Joachim D. Raese

Distribution of catecholamine-containing neurons in the normal human hypothalamus

We have studied the distribution of catecholamine-containing neurons in the hypothalamus of 8 normal adult human brains, using Schmorls stain for melanin and immunohistochemical staining for tyrosine hydroxylase (TH). TH immunoreactive perikarya were found in the wall of the third ventricle, in the areas in which dopaminergic neuroendocrine neurons are found in other primate species. Many of these neurons contained melanin pigment, and the percentage increased with age. Other melanin-pigmented neurons in the same distribution did not stain for TH, suggesting that postmortem TH immunostaining may not be sufficiently sensitive to visualize all catecholaminergic neurons. A separate group of larger TH-positive perikarya was seen in the lateral hypothalamic area. These may correspond to the incerto-hypothalamic dopamine neurons in other primate species. Only rare melanin-pigmented neurons were seen in this cell group, even at 66 years of age. Our data indicate that the hypothalamic neuroendocrine dopamine neurons in the human brain are distributed in a pattern similar to that in other primate species, and that both postmortem tyrosine hydroxylase and melanin staining provide an incomplete but representative sampling of the periventricular-arcuate cell group.

Cerebellar blood flow in schizophrenic patients and normal control subjects

We used 133Xe dynamic single-photon emission computed tomography (DSPECT) to measure the resting cerebellar blood flow in 17 neuroleptic-free schizophrenic and schizophreniform patients and 13 normal control subjects. A subset of these subjects (11 patients and 7 control subjects) additionally underwent activation studies during the Wisconsin Card Sorting (WCS) and Number Matching (NM) tests. Baseline relative cerebellar blood flow was significantly lower in older patients than in age-matched control subjects. For absolute cerebellar flow, there was a significant difference between patients and control subjects in the overall activation response (patients: NM 13.4% increase, WCS 15.7% increase; control subjects: NM 3.1% decrease, WCS 0.0% change). This difference was more pronounced in older subjects. Cerebral blood flow significantly increased during NM (patients: 21.3% increase, control subjects: 6.5% increase) and WCS (patients: 16.5% increase, control subjects: 9.7% increase). The difference in the magnitude of cerebral NM activation between schizophrenic patients and control subjects, although not statistically significant, may call into question the appropriateness of using NM as a control task in schizophrenic patients. Finally, we found no differences between the effects of WCS and NM on cerebellar or cerebral blood flow. Because of the small number of subjects in each group, the results of this study should be interpreted cautiously.

Serum homovanillic acid levels in schizophrenic patients and normal control subjects

Schizophrenic patients with an early age at onset of illness had low baseline levels of homovanillic acid (HVA) in serum compared with schizophrenic patients with a late age at onset. After adjustments were made for age at onset, there was a significant partial correlation between positive symptoms and serum HVA. The relationship between positive symptom scores and serum HVA was shifted to the left in the early onset patients, suggesting a relatively increased sensitivity of dopamine-associated response. Patients with severe negative symptoms also had an earlier age at onset and a trend toward lower serum HVA. This study found no difference between mean serum HVA values in schizophrenic patients and normal control subjects.

Wisconsin card sort activated blood flow in dorsolateral frontal cortex in never medicated and previously medicated schizophrenics and normal controls

and to examine if altered function in these areas is related to dysfunction in subcortical areas, the metabolic activity of cortical and subcortical structures were examined in 11 neuroleptic free DSM-III schizophrenics, four deficit and seven non-deficit, and 12 normal controls using PET imaging with i8F-2-DG. All subjects were examined, at rest, on the NeuroPET, with eyes covered and ears plugged. Glucose utilization (mg glu/lOO gm tissue/minute) was significantly lower in the thalamus of deficit (8.1 + 0.8; mean 5 S.D.) compared to non-deficit patients (10.4 ? 0.7; mean + S.D., p < .Ol); there were no differences in any of the other subcortical areas. Glucose utilization was also lower in multiple regions of the frontal, parietal, and temporal cortices in the deficit patients. In contrast, there were no differences in these areas between the total schizophrenic group and the normal controls. The results suggest that deficit patients may be characterized by decreased thalamic and cortical metabolism, and raise the possibility that these areas mediate the production of deficit symptoms.

Heat-shock protein induction by herpes simplex virus type 1 in MD canine kidney cells

Abstract 1. 1.|Heat-shock increased synthesis of 99 polypeptides in MD canine kidney (MDCK) cell fibroblasts, including fourteen 40 kDa, eight 70 kDa and four 90 kDa polypeptides. 2. 2.|Type 1 herpes simplex virus (HSV-1) enhanced the synthesis of 15 of these same heat-shock proteins (HSPs), including four 40 kDa but no 90 kDa polypeptides.

Heat-shock protein induction by herpes simplex virus type 1 in human embryonic lung cells

Abstract 1. 1.|Heat-shock increased synthesis of 40 polypeptides in human embryonic lung (HEL) fibroblasts. 2. 2.|Six of these same heat-shock proteins (HSPs) exhibited ⩾ 20-fold increased accumulation in HEL cells following infection with type 1 Herpes simplex virus (HSV-1). 3. 3.|Accumulation of HSV-1-induced HSPs coincided with synthesis of early immediate viral antigens.

Regional cerebral function and blood flow: Complementary single photon emission computed tomography of the brain using xenon-133 and [123I]iodoamphetamine

Regional cerebral function and blood flow can be imaged using isopropyl[123I]iodoamphetamine (IMP), or 133Xe (DSPECT), respectively. Both of these essentially non-invasive, quantitative, methods are suitable for many nuclear medicine laboratories. This study assessed the in vivo information about intracerebral disease provided by IMP and DSPECT techniques to determine the optimal diagnostic use of these modalities. Single photon emission computed tomograms of 53 subjects were acquired using similar displays for IMP and DSPECT data. Lobar tracer distributions were graded by three experienced observers and analyzed using a kappa statistic to eliminate chance agreements. Overall, both IMP and DSPECT had similar patterns. However, while similar, one or the other technique often displayed abnormalities not present on both. Although technical factors may account for some differences between the modalities, a case of arteriovenous malformation proves that discordant findings can result directly from tracer localization properties. Thus at least some discordances provide truly complementary diagnostic information lacking in either single study taken alone.

Neuropsychological function in positive and negative schizophrenia

Several studies have suggested a relationship between positive and negative symptoms and neuropsychological function in schizophrenia. Specifically, negative symptoms (affective flattening, alogia, avolition-apathy, anhedonia-asociality, attention deficit) have been found to relate to greater neuropsychological impairment than positive symptoms (hallucinations, delusions, bizarre behavior, formal thought disorder). Other investigations have alternatively suggested a relationship between positive/negative symptoms and lateralized neuropsychological deficit. This study examined the relationships between general and lateralized neuropsychological abilities and positive/ negative symptoms in well-characterized schizophrenics (mean age = 35.2 years, mean education = 11.7 years) with a mean duration-of-illness of 12 years were studied. All patients were well screened for CNS disease, drug/alcohol abuse, and focal lesions on CT scan. The Halstead-Reitan Neuropsychological Test Battery was administered and the patients were characterized by Andreasen’s Scale for the Assessment of Positive and Negative Symptoms (SAPS/SANS). Results indicated that schizophrenics as a group manifested mild to moderate general neuropsychological impairment. Positive and negative symptoms of schizophrenia were not strongly associated with either general or lateralized neuropsychological deficit, in contrast to previous research. Current findings suggest that the moderate correlation between negative symptoms and neuropsychological impairment in other studies may result in part from other variables such as severity and duration of illness.

Adrenal steroids in rdc schizophrenia

352 abnormalities of a specific isozyme. We determined in 20 schizophrenic patients and ten normal controls serum levels of 8 ChE isozymes by slab-gel electrophoresis followed by quantitative densitometric analysis of enzyme products. Twelve patients were studied both while drug free and while receiving haloperidol; the other eight were examined only while on haloperidol. A major isozyme (isozyme 2, predominantly acetylcholinesterase and representing > 80% of total ChE activity) was significantly higher in patients (.94 umol/ml/minute) than in normals (.61 umol/ml/minute) [p < .OOl]. There was no neuroleptic effect on isozyme 2 levels. There was no effect of age, sex or duration of illness on isozyme 2 levels. Additional data will be presented on a larger sample of patients with data also on other isozymes. The clinical significance of the findings will be examined with particular reference to cognitive impairment and other features of the schizophrenic defect state.