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Biomedical subjects

M Berg

Publications and source records attributed to M Berg.

At least 37 records · Page 2Linked to original sources

Kainic acid-induced seizures and brain damage in the rat: role of calcium homeostasis.

Seizure activity induced by kainic acid (KA) and subsequent neuronal death are thought to be associated with an increase in cytoplasmic free calcium ([Ca2+]i) and can be prevented by N-methyl-D-aspartate (NMDA) antagonists. In addition to influx through receptor operated Ca2+ channels the increase in [Ca2+]i may be the result of an increased influx through voltage-operated calcium channels and/or release from intracellular deposits. It was therefore investigated whether compounds other than NMDA antagonists with known actions on the intracellular Ca2+ homeostasis had any protective effect against KA-induced neuronal death. Voltage-operated calcium channels in the cell membrane were blocked with the L-type ion channel antagonist, Nimodipine (1.0 mg/kg), and release of Ca2+ from internal stores was prevented with Dantrolene (10 mg/kg). Animals from two control groups injected with kainate (8 mg/kg) exhibited a survival rate of 67 and 53%, respectively. Countings of neurons in dorsal hippocampus showed subtotal or total loss in the CA1 and CA3 subregions. There were no significant differences concerning seizure and survival rates in the groups injected with kainate and treated with Dantrolene or Nimodipine and the control groups. The group treated with Dantrolene showed no neuropathological changes in the hippocampal CA3 region and only slight changes in the Ca1 region, while the neuron loss in the Nimodipine group did not differ from that of its control group. The results emphasize the importance of Dantrolene-sensitive Ca2+ release from intracellular stores for the development of seizure-induced neuronal death.

Animals

A nonconventional approach to the treatment of "environmental illness".

Twenty patients with symptoms of "environmental illness" were subject to a controlled study of deep versus superficial acupuncture. The patients were evaluated by a detailed questionnaire concerning their occupational, environmental, and medical history. Blood samples were taken as well. Patients were randomized to deep or superficial acupuncture. Both groups improved significantly in key variables during and after treatment. There were no group differences. There were no changes in biological variables apart from a gradual and continuous increase in serum cortisol and a decrease in neuropeptide Y, which was somewhat more accentuated in those receiving deep acupuncture. This rise in cortisol may have contributed to decreased dermal symptoms among the participants. It is hypothesized that the positive treatment results observed are partly due to weakening of the conditioned response, linking bodily symptoms to environmental agents. To date, a number of different methods have been tried in the management of patients with environmental illness. However, only rarely have the treatments been evaluated in controlled studies.

Acupuncture Therapy

Regulation of the segmental swim-generating system by a pair of identified interneurons in the leech head ganglion.

1. The aim of this study was to identify neurons that modulate activity of segmental swim gating interneurons. We found a pair of bilaterally symmetrical interneurons, cells SE1, whose activity level directly influences three groups of segmental neurons associated with generating swimming in the medicinal leech. 2. The somata of cells SE1 are located on the dorsal surface of the subesophageal ganglion. Their axons extend most, if not the entire, length of the ventral nerve cord and appear to make identical connections with the same group of swim-generating neurons in all segmental ganglia. 3. Cells SE1 excite monosynaptically all segmental swim gating interneurons, cells 204, examined. The level of excitation in cell 204 is directly correlated with the firing frequency of cell SE1. In most quiescent preparations (when the preparation is not swimming) hyperpolarization of a single cell SE1 eliminates all excitatory synaptic input to cells 204. 4. Cells SE1 excite monosynaptically three swim oscillatory interneurons, cells 115, 28, and 208. The strength of the connection from cell SE1 to cell 115 is stronger than the connection from cell SE1 to either cells 28 or 208. The level of excitation in cell 115 is directly correlated with the firing frequency of cell SE1. In most quiescent preparations, hyperpolarization of a single cell SE1 eliminates all excitatory synaptic input to cell 115 but has only a minor effect on the level of activity in cells 208 and 28. 5. Due most likely to the strong and direct connections cells SE1 have with swim gating and oscillatory interneurons, brief stimulation of cell SE1 can elicit swimming. Swimming generally occurs within 1 s after stimulation of cell SE1. During swimming, the membrane potential of cell SE1 depolarizes by 2-5 mV, and its firing frequency increases. Brief depolarization of cell SE1 during swimming reliably shifts the phase of the swimming rhythm, whereas longer periods of depolarization increase both swim period and burst duration. 6. Excitatory motor neurons to the dorsal longitudinal muscles, cells 3, 5, and 7, are strongly excited by stimulation of cell SE1. The firing frequency of cell 3 is positively correlated with the firing frequency of cell SE1. 7. The results of this study indicate that cells SE1 can modulate the level of excitation in three groups of neurons associated with generating leech swimming.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.

Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.

Amino Acid Sequence

Facial nerve involvement in patients with acoustic neurinomas. Examination with magnetic single- and bi-stimulation.

The diagnosis of acoustic neurinomas is usually made by auditory and vestibular testing and magnetic resonance imaging. As clinical involvement of the facial nerve is infrequent, occurring only in large tumours, only little is known about the subclinical involvement of the facial nerve. Transcranial magnetic stimulation of the VIIth cranial nerve in the temporal bone, adjacent to acoustic neurinoma growth, seems to be an adequate instrument for electrophysiological measurements of minimal nerve lesions without clinically obvious facial palsy. In 70% out of 97 patients with surgically and histologically confirmed acoustic neurinomas, obvious elongation of the intratemporal conduction time of the facial nerve was found. This affection was dependent on tumour size. No correlation was found to preoperative or postoperative facial nerve function and hearing function. The latencies of the conduction time showed a tendential increase in patients with a more difficult grade of surgery and of facial nerve preparation due to fibrous adhesions and nerve spreading on the tumour capsule. A completely new stimulation modality, the application of two magnetic stimuli in quick succession, was applied for the first time in acoustic neurinoma patients, and revealed facial nerve involvement by acoustic neurinoma growth. Facial nerve involvement in acoustic neurinoma can be detected by transcranial magnetic stimulation even in patients with small and medium sized tumours but with clinically normal facial function.

Cranial Nerve Neoplasms

Clinical survey of Meniére's disease: 574 cases.

Only 27% out of 574 patients suffering from Meniére's disease initially started with the typical Meniére's triad. A great advantage in order to diagnose Meniére's disease can be established with the telemetric-ENG. With this equipment it is possible to verify a nystagmus outside the clinic (at home, at work) at any time in patients suffering from vertigo attacks. Most of our patients showed an omnifrequent sensorineural hearing loss on the affected side. Many of our patients with Meniére's disease suffered from internal diseases (e.g. hypotonia, hyperlipidemia, diabetes mellitus), allergy or an affection of the paranasal sinuses, which may constitute co-factors triggering Meniére's disease.

Adolescent

[What should be recommended to a patient with a small radiologically suspected acoustic neuroma?].

OBJECTIVE: Criteria for therapeutic decision-making for intrameatal acoustic neurinomas that are suspected radiologically. DESIGN: Retrospective evaluation. PATIENTS: 114 surgically treated patients of the ORL Dept. of the University Erlangen-Nuremberg. OUTCOME MEASURES: Rate of complications. Preservation of facial nerve function and hearing. Preoperative time course of hearing. Reliability of radiological examination. Progression of symptoms and tumor growth. THERAPY: Surgical exposure and complete removal by the enlarged middle cranial fossa approach. RESULTS: In 47% of cases surgery confirmed a neurinoma limited to the internal auditory meatus. In 41%, tumors were larger than expected and had protruded into the cerebellopontine angle, indicating preoperative tumor growth during an average period of 5.4 months before surgery could be completed. The remaining 12% of patients were found to have a facial neurinoma, meningioma or non-tumorous lesion of the internal auditory canal. No permanent neurological deficits or fatalities occurred in any of the patients treated. Facial function was favorable in 88% and moderate pareses or synkineses occurred in 12%. The degree of hearing preservation depended on the preoperative situation. When the preoperative pure-tone average (at 0.5, 1, 2 and 4 kHz) was 30 dB or less, hearing levels of less than 90 dB could be preserved in 70% of cases. Findings also demonstrated that the complication rate and success of function preservation were similar to younger patients in patients older than 60 years (n = 21). Without surgery auditory acuity decreased by 10 dB per year. The volume of intrameatal neurinomas in 7/10 cases followed by MRI doubled during a median following time of 32 months. CONCLUSIONS: Acoustic neurinoma surgery by the enlarged middle cranial fossa approach is a safe procedure with low complication rates. The percentages of preservation of facial function and hearing can be excellent in cases with small tumors and good preoperative hearing. To date no parameter has been found to predict tumor growth or the time course for hearing loss in individual cases. Surgical ablation of radiologically suspected, small acoustic neurinoma by the transtemporal approach is recommended.

Adolescent

Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID.

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.

Animals

Turing's game and the clinical significance of outcome with borderline patients at a day hospital.

Clinical significance of a treatment effect is indicated when a treated patient, after discharge, cannot be distinguished clinically from a person who is functioning on some criterion level in terms of adjustment and normality. This principle is demonstrated in a questionnaire follow-up of patients at a day hospital. Defining the criterion level, a sex- and age-matched nonpatient group completed the same questionnaire. On the basis of the questionnaires, four judges independently guessed whether or not each respondent was an ex-patient. The agreement among the judges was high, and their classification agreed with that of a discriminant analysis in eventually declaring approximately 25% of the patients to be nonpatients. A simple model was proposed to account for the judges' performance.

Analysis of Variance

Food-induced increase in bioavailability of 5-methoxypsoralen.

5-Methoxypsoralen (5-MOP) in combination with ultraviolet light exposure is used for the treatment of psoriasis. The effect of food on the pharmacokinetics of 5-MOP was evaluated in a randomized, crossover study in nine healthy subjects. Each subject received the tablets with a standardized breakfast or under fasting conditions. The food had a dramatic effect on the bioavailability of 5-MOP. Five of the subjects showed no measurable quantities (detection limit of the analytical technique 1 ng.ml-1) of 5-MOP when the drug was given under fasting conditions. However, plasma peak concentration within the range 37-144 ng.ml-1 (median 102 ng.ml-1) was measured when the drug was taken with food. The time for the plasma peak concentration was within the range 2.0-5.1 h (median 3.0 h) under non-fasting conditions. The elimination half-life was within the range 1.4-2.7 h (median 1.9 h). We conclude that it is imperative that 5-MOP tablets are administered together with food.

5-Methoxypsoralen

Principles and practices of medicine. The co-existence of various anemias.

The medical textbooks in our university library present 'principles' as the basis which underlies medical 'practice'. In this article it is argued that this helps different medical logics to co-exist. The example analyzed is that of anemia in the Netherlands. Currently this is defined pathophysiologically, statistically and clinically. These three definitions are intertwined with different strategies for the creation of normal hemoglobin levels and the detection of patients with anemia. The discrepancies between them, however, do not lead to the controversies that might be expected by those who believe in consistency. Instead, the rhetoric of principles-and-practice helps to bring about peaceful co-existence.

Adult

Evolution of H3N8 equine influenza virus from 1963 to 1991.

The antigenic properties of H3N8 influenza viruses isolated from outbreaks of equine influenza in Sweden between 1979 and 1991 have been studied in hemagglutination inhibition tests with polyclonal and monoclonal antisera, and antigenic drift of the virus has been demonstrated. To clarify the basis of the antigenic drift, amino acid sequences of the globular head regions (HA1) of the hemagglutinin membrane glycoproteins of virus strains from 1979, 1984, 1988 and 1990 have been deduced from the nucleotide sequences of the hemagglutinin genes, and the sequence information has been used to construct a phylogenetic tree of H3N8 equine influenza strains. Several strains from previous studies have been included to give a clearer picture of viral evolution in an international context.

Amino Acid Sequence

Characterization of differentiation factor/leukaemia inhibitory factor effect on lipoprotein lipase activity and mRNA in 3T3-L1 adipocytes.

Alterations in lipid metabolism characterized in major part by a decrease in lipoprotein lipase (LPL) activity in adipose tissue are a central feature of cachexia from chronic infection or malignancy. These metabolic derangements may be mediated in large part through endogenous host proteins produced in response to various pathological stimuli. Differentiation factor/leukaemia inhibitory factor (D-factor) is a cytokine whose functions overlap those of tumour necrosis factor-alpha (TNF), IL-6 and IL-1. Recombinant murine D-factor produced a dose- and time-dependent inhibition of heparin-releasable LPL activity in differentiated 3T3-L1 adipocytes. Although 2-10 fold less potent than recombinant murine TNF, D-factor inhibited LPL activity at concentrations of 1-10 ng/ml. When added together, D-factor and TNF produced a synergistic inhibition of LPL activity. Interleukin 6 (IL-6) was 100-fold less potent than D-factor; 0.1 ng/ml of D-factor or 10 ng/ml of IL-6 caused a 50% inhibition of LPL activity. D-factor and TNF increased IL-6 production in 3T3-L1 cells. Ten ng/ml of D-factor or 1.0 ng/ml of TNF stimulated the release of < 1 ng/ml of IL-6 and inhibited LPL activity to 11 +/- 3% and 3 +/- 2% of control, respectively, whereas 50 ng/ml of recombinant IL-6 was required to decrease LPL activity to 24 +/- 19% of control. TNF produced a marked decrease in LPL mRNA, whereas D-factor had minimal or no effect at doses which inhibited LPL activity almost completely. Western blot analysis of cell extracts showed that TNF caused a greater decrease in LPL protein production than D-factor.2+ with TNF, may contribute to the manifestations of cachexia.

3T3 Cells

Synthetic lipopeptide Pam3CysSer(Lys)4 is an effective activator of human platelets.

Lipopeptide analogues of the NH2-terminus of bacterial lipoprotein are known to induce activation of macrophages, neutrophils, and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-( S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3CysSer(Lys)4] on several functions of human platelets. Pam3CysSer(Lys)4 led to the aggregation of platelets and induced the secretion of serotonin with an effectiveness similar to thrombin. These cellular effects of Pam3CysSer(Lys)4 were concentration dependent, being half maximal at 2-3 microM and maximal at 10-30 microM. Another lipopeptide also induced platelet aggregation and serotonin secretion but was less potent and less effective than Pam3CysSer(Lys)4. The lipid moiety and the peptide moiety of Pam3CysSer(Lys)4 alone were without any effect. Lipopeptides also stimulated tyrosine phosphorylation of several proteins with molecular masses similar to those found to be tyrosine phosphorylated in response to thrombin, and Pam3CysSer(Lys)4 led to an increase in the cytosolic calcium concentration. All studied responses of platelets to lipopeptides were inhibited by the prostacyclin receptor agonist cicaprost. Taken together, our data show that lipopeptides are effective activators of human platelets and that this activation is susceptible to the action of physiological platelet inhibitors.

Blood Platelets

Ultraviolet A phototherapy and trimethylpsoralen UVA photochemotherapy in polymorphous light eruption--a controlled study.

Twenty-two patients with polymorphous light eruption were prophylactically treated with ultraviolet A (UVA) with and without trimethylpsoralen in the first randomized double-blind study in this subject. Twelve of the patients were treated during 2 consecutive springs with placebo during one spring and psoralens during the other. Eighteen of the patients improved after the therapy, but there was no clear-cut difference between the 2 regimens. As many as 12 patients got light eruptions during the treatment, but all but one continued with the therapy. This study indicates that UVA alone is as good prophylactic therapy for polymorphous light eruption as PUVA with trimethylpsoralen. However, because of the high incidence of provoked eruptions during therapy, the treatment may be difficult to handle for the patients themselves, at least during the initial treatment.

Adult

Treatment of psoriasis with psoralens and ultraviolet A. A double-blind comparison of 8-methoxypsoralen and 5-methoxypsoralen.

Thirty-eight patients with plaque-type psoriasis were enrolled in a double-blind psoralen plus ultraviolet A (PUVA) treatment study comparing the efficacy and side effects of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP). Patients treated with 8-MOP healed significantly faster than those on 5-MOP for 6 weeks of treatment, but there was no significant difference after 9 weeks. There was no significant difference in side effects between the two groups, but nausea tended to be more common in the 8-MOP group. One patient on 5-MOP had signs of toxic hepatitis. The importance for maximizing absorption of taking 5-MOP with food is stressed, and PUVA treatment should be given 3 h after intake of the drug.

5-Methoxypsoralen