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Biomedical subjects

R Kellner

Publications and source records attributed to R Kellner.

At least 73 records · Page 4Linked to original sources
PubMed1994

Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale.

BACKGROUND: Validation of animal models of hallucinogenic drugs' subjective effects requires human data. Previous human studies used varied groups of subjects and assessment methods. Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs' dysphoric properties. We describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. We also present preliminary data from a new rating scale for these effects. METHODS: Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a double-blind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. They also were administered a new instrument, the Hallucinogen Rating Scale (HRS). The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users, and modified during early stages of the study. RESULTS: Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 minutes. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects. Clustering of HRS items, using either a clinical, mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously. CONCLUSIONS: These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT's properties in humans. They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric populations.

Cognition↗
PubMed1994

A novel peptide in the AKH/RPCH family isolated from the corpora cardiaca of the Emperor dragonfly, Anax imperator.

Using a heterologous (in locusts and cockroaches) and a homologous bioassay, we have isolated the neuropeptide pGlu-Val-Asn-Phe-Ser-Pro-Ser-Trp-NH2 from extracts of corpora cardiaca of the Emperor dragonfly, Anax imperator. The sequence elucidation was achieved by Edman degradation of the deblocked peptide and by electrospray mass spectrometry. Low concentrations of the synthetic peptide injected into the Emperor dragonfly increased the hemolymph lipid concentration, suggesting a possible role of the peptide in lipid homeostasis during flight. Therefore, it is named Ani-AKH, Anax imperator adipokinetic hormone.

Amino Acid Sequence↗
PubMed1994

Psychosomatic syndromes, somatization and somatoform disorders.

A psychosomatic syndrome is defined as a syndrome in which psychological processes play a substantial role in the etiology of the illness in some of the patients. The main conclusions on the extent of the biological and psychosocial contributions to several psychosomatic syndromes are presented and the relationship of these syndromes to somatization and somatoform disorders is discussed. The syndromes summarized include fibromyalgia, chronic fatigue, motility disorders of the esophagus, nonulcer dyspepsia, irritable bowel syndrome, urethral syndrome, behaviors causing disturbances of physiology, and some defined pain syndromes. The findings suggest that the extent of the biological and psychosocial contributions vary among these syndromes as well as among individuals with the same syndrome. In some syndromes the extent and nature of the biological contribution has not been established with certainty. There is evidence to suggest that many of the phenomena of the somatoform disorders are caused by clustering of psychosomatic syndromes or their incomplete or atypical manifestations and a low sensation threshold. The results of the controlled studies of various methods of psychotherapy and drug treatments of the psychosomatic syndromes are listed; these studies have practical implications because the adoption of these methods is likely to enhance the efficacy of the treatment of somatoform disorders.

Diagnosis, Differential↗
PubMed1993

Imagery rehearsal treatment of chronic nightmares: with a thirty month follow-up.

Nightmare frequency and self-rated distress were assessed retrospectively in two groups of chronic nightmare sufferers 30 months after treatment. In the initial phase, the image group (N = 9) learned a cognitive-behavioral technique (imagery rehearsal) for the treatment of nightmares. They were taught in one group session to: (1) record a nightmare; (2) change it (usually to something positive); and (3) rehearse the new images daily. The record group (N = 10) recorded nightmares during the first month only and learned imagery rehearsal subsequent to 3-month follow-up measurements. At 3 months and at 30 months, both groups had significantly fewer nightmares, but only the rehearsal group had less total distress. The results support the theory that nightmares are a primary sleep disorder rather than a symptom of an underlying psychiatric problem.

Analysis of Variance↗
PubMed1993

Comparison of primary and secondary panic disorder: a preliminary report.

We examined the onsets of comorbid psychiatric disorders in patients with panic disorder (PD) (N = 54). In 42 patients (77.8%), PD was preceded by another psychiatric condition (secondary PD group), while in 12 patients (22.2%), PD occurred first or was the only diagnosed mental disorder (primary PD group). Patients with primary and secondary PD did not differ with respect to demographic variables, mean ages of onset of PD, mean duration of PD, number of patients with a personality disorder, and number of patients with different DSM-III-R subtypes of PD. Except for the anger and sleep scales of the Hopkins Symptom Checklist 90, patients with primary PD had significantly less self-rated psychopathology; they also displayed less extensive phobic avoidance, and had a lower rate of current psychiatric comorbidity. These findings are discussed in light of the value of the concepts of comorbidity and primary/secondary dichotomy.

Adult↗
PubMed1993

Comorbidity in panic disorder: II. Chronology of appearance and pathogenic comorbidity.

Ages of onset and the sequence of appearance of panic disorder (PD) and comorbid conditions were determined in a sample of 54 patients with the principal DSM-III-R diagnosis of PD. The onset of PD was earlier in patients with moderate to severe agoraphobia (AG) than in panic patients without AG. Patients with alcohol abuse and drug abuse before the onset of PD also had a tendency to develop PD earlier, which suggests that these conditions might have specifically predisposed to PD. All comorbid disorders, except for major depression, were more likely to precede the onset of PD so that, more often than not, PD appeared as a chronologically secondary condition. However, it was found that only for primary substance abuse such a temporal relationship might denote etiologic relatedness to PD, because of the reduced temporal distance between the onset of primary substance abuse and secondary PD.

Agoraphobia↗
PubMed1993

Annexin II is a major component of fusogenic endosomal vesicles.

We have used an in vitro assay to follow the proteins transferred from a donor to an acceptor upon fusion of early endosomes. The acceptor was a purified early endosomal fraction immunoisolated on beads and the donor was a metabolically-labeled early endosomal fraction in suspension. In the assay, both fractions were mixed in the presence of unlabeled cytosol, and then the beads were retrieved and washed. The donor proteins transferred to the acceptor were identified by two-dimensional gel electrophoresis and autoradiography. Approximately 50 major proteins were transferred and this transfer fulfilled all criteria established for endosome fusion in vitro. However, only a small subset of proteins was efficiently transferred, if donor endosomes were briefly sonicated to generate small (0.1 micron diam) vesicles before the assay. These include two acidic membrane proteins, and three alkaline peripheral proteins exposed on the cytoplasmic face of the membrane. Partial sequencing and Western blotting indicated that one of the latter components is annexin II, a protein known to mediate membrane-membrane interactions. Immunogold labeling of cryosections confirmed that annexin II is present on early endosomes in vivo. These data demonstrate that annexin II, together with the other four proteins we have identified, is a major component of fusogenic endosomal vesicles, suggesting that these proteins are involved in the binding and/or fusion process.

Amino Acid Sequence↗
PubMed1993

Staging: a neglected dimension in psychiatric classification.

The staging method, whereby a disorder is characterized according to seriousness, extension and features, has achieved wide currency in medicine but is currently neglected in psychiatry. Studies addressing or related to the issue of staging in schizophrenia, unipolar depression, bipolar disorder and panic disorder are discussed. The phenomenological development of these mental disorders may be categorized according to stages.

Bipolar Disorder↗
PubMed1993

Ifosfamide in the treatment of soft-tissue sarcomas: experience at the West German Tumor Center, Essen.

The response of ifosfamide-based chemotherapeutic regimens was retrospectively analyzed in adult patients with advanced soft-tissue sarcoma who were treated at the West German Tumor Center, Essen, between 1978 and 1990. Single-agent ifosfamide was given either in split doses of 60-80 mg/kg by 4-h infusion over 5 days or as a continuous 24-h infusion of 5 g/m2. Ifosfamide was given either in split doses of 40-50 mg/kg over 5 days or as a continuous infusion of 5 g/m2 in combination with doxorubicin (40-60 mg/m2, day 1), cisplatin (20 mg/m2, days 1-5), or etoposide (100 mg/m2, days 1, 3, and 5). Mesna was given to all patients as prophylaxis against urotoxicity. Of 54 evaluable patients receiving single-agent ifosfamide, 5 achieved a complete response (CR) and 10 showed a partial response (PR), for an overall response rate of 28%. Objective responses were more frequent in previously untreated patients (47%) than in pretreated patients (15%; P < 0.01). The addition of doxorubicin (n = 41) or cisplatin (n = 29) to ifosfamide did not significantly increase the response rate (29% and 41%, respectively) or median duration of remission as compared with ifosfamide alone. In addition, no significant difference was observed between the two ifosfamide regimens used: the 24-h continuous-infusion schedule (5 g/m2 per course, 27% response rate) and the 5-day fractionated regimen (10-15 g/m2 per course, 19% response rate). We conclude that the response and the median duration of remission produced by single-agent ifosfamide compare favorably with the results achieved using single-agent doxorubicin and the usually more toxic combination regimens.

Adolescent↗
PubMed1992

A tryptophan-substituted member of the AKH/RPCH family isolated from a stick insect corpus cardiacum.

A neuropeptide, Cam-HrTH-I, has been isolated from the corpus cardiacum of the Indian stick insect Carausius morosus. The peptide causes hyperlipaemia in Locusta migratoria and hypertrehalosaemia in Periplaneta americana and is related to the previously isolated Cam-HrTH-II (pGlu-Leu-Thr-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2) by substitution, apparently by a hexose, on the Trp residue. This appears to be the first example of such substitution on a Trp residue.

Amino Acid Sequence↗
PubMed1992

Purification, characterization and structure of protein phosphatase 1 from the cilia of Paramecium tetraurelia.

A type 1 serine/threonine protein phosphatase (PP1) which is mostly localized in the excitable ciliary membranes from the protozoan Paramecium, was purified to homogeneity. Approximately 4 micrograms enzyme of 37 kDa was isolated from 100 l axenic culture. The enzymic properties were characterized using phosphorylase a from rabbit skeletal muscle as a substrate and several known effectors of mammalian PP1. The protozoan PP1 was enzymically indistinguishable from its mammalian congener. The amino acid sequence of the Paramecium PP1 was deduced from its cDNA. The full-length clone was obtained in several steps starting with a pair of degenerate primers made according to the two most conserved peptides of rabbit PP1 and PP2A. The gene encodes a protein of 36,392 Da. The identity of the cloned gene and the isolated ciliary PP1 was unequivocally established by microsequencing of four tryptic and cyanogen-bromide peptides which were generated from the purified protein. Paramecium PP1 shows 75% amino-acid-sequence identity with rabbit PP1 alpha. Areas of major differences are the C-termini and N-termini and a sequence between residues 219-242.

Amino Acid Sequence↗
PubMed1992

Interactions of rab5 with cytosolic proteins.

Rab proteins, one of the subfamilies of ras-like small GTP-binding proteins, are attached to cellular compartments or transport vesicles and may determine the specificity of fusion between these compartments and vesicles. It has been proposed that they alternate between a membrane-bound and a cytosolic state during their functional cycle. We have used a photo-crosslinking approach to identify their cytosolic interaction partners. In vitro synthesized rab5 was cross-linked in the presence of ATP mainly to three cytosolic proteins of 52, 65, and 85 kDa. Sucrose density gradient centrifugation of the cross-linked products suggested that they were part of a 10-14 S complex. Furthermore, rab5 was cross-linked to these and additional cytosolic proteins of 42, 48, and 160 kDa in the absence of ATP. Unexpectedly, upon ATP depletion of the cytosol cross-linked and noncross-linked rab5 was found in a sedimentable high molecular weight structure. Other members of the rab subfamily, but not N-ras, also sedimented under these conditions. Electrophoretic and electron microscopic analysis of the pelleted material revealed that it contained actin filament bundles and intermediate filaments. Our data suggest that cytosolic rab proteins interact with several proteins in a 10-14 S complex, and that the rab proteins may interact directly or indirectly via this complex with the cytoskeleton.

Actins↗
PubMed1992

Primary structures of the hypertrehalosemic peptides from corpora cardiaca of the primitive cockroach Polyphaga aegyptiaca.

Two hypertrehalosemic neuropeptides from the corpus cardiacum of the cockroach Polyphaga aegyptiaca were isolated by reversed-phase high-performance liquid chromatography, and their primary structures were determined by pulsed-liquid phase sequencing employing Edman chemistry, after enzymically deblocking the N-terminal pyroglutamate residue. As neither peptide was cleaved by carboxypeptidase, the C-terminus of each peptide was also blocked. Both peptides were found to be uncharged octapeptides with the sequences: Peptide 1: pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp-NH2; and peptide 2: pGlu-Ile-Thr-Phe-Thr-Pro-Asn-Trp-NH2. Both peptides are clearly defined as members of the adipokinetic hormone/red pigment-concentrating hormone family of peptides. Whereas peptide 1 is identical in structure to the previously sequenced hypertrehalosemic neuropeptide from tenebrionid beetles (and is therefore designated the acronym Tem-HrTH), peptide 2 is a novel peptide and is designated the acronym Poa-HrTH. Both synthetic peptides caused an increase in the hemolymph carbohydrate concentration in P. aegyptiaca, specifically changing the trehalose concentration. The novel peptide Poa-HrTH was not very potent in elevating blood carbohydrates in the American cockroach.

Amino Acid Sequence↗
PubMed1992

Colorimetric determination of free and total cholesterol by flow injection analysis with a fiber optic detector.

A flow injection method for the determination of total and free cholesterol is presented. Cholesterol esterase and cholesterol oxidase are immobilized on aminoalkyl glass beads. The beads are packed into a tubular glass reactor. The cholesterol esters traversing through the esterase reactor are cleaved to cholesterol and fatty acids. The oxidase reactor converts cholesterol to cholest-4-en-3-one and hydrogen peroxide is generated. The sample stream is merged with reagent streams consisting of a peroxidase solution and a solution of 2,2'-azino-bis-(3-ethyl-benzthiazoline-6-sulfonic acid) diammonium salt, and a hydrogen peroxide-dependent color reaction takes place in a short coiled reactor. The signal is monitored by means of fiber optic instrumentation. Cholesterol concentration can be related to the absorption of the oxidized dye form at a wavelength of 425 nm. The working range is 0.5-0.8 mmol l-1, and the sample throughputs are 60 and 30 h-1 for free and total cholesterol, respectively.

Cholesterol↗
PubMed1992

Dyspnea, anxiety, and depression in chronic respiratory impairment.

In order to examine the relationship of dyspnea to anxiety and depression, the authors rated dyspnea using several methods in 50 patients with chronic respiratory impairment. Anxiety and depression were measured by the Symptom Checklist-90 and the Symptom Questionnaire. Results varied with the method of assessing dyspnea. Physician-rated dyspnea was significantly associated with patients' self-ratings of breathlessness as well as with pulmonary function tests, but not with any of the self-rating scales of emotions. Self-rated breathlessness was significantly associated with self-rated depression. In multiple regression analyses, depression was predictive of breathlessness. When the sample was limited to patients with chronic obstructive pulmonary disease, the results remained the same. The patients were significantly more depressed and anxious than matched family practice patients. In the study of the complex relationship of dyspnea to physical and emotional factors, it is desirable to use more than one measure of dyspnea because the results depend in part on the method of assessment.

Adult↗
PubMed1992

Panic disorder and hypochondriacal fears and beliefs.

The purpose of this study was to examine correlates of hypochondriacal fears and beliefs in patients with panic disorder (PD) (n = 54). They were evaluated using the structured diagnostic interviews for axis I and axis II disorders (SCID-UP-R and SCID-II). They were administered the Illness Attitudes Scales (IAS) as a measure of hypochondriacal fears and beliefs, the Hopkins Symptom Checklist 90 (HSCL), and the Fear Questionnaire (FQ). One half of the patients rated themselves as having substantial hypochondriacal fears and beliefs. The sample was divided into groups of patients seeking predominantly treatment or relief from symptoms (treatment-oriented), and those who were searching for a cause of their illness (explanation-seeking): the latter had significantly more hypochondriacal concerns. Avoidant, histrionic, and borderline personalities were more common in the hypochondriacal group. The results of several analyses suggest that patients with PD who are also agoraphobic, fear physical disease more and have more false beliefs of having a disease than PD patients without agoraphobia.

Adolescent↗
PubMed1992

Patterns of comorbidity in panic disorder and agoraphobia.

Diagnoses of comorbid disorders were determined in a sample of 54 patients with panic disorder as defined in DSM-III-R. The sample was divided into the following three groups: (1) uncomplicated panic disorder (PDU); (2) panic disorder with mild agoraphobia (PDM); and (3) panic disorder with moderate to severe agoraphobia (PDA). In comparison with patients with PDU, patients with PDA had higher comorbidity rates in general, received multiple comorbid diagnoses more frequently, had a higher prevalence of major depression, dysthymia, social phobia, generalized anxiety disorder, and obsessive-compulsive disorder, and scored higher on most measures of self-rated psychopathology. These findings support the notion that PDA may be a disorder essentially different from PDU.

Adult↗