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[Preparation and selection of monoclonal antibodies for detecting hepatitis B surface antigen in blood sera].

HV monoclonal antibodies (MAb) were produced in order to improve the quality of HBsAg detection and their specific characteristics were compared with those of other MAbs. MAbs were characterized by asymmetric interactions with the antigen when used as first or second antibodies. The reactivity of a panel of HV and X MAb to ad and ay subtypes was studied by enzyme immunoassay. Mutual blocking (epitope mapping) of MAb helped select antibody couples for the creation of highly effective test system for the diagnosis of the major HBsAg subtypes. The sensitivity and specificity of MAbs were evaluated on reference and control panels of HBsAg sera and on serum specimens from a random sampling of 300 blood donors. The sensitivity of the most specific MAb pairs was 0.1 ng/ml for HBsAg subtype ay and 0.25 ng/ml for subtype ad. The specificity of attested MAb was 98.5% in incubation with stirring and 97% in static incubation. The optimal combinations of attested MAbs were used in the manufacture of Recomnathep B test system in the sandwich format.

Animals↗

Pharmacologic treatment of autism.

Autism is a chronic and lifelong pervasive developmental disorder for which there is yet no effective cure, and medical management remains a major challenge for clinicians. In spite of the possible similarities with conditions that have an established pharmacotherapy, and despite improvements in some associated "problematic behaviors" following the use of available medications, effective medical treatment for the core symptoms involving language and social cognition remains elusive. The purpose of the present article is to review current biologic knowledge about autism in an attempt to correlate clinical trials with known mechanisms of disease. In addition, the need for controlled studies and for the creation of homogeneous subgroups of patients based on clinical and genetic characteristics is emphasized. The application of molecular genetic investigations and pharmacogenetics in the diagnostic work-up of autistic patients can lead to more effective individualized medical care.

Anticonvulsants↗

The EEG in metabolic encephalopathy and coma.

Excellent early work on stupor and coma can be found (particularly with regard to anoxia) in the work of Fischgold and Mathis (1959) in France, and Pamela Prior in England (1973a). These workers correlated deepening levels of coma with particular EEG patterns, and the suppression of EEG reactivity. Alpha frequency patterns in coma (alpha coma), spindle-like sleep patterns in coma (spindle coma) and "triphasic waves" are among the wide variety of endocrine disorders discussed in case reports and series leading to identification of particular EEG patterns. EEG correlations with prognosis are most reliable with cardiorespiratory arrest (CRA) with its consequent anoxic-ischemic insult. If etiology is known, EEG can often be a reliable predictor of outcome. EEG usually has little specificity with regards to etiology, but some patterns do favor particular diagnoses: for example, triphasic waves (TWs) are frequently seen with hepatic and renal insufficiency in young adults; spindle coma patterns are believed to indicate dysfunction at the brainstem level (Chatrian, 1990). EEG is most useful in differentiating organic from psychiatric conditions, in excluding nonconvulsive status epilepticus (NCSE), and in providing a rough guide as to the degree of cortical and subcortical dysfunction.

Alpha Rhythm↗

Brain receptors for hypothalamic hormones.

Angiotensin II and CRF are but two of the several regulatory peptides which exert specific actions in the brain that are complementary with their peripheral effects upon end organs such as the anterior pituitary and adrenal glands. In the pituitary, the two peptides act in a coordinate manner on the corticotroph to regulate ACTH release. In the adrenal gland, angiotensin II receptors are abundant in the zona glomerulosa but are also present in the medulla, where the occurrence of CRF receptors and actions on catecholamine release reveals an additional site at which the two peptides exert related actions, in this case in the peripheral neuroendocrine system. Within the brain, the mapping of AII and CRF binding sites by topical autoradiography has provided new information about the distribution and potential functions of receptors for the two peptides. The central receptors for AII are distributed in a characteristic pattern in brain regions concerned with drinking, regulation of adrenergic function and arterial blood pressure, and control of pituitary hormone secretion. Thus, in addition to its recognized modulatory effects in the peripheral adrenergic system, angiotensin II may be involved in the central control of catecholamine release and action. A central action of AII on the release of regulatory peptides such as vasopressin and CRF, both of which are present in neurones of the paraventricular nucleus, is indicated by the high concentration of AII receptors in this region. Also, the high density of AII receptors in the median eminence suggests that AII modulates the hypothalamic secretion of neuropeptides such as CRF by actions at their site of release, as well as on the cell bodies of neurones responsible for peptide synthesis. The highly localized pattern of AII receptors at numerous specific sites in the brain differs from the more general distribution of many other CNS receptors, and reflects the selective actions of AII on discrete neural systems that subserve precisely integrated functions within the central nervous system. The widespread distribution of CRF receptors, with prominent localization in the cortical and limbic regions, is consistent with the more general neuroregulatory actions of CRF in the brain, and with the presence of immunoreactive CRF in several regions of the brain including the cortex, limbic system, and centers involved in the control of autonomic function. The cortical and limbic receptors are clearly relevant to the effects of centrally administered CRF on both behavioral and visceral responses, with prominent autonomic changes including increased catecholamine release and hypertension.

Angiotensin II↗

Molecular genetics of the sickling syndromes: evolution of new strategies for improved diagnosis.

This survey is intended to illustrate some major areas relevant to the diagnosis and treatment of sickle cell syndromes that have benefited by the input of molecular genetic approaches. The development of gene mapping techniques has permitted the direct examination of the effect of co-inheritance of alpha-thalassemia and sickle cell anemia on clinical severity, providing, for the first time, a direct strategy for investigation of the clinical heterogeneity of these syndromes. In addition, antenatal diagnosis of these disorders is now best done by direct gene mapping whenever appropriate facilities are available. Treatment by manipulation of gamma-globin gene expression has been shown to be an effective means of achieving at least partial reversal of the hemoglobin F to hemoglobin A switch. Whether the magnitude of this reversal is sufficient to interfere with the clinical phenotype of sickle cell disease remains to be determined. Moreover, the agent currently available to accomplish this goal, 5-azacytidine, remains unsuitable for wide-spread clinical application for a variety of reasons. Nonetheless, the molecular geneticist has already demonstrated that desirable effects can be achieved by building on the knowledge of globin gene physiology. This knowledge is best acquired by application of the concepts and methodologies of molecular genetics.

Anemia, Sickle Cell↗

[Spectro-temporal mapping (STM)].

In recent years, various kinds of time-varying spectral analysis which estimate the frequency content of a signal as a function of time have been proposed. Spectro-temporal mapping (STM) is one of such methods with elaborate modification of a simple fixed period analysis. Merits and demerits of this method in clinical application are described in this chapter. Certain technical aspects pertinent to the interpretation of STM were also discussed. In conclusion, STM in present form is inferior to time domain analysis for the prediction of serious ventricular arrhythmias. But it has some usefulness to supplement time domain analysis in noise detection and application to patients with broad QRS complex.

Body Surface Potential Mapping↗

[Clinical value of signal averaged electrocardiogram for the prediction of ventricular tachycardia after myocardial infarction].

One of the most important predictors for mortality after myocardial infarction is the occurrence of malignant ventricular tachyarrhythmias. Reentry has been shown to play a major role in the development of ventricular tachycardia (VT) in the chronic phase of myocardial infarction. Signal averaged electrocardiogram (SAE) may reveal the substrate for VT, that is, the delayed and fragmented ventricular activation around the infarcted area. Since Simson's report, the relation between the detection of late potentials (LP) on the SAE and the occurrence of VT in the chronic phase of myocardial infarction has been described by many authors. In these reports, the result that the absence of LP can predict the lower risk for VT has been emphasized. However, several factors such as time of SAE recording, infarct location, effect of reperfusion therapy, infarct size, and ventricular function may modify the SAE findings. Accordingly, further prospective study considering these factors is needed to establish the clinical value of SAE after myocardial infarction.

Body Surface Potential Mapping↗

Gene assignment by quantitative hybridization analysis of somatic cell hybrids.

Since the inception of somatic cell hybridization technology, the number of genes mapped to a particular chromosome or region of a chromosome has increased exponentially. Conventional assignment relies on the interpretation and designation of concordance to the various panel members. Assignment of genes to individual chromosomes may be ambiguous if the representation of the individual chromosomes within the hybrid panel is not considered. To overcome this inherent limitation, we have developed a computer-assisted method to assign genes to chromosomes. This assignment utilizes an integrative statistical analysis procedure to reconcile chromosomal representation of each member of the somatic cell hybrid panel. In this manner, the intensity of the corresponding bands appearing on the autoradiographic image reflects the prevalence of that specific gene-containing chromosome within the somatic cell hybrid. The statistical method described above provides the foundation for an independent means to assign genes to a specific chromosome. We have utilized this method to assign the human lysyl oxidase gene to chromosome 5.

Animals↗

USDA's Plant Genome Research Program.

Biotechnology will provide U.S. farmers with another green revolution. The United States Department of Agriculture has put together the Plant Genome Research Program as a coordinated multi-agency effort within the department to help develop the "new agriculture." The Cooperative State Research Service is managing the program's competitive research grants. Research topics include high- and low-resolution chromosomal maps; the isolation and transfer of economically important genes; and new technology developments. The Agricultural Research Service is the lead agency for the Plant Genome Research Program and coordinates data collection and information management resources for the program. Five species groups are collaborating in the database development effort for the program by defining the user needs for their species and collecting and evaluating their species data for the database. A central database for the Plant Genome Research Program is under development at the National Agricultural Library (NAL) and ultimately will contain data for as many as seventy-one different plant species. NAL will provide user access via Internet, dial-up modem, and, at a later date, a CD-ROM product.

Chromosome Mapping↗

Developing strategies for intervention and prevention in hereditary breast cancer.

Prophylactic mastectomy, intensified breast cancer screening, and the use of chemopreventive agents have all been recommended to reduce breast cancer risk in women with a family history of breast cancer. Yet, little is currently known about the efficacy of these approaches in reducing breast cancer mortality. The recent identification of BRCA1 and the localization of BRCA2 lend urgency to the need to assess breast cancer intervention and prevention strategies for women likely to carry germline mutations at these loci. At present, families with a history consistent with a BRCA1 or BRCA2 mutation should be tested within the confines of a research protocol and encouraged to participate in intervention and prevention trials. Both retrospective studies and prospective clinical trials are critically needed. While randomized clinical trials would be the optimal mechanism to assess the relative efficacy of these potential interventions, no consensus was obtained as to whether such a trial would be feasible because of strong patient preference for intervention type. It is likely that optimal intervention and prevention strategies will consist of a combined approach to risk reduction. Participants must be appropriately informed of the potential risks as well as the potential benefits of such testing. The potential risks of testing for genetic susceptibility include not only potential psychosocial harm that may result from learning one's carrier status, but also the potential for altered family relationships and insurance and job discrimination. Participants and their family members must be counseled concerning the implication of their test results.

Breast Neoplasms↗