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Biomedical subjects

N Michael

Publications and source records attributed to N Michael.

At least 19 recordsLinked to original sources
PubMed2004

["Mild" cranio-cerebral trauma occasionally have grave psychic sequelae].

Cranial injuries appear as neurological symptoms such as unconsciousness and focal neurological deficits. Mild cranio-cerebral traumas, that is, brain injuries without a serious neurotraumatologic symptom complex occuroften in practice. Nevertheless, even slight injuries, above all in the frontal cortical brain areas, can be accompanied by characteristic psycho-organic symptoms ("mild cognitive impairment" in the form of a "pseudoneurasthenic syndrome"). They are detected only after a thorough clinical psychiatric examination with a concomitant neuropsychological test. The diagnostics should be carried out as earlyas possible in order to identify and to immediately treat the respective disease. Chronicity and development of a depressive disorder can be, thus, prevented.

Brain Concussion↗
PubMed2004

N-acetylaspartate levels of left frontal cortex are associated with verbal intelligence in women but not in men: a proton magnetic resonance spectroscopy study.

The left frontal cortex plays an important role in executive function and complex language processing inclusive of spoken language. The purpose of this work was to assess metabolite levels in the left and right prefrontal cortex and left anterior cingulum by proton magnetic resonance spectroscopy and relate results to verbal intelligence (Wechsler Adult Intelligence Scale revised) in a sample of college-educated healthy volunteers (dorsolateral prefrontal cortex [DLPFC]: n=52, 23 females, and left anterior cingulum: n=62, 22 females; age range: 20-75 years). In women only, N-acetylaspartate in the DLPFC and in the left anterior cingulate cortex was positively correlated with vocabulary scores. Our data support the hypothesis of existing gender differences regarding the involvement of the left frontal cortex in verbal processing as reflected in different correlations of specific metabolites with verbal scores.

Adult↗
PubMed2004

The impact of the selective monoamine reuptake inhibitors reboxetine and citalopram on visually-evoked event-related potentials in depressed patients.

OBJECTIVE: The aim of our study was to assess the possible relationship between event-related potentials (ERP) and serotonergic or noradrenergic activity in depression. Therefore, we were interested in the impact of different monoamine reuptake inhibitors on ERP. METHODS: Thirty-six inpatients with major depression were treated with either reboxetine (n = 17) or citalopram (n = 19) in a prospective randomized study. Before and after four weeks of treatment, visually-evoked ERP were investigated. Twenty-two patients completed the study. Monoaminergic function was determined by oral reboxetine and citalopram challenge tests. RESULTS: P3 latency significantly decreased after a four-week treatment with either drug. There was no significant difference in the decrease of P3 latency between both drugs. We detected a significant inverse correlation between serotonergic hypofunction before treatment and the P3 latency (r = -0.739, p = 0.001). CONCLUSIONS: These results show that, in depressed patients, the P3 latency is decreased by antidepressive treatment. Furthermore, the results suggest that P3 latency might depend on the serotonergic rather than the noradrenergic system.

Adolescent↗
PubMed2003

Metabolic changes within the left dorsolateral prefrontal cortex occurring with electroconvulsive therapy in patients with treatment resistant unipolar depression.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) is involved in the pathophysiology of major depression. In particular, metabolic (functional hypometabolism) and structural alterations have been described. In this study metabolic changes within the DLPFC of severely depressed patients before and after electroconvulsive therapy (ECT) were evaluated by proton STEAM spectroscopy (1H-MRS). METHOD: Twelve severely depressed patients with a diagnosis of major depressive episode, unipolar with melancholic features (DSM-IV), were enrolled, and the left dorsolateral prefrontal cortex (DLPFC) was investigated before and after unilateral ECT by 1H-MRS. Three of the four non-responding patients were remeasured a third time after a combined ECT/antidepressant pharmacotherapy. The results were compared with 12 age- and gender-matched controls. RESULTS: In depressed patients reduced glutamate/glutamine (Glx) levels were measured pre-ECT; Glx concentrations correlated negatively with severity of depression. After successful treatment, Glx increased significantly and levels no longer differed from those of age-matched controls. CONCLUSIONS: Our results indicate that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in glutamate/glutamine metabolism, which can be reversed by successful ECT.

Aged↗
PubMed2002

Visualization of auditory habituation by fMRI.

The aim of this study was to measure and quantify habituation phenomena within the auditory cortex of 18 healthy subjects by means of fMRI. Auditory stimulation was done by digitally generated pulsed (nu = 5 Hz) 800-Hz sine tones with three alternating ON (duration 2 min) and OFF (1 min) periods. Binaural stimulation resulted in symmetrical bihemispheric activation of the auditory cortex. Our data revealed a characteristic signal decay to repeated acoustic stimulation: the response to the second was even more pronounced, and the third stimulation block significantly lower compared to the first. Thus, our data clearly demonstrate habituation phenomena, probably due to reduced neuronal activity with increased duration and/or frequency of stimuli.

Acoustic Stimulation↗
PubMed2001

Somatic hypermutation of immunoglobulin and non-immunoglobulin genes.

Somatic hypermutation (SHM) of immunoglobulin (Ig) genes is a highly specific mechanism restricted to B lymphocytes during only a few cell generations. Data presented here suggest that transcription of the target genes is required, but not sufficient for SHM. Presumably, cis-acting elements, such as those present in the Ig enhancers, are required to target a mutator factor (MuF) to Ig and human BCL-6 genes. It is postulated that the MuF travels with the transcribing RNA polymerase and is deposited on the target gene when the polymerase pauses. Point mutations, and rare deletions and insertions, are created by the combined actions of MuF and certain DNA polymerases. A subset of the mutations is corrected during SHM by DNA mismatch repair.

Animals↗
PubMed2000

Reduction of plasma catecholamines in humans during clinically controlled severe underfeeding.

BACKGROUND: Sympathetic hyperactivity is one factor for alterations encountered in the plurimetabolic syndrome, a cluster of metabolic abnormalities including obesity, hyperlipidemia, sometimes hyperglycaemia, and hypertonia. It was interesting to know if prolonged severe underfeeding (230 kcal/day) leads to decreases in catecholamines in those patients. METHODS: The plasma concentrations of catecholamines in patients (n = 16) suffering from plurimetabolic syndrome were studied before and during a 16-day period of medically controlled severe underfeeding (230 kcal/day) at rest and in response to exercise. RESULTS: During the period of underfeeding, mean norepinephrine concentrations decreased at rest from 1.45 to 0. 96 nmol/liter, and in response to exercise, from 6.1 to 3.2 nmol/liter. Epinephrine concentrations decreased from 0.15 to 0.1 nmol/liter and from 0.26 to 0.17 nmol/liter, respectively. A significant decrease in catecholamine concentrations was observed only after 16 days of underfeeding. CONCLUSIONS: Clinically controlled underfeeding of patients with plurimetabolic syndrome may result in beneficial clinical and biochemical effects. The findings indicate that relatively long periods of underfeeding induce decreases in plasma catecholamine concentrations. Nevertheless, most of the fall in mean values in norepinephrine and also of the fall in blood pressure values occurred by Day 2. From those tendencies and from the significant changes in both parameters at Day 16 of severe underfeeding one could conclude that altered sympathetic nervous system activity could contribute to the fall in blood pressure.

Adult↗
PubMed2000

The cerebral hemodynamics of repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective in the treatment of affective disorders. However, only little is known about hemodynamic physiological and safety aspects of this method. We studied the cerebral hemodynamics as measured by transcranial Doppler sonography in 20 healthy subjects during different rTMS procedures. Mean cerebral blood flow velocity (CBFV), pulsatility index (PI), and oxygen consumption were recorded continuously and averaged directly after the rTMS procedure. RTMS did not influence blood pressure, pulse rate, or blood oxygenation. There was a maximal increase of CBFV in the middle cererbal artery (MCA) of 3.6% and 5.6% during 10 Hz and 20 Hz stimulation, respectively. This increase was only seen on the stimulated left hemisphere. The PI remained unchanged during the whole procedure. It is likely that the increase of CBFV is due to dilatation of the small resistance vessels rather than due to vasoconstriction of the MCA. In terms of cerebral hemodynamics, rTMS is a safe and well-tolerated technique with a lower increase of CBFV than that seen in electroconvulsive therapy.

Adult↗
PubMed2000

Green fluorescence protein as a transcriptional reporter for the long terminal repeats of the human immunodeficiency virus type 1.

Using the enhanced green fluorescence protein (EGFP), a transient reporter expression system was established to assess the transcriptional activity of the long terminal repeats (LTR) of primary isolates of the human immunodeficiency virus type 1 (HIV-1). Consistent with the conventional chloramphenicol acetyl transferase (CAT) reporter, EGFP expression, under the direction of HIV-1 LTR, was readily detected in the transient transfection and was elevated by co-transfection of HIV-1 tat-expression vector. Comparing to CAT, however, EGFP expression system has two advantages: (i) Using a fluorescence activated cell sorter (FACS), it was possible to simultaneously measure transfection efficiency and fluorescence intensity of the transfected live cells without the necessity of co-transfection of a reference plasmid for comparing the transcriptional activity of two promoters; and (ii) EGFP expression was readily detected at a DNA concentration where CAT activity was not detectable possibly because the transfectants could be 'gated'. On the other hand, at a higher concentration of DNA, CAT signal became more prominent than that of EGFP, possibly because the enzymatic activity of CAT 'amplified' the signal. EGFP fluorescence detected by FACS was a direct measurement of the expressed chromophore. It is concluded that the system is rapid, reproducible, convenient and useful for quantitative analysis of transcription.

Chloramphenicol O-Acetyltransferase↗
PubMed2000

Sex ratio of transsexuals in Germany: the development over three decades.

OBJECTIVE: The higher incidence of man-to-woman transsexuals compared to woman-to-man transsexuals varies markedly from country to country. This is the first survey of the sex ratio to be made in Germany. METHOD: It covers 1785 patients who between 1964 and 1998 were diagnosed as transsexual at the four largest German centres offering treatment. RESULTS: From 1970 to 1994 the sex ratio remained constant at 2:1 in favour of man-to-woman transsexuals. Over the past 4 years, however, it has altered considerably and reached 1.2:1. CONCLUSION: Up to 1994 our results do not support the assumption that transsexualism is gradually becoming equally prevalent in both sexes. The drop in the sex ratio after 1994 can be explained either as a reduction of an overhang of male-to-female transsexuals or as an artificial phenomenon caused by recent developments in therapy and by the views of transsexuals' groups on the treatment they are offered.

Adolescent↗
PubMed2000

Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

AIDS Vaccines↗
PubMed2000

The TATA binding protein, c-Myc and survivin genes are not somatically hypermutated, while Ig and BCL6 genes are hypermutated in human memory B cells.

Immunoglobulin (IG:) genes are hypermutated in mature B cells after interaction with antigen and T cells in a germinal center reaction. We and others have recently shown that the human BCL6 gene is also hypermutated in human peripheral blood memory B cells and tonsils. A preliminary analysis of other non-Ig genes (c-MYC:, S14 and AFP) suggested that they were not mutated in memory B cells. We have now performed an in-depth analysis of three non-Ig genes that are expressed in germinal center B cells in two human donors in whom BCL6 is highly mutated. It was found that the TATA binding protein (TBP), c-MYC: and survivin genes are not hypermutated. This lack of targeting by the Ig hypermutation mechanism must be due to the lack of regulatory DNA elements, since the primary sequences of the three tested genes have at least as high intrinsic mutability indices as the BCL6 gene.

B-Lymphocytes↗
PubMed1999

Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group.

OBJECTIVE: To describe persons with HIV infection and AIDS but with persistently negative HIV antibody enzyme immunoassay (EIA) results. DESIGN: Surveillance for persons meeting a case definition for HIV-1-seronegative AIDS. SETTING: United States and Canada. PATIENTS: A total of eight patients with seronegative AIDS identified from July 1995 through September 1997. MAIN OUTCOME MEASURES: Clinical history of HIV disease, history of HIV test results, and CD4 cell counts from medical record review; results of testing with a panel of EIA for antibodies to HIV-1, and HIV-1 p24 antigen; and viral subtype. RESULTS: Negative HIV EIA results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA concentrations of 105,000-7,943,000 copies/ml. Using a panel of HIV EIA on sera from three patients, none of the HIV EIA detected infection with HIV-1, and signal-to-cut-off ratios were < or = 0.8 or all test kits evaluated. Sera from five patients showed weak reactivity in some HIV EIA, but were non-reactive in other HIV EIA. All patients were infected with HIV-1 subtype B. CONCLUSIONS: Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients with illnesses or CD4 cell counts suggestive of HIV infection, but for whom results of HIV EIA are negative, should consider p24 antigen, nucleic acid amplification, or viral culture testing to document the presence of HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Comorbidity of schizophrenia and prelingual deafness: its impact on social network structures.

BACKGROUND: Prelingually deaf persons usually gain only a rudimentary command of speech and prefer sign language to communicate within the deaf community without the handicap they experience in the hearing world. Maintaining social contact within this rather scattered community, however, requires higher degrees of social initiative and mobility. The aim of the present paper was to study the quantity and quality of social integration among a group of prelingually deaf schizophrenic patients (n = 49) and two control groups comprising prelingually deaf psychiatric but non-psychotic patients (n = 38) and hearing schizophrenic patients (n = 30), with account being taken of the special socialisation conditions of deaf persons and of their cultural standards and values. METHOD: Data were collected with the help of semi-structured interviews; with the deaf patients these were conducted in German sign language. Using rating procedures we assessed seven social support components, selected items from a history schedule for schizophrenia, and the probands' visual and verbal language skills. RESULTS: The social networks of the two deaf groups were found to have larger gaps than those of the hearing schizophrenic patients, with significant differences being registered most clearly in the comparison between deaf schizophrenic and hearing schizophrenic patients. Comparison of the verbal and visual language skills of the two deaf groups revealed a substantial deficit among the deaf schizophrenics. Visual language skills were found to correlate more strongly than verbal language skills with the social support components. CONCLUSION: Prelingual deafness has a strong impact on the course of schizophrenia. In the long run, many of these patients belong to a "minority within a minority".

Adult↗
PubMed1998

The antigen-binding characteristics of mAbs derived from in vivo priming of avian B cells.

In most vertebrates, a primary antibody repertoire is created through the recombination of a diverse set of Ig variable (V), diversity (D), and joining (J) gene segments. In contrast, an avian immune repertoire is generated by gene conversion of rearranged Ig genes during B cell development within the bursa of Fabricius, a lymphoid organ unique to birds. To investigate the properties of antigen-specific Igs created through the process of gene conversion, we have developed a system for the production of avian-derived mAbs. This system was used to produce multiple antibodies after a single immunization with a conserved peptide from the human cystic fibrosis transmembrane conductance regulator gene. Each antibody isolated was found to have arisen independently through a distinct series of gene conversion events. These primary antibodies displayed evidence of diversity in all of the complementarity determining regions of both heavy and light chains, and both the heavy and the light chains contributed to antigen specificity. In the light chains, diversity could be attributed to gene conversion events. The measured affinity constants of two of the antibodies were between 10(8) and 10(9) M-1, and the antibodies were functional in quantitative ELISA as well as immunohistochemical studies of cystic fibrosis transmembrane conductance regulator expression. These data demonstrate that antigen-specific antibodies produced by Ig gene conversion display both high affinity and specificity. In addition, the methods developed here provide the description of a system for the production of mAbs derived from a nonmammalian species.

Amino Acid Sequence↗