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Biomedical subjects

M Baier

Publications and source records attributed to M Baier.

At least 91 records · Page 5Linked to original sources

Epidemiology and pathogenicity of human retroviruses.

The human retroviruses can be divided into oncovirus (HTLV-I and HTLV-II) and lentivirus strains (HIV-1 and -2). The HTLVs are endemic in Central Africa, the Caribbean Islands and in southwest Japan, but now tend to spread through the i.v.-drug user population in the USA and in some countries in Western Europe. HTLV infection is associated with a malignant form of adult T-cell leukemia, tropical spastic paraparesis (TSP) and an associated myelopathy (HAM). The pathogenic mechanisms of HTLV are as yet poorly understood. HIV infection is spreading rapidly almost world-wide and has reached epidemic proportions in Central Africa, parts of South America and in certain populations in industrialized countries that have risk behaviour for contracting venereal or blood-borne infections. The mechanisms of HIV-induced immune suppression are still not entirely clear, as direct T-lymphocyte destruction after viral infection cannot account for the almost complete loss of CD4 T-cells in the final stages of disease. Various indirect mechanisms of HIV-induced immune cell destruction are outlined below.

Biological Products↗

[Detection of retinal visual field defects by sectorial photic stimulation in scotopic luminance ERG].

We developed an electroretinographic procedure to assess visual field defects due to dysfunction of the outer retinal layers. For this objective we determined the amplitude/intensity function of the scotopic b-wave to full field (100 degrees of visual angle), quadrant and hemifield stimulation in 14 healthy volunteers and in patients with visual field disturbances. To prevent stray light effects, we confined the test light illuminance to 10(1.3) of the extrapolated normal ERG threshold (about 10(4.2) the sensory dark threshold). Whereas patients with dysfunction of the proximal retinal layers or the optic nerve did not show any change when the corresponding visual field was stimulated, those suffering from disturbances of the distal retinal layers (e.g., amotio, chorioretinal diseases) showed a reduction in the amplitude/intensity function, which was related to the extension and the degree of the field losses. The method reveals visual field defects caused by disturbances in the outer retinal layers where one-fourth or more of the corresponding retinal quadrant exhibits a sensitivity loss of more than 15 dB.

Adult↗

Simian immunodeficiency virus reverse transcriptase. Purification and partial characterization.

Native reverse transcriptase from simian immunodeficiency virus was purified from virus with good recovery to near homogeneity. The optimum reaction conditions of the enzyme were determined with respect to divalent cations, pH and ionic strength. The enzyme was shown to possess both RNA-dependent and DNA-dependent DNA synthesis activity. In addition, we could demonstrate an associated RNase H activity. Employing novel assay conditions, activated DNA as a heteropolymeric substrate was used more efficiently than the homopolymeric substrate poly(rA).oligo(dT) which in turn was used twofold more effectively as the template primer than poly(dC).oligo(dG). Other homopolymeric substrates, including poly(rC).oligo(dG), were also tested but were found to be poorly used by the reverse transcriptase. The Miachaelis-Menten constants were determined for each of the four nucleotides needed to elongate a natural template primer. Simultaneously, using dideoxyadenosine triphosphate as nucleotide analogue, we could show that this compound acts as a competitive inhibitor with respect to dATP, whereas it acts as a non-competitive inhibitor with respect to the other nucleotides. Gel electrophoretic analysis showed the enzyme to consist of two polypeptides with apparent molecular masses of 64 and 48 kDa. Using activity gel electrophoresis, we were able to demonstrate that both subunits exhibit DNA synthesis activity.

Animals↗

Complete nucleotide sequence of a simian immunodeficiency virus from African green monkeys: a novel type of intragroup divergence.

We have determined the entire nucleotide sequence of a full-length molecular clone, termed SIVagm3, which is infectious in vitro and in vivo. The genomic organization was found to be similar to other immunodeficiency viruses of human and simian origin. Comparison of SIVagm3 with SIVagmTYO-1, the only other completely sequenced molecular SIVagm clone, revealed a novel type of intragroup divergence, which is characterized by (1) an unusually high degree of variability in pol in relation to gag and env and (2) a high degree of divergence in the rev and tat genes. Thus, since SIVagm3 and SIVagmTYO-1 evolved from their common ancestor, they diverged in a different manner than human immunodeficiency viruses. Hypervariable regions in env were defined and shown to be relatively restricted in comparison to HIV-1 and HIV-2.

Amino Acid Sequence↗

Cloning and expression of the complete SIVagm pol region in E. coli. Purification and partial characterization of the reverse transcriptase.

The complete pol region of the simian immunodeficiency virus from African green monkeys was cloned and expressed in E. coli. The reverse transcriptase was purified to high specific activity and could be shown to contain both reverse transcriptase activity as well as an associated RNase H activity. As is observed with other reverse transcriptases the enzyme is composed of two subunits which cannot be separated by conventional techniques. When comparing the recombinant enzyme with the authentic enzyme isolated from virus no differences were found by biochemical, enzymological, or immunological criteria. Moreover, the action of inhibitors against this enzyme did not show significant differences when compared to reverse transcriptases from HIV-1 and HIV-2.

Bacterial Proteins↗

Isolation of human immunodeficiency virus-related simian immunodeficiency viruses from African green monkeys.

We have isolated lentivirus strains that are related to the human immunodeficiency virus (HIV) from African green monkeys (Cercopithecus aethiops; AGM). Although immunologically related, these SIVagm are clearly distinct from other simian immunodeficiency virus (SIV) isolates, including isolates from Macaca mulatta (SIVmac) or even from other AGM. The SIVagm strains described in this communication grow well in a limited number of human T-lymphoma lines. Virus density, morphology, and reverse transcriptase activity are characteristic of the lentivirus group. SIVagm exhibits the following pattern of major virus proteins: p18, p28, gp45, p64, gp140. They appear to bind to the target cell via the CD4 or its primate analogue. Four virus isolates have already been molecularly cloned for detailed genomic analysis and within this SIV agm group they exhibit the genomic variability that is typical of lentiviruses. AGMs infected with this virus apparently remain healthy and therefore SIVagm not only provides a virus model for vaccine studies but also allows investigation of the defense mechanisms (immunological and others) that keep the AGMs healthy. Furthermore, precise genomic analysis of these and other SIV strains will lead to a better understanding of the evolution and pathogenicity of human lentiviruses like HIV.

Animals↗

Molecularly cloned simian immunodeficiency virus SIVagm3 is highly divergent from other SIVagm isolates and is biologically active in vitro and in vivo.

Simian immunodeficiency viruses have been isolated from African green monkeys originating from Ethiopia. A molecular clone, termed SIVagm3, was found to be highly divergent from SIVagmTYO-1 in terms of its restriction map and partial nucleotide sequence. A premature stop codon present in the transmembrane protein of SIVagm TYO-1 was absent in SIVagm3. SIVagm3 was biologically active in vitro and in vivo and displayed characteristics reminiscent of the wild-type virus. Biological activity was demonstrated by seroconversion of juvenile African green monkeys and Macaca nemestrina after inoculation. In contrast to antibody reactivity mainly directed against env proteins in naturally infected African green monkeys. African green monkeys and M. nemestrina infected with the cloned virus showed antibody reactivity directed against all major proteins as demonstrated by immunoblot analysis. The availability of a biologically fully competent molecular clone of SIVagm allows us now to address various pertinent questions in an animal model system which should help to understand features of human immunodeficiency virus infection in human beings.

Amino Acid Sequence↗

Issues in the nursing management of patients with water intoxication.

The syndrome of water intoxication, experienced by a small percentage of hospitalized chronically mentally ill patients, is a two-stage process, usually beginning with polydipsia. In some patients the physiological ability to excrete excess free water is lost, and polydipsia progresses to hypervolemia and hyponatremia. The hyponatremia responds to fluid restriction. Nevertheless, nursing intervention associated with limiting a patient's fluids is complex, including psychodynamic, social, and behavioral factors. Because of the complexity of nursing care, and because of the unanswered questions about etiology and treatment of water intoxication, the area is fertile for nursing research.

Humans↗

Application of sandwich immunoassays for the determination of sample-specific background signals and its use for calibration of immunoassays.

Sample-related background signals in immunoassays can be measured by a variation of the double antibody sandwich principle, in which the unlabelled specific antibody is substituted by a similar unrelated non-specific antibody. This permits differentiation between the analyte-specific and the background signal components for each sample. The method permits selection of sera with no or low analyte content for use as analyte diluent and for defining the zero point of the calibration curve. The method also permits control of analyte content during production processes which may change the background signal as well as identification of samples with atypical background signals. The procedure has been used for the calibration of enzyme immunoassays for alpha-fetoprotein (AFP) and human thyroid-stimulating hormone (TSH).

Animals↗

Why research doesn't yield treatment.

This article has presented examples from nursing research with chronically mentally ill clients that illustrate problems with utilization of nursing research in this field. Obstacles to utilizing research in clinical practice include (a) difficulty in identification of treatment goals; (b) difficulty in measurement of treatment outcomes; (c) diversity of psychotherapeutic interventions; (d) attrition of clients over a relatively short period of time; and (e) variation among clients with regard to degree of impairment, response to medication, and social support. These problems were examined using the criteria described by Fawcett (1982) for utilization of research findings: scientific merit, clinical relevance, and clinical evaluation. Limitations for utilizing findings from research with the chronically mentally ill were illustrated in the areas of scientific merit and clinical evaluation. However, studies of the chronically mentally ill and their treatment showed definite clinical relevance, indicating the need for further research with the chronically mentally ill.

Chronic Disease↗

The standing potential of the human eye reflects differences between upper and lower retinal areas.

In 12 healthy subjects the "light peak" of the electrooculogram was measured following localized stimulation of various retinal locations. Significant differences in "light peak" amplitudes were found between central and peripheral stimulation, and at 10 deg eccentricity the "light peak" amplitudes were significantly larger following upper retinal stimulation than those elicited by lower retinal stimuli. In addition, the "light peak" amplitude produced by upper or lower retinal stimulation behaved differently when test light intensity increased. The upper retinal areas showed consistently a higher sensitivity to light intensity changes than the lower retinal areas. The "light peak" of the EOG is believed to index the rate of retinal metabolism elicited by light stimuli. Our findings show that upper retinal areas display a higher level of light-induced activity reflecting the interaction between the photoreceptors and the retinal pigment epithelium than lower retinal areas. The results are interpreted as a superiority of the upper over the lower retina and are related to other electrophysiological and functional differences between upper and lower retinal areas of man.

Action Potentials↗

Area-luminance relationship for a constant light peak of the standing potential in the human eye.

The area-luminance relationship of the light peak of the slow oscillation of the standing potential was investigated in man by determining luminance response curves for field sizes between 5 degrees and Ganzfeld after dark adaptation and at two levels of adaptive illumination. The luminance necessary for a low constant light peak was read therefrom and related to the area stimulated. With foveally and extrafoveally centered test lights a straight line with gradient -1 was found if the logarithm of the threshold luminance was plotted against the log area of the field. This indicates that the threshold of the light peak of the standing potential is inversely proportional to its area.

Adaptation, Ocular↗

Group therapy with parolees in a community mental health center.

Seeing parolees, who were reluctantly seeking mental health services, in individual therapy was unsatisfactory. Although there were identifiable mental health reasons for their referral, they did not recognize a need for individual therapy. In addition, as the therapist, I felt frustrated, and I lacked empathy. Recognizing a problem, I utilized the nursing process: assessment, planning, implementation, and evaluation, to solve the problem and provide better nursing therapy. A modified self-help group provided support to the parolees to resolve their disequilibrium, to enhance their self-esteem, to teach them to structure their own time and to satisfy the requirements of their paroles. This therapist, as well as the group members and cotherapist, gained personally from the group experience. I developed an awareness of the parolees disequilibrium and I broadened my capacity for empathy.

Adult↗

Change in alkaline phosphatase isoenzyme pattern in urine as possible marker for renal disease.

The human kidney contains two types of alkaline phosphatase (AP) isoenzymes: a hepatic type of AP and an intestinal-like AP. Intestinal-like AP, measured by immunotitration techniques, is a minor component (1 to 4%) of the total AP activity. It is found only in the particle-free fraction (cytoplasm) and is located, with immunofluorescent techniques, in some of the proximal convoluted tubules. Urinary AP activity is found after high-speed centrifugation in the supernatant (x 100,000g), as well as in the sediment, and may be extracted from the sediment after solubilization with n-butanol. Both types of these renal isoenzymes contribute to urinary AP activity. Biochemical characterization (effect of inhibitors, thermostability, denaturing with urea, and so on) revealed that urinary intestinal-like AP and renal intestinal-like AP are identical. Both, however, have been distinguished as multiple forms of AP from the small intestine. Most of the urinary AP activity of healthy persons (22 volunteers) was found in the sediment and consisted of liver-type AP. Urinary AP of patients with diseases, after application of potentially nephrotoxic drugs or during rejection episodes of renal allografts, contains little sediment activity, but it contains increased amounts of urinary intestinal-like AP.

Alkaline Phosphatase↗