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Biomedical subjects

R Hess

Publications and source records attributed to R Hess.

At least 19 recordsLinked to original sources

GCAP-II: isolation and characterization of the circulating form of human uroguanylin.

The systematic isolation of circulating regulatory peptides which generate cGMP as second messenger resulted in the identification of a novel member of the guanylin family. In the present study we describe the purification and amino acid sequence of a new guanylate cyclase C activating peptide (GCAP-II). GCAP-II contains 24 amino acids in the following sequence: FKTLRTIANDDCELCVNVACTGCL. Its molecular mass is 2597.7 Da. The 16 C-terminal amino acids are identical to uroguanylin from human urine. native and synthetic GCAP-II activate GC-C, the specific guanylate cyclase receptor, of cultured human colon carcinoma (T84) cells. GCAP-II stimulates chloride secretion in isolated human intestinal mucosa mediated by intracellular cGMP increase. GCAP-II specific antibodies were used to localize the peptide by immunohistochemistry in entero-endocrine cells of the colonic mucosa.

Amino Acid Sequence

Comparative pathology of microcystin-LR in cultured hepatocytes, fibroblasts, and renal epithelial cells.

The cyanobacterial toxin microcystin-LR (MCLR) is a potent inhibitor of protein phosphatases 1 and 2A, and is selectively toxic to the liver in vivo and to isolated hepatocytes in vitro. This selectivity is believed to be due to toxin uptake via bile acid carriers. We investigated at the light and ultrastructural levels the effects of high concentrations of MCLR and long incubation times to determine in vitro whether fibroblasts and kidney cells (non-target cells) respond in the same manner as do hepatocytes (target cells) at low concentrations and short incubation times. Cultured rat skin fibroblasts (ATCC 1213) and rat kidney epithelial cells (ATCC 1571) were incubated with with MCLR at 133 microM for 1-24 hr. Lesions in these cells were compared with those in cultured hepatocytes incubated MCLR at 13.3 microM from 1 to 32 min. Lesions in hepatocytes, kidney cells, and fibroblasts were noted at 4 min, 1 hr, and 8 hr, respectively, after initial exposure to MCLR. Lesions in all three cell types progressed and included plasma membrane blebbing, loss of cell-to-cell contact, clumping and rounding of cells, cytoplasmic vacuolization, and redistribution of cytoplasmic organelles. Loss of microvilli, whorling of rough endoplasmic reticulum, dense staining and dilated cristae in mitochondria, and pinching off of membrane blebs were noted only in hepatocytes. Nuclear changes typical of apoptosis were observed only in fibroblasts and kidney cells. Similarities in responses of different cell types to MCLR exposure probably reflect a common biochemical mechanism of action, i.e., inhibition of protein phosphatases 1 and 2A as described by others.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Characteristics of mitotic cells in developing and adult testes with observations on cell lineages.

This report describes characteristics of dividing cells, primarily in developing (10-40 day) rat testis and relates the structure of the dividing cells to the structure of interphase cells. Mitotic cells were characterized in seven zones. Dividing Sertoli cells were seen prior to day 15 and possessed distinct characteristics as compared with dividing germ cells. Myoid cells showed morphological characteristics of precursor myoid cells; 'clear cells' self-replicated in the myoid cell layer; adult-type Leydig cells, some containing lipid, differentiated early (10th-15th postnatal days) from fibroblast-like cells of the multilayered tubule wall and later (15th-25th postnatal days) from dividing differentiated and semi-differentiated Leydig cells within the lymphatic space; fibroblastic cells arose from cells with similar morphological characteristics; semi-differentiated Leydig cells divided, and differentiated Leydig cells in the lymphatic space self-renewed; undifferentiated perivascular cells most likely gave rise to Leydig cells, pericytes; arteriolar smooth muscle cells and vascular endothelial cells arose from division of the pre-existing respective cell types. Fetal Leydig cells appeared to remain but, with time, they appeared to lose their lipid. The data suggest that (1) early recruitment of Leydig cells from undifferentiated peritubular fibroblast-like cells, (2) later mitosis of differentiated and semi-differentiated Leydig cells primarily in the interstitium but also in the perivascular region, and (3) the continued presence of pre-existing Leydig cells from the fetus constitute the adult population. Leydig cell division in the adult mouse was documented. This study provides the necessary information for the recognition of cell divisions to study of cell lineages among testis cells.

Animals

Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro.

OBJECTIVES: This study was undertaken to characterize adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) phosphodiesterases (PDEs) in porcine detrusor smooth muscle and to define their possible role in tension regulation. METHODS: PDEs were isolated from porcine detrusor homogenate by Q-Sepharose anion exchange and calmodulin affinity chromatography. The effects of selective inhibitors of cAMP and cGMP PDEs were investigated on isolated PDEs and on carbachol (1 microM) precontracted detrusor strips. RESULTS: Six PDE isoenzymes were isolated by Q-Sepharose anion exchange and calmodulin affinity chromatography: one calmodulin-stimulated PDE (PDE I) which hydrolyzed mainly cGMP, one cGMP-stimulated cAMP PDE (PDE II), two cAMP-specific PDE (PDE IV alpha and IV beta), and two cGMP-specific PDE (PDE V alpha and V beta). PDE I was potently inhibited in a dose-dependent fashion by papaverine, vinpocetine, and zaprinast; the PDE IVs were potently inhibited by papaverine and rolipram; and the PDE Vs were weakly inhibited by papaverine. In organ bath studies, inhibitors of PDE III (milrinone), IV (rolipram), and V (zaprinast) caused only minor relaxations at high concentrations (200 microM), whereas papaverine and vinpocetine caused relaxations of more than 50%. CONCLUSIONS: Our findings support the involvement of cyclic nucleotide metabolism in the regulation of the detrusor smooth muscle tone in the pig and its regulation by PDEs. The weak action of PDE IV and V inhibitors in vitro may be explained by a possible intracellular compartmentalization of such PDEs and the low cyclic nucleotide turnover rate at the conditions used.

3',5'-Cyclic-AMP Phosphodiesterases

The cell-binding carboxyterminal undecapeptide of SV40 tumour antigen provides protective cell-dependent immunity.

This paper describes the use of the synthetic carboxyterminal undecapeptide of large SV40 tumour antigen, lys698-thr708 (KT) to protect Balb/c mice against growth of subcutaneously transplanted tumorigenic SV40-transformed cells (VLM). The vaccine was prepared by conjugation of KT with 3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide (SPDP). Addition of the SPDP-derivative of KT to syngeneic spleen cells rendered KT covalently linked to free thiol-groups of the cell membranes by the formation of -S-S-CH2-CH2-CO-epsilon-NH-lys698 bonds. Vaccination with KT-conjugated cells was intraperitoneal. Alternatively, KT-conjugated cells were generated in the peritoneum by injection of PDP-KT ((2-pyridyldithio)propionic acid-KT). As a control 60Co-irradiated VLM cells were used. In five experiments all VLM-vaccinated and the majority of the PDP-KT-(or KT-spleen cell)-vaccinated mice were protected against tumour growth. However, mice pretreated with saline, unconjugated spleen cells, free KT, KT conjugated to bovine serum albumin, or KT with incomplete Freund's adjuvant developed tumours. Treatment of PDP-KT-vaccinated mice with anti-CD4 or anti-CD8 immunoglobulin abolished tumour immunity completely. Thus, covalent binding of the carboxyterminal undecapeptide of SV40 tumour antigen to viable, untransformed cells yielded a vaccine which protects Balb/c mice against SV40 tumours.

Adjuvants, Immunologic

Preattentive information processing in schizophrenia.

Preattentive and attentive information processing was investigated in 24 schizophrenic patients and 24 control subjects using a texture discrimination task based on Julesz's texton theory. Texton theory essentially defines a certain limited number of texture elements that can be detected readily and simultaneously without attentional effort irrespective of the size and information content of the rest of the visual field. During the first task, subjects had to detect texton elements (one 'L' among 35 '+'), which were presented on slides for 40 ms and were followed by a mask after different stimulus onset asynchronies (SOA: 200-800 ms). At all SOAs tested schizophrenics reported significantly fewer correct responses compared to the control group. In the second task, subjects had to search for texton (one 'L' among 35 '+') and non-texton elements (one 'L' among 35 'T') in the stimulus displays, whereby response times were measured. Schizophrenics showed significantly slower response times only to texton elements, whereas response times to non-texton elements did not significantly differ from controls. Additionally, schizophrenics made significantly more errors detecting non-texton elements than controls. The results suggest a deficit in processing of visual information in schizophrenic patients, which is confined to preattentive processes and may consist of a slowing of those processes. Schizophrenics may also have difficulty in sustaining their attention during search tasks.

Adult

Radon in outdoor air in Nevada.

Measurements of radon at 50 sites with varying geology indicate that outdoor air in Nevada is comparable to that measured nationwide by Hopper et al. (1991). The statewide median of 15 Bq m-3 (0.4 pCi L-1) is essentially the same as the nationwide median. The range is considerable: from 2.6-52 Bq m-3 (0.07-1.40 pCi L-1). Variations in these measurements can generally be correlated with different concentrations of radon in soils and uranium and its progeny in rocks. Silica-rich igneous rocks (rhyolites and granites) appear to be the main sources of high levels of radon in outdoor air in Nevada. Concentrations of radon in outdoor air generally correlate with levels of radon in soil gas. Measurements taken from heights of 0.5, 1.0, and 2.0 m above the ground suggest that radon in outdoor air reflects the local geology throughout this range of heights. Towns for which > 20% of the homes have indoor-air radon concentrations > 48 Bq m-3 (4 pCi L-1) generally have relatively high soil-gas radon, relatively high outdoor-air radon, or both.

Air Pollutants, Radioactive

PAb1614, a monoclonal antibody reactive with the tumor antigens of SV40, JC, BK, and polyoma virus, and other JC virus tumor antigen cross-reactive antibodies of the PAb1601-1636 panel.

PAb1614, an SV40-specific monoclonal antibody of the panel PAb1601-1636 reacts with large and small tumor antigens of SV40, BK and JC virus, and with polyoma virus large and middle tumor antigens, but not with the large tumor antigen of the lymphotropic papova virus. Using immunofluorescence and immunoblot competition assays and ELISA with synthetic peptides, it is shown that the epitope is represented by the SV40 tumor antigen undecapeptide, K39-E49. This peptide comprises the tumor antigen consensus sequence, H42-G47, of the polyoma viruses. However, the epitope of PAb1614 probably does not exactly coincide with this hexapeptide. This explains why some cross-reactions are less strong, or absent, as in the case of the lymphotropic papova virus. Further antibodies of the PAb1601-1636 panel that cross-react with the JC virus large tumor antigen are PAb1602, 1604, 1606, 1618, 1621, 1622, 1623, 1624, 1626, 1629, and 1633.

Amino Acid Sequence

[Follicular and endometrial growth profiles in stimulated cycles with clomiphene citrate].

To study follicular and endometrial growth patterns in Clomiphene Citrate (CC) stimulated cycles, 50 CC cycles of 31 infertile women with patient Fallopian Tubes, were followed, 17 spontaneous conceptional cycles of fertile women were followed as controls. The pattern of follicular growth was similar in both groups until the day before ovulation in which CC cycles showed larger follicular diameters than spontaneous ones; 23.8 +/- 3.1 mm versus 21.6 +/- 2.9 mm (p = 0.013). Follicular rupture occurred on day 16.1 +/- 2.9 in CC cycles, and on day 15.1 +/- 1.85 on spontaneous conceptional ones. This suggests that the follicle, under the influence of CC, has to reach a larger critical mass to produce enough estradiol to revert the hypothalamic blockage produced by the drug, thus permitting the preovulatory LH surge. Endometrium under CC action, was always thinner than in natural cycles. On the day of follicular rupture, the CC cycle's endometrium measured 11.1 +/- 2.02 mm and the natural cycle's endometrium measured 10.6 +/- 1.8 mm (ns). This finding could be attributed to a antiestrogenic effect of CC on the endometrium. It is concluded that cycles under CC action have different follicular and endometrial growth patterns than spontaneous conceptional cycles.

Adult

[The atypical C-malleolar fracture].

Fractures of the ankle in adults are very common. Like every intraarticular fracture, they require perfect reduction and stable fixation to guarantee a good result. In most cases this can only be achieved by open treatment. The classification of ankle fractures according to Weber depends upon whether the fibular fracture is below (type A) at (type B) or above (type C) the syndesmosis. This classification also defines the importance of the tibio-fibular ligaments. From 1978 to 1992 more than 1000 ankle fractures were treated in our clinic by open reduction and fixation: 72 were type C ankle fractures, and the rest, either type A or type B fractures. When we reviewed our type C fractures we found 9 patients with so-called atypical type C fractures; these have an atypical fracture pattern insofar as a fracture of the medial malleolus is combined with tibiofibular ligament lesion and there is no fibula fracture. Definition, diagnosis, treatment and results are presented in this publication.

Adolescent

[Analysis of re-osteosynthesis in femur shaft fractures 1980 to 1989].

Between 1980 and 1989, 210 patients with 212 femoral shaft fractures were treated at our hospital, 191 patients with 193 fractures (91%) had a follow-up control. Of these 193 fractures only 16 required totally 26 (13.5%) reosteosynthesis, with AO-Switzerland performing 625 (14.5%) reosteosynthesis in the same period of time, with the methods of primary fracture care only varying inconsiderably. The different reasons for reinterventions were planned reosteosynthesis, malposition, delayed union and pseudoarthrosis, loose and broken implants and infection. In comparison with AO-Switzerland the main difference was that we had no case with malposition (AO-Switz. 20%) leading to reosteosynthesis. The early infection rate at our hospital was 0.9% (AO-Switz. 2.6%) in comparison to a late infection rate of 2.1% (AO 2.2%). The screw-plate osteosynthesis and reamed femur-nail have both proved to be safe methods for primary fracture care, whereas combined osteosynthesis (e.g. two plates/reamed femur-nail and a plate) has a high rate of reosteosynthesis and therefore should be avoided.

Bone Plates

[Simplified management of an in vitro fertilization program].

The development of in vitro fertilization has accelerated in a dramatic way the understanding on gamete physiology. Results obtained with the technique are easily reproducible and consistent between different centers. It is well known that cumulative pregnancy rates with 5 or 6 cycles can reach up to 60% of couples being pregnant. However, the main limitations to successive attempts have been the cost of the procedure and the surgical transfer of the embryos. In an attempt to overcome this difficulties, efforts has been made to simplify the monitoring of induction of ovulation, use of GnRh analogs and non surgical transfers whenever it is possible. Results presented in 47 of these cycles show non significant differences, with data published elsewhere, on oocyte maturity, fertilization and cleavage rates. Moreover pregnancy rates per aspiration are 28.6% and per transfer 33.3%. We can conclude that ultrasonography alone to monitor ovulation induction as well as uterine transfers do not affect the outcome of the cycle.

Adult

[The gestrinone (R-2323) treatment of endometriosis].

Results of medical treatment with gestrinone are evaluated in 29 women with minimal (10), mild (9) and moderate (7) endometriosis. After a diagnostic laparoscopy, patients started gestrinone 2.5 mg/day 2 times a week per 6 months. Clinical evaluations and blood samples were performed at the end of the ist, 3rd and 6th month of treatment. A second look laparoscopy, in 26 out of the 29 patients, was performed within a month after discontinuation of the drug. Nineteen patients (73.1%) showed a diminishing in endometriosis score. Moreover, 2 of them presented with a normal pelvis at the time of the 2nd laparoscopy. Overall post treatment scores were significantly lower than pre treatment scores (6.1 +/- 6.9 versus 11.3 +/- 10.2 respectively, p < 0.025). Nineteen out of the 26 patients had amenorrhea, most of them (18) since the second month of treatment. Nineteen patients presented with dysmenorrhea at the beginning of the treatment and in 13 of them it disappeared during the first 3 months of the drug. Reversible elevation in serum transaminases was observed in 4 patients. Red blood cells count and platelet concentration increased at the end of the treatment. A clear pituitary suppression to basal levels was seen. No significant changes on androgen levels were appreciated. Seven patients achieved a spontaneous pregnancy, out of 22 that desired fertility (31.8%), all of them were clinical pregnancies.

Adult

Polarized intestinal hybrid cell lines derived from primary culture: establishment and characterization.

A cell culture system has been developed that produces stable gastrointestinal (GI) polarized cell lines capable of maintaining hormone secretion. A spontaneously transformed rat mucosal epithelial cell was selected for hypoxanthine/guanine phosphoribosyltransferase deficiency and transfected with a plasmid conferring hygromycin resistance (BRIE 291 cells). Fusion of these cells with dispersed small intestinal epithelia cells resulted in hybrid cell lines that retained characteristic properties of the native GI cell more effectively than the transformed tumorigenic parental cell line. Hybrid hBRIE 380 cells are uniformly cuboidal with microvilli, contain villin, are contact inhibited, are anchorage dependent, require serum supplementation for growth, and are more sensitive to virus infection than the parental BRIE 291 cells. Fusion of BRIE 291 with dispersed pancreatic islet cells has resulted in a variety of pancreatic-hormone-producing cell lines. One of these, hybrid hBRIE 291-i2, forms confluent monolayers capable of synthesizing insulin-like immunoreactivity. These studies demonstrate that functionally polarized GI cells can be generated from primary cultures of nondividing committed epithelial cells by somatic cell hybridization and make feasible the selection and maintenance of specific GI epithelial cell types in confluent monolayer cultures.

Animals