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Biomedical subjects

H Peter

Publications and source records attributed to H Peter.

At least 19 recordsLinked to original sources
PubMed2002

[Comorbidity in narcoleptic patients].

BACKGROUND AND OBJECTIVE: Narcolepsy is a rare disease which remains undiagnosed in 90 %. The international literature so far has paid little attention to comorbid disorders. PATIENTS AND METHODS: In preparation for a German Narcolepsy Register this pilot study evaluated data from hospital records of 106 narcolepsy patients (60 men, 46 women, 8-83 years, mean 45.1 years) retrospectively emphasising comorbid diseases. RESULTS: The parasomnias sleepwalking and nightmares were 6 times as frequent as in the general population. With respect to the HLA findings the extremely high frequency of REM behavior disorder contributes to the assumption of a common pathomechanism. Obstructive sleep apnea and periodic limb movement disorder (PLMD) occurred much less than described in literature, while the results on obesity, headache and depression are in line with published findings. CONCLUSION: Diagnosis of one of these comorbid disorders should always be followed by thorough investigation for symptoms of narcolepsy i. e. excessive daytime sleepiness, sleep attacks and cataplexy.

Adolescent↗
PubMed2000

Diurnal variation of cortisol in panic disorder.

In patients with panic disorder (n=23), daytime salivary cortisol levels were determined in 2-h spans on 3 consecutive days and compared with 23 age- and sex-matched healthy controls. Additionally, nocturnal urinary free cortisol levels were measured. Daytime salivary cortisol levels were numerically higher in the patients, although the difference did not reach statistical significance. In a subgroup of 14 patients with higher illness severity (as expressed by a score >/=22 on the Panic and Agoraphobia Scale), salivary cortisol levels were significantly higher than in the controls. Mean nocturnal urinary cortisol levels were significantly higher in the whole group of patients and also in the more severely ill subgroup when compared with controls. Cortisol elevations seem to be more pronounced during the night and occurred mainly in more severely ill panic patients.

Adult↗
PubMed2000

Serum cholesterol in patients with obsessive compulsive disorder during treatment with behavior therapy and SSRI or placebo.

OBJECTIVE: Patients with panic disorder are reported to have elevated cholesterol levels. There is also some evidence that cholesterol elevation is not so much a specific condition in panic disorder but is generally associated with anxiety. So far, there is little data on cholesterol levels in patients with obsessive compulsive disorders (OCD) which is also classified as anxiety disorder. METHOD: Thirty-three patients with OCD participated in the study. Serum cholesterol was measured as pretreatment and at the end of a ten-week treatment-period. All patients received behavior therapy and, in a double-blind fashion, fluvoxamine or placebo. Severity of OCD was assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: Pretreatment cholesterol values of OCD patients were compared with cholesterol levels of thirty panic disorder patients and thirty normal controls. OCD patients had elevated cholesterol levels comparable with those of panic disorder patients. Cholesterol levels decreased significantly from pre- to posttreatment. OCD patients with high cholesterol levels (> or = 240 mg/dl, n = 7) could make best use of the treatment whereas patients with desirable cholesterol levels (< 200 mg/dl, n = 11) did not change their cholesterol during treatment. CONCLUSIONS: Our data support the assumption that not only panic disorder but also other anxiety disorders, e.g., obsessive compulsive disorders, may be associated with serum cholesterol elevations. Effective treatment (behavior therapy and/or treatment with a selective serotonin reuptake inhibitor [SSRI]) seems to decrease cholesterol levels, especially in patients with pathological cholesterol elevations.

Adult↗
PubMed1998

Osmo-sensing by N- and C-terminal extensions of the glycine betaine uptake system BetP of Corynebacterium glutamicum.

The major uptake carrier for the compatible solute glycine betaine in Corynebacterium glutamicum is the secondary transport system BetP. It is effectively regulated by the external osmolality both on the level of expression and of activity. BetP carries highly charged domains both at the N and at the C terminus. We investigated the role of these extensions in the regulatory response to hyperosmotic stress. Mutants of the betP gene coding for proteins with truncated N- and C-terminal extensions were expressed in the C. glutamicum betP deletion strain DHP1 and were functionally characterized with respect to regulation of activity. The optimum of activation at 1.3 osmol/kg in wild type was shifted in the recombinant strains to about 2.6 osmol/kg in mutants with deletions in the N-terminal part. Deletions in the C-terminal domain resulted in a complete loss of regulation. The altered response to changes in osmolality led to severe consequences in the cellular adaption to hyperosmotic stress. Whereas in the wild type, the steady state level of glycine betaine accumulation is maintained by activity regulation of the BetP system itself, in the mutant with BetP proteins carrying truncations in the C-terminal domain, the observed steady state betaine accumulation was found to be due to a kinetic balance of unregulated glycine betaine uptake by the modifed BetP and efflux via the mechanosensitive efflux channel for compatible solutes at the same time.

Amino Acids, Diamino↗
PubMed1998

In vitro cell models to study nasal mucosal permeability and metabolism.

Whereas in vivo studies represent the most crucial test for any nasal drug application or formulation, mechanistic aspects of nasal absorption may be more clearly approached by well defined and controlled in vitro studies. In this review the progress of nasal in vitro models to investigate drug permeation and metabolism in the epithelium is summarized and their potential and limitations are discussed. The following subjects will be covered: (i) primary cell cultures of human nasal epithelium, including sampling techniques and culture conditions, (ii) human nasal cell lines (in particular the human nasal cell line RPMI 2650), and (iii) excised nasal epithelium (rabbit, bovine, ovine, canine, human), also summarizing suitable preparation techniques and tissue characterization, test media, tissue equilibration, viability testing, and integrity tests. Furthermore, an overview on the various experimental set-ups suitable for in vitro transport studies (permeation rates; identification of permeation pathways; mechanisms and toxicity of absorption enhancers) and for metabolism studies (rates, saturation and pathways of enzymatic cleavage) is presented. Some attention is given to identify potential endocytotic uptake mechanisms. To date, the permeation and metabolic barrier function of excised nasal tissue derived from various animals has shown to mimic the in vivo situation 'ex vivo' at the highest degree possible. Supply of human tissue will continue to be short. Therefore, further studies are necessary to evaluate and improve culture conditions, handling, performance and physiologic relevance of primary human cell and cell line cultures.

Journal Article↗
PubMed1998

[The impact of the central serotonin system on alcoholism and therapeutic consequences].

Several studies support the assumption that the development and/or maintenance of alcoholism is due to a deficit of the central serotonergic system. But it still remains open whether the imbalance in the serotonergic functioning is due to genetic factors or whether it is a result of alcoholism. It has been hypothesised that both mechanisms interact with each other creating a vicious circle. The efficacy of serotonin reuptake inhibitors (SSRIs) in treating alcoholism supports the pathophysiological assumptions. Citalopram (40 mg) and Fluoxetine (60-80 mg) significantly reduce ethanol intake. However, treatment effects disappear after a treatment period of more than 4 weeks in most of the studies. Chronic and heavy alcoholics benefit less from treatment. Better treatment results were obtain in alcoholics with primary depression, especially with a prolonged treatment period. The promising treatment outcome in primary depressed alcoholics suggests an efficacy of SSRIs in alcoholism with primary anxiety disorders, although no data are available. The results of the studies in this field support the following therapeutic consequences: 1. Alcoholics with primary depression should be treated with SSRIs. 2. A short-term treatment with SSRIs in primary alcoholism without comorbid psychiatric diseases can be considered, e.g. to prevent treatment drop-outs or for relapse prevention. 3. So far, treatment in alcoholics with primary anxiety disorders is not supported simply due to a complete lack of data. Studies on this problem are imperative.

Alcoholism↗
PubMed1998

Corynebacterium glutamicum is equipped with four secondary carriers for compatible solutes: identification, sequencing, and characterization of the proline/ectoine uptake system, ProP, and the ectoine/proline/glycine betaine carrier, EctP.

Gram-positive soil bacterium Corynebacterium glutamicum uses the compatible solutes glycine betaine, proline, and ectoine for protection against hyperosmotic shock. Osmoregulated glycine betaine carrier BetP and proline permease PutP have been previously characterized; we have identified and characterized two additional osmoregulated secondary transporters for compatible solutes in C. glutamicum, namely, the proline/ectoine carrier, ProP, and the ectoine/glycine betaine/proline carrier, EctP. A DeltabetP DeltaputP DeltaproP DeltaectP mutant was unable to respond to hyperosmotic stress, indicating that no additional uptake system for these compatible solutes is present. Osmoregulated ProP consists of 504 residues and preferred proline (Km, 48 microM) to ectoine (Km, 132 microM). The proP gene could not be expressed from its own promoter in C. glutamicum; however, expression was observed in Escherichia coli. ProP belongs to the major facilitator superfamily, whereas EctP, together with the betaine carrier, BetP, is a member of a newly established subfamily of the sodium/solute symporter superfamily. The constitutively expressed ectP codes for a 615-residue transporter. EctP preferred ectoine (Km, 63 microM) to betaine (Km, 333 microM) and proline (Km, 1,200 microM). Its activity was regulated by the external osmolality. The related betaine transporter, BetP, could be activated directly by altering the membrane state with local anesthetics, but this was not the case for EctP. Furthermore, the onset of osmotic activation was virtually instantaneous for BetP, whereas it took about 10 s for EctP.

Amino Acids, Diamino↗
PubMed1998

Neuroticism, other personality variables, and serum lipid levels in patients with anxiety disorders and normal controls.

OBJECTIVE: This study evaluates the association between certain personality variables, especially neuroticism, and serum lipid levels in patients suffering from anxiety disorders as opposed to normal control individuals. It addresses the question whether in anxiety disorder patients neuroticism is associated with elevated serum cholesterol and serum LDL cholesterol levels. METHOD: Thirty (15 male, 15 female) patients with anxiety disorders as defined by DSM-IV and thirty normal matched controls were enrolled in this study. The patients were either admitted for inpatient treatment or referred to the behavioral therapy outpatient clinic at the Department of Psychiatry of the University Hospital Eppendorf (Hamburg/Germany). Control individuals were selected on a voluntary basis and recruited from the authors' colleagues and peers. Matching included Body-Mass-Index, age, and gender. RESULTS: This study showed a significant positive association of neuroticism and serum cholesterol (r = .29) and serum LDL cholesterol (r = .35) within the entire cohort of participants. An even higher significant positive relation (r = .43) could be detected between neuroticism and serum LDL cholesterol within the psychiatric patient group. As far as differences of personality variables between patients and normal controls are concerned, patients seemed to be significantly less satisfied with life, more generally inhibited, more irritable, more stressed, and more emotionally labile than controls. Anxiety disorder patients also tended to complain significantly more often about physical problems. CONCLUSIONS: Our data suggest that high scores of neuroticism in anxiety disorders patients may be involved in elevated serum LDL cholesterol levels and, thereby, may lead to an increased risk of coronary heart disease.

Adult↗
PubMed1997

Efflux of compatible solutes in Corynebacterium glutamicum mediated by osmoregulated channel activity.

Bacteria respond to hypoosmotic stress by releasing low-molecular-mass solutes in order to maintain constant turgor pressure. We have studied the function of osmoregulated channel(s) in Corynebacterium glutamicum, which are responsible for efflux of various solutes upon sudden decrease in osmotic pressure. The channels preferentially mediated efflux of compatible solutes such as glycine betaine and proline. The release of molecules of similar size, e.g. glutamate or lysine, was restricted, ATP was completely retained even after severe osmotic shock. The cells maintained high cytoplasmic K+ and Na+ concentrations under hypoosmotic shock. Several results suggest that the solute efflux is mediated by a channel and not by a carrier, e.g. by reversal of the glycine betaine uptake systems of C. glutamicum: the release of glycine betaine and proline was extremely fast reaching an efflux rate of 6000 micromol x min(-1) x g dm(-1) or higher; the efflux was not significantly influenced by addition of external transport substrate, e.g. glycine betaine; in spite of an extremely high chemical gradient, no significant efflux under isoosmolar conditions was observed; efflux of solutes was unchanged after full uncoupling of membrane energetics by carbonylcyanide m-chlorophenylhydrazone (CCCP). These results indicate the presence of an osmoregulated channel in C. glutamicum similar to the mechanosensitive channel(s) of Escherichia coli. The activity of the channel did not depend on the growth conditions, but we observed a tight regulation on the level of activity, i.e. the mechanosensitive channel behaved as a perfect osmometer. By monitoring release of glycine betaine under slow and continuous decrease of the external osmolality, we observed continous efflux whithout a stepwise release of solutes. This resulted in a significant steady-state decrease of the membrane potential.

Adenosine Triphosphate↗
PubMed1997

Isolation of the putP gene of Corynebacterium glutamicum and characterization of a low-affinity uptake system for compatible solutes.

Corynebacterium glutamicum accumulates the compatible solutes proline, glycine betaine, and ectoine under conditions of high osmolality. Uptake of proline is mediated by both a high-affinity and a low-affinity secondary transport system. The low-affinity uptake system also accepts glycine betaine and ectoine as substrates. In the present study, the gene encoding the high-affinity proline uptake system PutP was isolated by heterologous complementation of Escherichia coli mutant strain WG389, which lacks the transport systems BetT, PutP, ProP, and ProU and is unable to synthesize proline and glycine betaine. This gene (putP) encodes a protein of 524 amino acids that shares identity with the proline transport systems PutP of E. coli, Staphylococcus aureus, Salmonella typhimurium, Haemophilus influenzae, and Klebsiella pneumoniae. Functional studies of PutP synthesized in E. coli mutant strain MKH13, which also lacks the transport systems for compatible solutes and is unable to synthesize glycine betaine, revealed that this carrier system is not regulated by the external osmolality on the level of activity. Km values of 7.6 mM for proline and 1.3 mM for sodium as cotransported ion were determined. Deletion of the putP gene allowed the functional characterization of another proline uptake system with low affinity.

Amino Acid Sequence↗
PubMed1996

Isolation, characterization, and expression of the Corynebacterium glutamicum betP gene, encoding the transport system for the compatible solute glycine betaine.

Corynebacterium glutamicum accumulates glycine betaine under conditions of high osmolarity. Previous work revealed the existence of a high-affinity glycine betaine permease which is osmotically regulated. In the present study, the corresponding gene was cloned. The betP gene, encoding the glycine betaine uptake carrier, was isolated by heterologous complementation of mutant strain Escherichia coli MKH13. From sequence analysis it is predicted to encode a protein of 595 amino acids. This protein shares 36% identity with the choline transport system BetT and 28% identity with the carnitine transport system CaiT of E. coli, as well as 38% identity with a protein with an unknown function from Haemophilus influenzae. Analysis of hydropathy indicated a common structure for all four transport proteins. After heterologous expression of betP in E. coli MKH13, the measured Km values for glycine betaine and the cotransported Na+ were similar to those found in C. glutamicum, whereas the modulation of activity by osmotic gradients was shifted to lower osmotic values.

Amino Acid Sequence↗
PubMed1995

Acute and prolonged toxicity to aquatic organisms of new and existing chemicals and pesticides.

The relation of acute to prolonged toxicity of existing and new chemicals and active ingredients of numerous pesticides in the aquatic environment have been compared with their physico-chemical properties. The data had been presented to the authorities in behalf of the pesticide registrations, the notification of new chemicals or research projects. The ecotoxicity ratios are expressed as acute to prolonged ratios (APR). They are determined for fish and crustacea with existing and new chemicals and pesticides. In the case of the pesticides the data are subsummarized into fungicides, herbicides, insecticides. The variability of the APR is evaluated. According to the statistic evaluation of the data it must be summarized, that the toxic effects are often extremely specific and depend not only on the substance, but also on the aquatic species, the duration of the exposure, and the endpoint of the test. In general, a factor of 100 between the EC/LC50 of acute toxicity and NOEC of prolonged toxicity is scientifically justified. The data indicate that there is no significant correlation between lipophilic properties (logPow) or water solubility and toxicity in aquatic organisms. For that reason structure-activity relationships based on lipophilic properties of the substance cannot lead to reasonable results. It must be stated, that the prolonged ecotoxicity can not be exactly extrapolated from acute toxicity data on the basis of physico-chemical properties.

Animals↗
PubMed1994

Etiopathology of feline toxic nodular goiter.

We have discussed the etiopathology of feline toxic nodular goiter in the context of human nodular goiter pathogenesis. We have reviewed thyroid heterogeneity, growth regulation, functional and growth autonomy, nodule and tumor formation, and the evolution of toxic nodular goiter in the human being. By addressing toxic nodular goiter of the cat, the history, morphologic findings, xenotransplantation and cell culture studies, evidence for and against circulating thyroid stimulators and epizootiological studies of the feline disease have been summarized. Due to its structure, the thyroid gland offers some unique possibilities to study the mechanisms that are responsible for cellular heterogeneity, the emergence of autonomous nodular growth and function, and, ultimately, the development of tumors. The demonstration of naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of the thyroid has fostered promising new concepts on the genesis of nodular growth of benign and possibly malignant endocrine tumors. Hyperthyroid cat goiters contain single or multiple, autonomously (i.e., TSH-independently) functioning and growing nodules. Neither hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells. The factors enhancing the transformation of a normal thyroid into a nodular hyperfunctioning goiter over many years are still unknown. Immunological, environmental, and nutritional factors are the focus of ongoing studies, but an infectious agent can not yet be excluded.

Animals↗
PubMed1993

[DNA methylation of monohalogenated methanes of F344 rats].

Monohalogenated methanes (methyl chloride, methyl bromide and methyl iodide) are mutagenic and carcinogenic. The possible mechanism of these effects, DNA methylation, was studied. DNA adducts from organs of F344 rats exposed to these chemicals were separated and identified with high performance liquid chromatography (HPLC) and gas-chromatography/mass-spectrometry (GC/MS). DNA adducts, 7-methylguanine (7-MeG) and O6-Methylguanine(0(6)-MeG), incorporation of 14C into de novo synthesis of nucleobases could be observed in enzymatic DNA hydrolysates by HPLC and determination of the radioactivity in the fractions. The formation of DNA adducts in the studied organs was only quantitatively different. The formation of O6-MeG was further proved by analysing the acidic hydrolysates using HPLC with non-radioactive O6-MeG as internal standard. 7-MeG and 3-MeA were identified with GC/MS analysis.

Animals↗