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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 343 records · Page 19Linked to original sources
PubMed1996

Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases.

A retrospective immunohistological analysis of 100 patients with pT1-3 N0 and pT1-3 N1 gastric adenocarcinoma demonstrated a high frequency of micro-involvement in the removed lymph nodes. The presence of three or more tumour cells in more than 10 per cent of the lymph nodes was of significant prognostic value in the pN0 cases. Multivariate analysis identified micro-involvement as an independent prognostic factor. The results explain why patients benefit from lymphadenectomy even if the removed lymph nodes are not involved by tumour (pN0) in routine histological examination. The frequent occurrence of micro-involvement is a strong argument favouring routine D2 lymph node dissection in gastric cancer surgery in patients with lymph node metastasis.

Adult↗
PubMed1996

Genetic similarity among Arabidopsis thaliana ecotypes estimated by DNA sequence comparison.

DNA polymorphisms among Arabidopsis thaliana ecotypes are widely used as genetic markers in map-based cloning strategies. New PCR-based molecular markers do not only facilitate molecular mapping, but can also be used to obtain reliable sequence information for cladistic analyses. We have used CAPS (cleaved amplified polymorphic sequences) markers and a direct sequencing strategy to estimate genetic similarity among eighteen Arabidopsis ecotypes. Sequences at four loci, two from the nuclear and two from a non-nuclear genome, were analysed. For each ecotype more than 1000 bp of sequence information was obtained, and genetic similarity was calculated from a total of 35 polymorphic sites using a character-based approach. Divergence ranged from zero up to 50 discordant characters among the 72 characters defined by the polymorphisms. Separate calculations based on the nuclear and the non-nuclear sequences were performed and revealed a number of common features, including the existence of small clusters of very closely related ecotypes separated from each other by extensive sequence divergence. Our results provide information useful especially to investigators setting up crosses for chromosome landing strategies.

Arabidopsis↗
PubMed1996

Liver glycogen synthase deficiency: a rarely diagnosed entity.

UNLABELLED: Three children from two German families are described and the observation compared with the previously published three families comprising eight patients. The two index cases presented with morning fatigue, had ketotic hypoglycaemia when fasting which rapidly disappeared after eating, and hepatic glycogen deficiency and absent or very low hepatic glycogen synthase activity. Metabolic profiles comprising glucose, lactate, alanine, and ketones in blood were typical for hepatic glycogen synthase deficiency. Symptoms were rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and night-time feedings of suspension of uncooked corn (maize) starch. The discovery of oligosymptomatic and asymptomatic siblings suggests that there are more persons with undiagnosed hepatic glycogen synthase deficiency. CONCLUSION: Liver glycogen synthase deficiency is likely to be more common than is believed today. It should be sought in children who, before the first meal of the day, present with drowsiness, lack of attention, pallor, uncoordinated eye movements, disorientation or convulsions and who have hypoglycaemia and acetone in urine.

Age of Onset↗
PubMed1996

Macrophage-colony forming cells (M-CFC), with different sensitivities to colony stimulating factors, from peritoneal exudates and tissues of chronically inflamed mice.

OBJECTIVE AND DESIGN: To determine whether nonadherent macrophage precursors are present within the inflamed peritoneal cavity in mice, we analysed the mononuclear cell populations from different peritoneal tissues. OBJECTS: A group of 90 female mice BDF1 (C57BL/ 6 x DBA/2) was used for the study. Mononuclear cells were harvested from the peripheral blood, bone marrow, peritoneal exudate, omentum, mesentery, parietal peritoneum and diaphragm. TREATMENT: Mice were injected intraperitoneally with 0.2 ml of Freund's incomplete adjuvant. Animals were sacrificed at 6, 13, 16, 21 and 30 days. Three to six animals were examined for each time period. METHODS: Progenitor cell assay was performed in 1 ml of semi-solid agarose (0.3% Seakem GTG) DMEM which was supplied either with recombinant colony stimulating factors or with mesothelial cell-conditioned medium. RESULTS: Nonadherent macrophage-colony forming cells were present in all peritoneal compartments (35-140 precursor cells/5 x 10(4) mononuclear cells). Granulocyte/ macrophage-colony forming cells were found in the inflamed omentum. Combined simultaneous treatment with GM-CSF and M-CSF blocked the proliferation of the exudate and mesentery-derived macrophage precursors, but not other peritoneal tissue-derived macrophage precursors. Sequential stimulation with GM-CSF and M-CSF did not inhibit macrophage colony formation. CONCLUSIONS: GM-CSF can possibly influence the proliferative response induced by M-CSF. Nonadherent macrophage precursors recovered from different tissue compartments seem to differ in their sensitivity to growth regulation.

Animals↗
PubMed1996

A novel 5'-upstream mutation in the factor XII gene is associated with a TaqI restriction site in an Alu repeat in factor XII-deficient patients.

The factor XII gene from factor XII-deficient patients was screened for mutations at the genomic level. In patients negative for cross-reacting material, a T to C transition 224 bp upstream of exon 3 was identified (exon 3-224 (T --> C)) that creates an additional TaqI restriction site in intron B. This mutation is located within a putative hormone responsive element and within a B box promoter of an Alu repeat of the Sb0 family. The TaqI site is associated with a G to C transversion upstream of the transcription initiation site (exon 1-8 (G --> C)). We discuss the possible roles of these elements in factor XII gene regulation.

Adult↗
PubMed1996

The role of anti-p53-autoantibodies in pancreatic disorders.

CONCLUSION: Anti-p53-autoantibodies (a-p53-aabs) may suppress the development of distant metastases, but not lymph node metastases. This could explain the significantly prolonged survival of patients with UICC stage III tumors who have a-p53-aabs compared to those without a-p53-aabs. BACKGROUND: Mutation within the tumor suppressor gene p53 leads to increased intracellular p53 protein levels and an increased antibody formation against this molecule. Altered p53 has been proposed to be associated with poor prognosis, and the present study investigated whether the detection of a humoral response to p53 gives evidence for a prognostic or diagnostic parameter in pancreatic disorders. METHODS: We screened 145 patients with pancreatic cancer and 95 patients with chronic pancreatitis for the development of a-p53-aab via ELISA and Western-blotting. p53 expression was examined by immunohistochemistry. RESULTS: We found that 41% of the tissues of patients suffering from pancreatic carcinoma overexpressed p53, and 15.9% of the patients suffering from pancreatic cancer developed a-p53-aab. In pancreatic cancer, we could exhibit a significant correlation between grading, p53-overexpression, survival, and antibody response against p53. A-p53-aabs were significantly more frequent in patients with stage III tumors (tumors with lymph node metastases, but not distant metastases, p < 0.02).

Adult↗
PubMed1996

Long-term follow-up in pulmonary embolectomy: is NYHA (dyspnea) classification reliable?

In this retrospective investigation we carried out a thorough physical examination, ventilation/perfusion scintigraphy, echocardiography and lung function test in 19 of all 21 long-term survivors consecutively operated on for massive pulmonary embolism between 1968 and 1992. Two patients refused these investigations but were both asymptomatic. The mean follow-up was 8.4 years and 12 (57%) of the patients were in NYHA I and 6 (29%) in NYHA II. The three patients in NYHA III (there were none in class IV) underwent right heart catheterization and pulmonary angiography additionally. Our findings suggest that, generally, the results of scintigraphy, echocardiography, lung function tests and physical examination correspond to the subjective status expressed as NYHA (dyspnea) class, when evaluated in combination. However, in classes III and IV other causes of dyspnea apart from residual pulmonary vascular obstruction can be found. These may also occur in combination. We observed severe chronic obstructive lung disease, hemidiaphragmatic paralysis, obesity, pulmonary hypertension of unknown origin, atrial septal defect (ASD) and neurologic residual deficit with depressive state. Thus, in evaluating long-term results of pulmonary embolectomy with regard to vascular desobliteration, NYHA classification does not seem to be reliable for classes III and IV.

Adult↗
PubMed1996

Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins -1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty.

OBJECTIVE: Circulating IGF-I and IGF binding protein-3 (IGFBP-3) levels both increase in puberty where growth velocity is high. The amount of free IGF-I is dependent on the IGF-I level and on the concentrations of the specific IGFBPs. Furthermore, IGFBP-3 proteolysis regulates the bioavailability of IGF-I. However, the concentration of free IGF-I and possible IGFBP-3 proteolytic activity in puberty has not previously been studied. SUBJECTS AND MEASUREMENTS: We investigated serum levels of easily dissociable IGF-I concentrations and ultrafiltrated free IGF-I levels by specific assays in 60 healthy boys and in 5 boys with precocious puberty before and during GnRH agonist treatment. In addition, total serum IGF-I, IGFBP-1 and IGFBP-3 levels as well as IGFBP-3 protease activity were determined. RESULTS: Free (dissociable and ultrafiltrated) IGF-I concentrations were significantly higher in pubertal boys than in prepubertal children and correlated significantly with the molar ratio between IGF-I and IGFBP-3 (r = 0.69, P < 0.0001 and r = 0.54, P = 0.0008, respectively) and inversely with IGFBP-1 (r = -0.47, P < 0.0001 and r = -0.43, P = 0.0003, respectively). Multiple regression analysis suggested that IGFBP-3 level, and not IGFBP-1, was the major determinant of the free IGF-I serum level in normal boys. Free IGF-I levels were elevated in boys with precocious puberty and decreased during GnRH treatment. IGFBP-3 proteolysis was constant throughout puberty (mean 20%). CONCLUSIONS: We conclude that easily dissociable and ultrafiltrated free IGF-I serum levels are increased in boys with normal and precocious puberty and suggest that the increased free IGF-I serum concentration in puberty primarily reflects changes in total concentrations of IGF-I and IGFBPs secondary to increased GH secretion, but that it is not influenced by changes in IGFBP-3 proteolysis.

Adolescent↗
PubMed1996

Doppler assessment of flow velocity in the uterine artery during pubertal maturation.

The aim of this study was to investigate the possible changes in uterine artery flow velocity during puberty and young adulthood. In a cross-sectional study, 133 healthy volunteers aged 6.7 to 25.4 years were investigated. Pubertal development according to the Tanner classification was recorded in each subject. Uterine arteries were visualized by transabdominal color-coded ultrasound. Maximum, minimum and time averaged maximum flow velocities were measured and the pulsatility index (PI) was calculated electronically. When flow velocity was compared between patients at different rates of pubertal development, we found that the average velocity increased from Tanner breast stages I and II to V, followed by a slight decrease in adults (p < 0.0001). The PI varied significantly from stage I to adult (p < 0.0001). The PI was similar in breast stage I, stage II and in adults, with median 4.7 (range 2.7-8.5), 6.1 (range 3.0-7.8) and 4.3 (range 1.9-8.1), respectively. The PI decreased in stages III and IV to 2.6 (1.8-8.4) and 2.8 (1.2-7.9), respectively, whereas stage V was intermediate, at 3.7 (1.1-6.3). The variance of PI was independent of age. In summary, we demonstrated a significant increase in the uterine artery flow velocity during puberty. Furthermore, a significant decline in vascular resistance expressed by the PI was observed in the mid-pubertal period, reflecting increasing blood flow to the rapidly growing uterus.

Adolescent↗
PubMed1996

[Hysteroscopic treatment of tubal pregnancy by intratubal injection of methotrexate].

The treatment of 3 non-ruptured tubal pregnancies by hysteroscopic intratubal injection of methotrexate was reported. In all 3 cases the beta-hCG serum levels decreased after injection during clinical, serological and sonographical control. In 2 patients the tubes were patent at a later control. In selected cases the intratubal administration of methotrexate via hysteroscopy is an alternative minimal invasive treatment.

Adult↗
PubMed1996

[Early diagnosis of congenital and acquired intrauterine causes of abortion by post-abortion hysteroscopy].

A prospective study was conducted on the incidence of intrauterine pathology after abortions diagnosed by post-abortion hysteroscopy. In 80 patients outpatient hysteroscopy was performed 8-12 weeks after a dilatation and curettage for incomplete or missed abortions. Intrauterine pathological changes were found in 40 patients. There were 10 cases of uterus subseptus/ bicornis and 7 of uterus arcuatus, 2 submucous myoma and 1 corpus polyp. Intrauterine adhesions were diagnosed in 20 patients. The incidence of intrauterine adhesions was about the same after incomplete abortions and after missed abortions, but in patients with recurrent abortions the incidence was significantly higher than in patients after the first abortion (27.8% versus 14.9%). Post-abortion hysteroscopy is a simple and useful method for early diagnosis of congenital and acquired intrauterine pathology after abortions.

Abortion, Habitual↗
PubMed1996

Induction of steroidogenic enzymes by potassium in cultured rat zona glomerulosa cells depends on calcium influx and intact protein synthesis.

The effects of a calcium channel blocker (nifedipine) and a protein synthesis inhibitor (cycloheximide) on the induction of four steroidogenic cytochromes P450 (CYP11B2, CYP11B1, CYP11A1, and CYP21A1) by an elevated extracellular potassium concentration were studied in cultured rat zona glomerulosa cells. Each of these two pharmacological agents completely inhibited the initiation of CYP11B2 expression and aldosterone biosynthesis in response to a high extracellular potassium concentration (18 mM). They also suppressed the potassium-induced increases in CYP11B1, CYP11A1, and CYP21A1 messenger RNA levels. Increases of these latter parameters elicited by ACTH were also suppressed by cycloheximide but were not affected by nifedipine. According to these experiments, calcium is an important second messenger mediating the effects of a high extra-cellular potassium concentration on the expression of genes encoding steroidogenic enzymes in rat zona glomerulosa cells. Because these effects also depend on an intact protein synthesis, an unknown labile regulatory protein seems to play an important role in the intracellular signal transmission from the plasma membrane to the genome.

Adrenocorticotropic Hormone↗
PubMed1996

Short photoperiod-dependent down-regulation of thyrotropin-alpha and -beta in hamster pars tuberalis-specific cells is prevented by pinealectomy.

Hamster hypophyseal pars tuberalis (PT)-specific cells are characterized by the expression of common alpha-chain and TSH beta. Immunoreactivity for these subunits and the morphology of these cells are known to exhibit remarkable seasonal changes. The high density of melatonin (Mel) receptors on PT-specific cells leads to the supposition that fluctuations in circulating Mel levels induced by photoperiodic signals are a crucial factor for the morphological alterations. To more closely investigate transcriptional and translational activities in PT-specific cells, we cloned and sequenced hamster alpha and TSH beta complementary DNA fragments and assessed messenger RNA/protein formation by in situ hybridization and immunocytochemistry under short and long photoperiod and in pinealectomized animals kept in short photoperiod. Hamster common alpha-chain and TSH beta exhibited high sequence homology with the corresponding rat hormones [94% (alpha-chain) and 90% (TSH beta) on the nucleotide level and 100% (alpha-chain) and 96% (TSH beta) on the amino acid level]. Immunocytochemical staining with antibodies directed against the common alpha-chain and TSH beta revealed a reduced immunoreactivity of PT-specific cells under short photoperiod, but this was not altered in pinealectomized animals exposed to short photoperiod. In situ hybridization against both hormonal subunits paralleled these changes, with a dramatic decrease in hormonal messenger RNA in short photoperiod. This regulatory influence was also blocked in pinealectomy. Taken together, these results demonstrate that transcription and translation of hormonal subunits are regulated by photoperiod in hamster PT-specific cells, whereas expression remained unchanged in short photoperiod if pinealectomy was performed. We, therefore, conclude that in hamsters, the Mel Signal not the light regimen per se, is a direct or indirect Zeitgeber for the transduction of photoperiodic information to the secretory activity in this pituitary cell type.

Amino Acid Sequence↗
PubMed1996

Potassium induces multiple steroidogenic enzymes in cultured rat zona glomerulosa cells.

The effects of the extracellular potassium concentration on the expression of four steroidogenic cytochromes P-450 (CYP11B2, CYP11B1, CYP11A1, and CYP21A1) in cultured rat adrenal zona glomerulosa cells were studied by Northern blot analysis. At a potassium concentration of 6.4 mM, the CYP11B2 messenger RNA (mRNA) level and aldosterone production were undetectable. Upon increasing the potassium concentration to 18 mM, CYP11B2 mRNA and aldosterone production became measurable and reached a plateau within 4 days. The high potassium concentration also caused distinct increases in the levels of CYP11B1, CYP11A1, and CYP21A1 mRNA, comparable to those induced by ACTH. ACTH did not affect the CYP11B2 mRNA level at the lower potassium concentration. In zona fasciculata cells, CYP11B2 expression was not inducible by potassium; CYP11B1, CYP11A1, and CYP21A1 mRNA levels increased in response to ACTH, but not in response to a high potassium concentration. According to these results, potassium initiates CYP11B2 biosynthesis most likely at the level of transcription or by increasing mRNA stability. Potassium also has a zona glomerulosa-specific inductive effect on three other steroidogenic enzymes.

Adrenal Cortex Hormones↗
PubMed1996

Male reproductive health and environmental xenoestrogens.

Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

Animals↗
PubMed1996

Electric myocardial impedance registration in humoral rejection after heart transplantation.

BACKGROUND: Because of the absent lymphocyte infiltrate, humoral-mediated rejection after heart transplantation is not diagnosed by the usual staining technique (hematoxylin-eosin method) of the endomyocardial biopsy specimen. However, humoral rejection is characterized by a distinct myocardial edema caused by capillary leakage. Because tissue edema increases the electric myocardial impedance of the corresponding tissue compartment the electric myocardial impedance method should be able to detect these episodes more reliably than biopsy. METHODS: To evaluate this hypothesis eight DLA-matched beagle dogs were subjected to heterotopic neck heart transplantation after multiple sensitization by skin grafts of the heart donor. For electric myocardial impedance registrations rectangular impulses (wide 1 msec) were applied over two intramyocardial electrodes and the impulse response was registered. Day-to-day comparisons were made and an increase of electric myocardial impedance of 10% or more was used as an indicator of rejection. To assess the influence of edema caused by electrode implantation, cortisone administration, narcosis, ischemia, or reperfusion on the electric myocardial impedance, identical electrodes were implanted in the native hearts of five additional dogs via lateral thoracotomy. These animals each received 100 mg methylprednisolone between postoperative days 20 and 22 and underwent heterotopic neck heart transplantation on postoperative day 28 without previous sensitization (protocol 2). Electric myocardial impedance electrodes were also implanted in these allografts (protocol 3). After transplantation myocardial biopsies were done every 2 days and the samples graded according to the International Society for Heart and Lung Transplantation classification in all dogs. RESULTS: Despite triple-drug immunosuppression (cyclosporine A, prednisolone, azathioprine) humoral rejection developed in all sensitized dogs as established by immunofluorescent staining of myocardial biopsy samples and functional deterioration. All episodes were diagnosed by electric myocardial impedance (sensitivity 100%), whereas only in one case the biopsy specimen was positive (International Society for Heart and Lung Transplantation grade > 1) (sensitivity 12.5%). All eight episodes could be treated successfully, that is, myocardial performance and electric myocardial impedance showed an immediate and full recovery. During the first 12 days none of the nonsensitized dogs exhibited rejection. Protocol 2 indicated that narcosis and the administration of cortisone did not per se have an influence on electric myocardial impedance and the influence of electrode implantation was negligible. Contrarily, edema caused by ischemia and reperfusion during transplantation (protocols 1 and 3) led to a significant increase in electric myocardial impedance. However, after 2 days this edema had faded away such that it no longer disturbed rejection diagnosis. CONCLUSION: We conclude that the registration of the electric myocardial impedance diagnoses humoral rejection episodes after heart transplantation not only reliably but also early, that is, before the onset of irreversible graft damage.

Animals↗