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Biomedical subjects

M Huber

Publications and source records attributed to M Huber.

At least 217 records · Page 12Linked to original sources

Positron emission tomography with (18F)methylspiperone demonstrates D2 dopamine receptor binding differences of clozapine and haloperidol.

Four schizophrenic patients were investigated with dynamic positron emission tomography (PET) using (18F)fluorodeoxyglucose (FDG) and (18F)methylspiperone (MSP) as tracers. Two schizophrenics were on haloperidol therapy at the time of MSP PET. The other two schizophrenics were treated with clozapine, in one of them MSP PET was carried out twice with different daily doses (100 mg and 450 mg respectively). Neuroleptic serum levels were measured in all patients. Results were compared with MSP PET of two drug-free male control subjects and with a previous fluoroethylspiperone (FESP) study of normals. Three hours after tracer injection specific binding of MSP was observed in the striatum in all cases. The striatum to cerebellum ratio was used to estimate the degree of neuroleptic-caused striatal D2 dopamine receptor occupancy. In the haloperidol treated patients MSP binding was significantly decreased, whereas in the clozapine treated patients striatum to cerebellum ratio was normal. Even the increase of clozapine dose in the same patient had no influence on this ratio. Despite the smaller number of patients the study shows for the first time in humans that striatal MSP binding reflects the different D2 dopamine receptor affinities of clozapine and haloperidol.

Adult↗

Signs and symptoms from nicotine gum abstinence.

This study examined and compared withdrawal signs and symptoms from cessation of 0, 2 and 4 mg nicotine gum. In addition, a comparison was made between nicotine gum versus cigarette withdrawal symptoms. Smokers first underwent cigarette deprivation for 4 days and then were randomly assigned to 0 (N = 16), 2 (N = 25), and 4 (N = 21) mg gum. They were asked to chew the gum for 1 month and then to undergo a 4-day nicotine gum deprivation period. The results showed a number of significant changes occurring after deprivation from 4 mg gum, one change from 2 mg gum, and no changes from 0 mg gum. There were no significant differences in severity of withdrawal among the various doses of nicotine gum. There were more severe symptoms of withdrawal from cigarette as opposed to 4 mg nicotine gum deprivation.

Adult↗

Neurological cause of late postpartum seizures.

A 32-year-old primigravida showed signs of pre-eclampsia before delivery of a healthy boy at term. The CSF-space was accidentally punctured during epidural anaesthesia in labour. One day later hypertension was noted and the patient had a single generalized fit. For the next three weeks she had postural headaches, fluctuating hypertension, intermittent hearing loss and double-vision. On the 22nd day of postpartum, the patient had the first of a series of partial and later generalized seizures, followed by hemiparesis, alteration of consciousness, and finally slow recovery with corticosteroid therapy. Bilateral subdural effusions and generalized meningeal thickening were found on MR scans. Repeated MRI excluded sinus thrombosis and documented the response to treatment.

Adrenal Cortex Hormones↗

The peritrophic membrane as a barrier: its penetration by Plasmodium gallinaceum and the effect of a monoclonal antibody to ookinetes.

We studied the point at which a monoclonal antibody (mAb C5) to a surface protein (Pgs25) on Plasmodium gallinaceum ookinetes blocked the infection of Aedes aegypti mosquitoes. The antibody did not block the development of zygotes to ookinetes in vitro. Development of ookinetes to oocysts in the mosquito was blocked to the same extent whether zygotes grew to ookinetes in the presence of mAb C5 or the antibody was added after the ookinetes had reached full development. When ookinetes developed in vitro in the presence of mAb C5, antibody remained on the surface of the parasite for the next 50 hr and did not block attachment to the peritrophic membrane. When ookinetes were fed to mosquitoes, two subpopulations of mosquitoes were observed (high numbers of oocysts per midgut and low numbers of oocysts per midgut). mAb C5 reduced the number of oocysts per midgut in the subpopulation that had low numbers of oocysts. The subpopulation that had high numbers of oocysts was unaffected by antibody, indicating that the antibody did not block invasion of the midgut epithelium. When mAb C5 was fed with gametocytes, the parasites invaded the epithelium at the same time (between 30 and 35 hr after the blood meal) as in controls, although at a markedly reduced rate. The ultrastructural observations were consistent with a block of parasites within the peritrophic membrane and not with a block at the epithelium, as parasites were not seen to accumulate within the space between the peritrophic membrane and the epithelium. The mechanism by which mAb C5 to Pgs25 of P. gallinaceum blocks the penetration of the peritrophic membrane remains undefined. We present evidence that the parasite modifies the peritrophic membrane during penetration, an observation first made for Babesia microti during penetration of the peritrophic membrane in Ixodes ticks. Ookinetes in the absence of antibodies appeared to disrupt the layers of the peritrophic membrane, suggesting an enzymatic mechanism for penetration.

Aedes↗

Measles virus phosphoprotein retains the nucleocapsid protein in the cytoplasm.

Measles virus (MV) proteins were efficiently expressed in COS and Vero cells from vectors based on the strong cytomegalovirus enhancer-promoter and the simian virus 40 origin of replication. When expressed alone, nucleocapsid protein (N) migrates predominantly into the nucleus whereas phosphoprotein (P) is located in the cytoplasm. Coexpression of N and P proteins results in retention of the N protein in the cytoplasm, as seen also in infected cells. The retention of N protein is due to specific interactions with the P protein since coexpression of N with either the matrix or the hemagglutinin protein had no effect. Mapping of the regions of N-P interactions on P protein revealed that the carboxy-terminal 40% of P was sufficient for specific binding to N; however, the carboxy-terminal 60% of P was required for retention of N in the cytoplasm. Thus, the V and C proteins encoded within the first half of the P gene are not involved in the cytoplasmic retention of N protein. N protein might be fortuitously targeted to the nucleus as a result of its many basic amino acids, presumably destined to interact with the MV genome. However, this set of experiments has allowed to analyze in vivo the interactions between the N and P proteins.

Animals↗

Cloning and characterization of an unusual elongation factor-1 alpha cDNA from Entamoeba histolytica.

The coding sequence deduced from two overlapping cDNA inserts obtained from a pathogenic strain of Entamoeba histolytica revealed a striking homology (greater than 85%) with elongation factor EF-1 alpha from Saccharomyces cerevisiae and Artemia salina. The deduced amino acid sequence predicted a size of 49 kDa, and antibodies raised against the S. cerevisiae EF-1 alpha cross-reacted with an amoebic protein of similar size (45-47 kDa). Sequence analysis of the cDNA revealed that the 5' untranslated region contained a stretch of 190 nucleotides which was perfectly complementary to a segment of the 3' terminal coding region situated 1015 bases downstream of the methionine initiation codon. Electron microscopy of self-renatured cDNA confirmed the potential of such molecules to form a stem-loop secondary structure. The presence of the complementary sequences was confirmed at the genomic level by sequence analysis of polymerase chain reaction-amplified segments which span both the 3' and 5' terminal complementary regions. Comparison of the deduced amino acid sequence of E. histolytica EF-1 alpha with Ef-Tu from Escherichia coli and EF-1 alpha from different sources, suggested that the major functional domains of the protein are located within the loop structure.

Amino Acid Sequence↗

Functional and nonfunctional measles virus matrix genes from lethal human brain infections.

Subacute sclerosing panencephalitis (SSPE) is a lethal disease induced by the persistence of measles virus in the human brain. In many SSPE cases, the viral matrix (M) protein cannot be detected; in others, M proteins of the expected size are found and sequence analysis of M cDNAs has confirmed that the reading frames are intact, showing only several missense mutations. To determine whether these alterations result in nonfunctional proteins, we have replaced the M gene of an infectious full-length genomic cDNA (from vaccine strain Edmonston) with different M genes derived from four patients with SSPE. One of the SSPE M genes tested proved to be functionally competent, giving rise to a virus yielding titers similar to those of viruses containing the M gene from control lytic strains. The other three SSPE M genes were not functionally competent in the same test. In all three cases, the inactivating changes resided in the carboxyl-terminal half of the M protein, as shown by the exchange of either of the two genes halves. In summary, mutational M gene alterations, which either prevent synthesis of M protein altogether or only allow synthesis of nonfunctional M protein, have been detected by us and by others in 9 of 10 SSPE cases. The one functional M gene appears to be an exception to the rule, indicating that M gene alteration might not be an absolute requirement for disease development.

Animals↗

Complex sensory cross integration deficits in a case of corpus callosum agenesis with bilateral language representation: positron-emission-tomography and neuropsychological findings.

A 45-year-old right-handed patient with total callosal agenesis and absence of the anterior commissure was examined neuropsychologically and with magnetic resonance and positron emission tomography (PET with 18FDG) of the brain. PET results showed, in the resting state, a bilateral metabolic reduction in the hippocampal formation and a left hemispheric reduction in the amygdala, thalamus and in the occipital and temporoparietal junction areas of the cerebral cortex. Under speech activation hypermetabolic glucose activity was observed bilaterally in the region of the Wernicke area and within the left Broca area. Neuropsychologically, on the whole the patient behaved normally, the exceptions being an inability to associate olfactory stimuli with words, a clear left ear advantage in dichotic listening, and a similar high performance in recognizing verbal stimuli presented tachistoscopically to either hemisphere. From comparing the patient's behavior with that of other acallosals it appears that highly individual variants of cerebral organization and/or reorganization result from the lack of the brain's main commissural system and that the processing of sensory information deviates considerably especially in cases in whom the two main telencephalic commissures--corpus callosum and anterior commissure--are absent.

Brain↗

Antisense peptides: tools for receptor isolation? Lack of antisense MSH and ACTH to interact with their sense peptides and to induce receptor-specific antibodies.

The use of antisense peptides for receptor isolation as proposed by Blalock and his colleagues (e.g. TIBTECH 8, 140-144, 1990) was tested for human ACTH as well as alpha- and beta-MSH. We synthesized the corresponding antisense peptides HTCAh, HSM-alpha and HSM-beta and analyzed them for specific interaction with the sense peptides using several types of binding assay and bioassay. Similarly HTCAh antibodies were tested for binding to ACTH receptors and ACTH antibodies. All these experiments were negative, i.e. there was no specific interaction between sense and antisense peptides nor between the corresponding antibodies. Receptor binding of the sense peptides was not affected by the antisense peptides or HTCAh antibodies. Unexpectedly, HTCAh but not HSM-alpha or HSM-beta was a weak MSH agonist acting through a site independent of the MSH receptor. A detailed analysis of the concept of antisense peptides revealed that the theoretical background of the hypothesis of the 'molecular recognition theory' is rather weak, explaining the failure of various attempts to obtain specific receptor antibodies.

Adrenocorticotropic Hormone↗

Functional and mental status outcomes of clients discharged from acute gerontological versus medical/surgical units.

The goal of a specialized geriatric unit in an acute care hospital setting is to minimize losses and have the patient maintain or achieve an optimal level of functioning and cognition. This study showed that more acute clients on a geriatric unit maintained or improved functioning capacity at a significant level in fewer days and at a lowered cost. Nursing implications include inservice training specific to caring for geriatric clients and providing early assessment and identification of strengths. Interventions such as reality orientation and early proactive measures can be used to maintain or achieve optimal cognitive functional capacity.

Activities of Daily Living↗

[Analysis of polycyclic aromatic hydrocarbons in lipid-containing biological matrices--study of contamination of breast milk by benzo(a)pyrene along transit routes through Tyrol].

41 samples of human milk from the region of Tyrol were investigated with regard to benzo(a)pyrene content. A complicated analytical preparatory method had to be worked out. The percentage recovery of benzo(a)pyrene was 85-90. Analysis was carried out by means of capillary gas chromatography and flame ionization detection or mass spectrometry. The limit of benzo(a)pyrene detection is 0.1-1 microgram/kg (single ion monitoring). None of the investigated samples of milk showed the presence of benzo(a)pyrene.

Air Pollutants↗

Photoaffinity labeling of leukotriene binding sites in hepatocytes and hepatoma cells.

The method of direct photoaffinity labeling in the frozen state using the leukotrienes as suitable photolabile compounds may serve to identify and characterize polypeptides which interact with these eicosanoids during their hepatobiliary transport and metabolism. Furthermore, it will be a helpful technique to evaluate changes in the cell-specific protein pattern during neoplastic dedifferentiation of hepatocytes.

Affinity Labels↗

[Fatality of purulent meningitis in adults 1950 to 1985. Retrospective study of the case histories of 391 patients of the Cologne Neurologic University Clinic].

Although intensive care medicine and chemotherapy of bacterial infections have made great progress during the last 30 years, therapeutic efficacy in bacterial meningitis in adult patients could not be improved. Retrospective analysis of 391 cases of adult bacterial meningitis between 1950 and 1985 shows no significant changes in etiology and only slight reduction in mortality. The course of the disease depends mostly on age, state of consciousness and CSF cell count. Cases of meningitis in HIV patients and cerebral tuberculosis have not been evaluated in this study.

Adult↗