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Biomedical subjects

H Weiner

Publications and source records attributed to H Weiner.

At least 91 records · Page 5Linked to original sources
PubMed1994

Quantitative EEG in patients with AIDS and asymptomatic HIV infection.

Although neuropsychiatric abnormalities are common in subjects with the acquired immunodeficiency syndrome (AIDS), they are less frequent in asymptomatic human immunodeficiency virus (HIV) seropositive subjects. In contrast, others have reported high rates of electroencephalographic (EEG) abnormality among asymptomatic subjects. Here we report clinical and quantitative EEG findings across all stages of the disease in order to define when during the course of illness abnormalities are detectable. We studied 28 men with AIDS, 32 men with asymptomatic HIV infection, and 56 uninfected controls using clinical and quantitative EEG, measures of immunosuppression, and tests of neuropsychological performance. All were gay or bisexual without other significant risk factors for encephalopathy. We found very low rates of clinical EEG abnormality (less than 7%) among the asymptomatic HIV-infected group, a rate comparable to those of the uninfected group (7.1%). There were no differences between asymptomatic HIV-seropositive subjects and uninfected controls on quantitative EEG measures. Among AIDS patients 28.6% had abnormal clinical electroencephalograms. On quantitative measures, the greatest differences were found in the 6-10 Hz band, where AIDS patients had consistently increased absolute power, relative power, and coherence compared to the uninfected and asymptomatic seropositive groups. A subgroup (n = 9) of asymptomatic HIV-seropositive subjects had worsening performance on Trailmaking test, part B, at or after the time of recording. This subgroup had quantitative electroencephalographic measures similar to those of the AIDS patients and different from the remainder of the asymptomatic HIV-seropositive group.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1994

A repressive coping style protecting from emotional distress in low-renin essential hypertensives.

OBJECTIVE: To investigate the relationship between the behavioural characteristics and specified subgroups of patients with essential hypertension. DESIGN AND METHODS: Fifty-four patients were classified into groups with a high (n = 9), normal (n = 35) or low plasma renin activity (n = 10), and were compared with 20 normotensive subjects by psychological tests. Standardized tests were used to measure anger expression, defensiveness and the subjects' psychological status (e.g. anxiety, depression). RESULTS: A repressive coping style, defined by a high defensiveness and low anxiety levels, was found significantly more often in patients with low than in patients with high plasma renin activity and normotensive subjects. The patients with high plasma renin activity scored significantly higher on suppressed anger, anxiety and interpersonal sensitivity than did those with low plasma renin activity. The scores of the normal plasma renin activity group were similar to those of the normotensive group. CONCLUSIONS: The results underline that there is not one hypertensive 'personality'. Whereas the patients with a high plasma renin activity appear to be more susceptible to emotional conflicts, the patients with low plasma renin activity report low emotional distress and maintain an apparently well-adjusted facade.

Adaptation, Psychological↗
PubMed1994

Aldehyde dehydrogenase and acetaldehyde metabolism.

Ingested ethanol is first oxidized to acetaldehyde, primarily in the liver, then further oxidized to acetate. The oxidation of acetaldehyde is catalyzed by an NAD-dependent aldehyde dehydrogenase located in the liver mitochondrial matrix space. To date only one variant form of aldehyde dehydrogenase has been identified. Many Oriental people have an inactive mitochondrial form which possesses a lysine residue at position 487 rather than glutamate which is found in the active enzyme. We employed site directed mutagenesis to probe for active site residues in the enzyme and identified a number of residues which, if mutated, would produce an impaired or inactive enzyme. These mutations could be obtained by single base changes in the DNA coding for the enzyme. Though not identified in human populations, it is possible that these null mutants of the enzyme could exist in people deficient in active mitochondrial aldehyde dehydrogenase.

Acetaldehyde↗
PubMed1993

Sucrose-phosphate synthase phosphatase, a type 2A protein phosphatase, changes its sensitivity towards inhibition by inorganic phosphate in spinach leaves.

The activity of a type 2A protein phosphatase from spinach leaves was monitored using phosphorylated sucrose-phosphate synthase (SPS) as a substrate. After partial purification the overall activities of sucrose-phosphate synthase phosphatase (SPS-P) recovered from leaves harvested in the dark and in the light did not vary. However, SPS-P preparations from darkened leaves were more strongly inhibited by inorganic phosphate and certain phosphorylated compounds than preparations from illuminated or mannose fed leaves. We conclude, that activation of SPS involves an interconversion of multiple forms of SPS-P activity.

Catalysis↗
PubMed1993

Import, processing, and two-dimensional NMR structure of a linker-deleted signal peptide of rat liver mitochondrial aldehyde dehydrogenase.

Previous NMR studies (Karslake, C., Piotto, M. E., Pak, Y. M., Weiner, H., and Gorenstein, D. G. (1990) Biochemistry 29, 9872-9878) had shown that a 22-amino acid signal peptide of rat liver aldehyde dehydrogenase (ALDH) when bound to a micelle had two amphiphilic alpha-helices, one located at the N terminus and the other at the C terminus. It was shown that deletion of either helix caused the precursor protein not to be imported (Wang, Y., and Weiner, H., (1993) J. Biol. Chem. 268, 4759-4765). The two helices are separated by a Arg-Gly-Pro flexible "linker" region, and to test the role of this linker region in the import and processing of the precursor protein, we deleted it from the ALDH signal peptide and precursor protein. The 19-amino acid signal peptide of ALDH, to which has been added 3 residues at the C terminus and from which has been deleted the 3-residue flexible linker region, has been studied by two-dimensional NMR in a dodecylphosphocholine micelle. In this membrane-like environment the peptide contains a single alpha-helical segment that extends almost the entire length of the peptide. NH exchange experiments show residues on the hydrophobic face of the peptide to exchange much more slowly than those of the hydrophilic face. Combined with the previous study, these results suggest that precursor protein import simply requires a sufficiently long amphiphilic helix (or helices) to bind stably to the membrane. The N and C helices of native ALDH are only about 6-8 residues long; this represents only about two turns of a helix, and either helix on its own does not provide enough stabilization to ensure folding and binding to the membrane. The linker-deleted ALDH peptide contains a single helix of 12-14 residues that is long enough to provide a hydrophobic surface that can stably interact with the hydrophobic interior of the membrane. The function of the C helix in the native signal peptide is therefore to enhance the stability and binding of the N-terminal signal to the membrane. Significantly, unlike native ALDH precursor protein, the linker-deleted signal peptide precursor protein could no longer be processed after import into mitochondria. As explained by modeling of the alpha-helix and the NH exchange rate data, the precursor protein requires that the first several residues of the mature protein be part of the hydrophobic membrane associated face of the helix.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldehyde Dehydrogenase↗
PubMed1993

Serial quantitative EEG among elderly subjects with delirium.

Serial quantitative electroencephalographic (QEEG) studies were performed in 33 elderly delirious, demented, and control subjects to determine which QEEG variables were associated with changes in clinical state as measured by the Folstein Mini-mental State Examination (MMSE). Conventional EEGs and brain maps were independently rated by two electroencephalographers without knowledge of clinical diagnoses. Correlational analyses were performed using these ratings, along with numerical data from QEEG. In the delirium group (n = 15), changes in scores for the relative power map and changes in relative power in the alpha band had significant associations with changes in MMSE. In the dementia group (n = 10), changes in score for absolute power maps and changes in absolute power in the delta band had significant associations with changes in MMSE. In the control group, changes in MMSE over time were negligible. These findings have potential clinical utility in diagnosing delirium, and in providing a quantitative measure of its severity, which can be used serially.

Aged↗
PubMed1993

The presequence of rat liver aldehyde dehydrogenase requires the presence of an alpha-helix at its N-terminal region which is stabilized by the helix at its C termini.

Previous nuclear magnetic resonance data showed that the conformation of the signal peptide of rat liver mitochondrial aldehyde dehydrogenase in a micelle environment contained a N-helix and a C-helix which were separated by a flexible hinge region (Karslake, C., Piotto, M.E., Pak, Y.K., Weiner, H. and Gorenstein, D. (1990) Biochemistry 29, 9872-9878). Deletion of either helix from the presequence caused complete loss of the precursor import. Switching the positions of the two helices had little effect on import but decreased processing efficiency. Import was not affected by replacing the C-helix with the N-terminal helix of the presequence of cytochrome c oxidase subunit IV, however, it was decreased by replacing the C-helix with the C-terminal random coil of the oxidase's presequence. Circular dichroism studies on the synthesized signal peptides indicated that a helix in the C-segment of aldehyde dehydrogenase signal peptide was needed to stabilize the N-helix. It is concluded that a stable helix in the N-terminal region is necessary for a functional mitochondrial presequence. This helix could be obtained from its own sequence, or from the interaction with other portions of the presequence.

Aldehyde Dehydrogenase↗
PubMed1993

Role of the highly conserved histidine residues in rat liver mitochondrial aldehyde dehydrogenase as studied by site-directed mutagenesis.

One histidine residue (H235) is conserved in all known aldehyde dehydrogenases (ALDH), from Escherichia coli to human, except for those from P. oleovorans and rat hepatoma. Kinetic studies with horse liver mitochondrial ALDH indicated that a group with a pKa of 7 may be involved in the active site. Using site-directed mutagenesis, the four conserved histidine residues of the six histidines in rat liver mitochondrial ALDH were converted to alanines. Only modification of H235 and H29 caused alterations in properties of the enzyme. H29A had a decreased pI suggesting that this residue may normally be protonated. Its Vmax increased, as did the Km for NAD+, while the Km for propionaldehyde decreased. H235A had the same pI as the native enzyme but the Vmax decreased by 50%. Like native enzyme, H235A was active in Hepes and Mops buffer as well as in phosphate buffer. Purified H235A was thermally less stable than was native enzyme. H235 was also changed to F, Y, E, K, and Q. All of these substitutions resulted in the formation of insoluble aggregates or inclusion bodies when they were expressed in E. coli. It appears then that the highly conserved histidine residues may not be functioning as a general base in the deacylation step as we originally suggested. Instead, both H29 and H235 may be of structural importance and the presence of a histidine residue at position 235 may be required for the newly synthesized peptide to fold and/or assemble into the native conformation of ALDH.

Alanine↗
PubMed1993

Regional differences in brain electrical activity in dementia: use of spectral power and spectral ratio measures.

The pathologic changes in dementia of the Alzheimer's type (DAT) commonly affect selected brain regions. The cortical areas affected in multi-infarct dementia (MID) are less predictable and may be secondary to subcortical gray or white matter damage that is widespread in MID. We compared several types of quantitative EEG power measures (absolute and relative power, and ratios of power) to determine their regional distribution, and their association with changes in cognitive status and age. We examined 49 subjects with clinically diagnosed mild-to-moderate DAT, 29 with mild-to-moderate MID, and 38 elderly controls (CON). We used discriminant analysis to identify, for each parameter type, the brain region and frequency band where the parameter best distinguished between groups of subjects. The parameters showed regional differences in distinguishing between DAT and MID subjects, and in their association with age and cognitive status. All parameters were useful for detecting differences between normal and demented subjects and correctly identified comparable proportions of subjects as having dementia. Subjects who were abnormal on several parameters were much more likely to have dementia. The additive effects of these parameters in correct classification suggest that they may be monitoring different physiologic processes. Combinations of several types of parameters may be more useful than individual parameters for distinguishing demented from non-demented subjects.

Aged↗
PubMed1993

T cell responses to myelin basic protein in experimental autoimmune encephalomyelitis-resistant BALB/c mice.

In strains of mice that are susceptible to experimental autoimmune encephalomyelitis (EAE), cloned CD4+ T cells reactive with autologous myelin basic protein (MBP) have been shown to cause disease when transferred to naive syngeneic recipients. Recent reports indicate that under particular experimental conditions, 'resistant' strains of mice can also develop EAE, although cloned cells have not been isolated and characterized. An analysis of the characteristics of a panel of MBP-specific T cells and the antigen presenting capability of CNS-derived cells obtained from the resistant strain BALB/c is presented here. The data demonstrate that immunization of EAE-resistant BALB/c mice results in the activation of a heterogeneous group of T cells reactive with autologous MBP. Both peripheral antigen presenting cells, as well as microglia isolated from brains of BALB/c mice, are capable of stimulating these cloned MBP-specific T cells to proliferate. When optimally activated in vitro and then injected in vivo into syngeneic BALB/c recipients, three clones studied induced severe cachexia, resulting in loss of up to 35% of body weight before death. Two of the clones also induced clinical and histological EAE, while the third induced only occasional histological evidence of disease. Differences in epitope recognition, T cell receptor usage, cytokine profiles or regulatory mechanisms of self tolerance, may play important roles in preventing potentially destructive autoimmune reactions by these T cells capable of recognizing autologous myelin in the central nervous system.

Animals↗
PubMed1993

Cervical laminectomy and foraminotomy as surgical treatment of cervical spondylosis: a follow-up study with analysis of failures.

Ninety patients were followed after undergoing multilevel cervical laminectomy for cervical myeloradiculopathy secondary to cervical stenosis. Follow-up data was obtained by chart review and phone interview for all patients; 20% were examined at follow-up as well; 77% of patients were improved, 13% without change, and 10% worse at follow-up. No patients deteriorated in the immediate postoperative period. Greater than 50% of severely disabled patients had an excellent result, and 78% improved somewhat. It is concluded that cervical laminectomy is an effective procedure for treating patients with cervical spondylosis causing myeloradiculopathy. Reasons for failure of this procedure, although rarely identified on follow-up examination, are reviewed and briefly discussed.

Adult↗
PubMed1993

Cloning and expression of the full-length cDNAS encoding human liver class 1 and class 2 aldehyde dehydrogenase.

The amino acid sequences of both human class 1 and 2 aldehyde dehydrogenase (ALDH) and the sequences of the genes coding for them are known. Based on this sequence data, we designed primers and isolated the full-length cDNAs encoding both isozymes from a human liver mRNA pool. cDNAs were subcloned in the plasmid pT7-7 and expressed in Escherichia coli with a yield of approximately 3 mg ALDH protein/liter of cell culture, although only one-third of the enzyme was soluble. The soluble recombinantly expressed ALDHs were purified to homogeneity using a hydroxyacetophenone-Sepharose affinity column. The mitochondrial isozyme had a subunit molecular weight of 55 kDa, an isoelectric point of 4.9, and a specific activity of 1.10 units/mg, which were in good agreement with that from the native enzyme. The expressed cytosolic isozyme had the same subunit molecular weight (55 kDa) and pI (5.4) as that reported for the native enzyme and had a specific activity of 0.26 units/mg. The expressed mitochondrial isozyme could be recognized by antibodies raised against rat mitochondrial ALDH, whereas the cytosolic isozyme could be recognized by antibody raised against horse cytosolic ALDH.

Aldehyde Dehydrogenase↗
PubMed1993

EEG coherence in men with AIDS: association with subcortical metabolic activity.

The authors studied the relationship between cerebral metabolism and brain electrical activity in patients with acquired immunodeficiency syndrome (AIDS), using positron-emission tomography and quantitative electroencephalography. Electroencephalographic coherence in the 6-to 10-Hz band correlated positively with thalamic metabolic activity. Coherence adjusted for background activity correlated strongly and positively with basal ganglia metabolic activity. Posterior interhemispheric coherence showed the highest correlations with measures of metabolic activity. These results suggest that changes in coherence may reflect AIDS-related subcortical disease. The high correlations between the two different measures of cerebral activity support the validity of electroencephalographic coherence measures in studies of AIDS-related neuropsychiatric dysfunction.

AIDS Dementia Complex↗
PubMed1993

Applications of molecular biology to study aldehyde dehydrogenase.

Liver mitochondrial aldehyde dehydrogenase has been cloned and expressed in E. coli as the mature or the precursor form. This has allowed for site directed mutagenesis to be performed to study active site components of the enzyme. Residues investigated were cysteine, histidines and a glutamate. The import of the precursor into mitochondria in the presence and absence of added alcohols was investigated. Alcohols, in a dose dependent manner, inhibited the import of the precursor into isolated rat liver mitochondria.

Alcohols↗
PubMed1992

Crystallization and preliminary X-ray investigation of bovine liver mitochondrial aldehyde dehydrogenase.

Aldehyde dehydrogenase from bovine liver mitochondria has been crystallized using the sitting drop method of vapor diffusion at 22 degrees C. The crystals formed from solutions containing, 40 mM-sodium citrate, 1 mM-NAD+ and 21% to 24% polyethylene glycol 3400 (pH 5.3 to 5.5). X-ray diffraction data collected from these crystals indicate that the crystals belong to the orthorhombic space group P2(1)2(1)2(1) with cell dimensions of a = 153.7 A, b = 159.37 A and c = 101.45 A. The crystals diffract to at least 2.9 A and a tetramer may comprise the asymmetric unit.

Aldehyde Dehydrogenase↗
PubMed1992

Purification of liver aldehyde dehydrogenase by p-hydroxyacetophenone-sepharose affinity matrix and the coelution of chloramphenicol acetyl transferase from the same matrix with recombinantly expressed aldehyde dehydrogenase.

p-Hydroxyacetophenone was coupled to epoxy-activated Sepharose 6B to generate an affinity chromatographic matrix to purify aldehyde dehydrogenase. Purified beef liver mitochondrial aldehyde dehydrogenase specifically bound to the support and could be eluted with p-hydroxyacetophenone. A post-ammonium sulfate (30-55%) fraction of bovine liver was applied to the affinity gel column and aldehyde dehydrogenase was effectively purified, although not to complete homogeneity, indicating the potential selectivity of the matrix. Both beef liver cytosolic and mitochondrial aldehyde dehydrogenase bound to the column. A post-Cibacron blue Sepharose Cl-6B affinity-fractionated liver mitochondrial aldehyde dehydrogenase was purified to complete homogeneity by p-hydroxyacetophenone-Sepharose, thus eliminating the need for the isoelectric focusing step often employed. p-Hydroxyacetophenone was found to be a competitive inhibitor against propionaldehyde and noncompetitive against NAD. Escherichia coli lysates of recombinantly expressed aldehyde dehydrogenase were purified from E. coli lysates with one major 25-kDa protein contaminant also binding to the column, as detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The 25-kDa contaminant was found to be chloramphenicol acetyl transferase from sequence analysis and binding studies.

Acetophenones↗