During acute type B hepatitis, the proportion of inducer to cytotoxic/suppressor T-cells is decreased due to an increase in the concentration of suppressor cells. Similar changes are seen in chronically infected subjects with evidence of active viral replication (HBeAg positive) and chronic hepatitis of varying severity. This imbalance of the regulatory cells returns to normal when viral replication decreases during the recovery phase of acute hepatitis and in patients who become chronic carriers with minimal liver disease (HBeAb positive patient). Patients in whom viral replication has subsided (HBeAb positive) but who continue to exhibit chronic active liver disease have increased inducer to cytotoxic/suppressor cell ratios due to a decrease in the concentration of the cytotoxic/suppressor cell population. Further studies are needed to determine whether these alterations of the regulatory cells of the immune system are a causal factor influencing the duration of active hepatitis B virus replication and the degree of inflammatory liver damage, or merely changes secondary to the presence of a replicating virus.

Acute Disease↗

PubMedDate not supplied

A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes.

In this pilot study, brain high energy phosphate and membrane phospholipid metabolism were investigated in the dorsal prefrontal cortex of 11 high-functioning autistic adolescent and young adult men (the age range is 12-36 years) and 11 age-, gender-, IQ, race- and socioeconomic status-matched normal controls using in vivo 31P nuclear magnetic resonance spectroscopy (MRS). The autistic group had decreased levels of phosphocreatine and esterified ends (alpha ATP + alpha ADP + dinucleotides + diphosphosugars) compared to the controls. When the metabolite levels were compared within each subject group with neuropsychologic and language test scores, a common pattern of correlations was observed across measures in the autistic group, but not in the control group. As test performance declined in the autistic subjects, levels of the most labile high energy phosphate compound and of membrane building blocks decreased, and levels of membrane breakdown products increased. No significant correlations were present with age in either group or with IQ in the control group, suggesting that these findings were not the consequence of age or IQ effects. This pilot study provides tentative evidence of alterations in brain energy and phospholipid metabolism in autism that correlate with the neuropsychologic and language deficits. The findings are consistent with a hypermetabolic energy state and undersynthesis of brain membranes and may relate to the neurophysiologic and neuropathologic abnormalities in autism.

Adolescent↗

PubMedDate not supplied

A follow-up study of hospitalized adolescents.

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Adolescent↗

PubMedDate not supplied

Selected human T cell lines respond to thymopoietin with intracellular cyclic GMP elevations.

Ten established human cell lines were tested for their responsiveness to thymopoietin by measuring their intracellular cyclic nucleotide levels. Three T cell lines (CCRF-CEM, MOLT-4 and CCRF-HSB-2) responded to thymopoietin with elevations of intracellular cGMP but not cAMP; seven other human cell lines did not respond to thymopoietin (three T cell lines, three B cell lines and one erythropoietic stem cell line). Interestingly, only one cell line (MOLT-4) was also responsive to the closely related polypeptide splenin, and this reactivity was restricted to human and not bovine splenin. The detection of human cell lines with distinctive patterns of response to immunoregulatory peptides should provide support for understanding the immunopharmacological mechanisms by which these molecules act.

Cell Line↗

PubMedDate not supplied

Biologically active analogs of thymopentin with enhanced enzymatic stability.

Thymopentin, a synthetic pentapeptide fragment of thymopoietin (residues 32-36, Arg-Lys-Asp-Val-Tyr) is biologically active but susceptible to proteolytic digestion. Analogs were synthesized and studied for biological activity and susceptibility to peptidases. Amino acid changes were incorporated at positions known to not affect activity adversely and N-terminal acetylation and C-terminal amidation were used to increase resistance to proteolytic degradation by exopeptidases. Ac-Pro2-TP5-NH2 and Aib2-TP5-NH2 retained activity and were shown to exhibit a high degree of stability when incubated in human serum.

Cell Line↗

PubMedDate not supplied

Neuropsychological differences between young and old schizophrenics with and without associated neurological dysfunction.

Age differences among 134 schizophrenics with associated neurological dysfunction, 160 schizophrenics without such dysfunction, 285 nonschizophrenics with neurological dysfunction and 240 patient controls on the Halstead-Reitan neuropsychological Test Battery (HRB) were examined by splitting subjects at their median ages and performing two way analyses of variance for each HRB component test with diagnosis and age category as the independent variables. In the case of the schizophrenics with neurological dysfunction, significant interactions were found for several subtests of the Wechsler Adult Intelligence Scale (WAIS), and for the Speech Perception, Trail Making and Aphasia Screening Test. In the case of the neurologically intact subgroup, significant interactions were only found for the WAIS Comprehension subtest and Part B of the Trail Making Test. Only WAIS Comprehension produced a significant interaction in the nonschizophrenic group with neurological dysfunction. It was concluded that age differences in neurologically intact schizophrenics were generally comparable to those found in the controls, but that was less the case for the neurologically impaired schizophrenics. Furthermore, this pattern of findings is unlikely to be based upon the presence of associated neurological dysfunction alone, but probably reflects the particularly detrimental effect of compounding schizophrenia with neurological dysfunction.

Adult↗

PubMedDate not supplied

Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen.

Mature T cells segregate phenotypically into one of two classes: those that express the surface glycoprotein CD4, and those that express the glycoprotein CD8. The CD4 molecule is expressed primarily on helper T cells whereas CD8 is found on cytotoxic and suppressor cells. A more stringent association exists, however, between these T-cell subsets and the major histocompatibility complex (MHC) gene products recognized by their T-cell receptors (TCRs). CD8+ lymphocytes interact with targets expressing class I MHC gene products, whereas CD4+ cells interact with class II MHC-bearing targets. To explain this association, it has been proposed that these 'accessory' molecules bind to monomorphic regions of the MHC proteins on the target cell, CD4 to class II and CD8 to class I products. This binding could hold the T cell and its target together, thus improving the probability of the formation of the trimolecular antigen: MHC: TCR complex. Because the TCR on CD4+ cells binds antigen in association with class II MHC, it has been difficult to design experiments to detect the association of CD4 with a class II molecule. To address this issue, we devised a xenogeneic system in which human CD4 complementary DNA was transfected into the murine CD4-, CD8- T-cell hybridoma 3DT-52.5.8, the TCR of which recognizes the murine class I molecule H-2Dd. The murine H-2Dd-bearing target cell line, P815, was cotransfected with human class II HLA-DR alpha, beta and invariant chain cDNAs. Co-culture of the parental T-cell and P815 lines, or of one parental and one transfected line resulted in a low baseline response. In contrast, a substantial increase in response was observed when CD4+ 3DT-52.5.8 cells were co-cultured with HLA-DR+ P815 cells. This result strongly indicates that CD4:HLA-DR binding occurs in this system and that this interaction augments T-cell activation.

Animals↗

PubMedDate not supplied

Adolescent sons of alcoholics: neuropsychological and personality characteristics.

Adolescent sons of alcoholics and nonalcoholics were compared on a battery of intellectual, neuropsychological, personality, and behavioral measures. The former group demonstrated certain neuropsychological deficits in perceptual-motor ability, memory, and language processing. They also had auditory and visual attentional impairments and a lower level of achievement in reading comprehension. In addition, the sons of alcoholics presented a more neurotic personality profile than sons of nonalcoholics. They were, however, less impulsive than the comparison group. More development and familial problems were noted in the alcoholics' offspring as well. The implications of these findings for understanding the causes and consequences of alcoholism are discussed.

Adolescent↗

PubMedDate not supplied

Premature aging in male alcoholics: "accelerated aging" or "increased vulnerability"?

This study involved an evaluation of two versions of the "premature aging" theory of chronic alcoholism: the accelerated aging and increased vulnerability versions. The major dependent measures used were the tests included in Reitan's brain age quotient (BAQ), a series of neuropsychological tests known to be sensitive to the effects of alcoholism and aging. Subjects were 40 chronic alcoholic inpatients and 40 matched controls, divided into age groups by decade, ranging from the 30s to the 60s. It was proposed that an interaction between age and presence or absence of alcoholism, with BAQ test differences between alcoholics and controls widening as age increases, would support the increased vulnerability version, while the absence of such an interaction would support the accelerated aging version. The results clearly favored the accelerated aging version, with marked BAQ test differences between alcoholics and controls appearing even in the 30-year-old groups. It was concluded that chronic alcoholics tend to perform at levels found for nonalcoholics 10 years their senior, but the discrepancy between alcoholics and nonalcoholics does not increase with age.

Adult↗

PubMedDate not supplied

Healthy cities: overview of a WHO international program.

Health is the outcome of all the factors and activities impinging upon the lives of individuals and communities. The last decade has seen an emerging understanding within development circles that living conditions are greatly affected by local action, by the work of local government, and by community groups and organizations. In addressing health and environmental issues and making interventions, an integrated approach, based on 'settings', exemplified in the Healthy Cities approach, has proved most effective. A Healthy City project can involve people and organizations in the programs and activities that are needed for better health, and enables a city or neighborhood to mobilize the human and financial resources required to address many health and quality of life issues. The WHO program involves implementating city projects and networks in all regions of the world and serves as a vehicle for many health programs, including major disease control initiatives. Healthy City projects allow Ministries of Health to develop stronger partnerships with local government organizations (such as the Union of Local Authorities and its members, "Local Agenda 21" initiatives, and others). One focus for the program is the development of 'multi-'multi-city action plans' for major global priority issues, including AIDS, sanitation, women's health, and violence, to ensure that major public health programs are strengthened by wider community participation. It is recognized that city networking--at national, regional, and international levels--now must be better exploited by individual cities and municipalities to solve local health problems.

Environmental Health↗

PubMedDate not supplied

Meeting the needs of large employers.

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Delivery of Health Care, Integrated↗

PubMedDate not supplied

Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone beta1 receptor gene.

Resistance to thyroid hormone (RTH) is a human syndrome mapped to the thyroid receptor beta (TRbeta) gene on chromosome 3, representing a mutation of the ligand-binding domain of the TRbeta gene. The syndrome is characterized by reduced tissue responsiveness to thyroid hormone and elevated serum levels of thyroid hormones. A common behavioral phenotype associated with RTH is attention deficit hyperactivity disorder (ADHD). To test the hypothesis that RTH produces attention deficits and/or hyperactivity, transgenic mice expressing a mutant TRbeta gene were generated. The present experiment tested RTH transgenic mice from the PV kindred on behavioral tasks relevant to the primary features of ADHD: hyperactivity, sustained attention (vigilance), learning, and impulsivity. Male transgenic mice showed elevated locomotor activity in an open field compared to male wild-type littermate controls. Both male and female transgenic mice exhibited impaired learning of an autoshaping task, compared to wild-type controls. On a vigilance task in an operant chamber, there were no differences between transgenics and controls on the proportion of hits, response latency, or duration of stimulus tolerated. On an operant go/no-go task measuring sustained attention and impulsivity, there were no differences between controls and transgenics. These results indicate that transgenic mice bearing a mutant human TRbeta gene demonstrate several behavioral characteristics of ADHD and may serve a valuable heuristic role in elucidating possible candidate genes in converging pathways for other causes of ADHD.

Animals↗