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The study explored encoding, storage, and retrieval components of memory functioning in four groups of subjects: (1) normal elderly; (2) elderly subjects in the early prestages of DAT; (3) elderly subjects with a more advanced DAT; (4) younger subjects in the early prestages of AIDS dementia. Each group consisted of 26 subjects, who were administered the Rey Auditory-Verbal Learning Test. The results suggest impaired encoding and retrieval in the DAT groups. The AIDS group demonstrated deficient storage and retrieval. Their pattern of memory deficits was similar to that seen in normal aging. The results speak in favor of the hypothesis of subcortical nature of neurological changes in normal aging.

Our study investigates the nature of elevated depression scores on the MMPI-168 in human-immunodeficiency-virus- (HIV-)infected individuals. Comparison of MMPI scales, factor scores, and individual depression item endorsement rates were made between three groups of homosexual/bisexual men: asymptomatic HIV-1 seropositives (n = 156), symptomatic HIV-1 seropositives (n = 156), and a comparison group of HIV-1 seronegatives (n = 117). Elevated scores were found on the MMPI depression scale for all three groups, with HIV infection and the presence of symptoms being associated with significant elevations in depression. Analyses of these elevated scores through the use of factor scores and individual item analyses strongly suggest that endorsement of items related to physical symptoms and neuropsychological complaints accounted for much of the difference in overall depression scores between samples. Implications are discussed for measurement and diagnosis of depression in HIV populations.

In the area of adult development, Levinson's notion of the personal Dream is important in understanding the male midlife transition. Levinson suggests that during this period in the life cycle the status of the Dream becomes a prominent issue, as men become increasingly aware of the limits of their achievements. Sixty-four midlife men filled out questionnaires examining whether they had a Dream, and whether they experienced or anticipated experiencing success or failure of that Dream. The Beck Depression Inventory, the IPAT Anxiety Scale, and the Purpose-In-Life Test were included to assess the mental health status of the respondents. The results support the conclusion that whether a man has a Dream, and the degree to which he experiences success in achieving it are significantly related to his mental health status (i.e., depression, anxiety, and purpose-in-life) during the midlife transition.

The current study examines the effects of lateralized brain injury on Raven's Coloured Progressive Matrices (CPM) performance. Archival data on 106 unilateral brain-damage patients, 59 with right hemisphere damage and 47 with left, was utilized to examine four aspects of differential performance. Right brain-damaged subjects performed significantly lower than left brain-damaged subjects overall on the CPM. They also showed evidence of a higher incidence of and greater severity of hemi-neglect. After partialling out the effects of hemi-neglect, the subject groups were no longer significantly different on overall CPM performance. Evidence supporting the presence of heterogeneous subtests was not found. The results support the emerging pattern in research findings indicating that hemi-neglect plays a central role in differential performance. The CPM appears limited in its application and interpretation for patients with hemi-neglect.

Acutely ill psychiatric inpatients were examined for a deficit in sensory gating, measured as failure to suppress the P50 wave of the auditory-evoked response to the second of paired stimuli. Previously, we had found that in mania, this sensory gating deficit is correlated with increased plasma-free levels of the noradrenergic metabolite 3-methoxy, 4-hydroxyphenylglycol (pMHPG), whereas in schizophrenia, there is no correlation with catecholamine metabolism. To assess the generalizability of these findings, we examined inpatients with a broader range of diagnoses, including those with multiple DSM III-R Axis I, II, and III diagnoses. The patients were grouped into three diagnostic spectra for analysis: schizophrenic, manic, and depressive. In the schizophrenic patients, there was no relationship between pMHPG or other catecholamine metabolites and the sensory gating deficit. In manic patients, however, a positive correlation between pMHPG level and the sensory gating deficit was again observed. This relationship did not extend to the depressive patients, who uniquely showed sensory gating deficits that correlated negatively with the severity of their illness. The data suggest that sensory gating deficits are common to these three diagnostic spectra, but the deficits in each group have different relationships to catecholamine metabolism and symptom severity that may reflect differences in the underlying neuronal pathophysiology of these illnesses.

Hypersensitivity to sensory stimulation is a prominent characteristic of both schizophrenia and mania. Neurophysiological recordings suggest a common deficit in a central neuronal sensory gating mechanism which regulates sensitivity to repeated auditory stimuli. Dopamine and norepinephrine are hypothesized to have major roles in these illnesses, but their role in aberrant sensory processing has not yet been proved. Presumptive evidence for effects of catecholamines on sensory processing comes from psychophysiological studies of normal subjects challenged with stimulants who show decreased sensory gating, and studies of psychotic patients treated with neuroleptics who show improved function. Studies of similar phenomena in animals show comparable effects of catecholamines on sensory processing, both behaviorally and at the single neuron level. In this study, gating of auditory evoked potentials (EPs) during treatment of both illnesses was compared with plasma dopamine and norepinephrine metabolites. Comparisons of medicated and unmedicated states showed that schizophrenic patients have a fixed deficit in sensory gating, which is a familial trait, unchanged by medication. During acute illness, they have an additional transient hypersensitivity to stimuli, manifested as smaller EPs, which seems to be mediated by dopamine. Manic patients have only the deficit in sensory gating, which is transient and seems to be mediated by norepinephrine. Thus, similar neurophysiological deficits in the two psychoses are associated with different biochemical abnormalities, which may explain similarities in acute symptoms and differences in other aspects of the illnesses, such as their response to treatment.

Even patients with chronic myelogenous leukemia (CML) in blast crisis were treated with chemotherapy, followed by infusion of autologous bone marrow that had been collected during the chronic phase of the disease and cryopreserved at -198 degrees C. The mean age of the nine females and two males in this study was 34 years with an average duration of the chronic phase of the disease of 5.5 years. Seven out of the 11 patients had a splenectomy prior to intensive chemotherapy. The median survival of the first four patients who received 6-thioguanine, cytosine arabinoside, daunorubicin (TAD) chemotherapy was 2.6 weeks and no patient reachieved the chronic phase of CML. The second group of seven patients received more intensive chemotherapy (MAdHAT), which included melphalan 30 mg/m2 days 1, 2, and 3; Adriamycin 50 mg/m2 intravenously (iv) day 1, hydroxyurea 1500 mg/m2 by mouth for 5-7 days, cytosine arabinoside 100 mg/m2 continuous infusion for 5-7 days, and VM-26 100 mg/m2 iv on day 3. Six out of these seven patients reachieved chronic phase CML after bone marrow reinfusion. The median survival was 29.9 weeks for all patients and 33 weeks for the six patients who reachieved chronic phase CML. All patients subsequently died of recurrent blast crisis. There was no correlation between the time of bone marrow storage and the duration of subsequent chronic phase CML. These studies have shown that autologous bone marrow transplantation after high-dose chemotherapy can result in bone marrow engraftment with reestablishment of chronic phase CML, and prolongation of survival.

The mechanism which regulates granulopoiesis was investigated in C 57 BL mice injected i.p. with E.coli. The positive and negative feedback arm of the regulation was studied by correlating the number of bacteria, the number of granulocytes, serum CSF levels and the number of CFU-C in the bone marrow.

The object of this study was to determine the reproducibility of the measurement of plasma catecholamine metabolites in normal control subjects and to assess the influence of factors such as time of day, diet, activity, blood pressure, and mood on the variance of these measures. Plasma free homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid (VMA) were simultaneously measured by high performance liquid chromatography with electrochemical detection. Samples were collected from 15 doctors and nurses at 8 a.m. and at noon on 2 separate days. After the fasting 8 a.m. sample, the subjects ate a regular hospital breakfast. Activity in their usual tasks on an inpatient psychiatric unit was monitored electronically by an activity meter. Levels of each metabolite were not significantly different between days at the respective assay times and were highly correlated for individuals. MHPG showed a significant increase from morning to noon, while HVA showed a significant decrease. Activity, dietary intake of tyrosine and tyramine, blood pressure, pulse, scores on the Profile of Mood States, age, and sex were not related to plasma levels. The results demonstrate that measures of dopamine and norepinephrine metabolites have significant reliability in normal subjects in a setting used for research studies with psychiatric patients.

Two hundred and thirty normal human sera have been tested for colony stimulating factor (CSF) under carefully controlled conditions using human bone marrow and the semi-solid agar-gel technique. It has been shown that CSF can be detected in most sera when incorporated into underlayers to remove potential inhibitors. The effect of storage temperature on serum CSF has been determined. Storage at 4 degrees, --15 degrees, and --66 degrees for up to 80 days resulted in only a mild decrease in CSF levels. After 240 days of storage, CSF values fell to 50% of that found before storage. Repeated freeze-thawing of serum has not been shown to decrease CSF levels when done in Pyrex glassware. These studies will serve as a baseline for those wishing to study human serum CSA in hematopoietic disorders.

A program of nonfrozen autologous bone marrow rescue was used to treat patients with refractory nonhematological neoplasms. In vitro storage of bone marrow cells and CFU-C suggests that storage at 4 degrees or 10 degrees for periods up to five days can be undertaken with only minor loss of CFU-C. However, since the loss occurred in a gradual fashion, shorter duration of storage would probably be better. Hematological recovery after high dose chemotherapy occurred faster in patients given more CFU-C and those with shortest duration of storage prior to reinfusion.

These studies were undertaken to determine if schistosomal and ragweed antigens incubated with human peripheral blood mononuclear cells (MNC) would stimulate the production of an eosinophil colony stimulating factor (CSF) which was active on human bone marrow. These studies have shown that schistosoma mansoni antigen in a concentration of 5 micrograms/ml incubated with MNC's from unsensitized individuals lead to production of a conditioned medium which did not stimulate an increased number of total colonies but did increase the number of eosinophil colonies (44 to 61 colonies). Ragweed antigen also stimulated increased eosinophil CSF (from 44 to 63 colonies). The granulocyte response to parasitic antigens almost invariably involves the eosinophil system. Eosinophils play a vital role in the control of these diseases in humans. Further understanding of the interaction of parasitic antigens with the granulopoietic system will hopefully give new and important clues as to how such parasites interact with man and how they are controlled.

We report a procedure for the rapid determination of unconjugated homovanillic acid (HVA) in human plasma by cartridge filtration followed by direct injection into an isocratic HPLC system coupled with dual-electrode coulometric electrochemical detection. Sample preparation is rapid and more than 72 samples can be studied in 24 h using an automated HPLC system. The intra- and interassay precisions of the assay equal or exceed previously reported methods. While this methodology has been employed to study plasma free HVA, the concept of the technique may be applicable to other compounds, as well as different assay procedures, to greatly decrease sample preparation time.

A newly developed method for the simultaneous extraction and quantitation of the unconjugated levels of the catecholamine metabolites vanilmandelic acid (VMA), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and homovanillic acid (HVA) in plasma by high performance liquid chromatography with electrochemical detection was modified and applied to studies of human saliva. The assay had a mean coefficient of variation under 3% for each of the metabolites. Levels of plasma VMA, MHPG and HVA were measured in 28 normal subjects and compared to their saliva levels, obtained before and after stimulation by mastication. Significant correlations were found between plasma and saliva MHPG and HVA, but there was no correlation between plasma and saliva VMA. Salivary MHPG and HVA can be reproducibly assayed and may be useful tools for indications of changes in central and peripheral catecholamine metabolism.

Studies have been carried out to determine the viability of leukemic and normal human bone marrow, cryopreserved in liquid nitrogen at -196 degrees C, using changes in total cell numbers and granulocyte colony forming ability in vitro. These studies have shown that there is considerable variability in the recovery of CFU-C from individual specimens. When the overall recovery, in all patients, is taken into account, there is a gradual decline in CFU-C numbers to about 60% after 24 months of freezing. CFU-C recovery is closely correlated with recovery of total cell numbers.