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Biomedical subjects

J Müller

Publications and source records attributed to J Müller.

At least 415 records · Page 23Linked to original sources
PubMed1994

[Epidemiology of deep-seated, domestic mycoses].

The opportunistic character of deep-seated mycoses depends on granulocyte-based defense in candidosis and aspergillosis. Therefore, haematological, patients represent the group of highest risk. Mucocutaneous candidosis is controlled by macrophages. Cryptococcus neoformans forces its way into the human host via causing an imbalance in the CD8-T-cell suppressor system. An aggravating synergism exists between Cryptococcus invasion and HIV-infection which explains the severe course of cryptococcosis in AIDS patients. The following pathways of transmission are observed in opportunistic mycoses: In aspergillosis and cryptococcosis humans are infected by inhalation of fungal propagules and primary settlement of the pathogens in the lungs, a site from which dissemination may occur. Exposure to Aspergillus conidiospores is ubiquitous and can be remarkably intensified by construction activities. Exposure to Cr. neoformans is geographically highly variable; not all humans are exposed. Candidosis emerges from the commensal reservoir of the human gastrointestinal tract, caused by translocation of the pathogens from the GI tract into the blood-lymph circulation or by anal/oral or oral-oral infection respectively. The incidence of deep-seated mycoses in the northern hemisphere is estimated to be 600 mycosis situations per million population per year. The estimate for Germany amounts to 50,000 mycoses patients per year, i.e. 45,000 candidosis and 5,000 aspergillosis situations as well as 100 each of cryptococcal and other mycotic diseases. Beyond that the number of AIDS-patients with cryptococcosis in Germany amounts to about 200 cases.

AIDS-Related Opportunistic Infections↗
PubMed1994

Total intravenous anaesthesia with sufentanil-midazolam for major abdominal surgery.

Haemodynamic and endocrine stress responses were compared during total intravenous anaesthesia with sufentanil and midazolam or fentanyl and midazolam in patients undergoing elective major abdominal surgery. Twenty-two ASA I and II patients were allocated randomly to receive sufentanil (induction 1.5 micrograms kg-1 plus infusion 1.5 micrograms kg-1 h-1) or fentanyl (induction 10 micrograms kg-1 plus infusion 10 micrograms kg-1 h-1) supplemented with 0.15 microgram kg-1 sufentanil or 1 microgram kg-1 fentanyl as necessary. Midazolam was infused to obtain plasma concentrations of 500-600 ng ml-1. Ventilation was with oxygen-enriched air. The opioid infusion was reduced post-operatively by half and benzodiazepine effects were reversed by titration with flumazenil. Mean arterial pressure, heart rate and cardiac index decreased in both groups after induction (cardiac index: sufentanil 4.94 +/- 0.45 to 2.99 +/- 0.18 litre min-1; fentanyl 4.97 +/- 0.45 to 3.71 +/- 0.36 litre min-1), but all returned to baseline during surgery. With sufentanil; mean arterial pressure was lower throughout the study period, and heart rate was lower intra-operatively. Oxygen uptake decreased in both groups after induction (sufentanil 289 +/- 29 to 184 +/- 21 ml min-1; fentanyl 318 +/- 32 to 216 +/- 32 ml min-1) and remained low with sufentanil until flumazenil was given. Adrenaline concentrations increased in both groups but there was no intergroup difference. The median noradrenaline concentration was lower intra-operatively with sufentanil (0.47 nmol litre-1 (range 0.06-6.77)) than with fentanyl (0.73 nmol litre-1 (0.07-4.58)). Cortisol, glucose and lactate concentrations increased in both groups. Bradycardia occurred in four patients with sufentanil and in three with fentanyl. There were two cases of marked thoracic rigidity with sufentanil and one with fentanyl.

Abdomen↗
PubMed1994

[Pathogenesis, immunobiology and epidemiology of cryptococcosis].

Cryptococcus neoformans is taken up by the human host via the respiratory tract. The polysaccharide capsule is regarded as the pathogenetic principle inhibiting phagocytosis of the fungus by cells of the unspecific host defense. Unspecific opsonization of Cr. n. by early phase proteins causes a rapid and successful elimination in the non-compromised host. In case of non-elimination the presence of Cr. n. capsule antigen in excess results in a downregulation of antibody formation thereby inhibiting specific opsonization. Furthermore the blockade of specific T cells and cytotoxic cells by means of free antigen and/or immunocomplexes causes a downregulation of the cellular immunity: Cr. n. antigens of different character induce T suppressor cells inhibiting cellular immunity via a cascade of effector cells and soluble factors. The AIDS patient enters cryptococcosis in a state comparable to a Cr. n.-infected non-AIDS patient whose cellular immunity is already downregulated by this mycosis itself. Both phenomena--the mycosis-induced downregulation of cellular immunity as well as the AIDS-specific lack of CD4 helper cells and its consequences--act, therefore, synergistically in the same pathogenetic direction. This explains the fulminant development and sequel of cryptococcosis typical with AIDS patients. Most probably each exposition of an AIDS patient to Cr. n. results in clinically manifest cryptococcosis. The frequence of cryptococcosis in AIDS is, therefore, reflecting the general exposure of humans to Cr. n. in a given region. Cryptococcosis in AIDS is at least about 1000x more frequent than cryptococcosis in non-AIDS individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

[Anti-hypertensive therapy in pregnancy-induced hypertension with urapidil].

Urapidil is an antagonist of postsynaptic alpha 1 receptors, which leads to a diminution of the increased blood pressure by reducing the peripheral vascular resistance. With this pilot study we examined, whether it is possible to reduce the pregnancy-induced-hypertension with urapidil postpartum. The postpartum dosage of dihydralazine was diminished step by step and finally discontinued. We started i.v. treatment with urapidil at a diastolic blood pressure of more than 100 mm Hg. We observed a declining blood pressure in all cases without any tachycardia or serious side effects. Further studies will have to classify the rank of urapidil in the treatment of hypertension in preeclampsia.

Antihypertensive Agents↗
PubMed1993

[Acceptance, side-effects and reactive ability after medicamentous anxiolysis with midazolam. A prospective study with 519 gastroscopy and 506 colonoscopy patients].

In a prospective study 519 patients had gastroscopy (393 with and 126 without midazolam-premedication) and 506 patients had colonoscopy (377 with and 129 without midazolam-premedication) to evaluate acceptance, adverse reactions and reactivity after midazolam-premedication in outpatients immediately and 24 hours later by standard telephone interview. Patients could choose whether they would have midazolam or not. Normally 2 mg midazolam for gastroscopy and 4 mg for colonoscopy were given intravenously directly before endoscopy. 71.5% of gastroscopy and 75.3% of colonoscopy patients who received midazolam afterwards accepted endoscopy only with premedication. 27.7% of our gastroscopy and 14.1% of the colonoscopy patients who than received midazolam were beforehand unable to decide about premedication by themselves. 27.5% of the gastroscopy and 13.8% of the colonoscopy group were persuaded to have midazolam by the doctor examining. 12.7% of our gastroscopy- and 27.1% of our colonoscopy-patients who wished to have midazolam were persuaded to withdraw from it. There were no cardio-pulmonal complications but fatigue was found in 35.4% of the gastroscopy Patients with and 11.9% of those without premedication; colonoscopy patients: 50.4% with and 34.9% without premedication. The incidence of headache was: gastroscopy patients: 6.4% vs. 4%; colonoscopy patients: 11.1% vs. 10.9%. Dizziness: gastroscopy patients: 6.4% vs. 3.2%; colonoscopy patients: 7.6% vs. 7%. Nausea and vomiting were rare (0 to 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis.

BACKGROUND: Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell neoplasia would be strengthened by the finding of antigenic similarity between fetal germ cells, CIS cells, and invasive testicular germ cell tumors. METHODS: Monoclonal antibody (MoAb) TRA-1-60 raised against a human embryonal carcinoma cell line was immunohistochemically tested on 21 fetal gonads (11 male gonads and 10 female gonads; 11th-24th week of gestation). In addition, TRA-1-60 was tested on tissue from 27 testes with CIS, 11 testes with invasive testicular cancer, and 24 adult and 4 infant testicular control specimens. RESULTS: Expression of TRA-1-60 was found in germ cells of six female and two male fetal gonads. In addition, 26 of 27 adult human testes with CIS, 7 of 8 seminomas, and 3 of 3 embryonal carcinomas were TRA-1-60 positive. CONCLUSIONS: The study demonstrated an antigenic link between fetal germ cells, cells of CIS and seminomas, and embryonal carcinomas. The results provided additional evidence for the hypothesis that testicular neoplasia arises during early fetal life and CIS cells are malignant fetal gonocytes.

Adult↗
PubMed1993

Detection of recombinations between c-myc and immunoglobulin switch alpha in murine plasma cell tumors and preneoplastic lesions by polymerase chain reaction.

Virtually all murine plasmacytomas carry chromosomal translocations that activate c-myc. The predominant (approximately 90%) c-myc-activating chromosomal translocation in pristane (2,6,10,14-tetramethylpentadecane)-induced plasmacytomas in BALB/c mice is a reciprocal translocation t(12;15) in which an immunoglobulin heavy-chain switch sequence is joined to the 5' region of c-myc. The most common switch region involved is S alpha. We developed a direct PCR method to screen for recombinations between c-myc and S alpha. The critical step in establishing the method was the cloning and sequencing of the 5' flank of C alpha, a region with a reduced number of switch repeats that is much more favorable for designing specific PCR primers than the highly repetitive S alpha region. In applying this PCR method, we detected translocation-specific junction fragments in transplanted (10/16, 63%) and primary (5/15, 33%) plasmacytomas. Moreover, the sensitivity of a nested version of that technique allowed us to discern rare t(12;15)s in BALB/c mice in the preneoplastic stage of plasmacytoma-genesis (8/20 mice, 40%) as early as 30 days after administration of pristane. We conclude that t(12;15) is the probable primary, if not initiating, oncogenic step in plasmacytomagenesis.

Animals↗
PubMed1993

Modulation of the H2O2-induced SOS response in Escherichia coli PQ300 by amino acids, metal chelators, antioxidants, and scavengers of reactive oxygen species.

The SOS chromotest is a simple colorimetric genotoxicity assay that monitors DNA repair by measuring the induction of the gene sfiA in Escherichia coli K-12. E. coli PQ300, a diagnostic SOS tester strain for the detection of oxidative genotoxins, carries a mutation in a key gene for antioxidative defense, oxyR. This mutation renders PQ300 more sensitive to oxidative genotoxins, particularly to H2O2. We found that induction of the SOS response by H2O2 in E. coli PQ300 is dependent on the composition of the incubation medium; a substantially reduced response was obtained in minimal phosphate buffered saline (PBS) as opposed to complex Luria broth (LB) medium. Supplementation of PBS with histidine or cysteine stimulated H2O2-induced SOS induction to levels exceeding those found in LB medium. Low concentrations of glutathione (20-70 microM) also enhanced the H2O2-induced SOS response in E. coli PQ300, whereas higher concentrations (> 150 microM) were protective. Preincubation of tester cells with the chelators o-phenanthroline, 2,2-dipyridyl, and ethylenediaminetetraacetic acid (EDTA) protected cells from the effects of H2O2, although EDTA was only partially effective. Pretreatment of PQ300 with the antioxidant ascorbic acid or the hydroxyl radical scavenger dimethyl sulfoxide also diminished the SOS response, whereas mannitol and glucose were ineffective. The results show that the net effect of H2O2-induced DNA damage is influenced by the balance of oxidative and antioxidative factors and, furthermore, can be modulated by constituents of the extracellular milieu.

Amino Acids↗
PubMed1993

In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus.

The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIDS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIVmac251 strain as well as the infectious clone (SIV239). Infectious virus was produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.

Animals↗
PubMed1993

Cytogenetic differences between intestinal and diffuse types of human gastric carcinoma.

This study concerns the cytogenetics of 23 gastric carcinomas, classified histologically as intestinal or diffuse types. In carcinomas of the diffuse type, the only numerical changes observed were Y chromosome loss associated with X-chromosome disomy in four of seven male patients. A 46, XX karyotype without recognizable alterations was observed in three of five female patients, and rare structural changes in diffuse carcinomas involved chromosomes 1 and 18. In contrast, intestinal type tumors were exclusively aneuploid, with chromosome modes ranging from 48 to 84. The most consistent change was trisomy 20 in seven of 11 patients, each of which displayed a number of both single and clonal structural aberrations. Frequent structural changes were translocations involving chromosome 13 (including a putative isochromosome 13q in three of 11 patients), and alterations in chromosomes 1, 6 and 12. This study therefore suggests that diffuse and intestinal types of gastric carcinomas do not share a common sequence of genetic changes. The tumor with the worse prognosis (diffuse type) is surprisingly diploid, with uniform X-disomy in both males and females. The clinically less aggressive tumors (intestinal type) show multiple changes, both numerical and structural, of which some are reminiscent of changes seen in tumors of the lower gastrointestinal tract. Cytogenetics may thus be a valuable adjunct in establishing the diagnosis, classification, and prognosis of gastric carcinomas.

Adult↗
PubMed1993

Early phenotypic and functional alterations in lymphocytes from simian immunodeficiency virus infected macaques.

Phenotypic and functional changes in lymphocytes from rhesus monkeys (Macaca mulatta) were investigated during the first 6 months after infection with SIV mac 32H. Animals preimmunized with keyhole limpet hemocyanin (KLH) were sacrificed 1, 3, 6, 12, and 24 weeks post infection. Subset composition and function of lymphocytes from blood, spleen, lymph node and thymus were analysed. In addition to a rapid decline in CD4/CD8 ratios, a massive reduction in CD29+ CD4+ cells was seen in the periphery. Although depletion of this subset was observed throughout the course of this experiment, the loss of proliferative T cell responses was most pronounced very early after infection and partially recovered after Month 3. Polyclonal cytotoxic responses were only slightly affected. In the thymus, a gradual, but moderate loss of CD4+CD8+ immature thymocytes, and a relative increase in both CD4+ and CD8+ mature subsets was observed. Infectious virus was readily recovered from homogenates of lymph node and spleen, but not of thymus tissue. Interestingly, however, virus was detected in thymocytes from all infected animals by cocultivation with a simian immunodeficiency virus (SIV) susceptible cell line.

Animals↗
PubMed1993

Detection of subclinical motor dysfunctions in early symptomatic HIV infection with topographical EEG.

Motor dysfunctions are amongst the earliest and most common signs of brain impairment caused by human immunodeficiency virus (HIV) infection. Topographical EEG was recorded in patients both with asymptomatic and early symptomatic infection (without acquired immunodeficiency syndrome (AIDS) defining illness), as well as in seronegative controls under resting and motor activation conditions. While patients' motor performance did not differ from control values, the EEG showed a consistent increase in rhythmic activity in Theta, Alpha and Beta frequency bands in Symptomatics. This amplitude increase was evident in different topographical regions during resting states as compared with motor activation, findings which suggest concurrent involvement of several motor areas possibly due to a functional impairment in subcortical integratory mechanisms. Comparing motor task and baseline both patient groups showed less consistent patterns of task-related EEG amplitude reduction than found in the control group. Here topographical EEG in connection with motor activation procedures was found to be more sensitive than behavioral measures of motor performance and offers a technique to assess treatment effects before the development of motor abnormalities in patients with HIV infection.

Adult↗
PubMed1993

Postnatal development of ATPase-ADPase activities in synaptosomal fraction from cerebral cortex of rats.

ATPase-ADPase activities in synaptosomes from cerebral cortex was measured in rats of various ages (0-, 7-, 10-, 14- and 21- and 60-90-days). The activities (nmol Pi/min/mg) increased steadily from birth, reaching maximum values at 21 days of age. The increase was primarily due to increases in Vmax; the Km values are the same from birth until adult age. The developmental profile was similar for ATPase-ADPase activities and acetylcholinesterase from the same fraction. Several specific ATPase inhibitors and Ap5A (P1P5-di(adenosine-5)-pentaphosphate) did not interfere with the hydrolysis of ATP and ADP at all ages studied, suggesting that classical ATPases and adenylate kinase were not involved in the degradation of both nucleotides by synaptosomal fraction in the assay conditions. Other phosphatases were also ruled out. It is conceivable that ATPase-ADPase activities play an important role in neurotransmitter metabolism.

Adenosine Triphosphatases↗
PubMed1993

Two types of cytochrome P-450(11 beta) in rat adrenals: separate regulation of gene expression.

Northern blot hybridization with specific oligonucleotide probes was used for assaying steady state concentrations of the mRNAs encoding the two types of rat cytochrome P-450(11 beta), i.e. CYP11B1 (non-aldosterone-producing) and CYP11B2 (aldosterone-producing). The zona glomerulosa level of CYP11B2 mRNA was raised by potassium repletion or sodium restriction and was lowered by potassium depletion or by the administration of deoxycorticosterone, ACTH or dexamethasone. In all zones of the adrenal cortex, the CYP11B1 mRNA level was decreased upon dexamethasone treatment. Only in the zona glomerulosa it was increased upon mineralocorticoid treatment and decreased upon potassium repletion or sodium restriction. According to this evidence, the expression of the two genes encoding the two isozymes (CYP11B1 and CYP11B2) in rat zona glomerulosa cells is separately regulated. Whereas CYP11B2 expression is controlled mainly by angiotensin II and extracellular potassium, ACTH is the major but not the only factor controlling CYP11B1 expression in these cells.

Adrenal Cortex↗
PubMed1993

Separate induction of the two isozymes of cytochrome P-450(11) beta in rat adrenal zona glomerulosa cells.

In the rat adrenal cortex, two isozymes of cytochrome P-450(11) beta (CYP11B1 and CYP11B2) have been identified. They are encoded by two different genes with a homology much higher in their coding than in their 5'-flanking regions. CYP11B1 is found in all the zones of the gland and catalyzes a single hydroxylation of deoxycorticosterone (DOC) in the 11 beta- or the 18-position. CYP11B2 is produced exclusively in the zona glomerulosa and catalyzes all three reactions involved in the conversion of DOC to aldosterone. In vivo and in vitro, the expression of the genes encoding CYP11B1 and CYP11B2 is regulated by two separate control systems which appear to operate both independently and interdependently. In vivo zona glomerulosa expression of CYP11B1 was enhanced by ACTH treatment or potassium depletion and was lowered by potassium repletion. CYP11B2 expression disappeared upon potassium depletion or ACTH treatment, but reappeared during potassium repletion. In vitro, only CYP11B1 activity was detectable and responsive to ACTH treatment in zona glomerulosa cells cultured at a potassium concentration of 6.4 mmol/l. Aldosterone biosynthetic activity and mRNA encoding CYP11B2 could be detected only after at least 1 day of exposure to a high extracellular potassium concentration (> or = 12 mmol/l).

Adrenocorticotropic Hormone↗
PubMed1993

Final steps of aldosterone biosynthesis: molecular solution of a physiological problem.

The final two steps of aldosterone biosynthesis play a key role in the complex physiological adaptation of aldosterone secretion to changes in sodium and potassium content of the mammalian organism. The nature and identity of the enzyme catalyzing these steps have only recently been established. In the rat as well as in the human adrenal, two types of cytochrome P-450(11 beta) are encoded by two different genes. The major type of the enzyme catalyzes only the conversion of deoxycorticosterone to corticosterone or 18-hydroxy-11-deoxycorticosterone; it is present in all the zones of the adrenal cortex. The second type of the enzyme catalyzes the three steps involved in the conversion of deoxycorticosterone to aldosterone and occurs only in the zona glomerulosa. In rat zona glomerulosa cells, separate control systems independently regulate the expression of the two genes, according to long-term in vivo experiments or to experiments with primary cultures of zona glomerulosa cells. Expression of the non-aldosterone-producing enzyme is induced by ACTH, whereas the expression of the aldosterone-producing enzyme is dependent on the extracellular potassium concentration.

Aldosterone↗