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Biomedical subjects

K Kirsch

Publications and source records attributed to K Kirsch.

At least 37 records · Page 2Linked to original sources
PubMed1995

Blood volume regulating hormones response during two space related simulation protocols: four-week confinement and head-down bed-rest.

The volume of regulating hormones (renin, aldosterone, arginine vasopressin and atrial natriuretic factor), electrolytes and creatinine concentrations, and blood pressure were measured in two different four-week experimental protocols: respectively -6 degrees head-down bed-rest (5 subjects) and confinement (6 subjects). We observed a significant increase (P < 0.01 at D2 vs D-5) of systolic blood pressure during confinement and a different level of response for some hormones, especially for arginine vasopressin (300% increase during confinement instead of 50% during bed-rest). The renin-angiotensin-aldosterone system was enhanced during confinement and head-down bed-rest. In both conditions, we obtained a similar pattern of response for blood volume regulating hormones. During confinement, two main factors were inactivity and stress activation of the sympathetic nervous system. In the bed-rest study the response is principally due to the fluid shift and blood volume adaptation but it is not possible to exclude the role of inactivity and stress.

Adult↗
PubMed1994

Enhanced slow caudad fluid shifts in orthostatic intolerance after 24-h bed-rest.

To evaluate mechanisms of late orthostatic intolerance, slow fluid shifts along the body axis were studied during deconditioning by 24-h bed-rest and during 13-min upright tilts before and after this manoeuvre. In 11 healthy male subjects the fluid volumes of a thorax and a calf segment (impedance plethysmography) as well as tissue thickness at the forehead and the tibia (miniature ultrasonic plethysmograph) were recorded. Cardiovascular performance was monitored by recording heart rate (electrocardiogram), brachial and finger arterial pressure (by the Riva Rocci method and by the Finapres technique) as well as stroke volume (by impedance cardiography). Bed-rest led to a cephalad fluid shift with a mean interstitial leg dehydration of 2.2 ml.100 ml-1 with no changes in body mass and plasma volume. No syncope during the tilt occurred before bed-rest, while after bed-rest 8 subjects fainted between min 2.1 and 9.0 of the tilt. Bed-rest resulted in an augmented initial heart rate response to tilting which was similar in all subjects. In later orthostasis, bed-rest caused two- to threefold faster caudad fluid shifts with higher calf filtration rates in fainters (prior to hypotension) than in nonfainters. Through bed-rest the estimated extravasation within 10 min into general lower body tissue spaces increased by 192 ml in (late) fainters as opposed to only 23 ml in nonfainters. It was concluded that contributing factors to orthostatic intolerance may be slow transcapillary fluid shifts which are easily underestimated and whose quantity and time course call for further investigation after various deconditioning manoeuvres. In particular, the postflight fluid shifts in astronauts who will have markedly dehydrated legs, may impose a circulatory stress which needs to be evaluated. In general, the filtration rate in relevant areas appears to be an integrative and easily determined parameter, reflecting hormonal and neurogenic vascular as well as local interstitial control of the Starling forces.

Adult↗
PubMed1994

Time course of erythropoietin, triiodothyronine, thyroxine, and thyroid-stimulating hormone at 2,315 m.

Erythropoietin (EPO), triiodothyronine, thyroxine, thyroid-stimulating hormone (TSH), hemoglobin (Hb), reticulocytes, packed cell volume, and plasma volume changes were studied in 29 male Austrian mountain rescue soldiers before and several days after an ascent from 744 to 2,315 m in the Alps. EPO concentrations showed a remarkable increase 48 h after the ascent (P < 0.01). No significant changes were found in triiodothyronine, thyroxine, and TSH. Reticulocytes increased only slightly. Hb decreased during the week (P < 0.01). Packed cell volume did not change, whereas plasma volume showed a slight decrease for 48 h after the ascent but then increased constantly (P < 0.01). It seems that thyroid hormones, TSH, and Hb play only a minor role in the regulation of EPO production and release under mild hypobaric-hypoxic conditions (2,315 m).

Adult↗
PubMed1994

Fluid recruitment from shell tissues of the body during haemodialysis.

Patients with kidney failure are prone to accumulate fluids within the superficial tissues, leading to a puffiness of the face, hands, and feet. After dialysis these symptoms disappear. It was the aim of this study to quantify these changes. With the help of A-mode ultrasound in 49 patients (20 females, 29 males) the tissue thickness in the forehead and tibia was measured during dialysis. In the forehead the tissue thickness before dialysis was 4.01 mm (females) and 3.87 mm in the males, decreasing continuously during dialysis by 13.6% and 12.8% respectively (P < 0.001). In the tibia the tissue thickness was 3.87 mm (females) and 3.07 mm (males) and decreased by 12.8% and 23.9% respectively. The sex difference was significant (P < 0.05). From these values it was calculated that 45% of fluid withdrawn came from the superficial shell tissues of the body. It was concluded that these tissues serve as water stores in the interdialytic phase.

Adult↗
PubMed1993

Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains.

The cell surface glycoprotein MUC18, a member of the immunoglobulin superfamily and homologous to several cell adhesion molecules, is associated with tumor progression and the development of metastasis in human malignant melanoma. Immunohistochemical and Northern blot analysis revealed that expression of the antigen is restricted to advanced primary and metastatic melanomas and to cell lines of the neuroectodermal lineage. The genomic sequence encoding the cell surface antigen spans approximately 14 kb and consists of 16 exons. The organization of the gene, which is related to that of the neural cell adhesion molecule N-CAM, shows a structure where each immunoglobulin-related domain is encoded by more than one exon. Sequencing of the putative MUC18 promoter region revealed a G + C-rich promoter lacking conventional TATA and CAAT boxes. Several motifs for binding of transcription factor Sp1 are present in the regulatory region, and only a single transcription start site within a presumed initiator sequence was identified. Sequence elements which might confer melanocyte-specific expression were not detected. Instead, recognition sequences for the transcription factors CREB, AP-2, and c-Myb, as well as CArG-box motifs, were observed. These elements may contribute to the differential regulation of the MUC18 gene in normal and malignant tissues and suggest a role for this putative adhesion molecule in neural crest cells during embryonic development.

Amino Acid Sequence↗
PubMed1993

European isolation and confinement study. Water and salt turnover.

Intake and output of water were studied in six male subjects from six European countries during 28 days of isolation and confinement in order to assess whether the observed reactions can be compared with those observed during space travel. On the average, the subjects drank 17.5 ml/kg/day fluids. An additional 25 ml/kg/day was recruited from food intake and metabolism. The lowest fluid intake of 11.3 and 12.1 ml/kg/day was shown by two subjects who concurrently lost 3 to 4% of body weight. Three subjects maintained body weight, and one subject gained. A linear correlation existed between the total water output and the fluid intake by drinking. The time series of fluid intake, urine output, and sodium excretion revealed a weekly pattern for these parameters, characterized by low values on Sundays and high values on Fridays. This pattern was most apparent for sodium excretion. Low water turnover rates were seen in the first week of isolation; in the last week the values were above average. In conclusion, it can be said that with respect to the water balance, strong individual differences and time dependent variations (day to day, week to week) of the respective parameters have to be taken into account for the data analysis during such long-term studies.

Adult↗
PubMed1993

Effects of 28-day isolation (ESA-ISEMSI'90) on blood pressure and blood volume regulating hormones.

The aim of this study was to determine what effects social isolation and confinement stress had on the volume regulating hormones. In six healthy male subjects, during a 28-d isolation and confinement study (ESA-ISEMSI'90), hematocrit, blood pressure and resting heart rate, plasma cortisol, renin, aldosterone, arginine vasopressin levels besides the electrolyte (Na+, K+) balance and plasma creatinine were measured. During the confinement, an elevated systolic blood pressure (p < 0.01) was observed together with an increase in MHPG corresponding to an elevated mental work load. The pattern displayed by volume regulating hormones (increased values for renin, aldosterone (p < 0.05) and arginine vasopressin) was not only characteristic of confinement stress but also reflected changes in the water and electrolyte metabolism. The increased creatinine levels seen throughout the study were regarded as consequences of hypohydration, and an enhanced muscular catabolism due to reduced physical activity. A similar pattern of hormone modifications was obtained in a head down tilt of the same duration, indicating that some of the described modifications are probably related to isolation and confinement stress.

Adult↗
PubMed1992

Beta 2-microglobulin gene is mutated in a human colon cancer cell line (HCT) deficient in the expression of HLA class I antigens on the cell surface.

The human colon cancer cell line HCT does not express any detectable HLA class I antigens on the cell surface. RNA blot analyses showed that HCT cells synthesize easily detectable levels of heavy chains as well as beta 2-microglobulin (beta 2m) transcripts. Experiments of immunoprecipitation revealed the presence of intracellular HLA heavy chains and the absence of beta 2m molecules. Sequencing studies, performed on polymerase chain reaction-mediated amplification of beta 2m-specific complementary DNAs, indicated that in HCT cells both beta 2m genes are mutated. The first mutation consists of an 11-base deletion, corresponding to the first 11 base pairs of the second exon of the beta 2m gene. This mutation alters the reading frame, starting from the third amino acid residue of the mature beta 2m protein, resulting in the synthesis of a 31-amino acid peptide with no remarkable homology to any of the sequences stored in the protein database. The second mutation is a point mutation (C----A), resulting in a UAA stop codon corresponding to the 10th amino acid residue of the mature beta 2m. Therefore, it would appear that in HCT cells the beta 2m genes have undergone two different mutational changes. This is the first molecular demonstration of beta 2m mutations in a human epithelial cell line.

Base Sequence↗
PubMed1988

Partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the H-2 class I gene H-2Ld into a human colon cancer cell line (HCT).

Many human tumors, particularly those of epithelial origin, appear to express greatly reduced levels of major histocompatibility complex class I antigens on their surface. It has been previously reported that the class I gene H-2Ld, introduced into adenovirus type 12-transformed mouse cells, induces reversal of oncogenesis in immunocompetent BALB/c mice. We have tested the hypothesis that the H-2Ld gene, when transfected into HCT colon cancer cells, may alter their transformed phenotype. Two H-2Ld transfectants, HCT-Ii and HCT-If, were found to exhibit a markedly reduced-to-virtually suppressed ability to form colonies in soft agar in comparison to a transfectant (HCTh) carrying only the neomycin-resistance gene. We also compared the tumorigenicity of HCTh vs. HCT-If cells in two different strains of immunodeficient mice: nude (T-) and triple-deficient mutants (T-, NK-, B-). At 28 days postinjection of 10(7) and 10(6) cells, the size and growth rate of HCT-If tumors were greatly reduced compared to HCTh cells. Therefore, as assayed in immunodeficient animals, expression of the class I H-2Ld gene in HCT cells appears to correlate with partial suppression of the tumorigenic phenotype, suggesting that the expression of a transfected class I gene may by itself alter the phenotype of the recipient cell and that such phenotypic changes may be independent of the immune system.

Animals↗
PubMed1988

Islet cell antigens. Extraction studies and ELISA analysis.

Whole human and bovine pancreases were extracted in 20 mM Tris-HCl buffer without detergents and fractionated by high-speed centrifugation. The 80,000 x g supernatant was used to coat microtiter plates at a concentration of 5 micrograms protein/ml in phosphate-buffered saline. This solid-phase ELISA system was used for the detection of islet cell antigens defined by a series of monoclonal islet cell antibodies (HISL-1, -4, -5, -8, -14, and -19 and 4F2, 3G5, and A2B5). Both glycoprotein and glycolipid islet cell antigens in the total pancreatic extracts were detected by the monoclonal islet cell antibody in the ELISA system, indicating that epitope preservation had occurred during the extraction procedure. There was a good correlation between islet cell antigen quantitated by the ELISA system and the corresponding islet immunohistochemical reaction. Studies along these lines have the potential to facilitate the design of large-scale protocols for the purification of diabetes-related islet cell antigens to homogeneity.

Animals↗
PubMed1986

Correlation of HBV DNA and monoclonal reactivity to HBsAg in serum of patients with HBV infection.

Hepatitis B virus (HBV) DNA hybridization assay, a monoclonal radioimmunoassay (M-RIA) for hepatitis B surface antigen (HBsAg) and conventional polyclonal immunoassays for HBV associated antigens were used to study sera from patients on dialysis and with acute hepatitis B. HBV DNA was detectable in hepatitis B e antigen (HBeAg) negative patients with acute hepatitis but not in HBsAg+ HBeAg- dialysis patients. In acute hepatitis, HBsAg immunoreactivity by M-RIA could still be detected even though a commercial immunoassay for HBsAg, the AUSRIA II, and the HBV DNA assay were no longer positive. Unlike in acute HBV infection, serum HBV DNA was detectable in dialysis patients who were AUSTRIA II negative but M-RIA positive. Serial determination of HBsAg by M-RIA and HBV DNA revealed episodes of HBV DNA positivity months after both the HBsAg was no longer positive by polyclonal immunoassay. Thus, the M-RIA for HBsAg and the molecular hybridization technique for HBV DNA are sensitive and specific assays for the identification of potentially infectious individuals who would not have been characterized as such based on the results of conventional polyclonal immunoassays.

Acute Disease↗
PubMed1986

Expression of type C-related endogenous retroviral sequences in human colon tumors and colon cancer cell lines.

Type C-related human endogenous retroviral sequences have been previously discovered and characterized [Martin, M. A., Bryan, T., Rasheed, S. & Khan, A.S. (1981) Proc. Natl. Acad. Sci. USA 78, 4892-4896]. We investigated the transcriptional pattern of these sequences to determine whether and to what extent their expression is altered in colon tumors and colon cancer cell lines as compared to normal colon mucosa (NCM). Of two long terminal repeat (LTR)-specific transcripts [3.6 and 2.1 kilobases (kb)], the 3.6-kb RNA was particularly abundant in NCM but strikingly decreased in most primary colon cancers tested. In NCM we identified three envelope gene (env)-related transcripts--namely, 3.0, 1.7, and 0.6 kb. Colon tumors appeared to express higher levels of these transcripts, especially the 1.7-kb species. In one case of dysplasia and in one benign tumor, this 1.7-kb transcript was clearly increased. We also examined the pattern of transcription in colon cancer cell lines HCT and Caco2. The LTR-homologous 3.6-kb transcript, very abundant in NCM, was decreased in primary tumors and in HCT cells and virtually absent in Caco2 cells. The latter, however, appeared to produce the transcript when growing exponentially, indicating that Caco2 cultures provide an inducible system susceptible to in vitro manipulation. Both cell lines also contained higher amounts of the 1.7-kb env-related transcript. The decrease of the 3.6-kb RNA in colon tumors versus NCM may be the result of an altered pattern of differentiation, whereas the increase of the 1.7-kb RNA in tumors may represent an early marker of colon neoplasia.

Base Sequence↗