endometrial samples. CONCLUSIONS AND CLINICAL RELEVANCE: Glycoconjugate patterns of uterine glands were altered in mares with chronic endometrial degeneration. Therefore, uterine secretions are likely to be altered. These changes are not induced by changes in content of estrogen and progesterone receptors in endometrial tissues.

Animals↗

Association of endometriosis in horses with differentiation of periglandular myofibroblasts and changes of extracellular matrix proteins.

Periglandular fibrosis and cystic dilation of uterine glands are associated with equine endometriosis. The presence of extracellular matrix proteins (collagen type I, III and IV, laminin and fibronectin) in healthy and endometriotic specimens was demonstrated by immunohistochemistry. The distribution of collagen I, but not collagen III, was dependent on the stage of the oestrous cycle. The arrangement of collagen I and collagen III in endometriotic specimens was similar to that in normal endometrium. In periglandular fibrosis, collagen IV, laminin and fibronectin deposition outside the basement membrane was observed. In these regions, stromal cells were characterized immunohistochemically as myofibroblasts because of their expression of a-smooth muscle actin, and occasionally tropomyosin and desmin. Periglandular differentiation of contractile cells could be interpreted as a reaction to support the extrusion of secretions in cystic dilated glands. Moreover, the changes of extracellular matrix proteins are characteristic for neoplastic lesions, although further development of endometriosis to benign or malignant tumours is not known in horses. Knowledge of the factors responsible for these fibroblastic modulations may be the key to explaining the pathogenesis of endometriosis.

Animals↗

Evaluation of the patient with syncope: an evidence based approach.

The cause of syncope often eludes the clinician despite extensive efforts to make a definitive diagnosis. In that group of patients for whom the cause has eluded the clinician, it is unclear which patients need a rapid inpatient work-up and which patients can be safely discharged for outpatient evaluation. The authors present the results of a systematic literature search to determine the diagnostic value of the emergency department work-up of the patient with syncope.

Diagnosis, Differential↗

Uterine androgen receptor mRNA expression in metestrous and anestrous bitches being healthy or suffering from Pyometra.

The importance of androgens for the female reproductive system has been investigated for decades and a number of androgen sensitive processes has now been identified in female reproductive organs. For carnivore species no data were available so far about uterine androgen sensitivity and its regulation. The present study therefore aimed to investigate whether androgen receptors (AR) are present in the dog uterus, whether they are regulated throughout the ovarian cycle and whether pyometra affects their expression rate. Uterine tissue samples were collected from 28 bitches of different ages and various breeds. The samples were grouped according to the stage of estrous cycle (metestrus ME or anestrus AE) and the pathological status of the uterus (i.e. suffering from pyometra or not). Androgen receptor mRNA (AR mRNA) was quantified from 500 ng of total RNA isolated from the tissue samples using an internally standardized reverse transcription polymerase chain reaction (RT-PCR) described previously. The amount of total RNA extractable per g tissue was elevated during pyometra. The successful amplification of the expected 172 bp fragment from canine uterine RNA together with the confirmation of the identity of this fragment by sequence analysis, demonstrates that AR is expressed in this particular tissue. Comparing the expression rates in uteri from bitches during ME or AE being healthy (H) or suffering from pyometra (P), the only significant (p < 0.01) difference was found between H and P uteri during ME with 3.5-fold lower expression rates in P. Although the same seems true for AE bitches, a significant difference could not be demonstrated due to the low number (n = 2) of diseased animals in the AE group. There was no evident effect of the stage of ovarian cycle on uterine AR mRNA levels.

Anestrus↗

Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia.

We studied transepithelial transport of 3H-labeled hydrophobic cationic drugs in epithelia formed by wild-type and by drug-resistant Madin-Darby canine kidney (MDCk) cells that had been infected with a retrovirus carrying the multidrug-resistance (MDR1) cDNA which encodes the P-glycoprotein. P-glycoprotein is an ATP consuming plasma membrane multidrug transporter responsible for the efflux of cytotoxic chemotherapeutic drugs from resistant cancer cells. Wild-type MDCK cells have small amounts of P-glycoprotein detected by immunoprecipitation. Net transepithelial transport across wild-type MDCK epithelia was demonstrated. Basal to apical flux of 100 nM vinblastine was about six times higher than apical to basal flux. Addition of unlabeled vinblastine reduced basal to apical flux of tracer and increased apical to basal flux of tracer, a pattern expected if there is a saturable pump that extrudes vinblastine at the apical plasma membrane. Daunomycin, vincristine, and actinomycin D were also actively transported and at 20 microM these agents inhibited transport of vinblastine, suggesting that wild-type MDCK cells have a common transporter for all these drugs. Vinblastine transport was also inhibited by 20 microM verapamil, which inhibits the multidrug transporter and reverses multidrug-resistance in non-polarized cells. Net transepithelial transport of all these cytotoxic drugs and of verapamil was much higher in epithelia formed by MDCK cells infected with a human MDR1 virus (MDR-MDCK) which is expressed on the apical surface of MDR-MDCK monolayers. Because the transport of these cytotoxic drugs and verapamil is increased in MDR-MDCK epithelia compared to wild-type MDCK epithelia, transport in both these cell populations can be attributed to P-glycoprotein. These results are consistent with a role for P-glycoprotein in multidrug secretory transport across the epithelium of the proximal tubule since P-glycoprotein is normally expressed on the apical membrane of proximal tubule cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Lead poisoning in Wilmington, Delaware, 1974-1984.

This paper demonstrates the efficacy of screening for lead poisoning by determining FEP for a rapid, accurate identification of children at risk and in need of treatment. Early detection and prompt treatment significantly reduces morbidity and mortality. With improvements in childrens' environments, screening procedures and treatment regimes, lead poisoning should eventually become obsolete.

Child↗

Aldosterone-induced proteins in renal epithelia.

Similar aldosterone-induced proteins have been demonstrated in two renal epithelia, the urinary bladder of the toad, Bufo marinus, and epithelia formed by cells of the A6 line derived from the kidney of the toad, Xenopus laevis. The proteins are induced along with the stimulation of Na+ transport but their synthesis is not dependent on Na+ transport per se. In view of the similar characteristics of the aldosterone-induced proteins in these two different epithelia, we suggest that they may have an important role in aldosterone-induced Na+ transport.

Aldosterone↗

Differentiated function in cultured epithelia derived from thick ascending limbs.

Medullary thick ascending limbs were dissected from rabbit kidney and cultured on thin collagen membranes. The collagen membranes were supported by a special device that limited the exposed surface area to a disk 1 mm in diameter. The cells usually proliferated to form a confluent epithelial monolayer covering the collagen membrane within 8-10 days. Transepithelial voltage was measured between bridges immersed in the solutions bathing the bottom of the collagen membrane and the apical (upper) surface of the epithelium. The voltage typically was oriented positive toward the apical surface and persisted for a few weeks. Furosemide but not amiloride reduced the voltage reversibly. Both the orientation of the voltage and its reduction by furosemide are characteristic of thick ascending limbs. Therefore, the observed voltage supports the identification of the epithelial cells in culture and is evidence of differentiated function.

Amiloride↗

Renal papillary necrosis in thyroid carcinoma.

A thirty-four-year-old man with progressive visual impairment was found to have thyromegaly and renal insufficiency at the time of admission. Subsequent evaluation demonstrated bilateral optic neuritis and a thyroid nodule which proved to be a follicular carcinoma. Nephrologic studies revealed bilateral papillary necrosis and chronic interstitial nephritis on biopsy. The patient's renal function stabilized and twenty-four-hour protein excretion diminished after hemithyroidectomy. Carcinoma-related protein production may have played a role in the development of the observed renal lesions. Carcinoma should be a consideration in patients with unexplained papillary necrosis.

Adenocarcinoma↗

Effect of parathyroid hormone and cyclic AMP on protein phosphorylation in rabbit kidney cortex.

Suspensions of renal cortical tubules were incubated with 33Pi and exposed to parathyroid hormone (40 mlg/ml) or 1 mM dibutyryl cyclic AMP. In other experiments homogenates of renal cortex were assayed for protein kinase and phosphoprotein phosphatase activity using [gamma-32P]ATP with or without 5 mM cyclic AMP. Proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and phosphorylation of proteins measured by liquid scintillation counting of gel slices. The pattern of protein phosphorylation was similar in control tissue from both tubule suspensions and homogenates. In intact tubules, parathyroid hormone stimulated the phosphorylation of four proteins with molecular weights of approx. 150 000, 125 000, 100 000 and 50 000 by 28%, 24%, 13%, and 20%, respectively. Results with dibutyryl cyclic AMP were comparable but more variable. Stimulation of phosphorylation by cyclic AMP in homogenates was more generalized with the major effect on a 50 000 dalton protein (50% stimulation). No effect of cyclic AMP on dephosphorylation of proteins was observed. The results are interpreted as indicating that increased phosphorylation of cell proteins is part of the cyclic AMP-mediated response of the renal cortex to parathyroid hormone.

Animals↗