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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 325 records · Page 18Linked to original sources

Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone.

Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, leptin levels and various hormonal parameters were investigated in a large cohort of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a specific and sensitive RIA was developed that allowed the accurate measurement of low leptin levels in young lean children. With this assay, leptin proved to be a comparatively stable protein under common conditions of blood sampling and storage. Leptin levels increased in girls with age (r = 0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0.0001). An analysis according to pubertal stage showed a steady increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further progression of puberty that was much less pronounced in girls. Although the relative increase of leptin with BMI and percent body fat was the same in both genders, the absolute values at a given BMI or percent body fat were significantly lower in boys in late puberty and in adolescents. In boys, but not in girls, there was an inverse correlation with testosterone concentrations (r = -0.43, P < 0.0001), which explained 10.5% of the variation of leptin levels in a multiple regression model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression line of the form leptin = a*e(b*BMI) and stratifying ranges according to gender and pubertal stage. In conclusion, these data suggest that 1) plasma leptin levels increase in girls and decrease in boys after Tanner stage 2 as the pubertal development proceeds; 2) they show a significant gender difference especially in late puberty and adolescence, even after adjustment for BMI or percent body fat; 3) the lower levels in males may be explained at least in part by a suppressive effect of androgens; 4) reference ranges with BMI as the independent variable should be stratified according to gender and pubertal stage.

Adipose Tissue↗

Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment.

UNLABELLED: In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with GnRH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys. METHODS: PSA was measured by an ultrasensitive immunofluorometric assay with a detection limit of 0.03 microgram/l. Testosterone was measured by an RIA with a sensitivity of 0.23 nmol/l, and sex hormone binding globulin was measured by a time-resolved immunofluorescence assay (sensitivity 0.23 nmol/l). Five boys with central precocious puberty (CPP) were studied before and after 12 months of GnRH agonist treatment. Sixty healthy boys (12 in each Tanner stage of puberty) and 37 healthy young males served as controls. RESULTS: PSA levels were immeasurable in all prepubertal boys, whereas PSA levels increased with increasing stage of pubertal maturation. There was a significant correlation between PSA and testosterone and free androgen indices (r = 0.61 and r = 0.65 respectively, both P < 0.001). All 5 boys with CPP had significantly elevated PSA levels which decreased to very low or immeasurable levels after GnRH agonist treatment. CONCLUSION: PSA may be a useful marker of testosterone activity in boys with normal or precocious puberty.

Adolescent↗

Short- and long-term metabolic effects of recombinant human IGF-I treatment in patients with severe insulin resistance and diabetes mellitus.

UNLABELLED: In patients suffering from the genetic syndromes of severe insulin resistance it appears that diabetes develops when the adaptive hypersecretion of insulin fails and often these forms of diabetes will be insensitive to insulin treatment. The objective of the present study was to examine the metabolic and hormonal responses to an unchanged insulin therapy with the addition of a subcutaneous administration of recombinant human IGF-I (rhIGF-I) during (a) a short-term (2 weeks) period with rhIGF-I given twice a day in a high dose (80 micrograms/kg body weight) in four patients with extreme insulin-resistant diabetes mellitus and (b) during a long-term (10 weeks) period with rhIGF-I given once a day in a low dose (40 micrograms/kg body weight) in three of the four patients. Two siblings had known mutations in the tyrosine kinase domain of the insulin receptor and a deletion of exon 17 in part of their insulin receptor mRNA, whereas the remaining two patients were suspected to have defects at receptor and/or post-receptor sites. In the short-term study period, plasma glucose levels decreased more than 35% in response to rhIGF-I in all but one patient which was paralleled by reduced levels of serum insulin (25-50%), proinsulin (40-50%) and C-peptide (10-65%) and an improvement in glycaemic control as evaluated by decreased glycosylated haemoglobin and serum fructosamine. During the long-term study period blood glucose-lowering effects of rhIGF-I were seen after 2 weeks of treatment and fasting plasma glucose and serum insulin and C-peptide levels were decreased by 40-55% after 6 weeks in the two siblings with known insulin receptor mutations. After 10 weeks of treatment fasting plasma glucose levels were still decreased whereas fasting serum insulin and C-peptide levels were increased almost to pretreatment values. IN CONCLUSION: 2 weeks of high-dose rhIGF-I therapy in insulin-treated patients with severe insulin resistance has a marked lowering effect on fasting plasma glucose and serum insulin levels whereas the metabolic and glycaemic effects of 10 weeks of treatment with low-dose rhIGF-I may be modest and transient.

Adolescent↗

Cryptorchidism.

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Child↗

Long-term mechanical circulatory support as a bridge to transplantation, for recovery from cardiomyopathy, and for permanent replacement.

Since 1988, 295 patients have undergone MCS at the German Heart Institute Berlin; 246 received biventricular support with the extracorporeal pneumatically-driven Berlin Heart Assist Device, 49 received left ventricular support with implantable assist devices (33 Novacor, 16 TCI). Longer waiting periods for heart transplantation has caused the mean duration of MCS to increase from 12 days in 1988 to 76 days in 1994. Of the 24 patients who underwent MCS for more than 90 days, nine were implanted with a biventricular device, 12 with a Novacor device, and 15 with a TCI device. Eight patients with uni-ventricular devices remain on support after 200 days (range 203-600 days). Six of the Novacor patients could be discharged to a nursing home or to their own residences. One patient still on NC support after more than 600 days currently resides at his home and has regained normal physical activity. Minor pocket infections occurred in two TCI and four Novacor patients; one patient died of sepsis. A total of four patients could be weaned from LVAD after 160-347 days of MCS. An initial high level of beta1 receptor antibodies disappeared completely during left ventricular support. This decline in auto-antibodies was paralleled by a dramatic improvement in cardiac function. LVEF remained unchanged up to 6 months after explantation. Long-term mechanical support has become a reality. Heart transplantation after prolonged MCS yields results comparable to primary HTx. Some patients exhibit immunological changes and a dramatic improvement in ventricular function under long-term MCS and can be weaned with extremely satisfying results.

Adolescent↗

Optimization of channel number and stimulation rate for the fast continuous interleaved sampling strategy in the COMBI 40+.

OBJECTIVE: To investigate the interrelation between number of channels and stimulation rate in the continuous interleaved sampling strategy (CIS). SUBJECTS AND METHODS: Three of the first recipients of the new COMBI 40+ cochlear implant participated in consonant, vowel, number, and sentence tests. Speech understanding was evaluated for different combinations of number of active channels from two to twelve and stimulation rate per channel between 1,515 and 9,090 pulses per second. RESULTS: The results indicate that the optimum number of active channels is not necessarily the maximum number of usable channels.

Adult↗

Successful mechanical circulatory support for more than two years with a left ventricular assist device in a patient with dilated cardiomyopathy.

A 36-year-old man with dilated cardiomyopathy was supported with a left ventricular assist device for 795 days. During this support time gradual functional recovery was noted. The patient tolerated the device well, enjoyed a good quality of life, and experienced no technical device-related problems. When a suitable donor heart became available, the device was switched off, and native ventricular function was assessed. This was judged to be acceptable, and the left ventricular assist device was successfully explanted. Postexplantation function remained acceptable and improved over the following days. The patient was discharged on the twentieth postoperative day and remains well.

Adult↗

[Speed S sensitivity of film-screen systems and mode of action of different automatic illumination in general practice. I: Film-screen systems].

A new test procedure is presented to check the correspondence between various screen-film systems (SFS) with the specification of the manufacturer in respect to the speed S according to DIN 6867-1 or rather which dose K is required for the SFS in dependence on the X-ray tube voltage (kV) to give the net density Dn = 1.00, it is based on measurements of dose and density using on X-ray equipment with water as an absorber and scatter test tool. The characteristic curves of the automatic exposure control (AEC) can be recorded and compared with those of SFS, i.e., how is the dose K in the image-receptor-plane regulated by the AEC in dependence on different radiation qualities. It is also possible to check the modes of operation of SFS and AEC with sufficient accuracy but lower time and energy requirements. The consequences of finding the right values to test the X-ray equipment under DIN 6868-50/-3 and for constancy-testing according to DIN 6868-3 are discussed.

Calibration↗

[Sensitivity S of film-screen systems and mode of operation of different automatic exposure systems in general practice conditions. II: Automatic exposure systems].

A new method is presented to check several automatic exposure control systems (AEC) for their suitability in radiological image production. It is based on measurements of dose and density with water as an absorbing and scattering medium. The characteristic curves of an AEC can be recorded, i.e., in what way is the dose K in the image receptor plane regulated by the AEC in dependence on the different radiation qualities and the specific water volume. These characteristics can be compared with several screen-film systems (SFS), i.e., which dose K is required by the SFS in dependence on the X ray tube voltage (kV) to get the net density of Dn = 1.00. It is possible to check the way of operating of an AEC with sufficient accuracy but less time and energy are needed. The disparity of the characteristics of AEC and SFS and their results on radiological examination are discussed.

Humans↗

Cloning of heterologous genes specifying detrimental proteins on pUC-derived plasmids in Escherichia coli.

A system is described that enables the cloning of genes specifying detrimental proteins in Escherichia coli. The system is based on pUC plasmids and was developed for the expression of the Bacillus subtilis csaA gene, which is lethal when expressed at high levels. Suppressor strains that tolerate the presence of plasmids for high-level expression of csaA were isolated, which contained small cryptic deletion variants of the parental plasmid in high copy numbers. The cryptic plasmids consisted mainly of the pUC replication functions and lacked the csaA region and selectable markers. The co-resident, incompatible, cryptic plasmids enabled the maintenance of the csaA plasmids by reducing their copy number 20-fold, which resulted in a concomitant 3- to 7-fold reduction in the expression of plasmid-encoded genes. Strains carrying these cryptic endogenous plasmids proved to be useful for the construction of pUC-based recombinant plasmids carrying other genes, such as the skc gene of Streptococcus equisimilis, which cannot be cloned in high copy numbers in E. coli. Several strategies to reduce production levels of heterologous proteins specified by plasmids are compared.

Bacterial Outer Membrane Proteins↗

Depression as a dynamical disease.

Mathematical models are helpful in the understanding of diseases through the use of dynamical indicators. A previous study has shown that brain activity can be characterized by a decrease of dynamical complexity in depressive subjects. The present paper confirms and extends these conclusions through the use of recent methodological advances: first episode and recurrent patients strongly differ in their dynamical response to therapeutic interventions. These results emphasize the need for clinical follow-ups to avoid recurrence and the necessity of specific therapeutic intervention in the case of recurrent patients.

Adult↗

Combined detection of CD44 isoforms by exon-specific RT-PCR and immunohistochemistry in primary human brain tumors and brain metastases.

Expression of CD44 has been implicated in tumor growth and metastasis. Here we demonstrate CD44 expression in primary human brain tumors (n = 44) and brain metastases (n = 7) by RT-PCR and immunohistochemistry. Standard CD44 was found to be expressed by the majority of primary brain tumors and brain metastases. For the first time to our knowledge, CD44 expression is demonstrated for acoustic neurinomas and pituitary adenomas. Exon-specific analysis by RT-PCR and indirect immunofluorescence revealed expression of alternatively spliced CD44 isoforms in the group of brain metastases only. However, in one glioblastoma multiforme, expression of CD44v5 and CD44v6 was found immunohistochemically. This tumor took an unusual clinical course giving rise to multiple intrahepatic and lymph node metastases. Quantitatively different expression of standard CD44 in gliomas versus meningiomas is reported (p < 0.01).

Alternative Splicing↗

Structural and functional analogs of CuZn superoxide dismutase inhibit rat brain nitric oxide synthase by interference with the reductase (diaphorase) domain.

Copper complexes with superoxide dismutase (SOD) activity show a wide range of pharmacological activities. We have investigated the effect of ([N,N'-bis(2-pyridylmethylene)-1,4-butanediamine]-(N,N',N", N"')]-Cu(II)-chloride (Cu-PuPy) and ([N,N'-bis(2-pyridyl-phenyl)methylene-1,4-butanediamine]-(N,N',N", N"'))-Cu(II)-chloride (Cu-PuPhePy) on the multiple catalytic functions of rat brain NO synthase (NOS). Both drugs inhibited the formation of L-citrulline as well as the enzymatic reduction of cytochrome c. The uncoupled oxidation of NADPH, catalyzed by neuronal NOS in the absence of L-arginine, was inhibited by Cu-PuPy but stimulated by Cu-PuPhePy, suggesting that the phenyl-substituted compound acts as a parasitic electron acceptor. Our data identify copper complexes with SOD mimicking activity as a novel class of neuronal NOS inhibitors blocking the reductase (diaphorase) activity of the enzyme.

Animals↗

[Aneurysm of the ascending aorta in tertiary syphilis].

HISTORY AND CLINICAL FINDINGS: A 58-year-old man was admitted after he was found to have a huge aneurysm of the thoracic aorta. 38 months previously he had first experienced subacute pain in the right thorax. After this the aneurysm gradually increased in size. On admission a pulsating mass, 20 cm in diameter, was obvious, having broken through the right ventral thoracic wall. It was causing venous inflow congestion in the upper part of the body. The patient's general condition was poor: he had marked orthopnoea. INVESTIGATIONS: Serological tests for syphilis gave the following results: VDRL test, 1:32; FTA-ABS test reactive; TPHA test, 1:8000; treponema-specific IgM negative. Computed tomography with contrast-medium injection exactly defined site and extent of the aneurysm. It started at the aortic root and extended to the aortic arch. Third-degree aortic valvar regurgitation was demonstrated on echocardiography. Pulmonary function tests indicated severe restrictive ventilatory abnormality with clearly reduced respiratory reserve. TREATMENT AND COURSE: The symptoms improved after 2 weeks on oral medication of captopril (25 mg/d), furosemide (80 mg/d), spironolactone (100 mg/d), codeine phosphate (90 mg/d) and thick paraffin (20 mg/d as needed). The patient declined further treatment. He died 8 weeks later at home.

Angiotensin-Converting Enzyme Inhibitors↗

Reactivity of lipophilic diSchiff-Base coordinated copper in rat hepatocytes.

The membrane permeability and intracellular fate of ([N,N'-bis(2 pyridyl-phenyl-methylene)-1,4-butanediamine](N,N ',N",N"')-copper(II))-diperchlorate (CuPuPhePy), a copper-diSchiff-base complex of superoxide dismutase(SOD)-mimetic activity surviving biochelation, were examined using rat hepatocytes. Lipophilicity was quantified by determining the octanol/water partition coefficients (K(p)) employing PBS as the aqueous phase. K(p)(octanol/water) was close to 1 (0.7 +/- 0.31) for Cu-PuPhePy. The complex associates with phosphatidylcholine liposomes, as deduced from ultracentrifugation and gel filtration experiments. The ability of the complex to permeate cellular membranes was proven by correlating copper release and viability of rat hepatocytes preincubated with CuPuPhePy and treated with digitonin and diethylmaleate (DEM), respectively. The toxicity and reactivity of CuPuPhePy (LD (50) approximately 10 muM for rat hepatocytes under the given conditions) were higher than those of CuSO (4)(LD(50) approximately 16 mu M) and CuZn-SOD (no toxicity in the tested range of concentration). Unlike CuSO(4) and CuZn-SOD, the toxicity and reactivity of the diSchiff-base complex were increased (LD(50) approximately 5 muM) when the concentration of intracellular glutathione was reduced to 16% of the initial content, by preincubating the cells with DEM. The toxicity of Cu-PuPhePy paralleled lipid peroxidation. This phenomenon was strongly enhanced when Cu-PuPhePy and cumene hydroperoxide (CumOOH) were simultaneously allowed to react with rat hepatocytes. This effect was intensified following preincubation with DEM. A decline in Cu(II)-EPR signals was indicative of the reduction of CuPuPhePy by GSH and liver extract, respectively. The concomitant formation of the Cu(I)-GSH complex during this reduction was monitored by the formation of luminescent Cu(I)-thiolate chromophores.

Animals↗

Repression of lac promoter as a function of distance, phase and quality of an auxiliary lac operator.

The tetrameric Lac repressor can bind simultaneously to two lac operators on the same DNA molecule, thereby including the formation of a DNA loop. We investigated the phasing dependence of DNA loop formation between lac operator O1 and an auxiliary ideal lac operator (O(id)) on the bacterial chromosome, with inter-operator distances varying from 57.5 to 1493.5 bp. Repression of a CAP-independent lac UV5 promoter by O1 at its natural position increased up to 50-fold in the presence of an optimally positioned auxiliary O(id)). Repression values alternated between local maxima and minima with a periodicity of 11.0 to 11.3 bp, suggesting that the chromosomal helical repeat is in this range in vivo. Repression increased significantly with decreasing inter-operator DNA length, indicating that the local Lac repressor concentration at O1 is crucial for tight repression. Maximal repression, attributed to stable DNA loop formation, was obtained at an operator spacing of 70.5 bp. Other repression maxima occurred at operator distances of 92.5 and 115.5 bp, corresponding to natural operator spacings in the lac and in the gal operon, respectively. Substitution of the auxiliary O(id) with the weaker binding lac operator O3 lowered repression efficiency, presumably due to the reduced local concentration of Lac repressor.

Base Sequence↗