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Biomedical subjects

K Klein

Publications and source records attributed to K Klein.

At least 55 records · Page 3Linked to original sources
PubMed1996

Evidence for redundancy in propeptide/prohormone convertase activities in processing proglucagon: an antisense study.

To further examine the physiological roles of the neuroendocrine prohormone convertases (PCs) in proglucagon processing, alpha TC1-6 cells were transiently transfected with PC1/3 and PC2 expression vectors containing either antisense or sense encoding cDNAs. PC1/3- and PC2-directed RIAs were used to determine that the PC1/3 antisense transfections lowered endogenous levels of PC1/3 by 40 +/- 7.9% but did not alter the levels of PC2. The PC2 antisense transfections decreased the endogenous levels of PC2 by 91 +/- 11.7% without affecting the levels of PC1/3. To quantitate the levels of proglucagon and proglucagon-derived products, transfected cells were metabolically labeled with [3H]tryptophan, and extracts were chromatographed by reversed-phase HPLC. Recovered peptides were then subjected to peptide mapping analyses, allowing precise quantification of 3H-radioactivity incorporated into proglucagon and its cleavage products. Product-precursor ratios were determined, and percent change in the proportion of products generated in antisense-transfected vs. sense-transfected cells was calculated. The decrease in PC1/3 after antisense treatment significantly reduced the amounts of glicentin produced and partially reduced the levels of all other proglucagon cleavage products. PC2 antisense treatment significantly reduced the levels of glicentin and 9K glucagon generated but had no significant effect on the remainder of the proglucagon-derived peptides. These results suggest the existence of redundant mechanisms that ensure the production of each of the intermediate and product peptides derived from proglucagon. PC1/3 is potentially an important enzyme in the processing of most proglucagon-derived peptides, whereas PC2-processing activity appears to predominate at only two of the four potential cleavage sites.

Animals↗
PubMed1996

Sexual risk-taking by Muscovite youth attending school.

Sexual behaviors of adolescents place them at a high risk for HIV and other sexually transmissible infections. Studies of sexual risk-taking and other health compromising practices by youth in countries other than the United States are relatively rare. Examination of health practices across cultures provides insights with respect to explaining international differences in disease rates, helps predict future trends in disease transmission, and identifies health education needs of particular populations or settings. Sexual behavioral risk factors were studied in a sample of 1,090 youth (mean age = 14 years) in Moscow using a translated version of the Youth Risk Behavior Surveillance (YRBS) survey developed by the U.S. Centers for Disease Control and Prevention. Only 26.3% of Muscovite youth report being taught about HIV/AIDS infection in school, and just 41.7% indicate discussion of HIV/AIDS occurred with parents or other familial adults. Overall, 15.7% of females and 23.7% of males report at least one sexual intercourse in their lifetime. About 8.8% of the sample reported participation in sexual intercourse before age 12, and 34.9% indicated having had sexual intercourse with four or more partners. Concomitant use of alcohol and other drugs is common (24.4%) prior to the most recent intercourse, and use of a condom occurs in fewer than half (41.7%) of recent sexual episodes.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Breast cancer in the inner city: intensive efforts may be succeeding.

Breast cancer is a significant problem in a 518 bed government supported university hospital in New Jersey's largest city. The following records were reviewed: tumor registry abstracts of the 367 analytic breast cancer patients admitted from 1/1/91 to 12/31/92; the 455 participants in the Breast Cancer Detection Awareness Program (BCDAP) from 1987 to 1992; and the 460 breast biopsies performed from 1990 to 1992. Breast cancer is less common at this inner city hospital than in the U.S. in general; the stage is more advanced at presentation than in the U.S. overall; and the overall survival is only 54% at five years. Approximately 40% of the patients were African-American women from the inner city. Their median age was 53, seven years younger than the median age for diagnosis in the U.S. overall, and their five year survival was only 46%. Intensive efforts have recently produced improvement in the proportion of cases diagnosed at early stages (T0 and T1), but a decrease in mortality has not yet been seen.

Black or African American↗
PubMed1995

[Goiter incidence in Germany is greater than previously suspected].

BACKGROUND: The data regarding goitre prevalence in Germany is based on calculation arising out of dissimilar studies conducted among inhomogeneous study groups. The aim of our study was to collect data towards prevalence of goitre, thyroid size and structure through a prospective nationwide survey conducted using identical examination methods and study protocol. PATIENTS AND METHOD: A total number of 6815 subjects belonging to various age groups and spread over 32 regions in Germany participated in our thyroid ultrasound study conducted with a 7.5 MHz transducer. Information regarding nutrition, use of iodised table salt and iodine containing medicine and/or substances were collected through a questionnaire. The volumetry and age related normal values were followed as per the guidelines set by Deutsche Gesellschaft für Endokrinologie. RESULTS: Enlarged thyroid was seen in 50% of 18 to 70 year age group, 52% of 11 to 17 year age group and in 21% of children up to 10 years. Focal lesions were detected in 2.5% of subjects below 18 years and in 30% of women and 21% of men over 18 years. A positive correlation between age, thyroid volume and number of thyroid nodules was seen. Up to 83% of the examined subjects admitted to using iodised table salt. Children consuming iodised salt were found to have smaller thyroid glands. No correlation was found between the consumption of iodised salt and thyroid size in the adolescent age group and young adults. CONCLUSION: The prevalence of goitre in Germany is higher than it has been reported. The study underlines the insufficiency of the present goitre prophylaxis. Only an iodine prophylaxis (table salt, food products, fodder) backed by legislative measures can bring about a real breakthrough.

Adolescent↗
PubMed1995

Processing of mouse proglucagon by recombinant prohormone convertase 1 and immunopurified prohormone convertase 2 in vitro.

The mouse tumor cell line alpha TC1-6 was used as a model system to examine the post-translational processing of proglucagon. Determination of the mouse preproglucagon cDNA sequence and comparison with the published sequences of rat and human preproglucagons revealed nucleic acid homologies of 89.1 and 84%, respectively, and amino acid homologies of 94 and 89.4%, respectively. Immunohistochemical analyses with antibodies directed against PC2 and glucagon colocalized both the enzyme and substrate within the same secretory granules. PC1 was also immunolocalized in secretory granules. Cells were metabolically labeled with [3H]tryptophan, and extracts were analyzed by reverse-phase high pressure liquid chromatography. Radioactive peptides with retention times identical to those of synthetic peptide standards were recovered and subjected to peptide mapping to verify their identities. To determine the potential role of PC1 and PC2 in proglucagon processing, 3H-labeled proglucagon was incubated in vitro with recombinant PC1 and/or immunopurified PC2. Both enzymes cleaved proglucagon to yield the major proglucagon fragment, glicentin, and oxyntomodulin, whereas only PC1 released glucagon-like peptide-I from the major proglucagon fragment. Neither PC1 nor PC2 processed glucagon from proglucagon in vitro. These results suggest a potential role for PC1 and/or PC2 in cleaving several of the normal products, excluding glucagon, from the mouse proglucagon precursor.

Amino Acid Sequence↗
PubMed1995

Rat monoclonal antibodies differentiating between the Epstein-Barr virus nuclear antigens 2A (EBNA2A) and 2B (EBNA2B).

Rat monoclonal antibodies were produced against the C-terminus of Epstein-Barr virus nuclear antigens 2A (EBNA2A) and 2B (EBNA2B) expressed as bacterial trpE fusion proteins. The initial screening was performed using a soluble bacterial extract containing the fusion proteins. Positive hybridomas were confirmed by immunofluorescence on SF158 (Spodoptera frugiperda) insect cells infected with recombinant baculovirus (Autographa californica nuclear polyhedrosis virus) and expressing the complete EBNA2A or EBNA2B genes. We selected a panel of antibodies which reacted either with both antigens or specifically with EBNA2A or with EBNA2B. The antibodies were extensively characterized using immunoprecipitation, Western blotting, epitope mapping on synthesized peptide segments of EBNA2A, immunocytology, and immunohistology on both cryostat sections and paraffin sections of AIDS-associated primary central nervous system lymphomas.

Animals↗
PubMed1995

Dual-energy X-ray absorptiometry at the lumbar spine in German men and women: a cross-sectional study.

A cross-sectional, population-based study of 238 randomly selected females and 224 males with German ethnic background (aged 20-80 years) was carried out to establish lumbar spine bone mineral density (BMD) values, using dual X-ray absorptiometry (DXA), for a German population. Comparison was made to the reference range provided by the manufacturer of the DXA equipment. No sex difference in peak spine BMD was found in our study (1.091 +/- 0.114 g/cm2 for males versus 1.070 +/- 0.113 g/cm2 for females, n.s.). Different patterns of bone loss could be detected in both sexes. In premenopausal women there was no significant correlation between age and BMD (y = 1.044 + 0.00047x, r = 0.03, P = 0.73) whereas reduction of female BMD at the spine was demonstrated in postmenopausal women (y = 1.189-0.0041x, r = -0.28, P = 0.01), underscoring the important role of the menopause for later manifestation of spinal osteoporosis in women. In contrast, in males we found no significant change of BMD with aging (y = 1.071-0.0007x, r = -0.08, P = 0.25). Employing commonly used exclusion criteria, BMD values of the study subjects were found mostly within the normal range of BMD. The major finding of our study was good concordance between female data of our study population and the reference data provided by the manufacturer. Clinically significant discrepancies between our data and the Hologic reference range for males could be detected. Our data on males (30-39 years of age) were up to 7% lower than those provided by the manufacturer, probably due to differences in sampling procedures.

Absorptiometry, Photon↗
PubMed1995

Distribution of peptidyl-glycine alpha-amidating monooxygenase immunoreactivity in the brain, pituitary and islet organ of the anglerfish (Lophius americanus).

Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is an enzyme that catalyzes conversion of glycine-extended peptides to alpha-amidated bioactive peptides. Two peptides that are processed at their carboxyl-termini by this enzyme are neuropeptide Y and anglerfish peptide Y, both of which possess a C-terminal glycine that is used as a substrate for amidation. Results from previous reports have demonstrated that neuropeptide Y-like and anglerfish peptide Y-like immunoreactivities are present in the brain of anglerfish (Lophius americanus). Furthermore, neuropeptide Y-like peptides, namely anglerfish peptide Y and anglerfish peptide YG (the homologues of pancreatic polypeptide) are present in the islet organ of this species. Neuropeptide Y has also been localized in the anterior, intermediate and posterior lobes of the pituitary gland in a variety of species. In order to learn more about the distribution of the enzyme responsible for alpha amidation of these peptides in the brain and pituitary and to specifically investigate the relationship of this enzyme to peptide synthesizing endocrine cells of the anglerfish islet, we performed an immunohistochemical study using several antisera generated against different peptide sequences of the enzyme. PAM antisera labeled cells in the islet organ, pituitary and brain, and fibers in the brain and pituitary gland. The PAM staining pattern in the brain was remarkably similar to the distribution of neuropeptide Y immunoreactivity reported previously. Clusters of cells adjacent to vessels in the anterior pituitary displayed punctate PAM immunoreactivity while varicose fibers were observed in the pituitary stalk and neurohypophysis. Endocrine cells of the islet organ were differentially labeled with different PAM antisera. Comparison of the staining patterns of insulin, glucagon, and anglerfish peptide Y in the islet organ to PAM immunoreactivity suggests a distribution of forms of PAM enzyme in insulin and anglerfish peptide Y-containing cells, but no overlap with glucagon-producing cells. The results also indicate that PAM immunoreactivity is widely distributed in the brain, pituitary and islet organ of anglerfish in cells, that contain peptides that require presence of a C-terminal glycine for amidation.

Animals↗
PubMed1995

Sevoflurane for outpatient anesthesia: a comparison with propofol.

Three different anesthetic techniques were compared in 146 healthy outpatients undergoing ambulatory surgery. In Groups I and II, anesthesia was induced with propofol (1.5-2.0 mg/kg, intravenously [iv]) and maintained with nitrous oxide (N2O) 60% in oxygen and either a propofol infusion, 75-160 micrograms.kg-1.min-1 IV, or sevoflurane, 1%-2% end-tidal, respectively. In Group III, anesthesia was induced and maintained with sevoflurane, 1%-4% end-tidal and N2O 60% in oxygen. In addition to 60% N2O in oxygen at a total gas flow of 3 L/min, all patients received fentanyl, 2-3 micrograms/kg IV, and vecuronium, 0.1 mg/kg IV. IV induction of anesthesia with propofol (90 +/- 53 s and 94 +/- 48 s in Groups I and II, respectively) was significantly faster than inhalation induction with sevoflurane (153 +/- 100 s). There were no significant differences in the incidence of coughing, airway irritation, or laryngospasm during induction of anesthesia. Although the mean arterial blood pressure values were similar in all three groups, the use of sevoflurane was associated with consistently lower heart rate values during the early maintenance period. Early and intermediate recovery times were the same in all three treatment groups. The use of sevoflurane for induction and/or maintenance of anesthesia was associated with a higher incidence of postoperative emetic sequelae compared with propofol. Finally, the times at which patients were considered "fit for discharge" and the actual discharge times were similar in all three groups. Sevoflurane is an acceptable alternative to propofol for induction and maintenance of outpatient anesthesia.

Adult↗
PubMed1995

A comparison of survival at different degrees of hemorrhagic shock in germ-free and germ-bearing rats.

We have previously reported superior survival after one level of hemorrhagic shock in germ-free (GF) rats compared with germ-bearing (GB) rats. The objective of this study was to determine the effect of the GF state on survival at different degrees of hemorrhagic shock. GF and GB rats were bled to a mean arterial blood pressure of 30 mmHg. Shock was terminated after 10, 20, 40, or 80% of the maximum shed blood volume was reabsorbed spontaneously. Both shock time and time to decompensation were significantly longer in GF rats (p < .05). Comparative survival was greater for GF rats at most levels of shock (p < .01). This superiority in survival was greatest at moderate shock levels and decreased at severe shock levels. There may be several reasons for the increased tolerance of GF animals to hemorrhagic shock such as metabolic or immunologic variations. It is hard to avoid the fact, however, that the most notable difference between the GF and GB rat is the presence or absence of bacteria.

Animals↗
PubMed1995

Comparison of the pharmacokinetics of parenteral parathyroid hormone-(1-34) [PTH-(1-34)] and PTH-related peptide-(1-34) in healthy young humans.

The amino-terminal fragments of human PTH [hPTH-(1-34)] and PTH-related peptide [PTHrP-(1-34)] appear to be equipotent in several rodent models. However, continuous i.v. infusions of these peptides to young human volunteers suggested that a 10-fold higher molar dose of PTHrP was required to produce comparable circulating levels of the peptide and biochemical responses similar to PTH. As PTHrP has a wide variety of target tissues in mammalian species and may, therefore, play a paracrine, rather than an endocrine, hormonal role in vivo, we evaluated whether enhanced metabolic clearance of injected PTHrP might explain its apparently reduced potency as a PTH-like hormone. Ten healthy subjects [age, 25 +/- 9 (+/- SD) yr] received in random order either hPTH-(1-34) or hPTHrP-(1-34) given by bolus i.v. injections in a dose of 10.7 nmol. Measurements of plasma immunoreactive peptide indicated a comparable volume of distribution for each, but the apparent t1/2 (8.3 +/- 1.6 min) and plasma clearance (4.0 +/- 1.4 L/min) for hPTHrP were significantly (P < 0.05) accelerated compared to those of hPTH (t1/2, 10.2 +/- 0.5 min; clearance, 2.0 +/- 0.4 L/min). Peak plasma cAMP levels were 9-fold lower in response to hPTHrP (29.5 +/- 19 vs. 190 +/- 63 pmol/L; P < 0.01), and increases in urinary cAMP excretion were 5-fold lower (2.1 +/- 1.1 vs. 11.2 +/- 3.7 nmol/mmol creatinine; P < 0.01). No major differences were observed in the urinary excretion of phosphate, calcium, or sodium between the two peptides. Although hPTHrP-(1-34) has a 2-fold higher MCR than hPTH-(1-34), this may not explain the more than 5-fold lower plasma or urinary cAMP response to PTHrP in humans. The comparable effects of PTH and PTHrP on urinary phosphate, calcium, and sodium may indicate a non-cAMP-dependent pathway for these responses, although the intracellular pool of cAMP generated to either peptide, and thus the local target tissue response, could not be estimated in the present study.

Adult↗
PubMed1995

Multicenter German reference data base for peripheral quantitative computer tomography.

The wide spread use of bone densitometers in Germany and other European countries has required the establishment of a validated reference population data base. A semianthropomorphic forearm cross-calibration phantom (EFP), developed during a concerted research action of the European Union's programme in Biomedical Engineering (COMAC-BME), was used to cross-calibrate the peripheral quantitative computer tomography (pQCT) devices at four German centers participating in the multicenter study. In total, 723 women and 208 men were included in the normal data base. No significant regional differences were found between the data of the different centers. In addition to the manufacturers calibration standard, proper calibration of the pQCT devices could be monitored during collection of the normal female and male data base. As a merit of the COMAC-BME study the measurements obtained with all pQCT devices thus ensured an uniform reference data base for distal radius measurements in Germany.

Adult↗
PubMed1994

Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin's disease.

Monoclonal antibodies directed against the Epstein-Barr virus nuclear protein 1 (EBNA1) were used to examine conventional paraffin sections from a series of EBV-associated lymphoproliferative disorders by immunohistochemistry. The presence of latent EBV infection in tumor cells was determined by in situ hybridization for the Epstein-Barr virus early RNAs (EBERs). Of those EBER-positive cases a total of 28 of 40 cases of Hodgkin's disease, 3 of 3 cases of Burkitt's lymphoma, and 8 of 8 cases of human immunodeficiency virus-associated cerebral B-cell lymphoma expressed detectable amounts of EBNA1. In the positive cases, expression was confined to the tumor cells. No reactivity was detected in EBV-negative cases of the above tumors or in 8 cases of EBV-negative cases of large cell anaplastic non-Hodgkin lymphoma. This report provides the first unequivocal evidence for the expression of the EBNA1 protein in the tumor cells of Hodgkin's disease and validates an important reagent with which to analyze the role of EBV in various virus-associated malignancies.

Amino Acid Sequence↗
PubMed1994

Precision of dual X-ray absorptiometry and peripheral computed tomography using mobile densitometry units.

Irrespective of the method used for noninvasive bone mass determination, data comparison between different centers is a major problem as significant interunit variation may occur. We, therefore, have employed mobile densitometry units to reduce interunit variability in two large epidemiologic studies in Germany. Two cars were equipped with either two dual X-ray absorptiometry (DXA) instruments (QDR 1000 Hologic, USA) (car I) or a special purposed scanner for peripheral quantitative computed tomography (pQCT) (XCT 900, Stratec, FRG) (car II). The cars were moved across Germany 11,090 km and 1651 km during the studies over a period of 30 and 7 months, respectively. Precision in vitro was determined using hydroxyapatite phantoms. Forty-eight patients underwent duplicate measurements at the lumbar spine (n = 22) and hip (n = 26) for assessing reproducibility in vivo. Between the two series of scans, the car was moved 63 km. Long-term precision in vitro of the QDR 1000 instruments were 0.41% and 0.59% for BMD with no evidence of machine drift (rate of change per year 0.04% and 0.05%, respectively). Short-term reproducibility in vivo showed a coefficient of variation (cv) of 1.02% for spinal BMD (L2-L4) and 1.72% for femoral neck. Long-term precision in vitro of the pQCT scanner was 0.9%. Our study shows precision in vivo and in vitro and stability of the mobile densitometers similar to that achieved with stationary equipment. In conclusion, mobile densitometry may become a useful tool not only for epidemiologic surveys and clinical trials but also for routine evaluation in less densely populated areas.

Absorptiometry, Photon↗
PubMed1994

The determination of ultrasound velocity in the os calcis, thumb and patella during childhood.

Maximising the accumulation of bone tissue during growth and puberty is one of the most important aims in the prevention of osteoporosis. For prevention studies in children it is necessary to develop methods for skeletal status without radiation. Ultrasonic velocity (speed of sound = SOS) has been proposed as an alternative method. Using a new ultrasonic system (Osteoson K4, Minhorst, Germany), we investigated the reproducibility and age-dependency of SOS in several peripheral bones in 218 children and young adults. Intra-observer (day to day) reproducibility: calcaneus CV = 0.64%, patella CV = 1.18% and thumb CV = 0.43% (n = 25). Inter-observer reproducibility: calcaneus CV = 1.1%, patella CV = 2.48% and thumb CV = 0.62% (n = 16). SOS in thumb and patella increased with age and peaked at 20-25 years. SOS in the calcaneus showed no increase after puberty. Studies in bones from pigs show no dependency of SOS from the thickness of analysed cortical or trabecular bone slices. We conclude that the reproducibility of SOS measurements especially in the thumb is comparable with those of radiation methods. The SOS data in growing, healthy children and the independency from bone dimensions provides more evidence that SOS describes the elastic qualities of the bones.

Adolescent↗
PubMed1994

Pain management for the postoperative patient.

Studies have shown that patients often experience suboptimal analgesia in the postoperative period. In the past decade, a number of advances have been made to improve patient comfort after undergoing surgery. In addition to the obvious desirability of better pain control, adequate postoperative analgesia may decrease the incidence of cardiac and pulmonary complications. Opioid analgesics continue to be the main class of drugs used for postoperative analgesia. However, new methods and routes of administration, including patient-controlled analgesia and epidural and intrathecal drug administration, are currently being used. These modalities, when used appropriately, provide better analgesia, often with fewer side effects than when opiates are given by the traditional intramuscular route.

Analgesics, Opioid↗