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R Lehmann

Publications and source records attributed to R Lehmann.

At least 181 records · Page 10Linked to original sources

Genetics of nanos localization in Drosophila.

The Drosophila gene nanos is required for two processes. During oogenesis, nanos function is required for the continued production of egg chambers, and nanos is expressed in the early germarium. During embryogenesis, nanos is required maternally to specify abdominal segmentation. Nanos shares this latter function with nine other genes, collectively known as the posterior group. Of this group, nanos encodes a determinant, and is localized as an RNA to the posterior pole of early embryos. This RNA is translated to form a gradient of nanos protein with highest concentrations at the posterior. Analysis of the distribution of nanos gene products in embryos mutant for posterior group genes shows that eight of these genes are required for localization, but not stability, of the nanos RNA. Embryos mutant for posterior group alleles which produce weak abdominal phenotypes show reduced amounts of localized nanos RNA. This correlation between nanos RNA localization and abdominal phenotype suggests that nanos acts as a localization-dependent posterior determinant. Localization of nanos is not affected by mutations in bicoid or torso, confirming that the three maternal systems of anterior-posterior determination initially act independently.

Alleles↗

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↗

A role of polycomb group genes in the regulation of gap gene expression in Drosophila.

Anteroposterior polarity of the Drosophila embryo is initiated by the localized activities of the maternal genes, bicoid and nanos, which establish a gradient of the hunchback (hb) morphogen. nanos determines the distribution of the maternal Hb protein by regulating its translation. To identify further components of this pathway we isolated suppressors of nanos. In the absence of nanos high levels of Hb protein repress the abdomen-specific genes knirps and giant. In suppressor-of-nanos mutants, knirps and giant are expressed in spite of high Hb levels. The suppressors are alleles of Enhancer of zeste (E(z)) a member of the Polycomb group (Pc-G) of genes. We show that E(z), and likely other Pc-G genes, are required for maintaining the expression domains of knirps and giant initiated by the maternal Hb protein gradient. We have identified a small region of the knirps promoter that mediates the regulation by E(z) and hb. Because Pc-G genes are thought to control gene expression by regulating chromatin, we propose that imprinting at the chromatin level underlies the determination of anteroposterior polarity in the early embryo.

Abdomen↗

A new extracellular protein of Pseudomonas aeruginosa PA103 regulated by regA.

The expression of exotoxin A (ExoA) from Pseudomonas aeruginosa is influenced by iron and is under the control of the regulatory gene regA. To test whether regA plays a role in the expression of other iron-regulated proteins a RegA- mutant was constructed by insertional mutagenesis. The polypeptide pattern of this mutant (PA103R) was compared with the parental strain (PA103) and a trans-complemented strain PA103R(pREX18) after growth of the strains in conditions containing low or high concentrations of iron. An iron-regulated 42 kDa protein (RRP) was identified and purified from the culture supernatant of PA103 and PA103R(pREX18) which was missing in PA103R. Database analysis of the N-terminal sequence of this regA-regulated protein (RRP) revealed no similarity to other proteins. Preliminary investigations into the function of RRP revealed that it has no proteolytic or cytotoxic activity. Using two-dimensional electrophoretic analysis of whole cells, a technique which allowed separation of over 600 polypeptides, we were unable to identify any other iron-regulated protein whose expression was regulated by regA.

ADP Ribose Transferases↗

Symptomatic hypoparathyroidism in acquired immunodeficiency syndrome.

Involvement of endocrine organs is frequent in patients with HIV infections. We report the first case of symptomatic hypoparathyroidism in a patient in the course of HIV infection. He presented with tetany and hypocalcemia in the presence of decreased levels of parathyroid hormone, which persisted after correction of hypomagnesemia. The family history was negative and none of the autoimmune diseases associated with hypoparathyroidism was present. No local destruction by tumor or infection could be demonstrated apart from HIV infection. We propose a causal role of HIV infection in the development of hypoparathyroidism and discuss the possible mechanisms of parathyroid involvement in AIDS.

Acquired Immunodeficiency Syndrome↗

[Is prevention of diabetes mellitus possible?].

Despite recent progress in therapy and management of diabetes mellitus, diabetes remains a serious disease with life-threatening complications. It is by far the most common metabolic disease and affects 5% of the population in industrialized countries. Noninsulin-dependent diabetes mellitus (NIDDM) is a complex disorder characterized by insulin resistance and impaired insulin secretion and is associated with an increased risk of coronary heart disease, peripheral vascular disease, arterial hypertension and dyslipidemia. Predisposing factors for NIDDM are obesity and a family history of diabetes. Greater physical activity has been associated inversely with the prevalence of NIDDM in several cross-sectional studies. Physical activity increases the sensitivity to insulin, and regular endurance exercise can induce and maintain weight loss, improve glucose tolerance and ameliorate most of the abnormalities in the metabolic syndrome. Type I diabetes mellitus arises as a consequence of immunologically mediated pancreatic islet beta-cell destruction in genetically susceptible individuals. It is an insidious process that may occur over years. During the stage of disease evolution (prediabetes), individuals may be identified by the presence of immunological markers and a decline of beta-cell function. The autoimmune nature of the disease process has led to attempts to stop this process by immune intervention strategies. A variety of immune interventions has been used, some immunosuppressive and some immunomodulatory. Several screening programs are used in order to identify high-risk subjects (i.e. first-degree relatives of individuals with type I diabetes) who may benefit from an early intervention. The ultimate goal of all these efforts is to prevent the development of overt type I diabetes mellitus in those at risk for the disease, using strategies that are both safe and specific. This review summarizes the results of the various studies conducted to date and outlines the approaches currently being tested.

Adjuvants, Immunologic↗

Overestimation of osteopenia using standard analysis software for peripheral quantitative computed tomography.

It is well established that measurement of bone mineral density (BMD) can estimate the risk of future fractures. To assess individual fracture risk BMD measurements are compared with a reference range provided by the manufacturer of the respective BMD technology. However, the power of trabecular bone measured by peripheral quantitative computed tomography (pQCT) to predict future fractures has not been shown up to now. We conducted measurements of trabecular bone density (TBD) at the distal radius (pQCT XCT 900, Stratec, Germany) in a sample of 506 healthy white women aged 40-60 years (mean 48) and compared the results with the manufacturer's normal range. We found a remarkable difference in TBD values between our healthy study population and the manufacturer's reference data in all age groups (e.g., age 50-54 years, 143.1 +/- 43.2 mg/cm3 versus 181.1 +/- 39.0 mg/cm3). Compared to the +/- 2 SD limits of the manufacturer's reference range our study population showed mean TBD values that were about 1 SD below the mean of the reference range. About 50% of our healthy cohort were below the -1 SD limit of the reference range. Almost ten times as many normal subjects as expected (22.1%) were found below the -2 SD limit and therefore classified as individuals with increased fracture risk. This overestimation of fracture risk leads to discomfort of the patient, unnecessary therapeutic intervention, and significant costs to the public.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Velocity of ultrasound at the patella: influence of age, menopause and estrogen replacement therapy.

Determination of apparent velocity of ultrasound (AVU) in bone has been proposed as a valuable tool for discriminating between normal and osteoporotic women. We have studied the influence of age, menopause and estrogen replacement therapy (ERT) on AVU at the patella in a large sample of pre- and postmenopausal women. Three hundred and eighteen woman aged 40-60 year participated in the study (112 women were premenopausal, 21 were perimenopausal and 185 were postmenopausal of whom 110 had received ERT for a minimum of 1 year). AVU was determined as the mean of four measurements at each patella using a Signet instrument (Osteo-Technology, Framingham, MA). An age-dependent decline in AVU was observed only after menopause (r = -0.33, p = 0.0055); in premenopausal women there was a slight but not significant decrease in AVU with age (r = -0.12, p > 0.05). AVU was significantly lower in postmenopausal women compared with premenopausal women (1882 +/- .84 m/s vs 1961 +/- 73 m/s, p < 0.05). ERT prevented the menopause-related fall in AVU. There was a significant positive correlation between the duration of ERT and AVU measurements. Our findings demonstrate a pronounced influence of estrogens on AVU at the patella, supporting the concept of a protective role of ERT in bone stability. AVU measurements therefore merit further investigation as an inexpensive method for predicting fracture risk that does not expose the subject to radiation.

Adult↗

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis).

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks--5 and -1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11-14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that Cmax and AUC (0-3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women. The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions. The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac.-treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.

Animals↗

Apparent velocity of ultrasound (AVU) at the patella in comparison to bone mineral density at the lumbar spine in normal males and females.

It has been reported that apparent velocity of ultrasound (AVU) at the patella discriminates as well between osteoporotic and normal subjects as measurement of bone mineral density (BMD) using dual photon absorptiometry. To investigate the relationship between AVU and peak bone mass, we compared AVU (Signet, Osteo-Technology, Framingham, MA) at the patella and BMD (QDR 1000, Hologic, Waltham, MA) at the lumbar spine in a large sample of healthy males and females. The study population consisted of 153 males (aged 20-60 years) and 129 premenopausal females (aged 20-52 years). Vertebral BMD showed no significant difference between males and females (1.03 +/- 0.16 g/cm2 for males vs. 1.07 +/- 0.14 g/cm2 for females, NS), while AVU values were significantly higher in males compared with females (1967 +/- 64 m/s vs. 1938 +/- 76 m/s, P < 0.05). In men there was a significant decrease in BMD with aging (r = -0.27, P < 0.05), in premenopausal females we found no age-related change in BMD. Similarly in males AVU decreased significantly with age (r = -0.2, P < 0.05), whereas in females AVU values showed relative stability over the age range. There was a significant correlation between AVU and BMD (r = 0.36 for males, r = 0.34 for females, P < 0.05). Our study demonstrates only a weak correlation between AVU at that patella and BMD at the lumbar spine, supporting the view that AVU not only reflects bone quantity but possibly also qualitative properties of bone structure. The sex difference in AVU but not in BMD suggests that the trabecular bone at the patella differs significantly from axial trabecular bone. The identical peak BMD at the lumbar spine for young males and females underscores the importance of the menopause for later manifestation of vertebral fractures.

Absorptiometry, Photon↗

Serum lipoprotein pattern in rats, dogs and monkeys, including method comparison and influence of menstrual cycle in monkeys.

The serum lipoprotein pattern (HDL-, LDL- and VLDL-cholesterol) was determined in normal untreated rats, dogs and monkeys using the density gradient centrifugation method, and compared with that in humans. The serum of rats (Wistar) and dogs (Beagle) was found to contain mainly HDL-cholesterol, whereas the serum of monkeys (Macaca fascicularis) consists of similar amounts of HDL-cholesterol and LDL-cholesterol, as in humans. In contrast to rats and dogs, monkeys showed a very low amount of serum VLDL-cholesterol. Comparison of four different methods (density gradient centrifugation, FPLC, agarose gel electrophoresis and precipitation methods) for determination of HDL- and LDL-cholesterol in monkey serum showed that density gradient centrifugation and FPLC-methods have the highest accuracy and recovery rate. The FPLC-method offers the extra advantages that it requires less sample volume and is less laborious. In a separate experiment, the influence of the menstrual cycle on the serum lipoprotein pattern was investigated in female monkeys. No changes in total cholesterol, HDL- or LDL-cholesterol were detected in serum samples obtained in the follicular and luteal phases of the cycle. In conclusion, monkeys (Macaca fascicularis) may be more suitable than rats or dogs for the comparison of the effect of different compounds on serum lipoproteins in pharmacological and toxicological studies, because the lipoprotein pattern in this species is similar to that of humans.

Animals↗

Localization of nanos RNA controls embryonic polarity.

Anterior-posterior polarity of the Drosophila embryo is initiated during oogenesis through differential maternal RNA localization. The RNA of the anterior morphogen bicoid is localized to the anterior pole of the embryo, where bicoid protein controls head and thorax development. The RNA of the posterior morphogen nanos is localized to the posterior pole, where nanos protein is required for abdomen formation. Here we show that the nanos 3' untranslated region, like that of the bicoid RNA, is sufficient for RNA localization. We have used the bicoid RNA localization signal to mislocalize nanos, producing embryos with two sources of nanos protein. Such embryos form two abdomens with mirror image symmetry. Embryos with nanos RNA localized only to the anterior have greater nanos gene activity than embryos with nanos RNA localized posteriorly. We propose a role for RNA localization in regulating nanos activity.

Abdomen↗

Induction of germ cell formation by oskar.

The oskar gene directs germ plasm assembly and controls the number of germ cell precursors formed at the posterior pole of the Drosophila embryo. Mislocalization of oskar RNA to the anterior pole leads to induction of germ cells at the anterior. Of the eight genes necessary for germ cell formation at the posterior, only three, oskar, vasa and tudor, are essential at an ectopic site.

Abdomen↗

Tumor necrosis factor alpha levels in cats experimentally infected with feline immunodeficiency virus: effects of immunization and feline leukemia virus infection.

Tumor necrosis factor alpha (TNF alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA) and by cell culture bioassay in supernatants of lipopolysaccharide-stimulated feline monocyte cultures and in cat serum samples. There was a good correlation between the results obtained by the two methods. From the fact that TNF alpha was neutralized quantitatively by antibodies to human TNF alpha in feline monocyte supernatants and in feline sera, it was concluded that feline TNF alpha immunologically cross-reacts with human TNF alpha and that the human TNF alpha ELISA can be used to quantitate feline TNF alpha. During the first 6 months after experimental feline immunodeficiency virus (FIV) infection no differences in serum TNF alpha values were observed between infected and non-infected cats. TNF alpha levels increased significantly after primary vaccination with a feline leukemia virus (FeLV) vaccine in FIV infected cats over those in the non-infected controls. During secondary immune response TNF alpha levels rose transiently for a period of a few days in both the FIV positive and the FIV negative cats. After FeLV challenge, TNF alpha levels increased in all animals challenged with virulent FeLV for a period of 3 weeks. This period corresponded to the time necessary to develop persistent FeLV viremia in the control cats. It was concluded from these experiments that in the asymptomatic phase of FIV infection no increased levels of TNF alpha are present, similar to the situation in asymptomatic HIV infected humans. Activation of monocytes/macrophages in FIV infected cats by stimuli such as vaccination or FeLV challenge readily leads to increased levels of TNF alpha.

Animals↗

Immunization-induced decrease of the CD4+:CD8+ ratio in cats experimentally infected with feline immunodeficiency virus.

In a previous experiment a group of 15 specified pathogen free (SPF) cats were experimentally infected with a Swiss isolate of feline immunodeficiency virus (FIV). A group of 15 SPF cats served as FIV negative controls. Nine cats of each group were vaccinated with a recombinant feline leukemia virus (FeLV) vaccine, six cats in each group with a placebo vaccine. All vaccinated cats developed high antibody titers to FeLV and were protected against subsequent FeLV challenge infection. In both control groups five of six cats became persistently infected with FeLV. Unexpectedly, the primary immune response to the vaccine antigen was significantly higher in the FIV positive group than in the FIV negative. The secondary response was stronger in the FIV negative cats. The goal of the present investigation was to further study the immune response in these 30 cats. They were immunized twice with the synthetic peptide L-tyrosine-L-glutamic acid-poly(DL-alanine)-poly(L-lysine) (TGAL) 21 days apart. Blood samples were collected on four occasions during the immunization process. They were tested for antibodies to TGAL, complete blood cell counts and CD4+, CD8+ and pan-T-lymphocyte counts. The following observations were made: (1) in contrast to the FeLV vaccine experiment, the primary immune response to TGAL was not significantly stronger in the FIV positive cats when tested by enzyme-linked immunosorbent assay (2). The absolute size of the CD4+ lymphocyte population was distinctly smaller in the FIV positive than in the FIV negative cats. The lowest CD4+ values were found in the dually FIV/FeLV infected cats. (3) A population of CD8+ lymphocytes was identified that was characterized by a distinctly weaker fluorescence. The size of this population increased in FIV positive and decreased in FIV negative cats during the TGAL immunization experiment. (4) The CD4+:CD8+ ratio increased in FIV negative cats during TGAL immunization from 1.9 to 2.3. In contrast, in FIV positive animals the CD4+:CD8+ ratio decreased significantly from 1.9 to 1.3 during the same period. From these and earlier data it was concluded that in short-term FIV infection the immune response to T-cell dependent antigens may be increased over that of the controls. Immune suppression develops gradually with duration of the infection. The significant drop of the CD4+:CD8+ ratio over a 5 week immunization period suggests that antigenic stimulation may accelerate the development of immune suppression in FIV positive cats. If this is a general feature, FIV infection may provide a particularly interesting model for studying the pathogenesis of AIDS.

Amino Acid Sequence↗

Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus.

An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg(2+)-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30/53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic lions were negative for FIV antibodies. Some of the FIV positive lion sera had high antibody titers producing strong bands on Western blot strips even in dilutions of >> 1:1000. The Western blot pattern of the lion sera differed from that of domestic cats in that primarily p24 and to a lesser degree p17 was recognized. Antibodies to FeSFV were found in 14 animals (seven with strong, seven with intermediate, reaction). No correlation was found between FIV and FeSFV infection. Antibodies to FeLV were found in two cheetahs which later turned out to have been vaccinated with Leukocell, a FeLV vaccine.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Germ-plasm formation and germ-cell determination in Drosophila.

Germ cells in Drosophila form in a specialized cytoplasm that is critical for germ-cell development. Several genes involved in this process have been identified. By studying the temporal and functional sequence of interactions between their products, these genes can be ordered into a pathway for germ-plasm formation.

Animals↗