Aromatic and branched-chain amino acid levels in alcoholics.

Plasma aromatic amino acid (AAA) and branched-chain amino acid (BCAA) concentrations were determined in 292 alcoholics. The BCAA/AAA molar ratio in patients with alcohol withdrawal symptoms was compared with the ratio in patients without such symptoms. The BCAA/AAA molar ratio in patients with transient hallucinations or with delirium tremens was significantly lower than that in patients without these symptoms. The BCAA/AAA molar ratio tended to be lower in patients with alcohol withdrawal seizures than in patients without such symptoms. The BCAA/AAA molar ratio had a negative correlation with plasma total bilirubin and LDH, and a positive correlation with plasma cholinesterase and albumin. These results indicate that abnormalities of amino acid metabolism caused by liver damage in alcohol dependence may have an important role in the pathogenesis of the alcohol withdrawal syndrome.

[Gastric emptying in elderly patients with cerebral vascular diseases and the effect of trimebutine].

The authors investigated gastric emptying in 18 elderly patients with cerebral vascular diseases using the acetaminophen method. Subjects were divided into 2 groups according to their levels of daily activity. One group consisted of 10 comatose patients (71-92 years old), the other consisted of 8 patients (74-95 years old) who could walk by themselves. We also investigated gastric emptying in 6 comatose patients (38-83 years old) because of other diseases such as amyotrophic lateral sclerosis and in 11 elder controls (75-95 years old). In elderly controls, the acetaminophen concentration at 45 minutes was 9.08 +/- 1.71 micrograms/ml. In comatose patients due to cerebral vascular diseases, the concentration was 3.89 +/- 1.60 micrograms/ml, which showed significantly delayed gastric emptying (p < 0.05). In patients with cerebral vascular diseases who could walk, the concentration was 6.51 +/- 0.99 micrograms/ml. In comatose patients by another diseases, the concentration was 5.82 +/- 1.13 micrograms/ml. We suspected that delayed gastric emptying is related to the comatose state. Trimebutine significantly (p < 0.01) improved gastric emptying in comatose patients with cerebral vascular diseases.

Herpes simplex encephalitis: further evidence for persistent infection in the CNS.

Herpes simplex virus (HSV) antibody titers and IgG, IgM and IgA concentrations in the cerebrospinal fluid were serially measured in a patient with HSV encephalitis during a follow-up period of 32 months. HSV antibody titers, all classes of immunoglobulins and Ig% showed significant elevation during the course of illness, though IgM% and IgA% gradually declined after the acute phase. Autopsied brain tissue failed to yield a virus isolate, but conspicuous perivascular lymphocyte infiltrate, which is compatible with HSV encephalitis, was seen. These observations suggest the occurrence of HSV persistence and persistent antigen stimulation in the central nervous system, analogous to the well-recognized latent condition within the trigeminal ganglion.

Correlation of local cerebral blood flow, glucose utilization, and tissue pH following a middle cerebral artery occlusion in the rat.

The use of three sets of the double-tracer autoradiographic technique to measure topographical changes of local cerebral blood flow (LCBF), glucose utilization (LCGU), and tissue pH following a 3 h middle cerebral artery (MCA) occlusion in the rat is described. In a sham-operated group of animals there was 10% reduction of LCBF and 7% reduction of LCGU in the most affected areas as compared to the contralateral homologous regions. However, the ratio of LCGU/LCBF in the affected areas remained within normal limits. In the MCA-occluded animals, LCGU showed a bimodal response to decreased LCBF. LCGU decreased with reduced LCBF until LCBF fell to 38% of normal. Below this LCBF level LCGU increased, most likely implying anerobic glycolysis. Decline of tissue pH corresponds to the mismatch of LCBF and LCGU. These results suggest that brain tissue pH change cannot be predicted on the basis of LCBF or LCGU alone.

[The effect of large dose dexamethasone on local cerebral blood flow (L-CBF) in ischemic rat brain].

Changes of local cerebral blood flow (l-CBF) were estimated by autoradiographic techniques in middle cerebral artery occlusion rats given a large dose of (3 mg/kg) dexamethasone. The sensory-motor, parietal, auditory and olfactory cortices showed a significant reduction (greater than 25%) of l-CBF. In MCA occlusion with large dose dexamethasone group, ischemic cortices showed significant reduction from the only MCA occlusion group (highest 36%). There was no significant reduction of l-CBF in the deep structures. The effects of dexamethasone on drains with various pathologies have been studied both clinically and experimentally with many kinds of techniques. These effects are now being reevaluated. Still controversial however, is the mechanism that determines whether dexamethasone has beneficial, non-beneficial, or harmful effect. This study may help us to unravel the mechanism of steroid effects, as well as the relationship between corticosteroid and central nervous system.

[Quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow and local cerebral glucose utilization using 14C-IAP and 18F-FDG].

We have reported a quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) using 14C-IAP and 18F-FDG respectively. Six awake normal rats and 3 left middle cerebral artery (MCA) occluded rats were used for this experiments. A 50-hold greater radioactivity of 18F was administered and the first exposure was done for 2 hours to obtain a 18F image. Three days later (39 half-lives of 18F), a second exposure was done for 5 to 6 days to obtain the 14C image. Tissue concentration of 14C was measured relative to the commercially available 14C-methyl methacrylate standards. 18F standards were prepared in each experiment. Cross contamination of 14C in the first exposure was less than 2% in the normal state and less than 4% even in the uncoupling condition. The values obtained by this methods for LCBF and LCGU agreed closely with those obtained by a single tracer technique previously reported in the literature. The technique outlined in this paper also provided local glucose utilization flow ratio (LGFR) for the first time. LGFR was obtained by dividing the LCGU image by LCBF image and was expressed as percent mumol/ml. The mean LGFR of control rats was 76 +/- 8% mumol/ml. In a MCA occlusion group, LGFR of ischemic cortex increased until 2 to 3 times higher than that of contralateral non-ischemic cortex. Oxygen glucose index image which was obtained from the LCGU and A-V differences of O2 showed that approximately half of the glucose was metabolized anerobically.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiographic determination of brain pH following middle cerebral artery occlusion in the rat.

A method of quantitative autoradiography using 14C-labelled 5,5-dimethyl-2, 4-oxazolidinedione 14C-DMO to evaluate the local changes in brain pH after ischemia is described. In normal control rats the calculated tissue pH values in gray matter were slightly lower than those in white matter, and there was no significant difference in the calculated pH among the various structures in cortical and subcortical gray matter. Four hours after a left middle cerebral artery (MCA) occlusion, marked reductions in 14C-DMO concentrations were demonstrated in the anterior two-thirds of the cerebral cortex and in the lateral part of the caudate nucleus indicating tissue acidosis in these areas. Although several assumptions are required for the calculation of pH in brain tissue, this method would appear very useful in the investigation of the altered metabolic state in ischemic brain.

Ataxic hemiparesis in patients with primary pontine hemorrhage.

Two patients with small primary pontine hemorrhage developed a syndrome identical to ataxic hemiparesis, one of the lacunar syndromes of Fisher. The possible mechanisms of the homolateral cerebellar signs, pyramidal signs, and dysarthria are discussed. Lesions of the ipsilateral pontine nuclei may be responsible for the homolateral ataxia.

Impairment of smooth pursuit eye movement in chronic alcoholics.

Smooth pursuit eye movement was quantitatively evaluated in 99 chronic alcoholics and in 100 nonalcoholic control subjects. In both groups the smooth pursuit was increasingly impaired with advancing age, but in chronic alcoholics the smooth pursuit eye movement was more frequently (42.4%) impaired than in age-matched controls (20.0%, p less than 0.005). The characteristic feature of the impairment observed in chronic alcoholics was prominent saccadic movement of the eyes; ataxic pursuit was less common. It is suggested that the impairment of smooth pursuit eye movement in alcoholics is probably attributable to 'premature aging' of the cerebral cortex caused by chronic alcohol abuse.

Influence of cerebral venous obstruction on cerebral circulation in humans.

The influence of cerebral venous obstruction on cerebral circulation was investigated in three patients with cerebral venous and sinus thrombosis in the chronic stage. The xenon Xe 133 intracarotid injection method was used to evaluate the cerebral blood flow (CBF). Values for CBF showed a slight decrease in all patients, despite intact cerebrovascular autoregulation. In two of the three patients, hypercapnia failed to increase CBF, but hyperventilation decreased CBF normally. This phenomenon can be explained on the basis of both failure of the capacitance vessels on the venous side to dilate and an increased intracranial pressure and is not attributable to decreased carbon dioxide reactivity. Long-lasting obstruction of the venous system can lead to a slight reduction in CBF and not affect cerebral autoregulation or CO2 reactivity itself in humans.

Purification and characterization of 1,2-alpha-mannosidase of Aspergillus oryzae.

1,2-alpha-Mannosidase was purified approximately 1,400-fold from an enzyme product of Aspergillus oryzae. The enzyme showed a single band in disc gel electrophoresis and the molecular weight was estimated to be about 49,000 daltons by gel exclusion chromatography. The substrate specificity of the enzyme was examined with mannooligosaccharides, yeast mannan, glycopeptides, and a glycoprotein. The alpha-(1 leads to 2)-linking mannose residues located at the nonreducing-ends of the substrates were selectively removed by the enzyme, whereas p-nitrophenyl alpha-D-mannopyranoside was completely stable to the enzyme. alpha-(1 leads to 2)-Linking mannose residues in intact bovine pancreatic ribonuclease B were also removed completely with the enzyme. The enzyme showed an optimum pH in the range of pH 4.9 to 5.3 and had a Km value of 0.57 mM with 1,2-alpha-mannobiose. The present alpha-mannosidase was quite stable, and the activity was inhibited by D-mannono-gamma-lactone and by heavy metal ions, including zinc ions.

Immunoglobulins in cerebrospinal fluid--enzyme-immunoassay.

Using an enzyme-immunoassay (EIA) technique we established control values for IgA and IgM in cerebrospinal fluid (CSF). These values, together with IgG values determined by single radial immunodiffusion (SRID) technique, showed significant positive correlations with CSF total protein values. The CSF IgA and IgM levels were related to corresponding levels determined in serum. In addition, the values for all 3 immunoglobulin classes in CSF as well as CSF total protein values showed positive correlation with age of subjects, and IgG% and IgA% inreased with age. This new EIA procedure can be completed within 24 h and is sensitive enough for determining all 3 immunoglobulin classes using a small amount (100 microliter or less) of native CSF.