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B Hahn

Publications and source records attributed to B Hahn.

At least 55 records · Page 3Linked to original sources

Human T-lymphotropic virus type I-associated myelopathy in patients with the acquired immunodeficiency syndrome.

We describe two cases of serologically confirmed human T-lymphotropic virus type I (HTLV-I)-associated myelopathy involving North American men coinfected by the human immunodeficiency virus type 1. Our first patient suffered from a gradually progressive spastic paraparesis for 10 years prior to presenting with Kaposi's sarcoma, while our second patient developed subacutely progressive spastic paraparesis in the setting of full-blown acquired immunodeficiency syndrome. Autopsy examination of the spinal cords from these two cases revealed widespread axonal loss and demyelination principally involving the lateral columns of case no. 1 and the lateral and anterior columns of case no. 2. Vascular sclerosis and hyalinization were prominent in both cases, but in neither was there a conspicuous inflammatory component. In case no. 2, HTLV-I mRNA was not detected by in situ hybridization, but HTLV-I proviral DNA sequences were detected in this case by polymerase chain reaction. Neither case exhibited multinucleated cell (human immunodeficiency virus type 1) myelitis, vacuolar myelopathy, or evidence of HTLV-II infection by polymerase chain reaction assay.

Acquired Immunodeficiency Syndrome↗

Comparison of DNA antibody idiotypes in human sera: an international collaborative study of 19 idiotypes from 11 different laboratories.

The distribution of and relationships between 18 anti-DNA antibody idiotypes and one anti-acetylcholine receptor antibody idiotype have been tested in an international collaborative study of human sera from 180 individuals. The main finding is that the serum levels of many of these idiotypes, whether of murine or human origin, show a high degree of statistical correlation. The studies in a wide range of autoimmune rheumatic diseases confirm that none of the idiotypes tested is disease specific, but 13 of 15 (87%) whose levels were recorded as OD units or cpm correlated strongly with anti-ssDNA antibody levels and 11 of 15 (73%) with total serum IgM. Expression of several idiotypes was found to fluctuate in parallel with disease activity in SLE; levels of others were also elevated in the healthy relatives of lupus patients whilst a few were also raised in the spouses of these patients. The data support the notion that there may be only a few groups of related DNA antibody idiotypes. The correlations between the idiotypes with regard to their quantities, association with disease activity, and wide distribution in different diseases and healthy individuals suggest at least two explanations. First, all of these idiotypes may be present in normal immunoglobulin repertoires and simply increase in response to poly- or oligoclonal B-cell activation in autoimmune diseases. Secondly, these idiotypes may be structurally linked to each other, so that their behaviour under conditions of specific antigenic stimulation is similar. Genetic and structural studies will be required to distinguish between these possibilities.

Autoantibodies↗

[The effect of radio- and chemotherapy on lung function in children with malignant diseases].

Treatment of malignant diseases in children has become more an more aggressive during the last 15-20 years. In order to detect unwanted side-effects on the lung we investigated several parameters of lung function in 78 children with different malignancies. 1.5-15 years after termination of therapy, 43 patients (55.1%) showed a disturbed lung function. In 33.3% we found a restriction; 22 of 64 patients (34.9%) had a drop of PaO2 during exercise as an expression of disturbed diffusion. The number of patients with pathological pulmonary function raised with the intensity of irradiation of the lung. But also in 10 of 25 children who had only received a chemotherapy we could detect a disturbed lung function. Check-up at different times after completion of therapy (5, 8 and 11 years) revealed nearly the same percentage of patients without normal pulmonary function. Younger children (at the time of therapy) were more concerned (66.7%) than older ones (33.7%).

Adolescent↗

Diversity of Ig V gene segments found in anti-DNA autoantibodies from a single (NZB x NZW)F1 mouse.

We have studied 18 anti-DNA secreting hybridomas derived from a single, nephritic NZB/NZW mouse. The antibodies were analyzed for the expression of idiotypic families that are enriched in the antibodies to DNA from diseased animals (IdGN2 and IdX), and for the expression of VH and V kappa gene segment subfamilies. Most of the mAb have characteristics similar to those that may be pathogenic because they 1) bound to native DNA, 2) were of the IgG2a or IgG2b isotype, and 3) expressed idiotopes associated with glomerulonephritis in NZB/NZW mice and human lupus. Among the 18 mAb, at least six VH subfamilies and six V kappa subfamilies were expressed. A majority of the antibodies utilized a VH gene segment from the large J558 subfamily. Slot blot analyses of total spleen cell RNA revealed that as NZB/NZW mice aged and developed nephritis, they expressed progressively higher quantities of Ig transcripts. The proportion of these transcripts derived from the VH J558 subfamily also increased. Our results indicate that a diversity of B cell clones participate in the anti-DNA response of a single NZB/NZW mouse. There was no preferential utilization of 3' Ig V gene segment subfamilies. Furthermore, there was no marked difference in the pattern of VH and V kappa gene segment expression in antibodies defined by their isotypes or idiotopes.

Animals↗

[Absorption, distribution and metabolism of [14C]-levomenol in the skin].

The purpose of the present investigations was to study the cutaneous absorption of sesquiterpenic alcohol, the major active principle of chamomile. For these investigations 14C-labelled levomenol ((-)-6-methyl-2-(4-methyl-3-cyclohexen-1-yl)-5-hepten-2-ol; (-)-alpha-bisabolol) was prepared by biochemical incorporation of [14C]-acetate into the molecule. 5 h after topical application of the radiolabelled substance onto nude mice half of the radioactivity was found in the skin. The other part was measured in tissue and organes. 90% of this radioactivity was analysed as intact levomenol. To demonstrate the distribution of the substance in the skin a part of this tissue was cutted into horizontal slices by a cryotome. From the slices autoradiograms were produced. The densitometric measuration showed that there was a fast penetration of levomenol into the skin. 5 h after the topical application the substance was displaced from outermost to innermost areas. From these results a fast cutaneous absorption and a long therapeutical effect of the antiphlogistic and spasmolytic levomenol in the skin can be expected.

Administration, Topical↗

Alterations of amphetamine elicited perseveration and locomotor excitation following acute and repeated stressor application.

The effects of acute and repeated stressor application on amphetamine-induced Y-maze perseveration and locomotor activity were assessed. When the stimulus context associated with an acute stressor (restraint or restraint plus shock) was distinctively different from that in which an amphetamine test was conducted 72 hr afterward, neither perseveration nor locomotor excitation were augmented. However, following three restraint sessions the amphetamine elicited perseveration was enhanced. With a more protracted regimen applied over 15 days the augmented perseveration was absent, whereas the amphetamine-provoked motor excitation was increased. While stimulus factors have been shown to be fundamental, it is provisionally suggested that the stressor induced enhancement of amphetamine-elicited perseveration is influenced by sensitization processes. However, the sensitization is apparent only under some stress regimens, and the behavioral expression of the sensitization may be obfuscated if the stressor is too severe. Furthermore, it appears that the mechanisms operative in enhancing the stressor provoked amphetamine motor excitation are independent of those which subserve the augmented perseveration.

Amphetamine↗

Effect of hair growth cycles on experimental cutaneous candidiasis in mice.

Experimental cutaneous Candida albicans infections were produced in mice by inoculating the organisms onto areas of shaved flank skin where the hair follicles were in either the anagen (growing) or telogen (resting) phase of the growth cycle. Infection with Candida occurred in a majority of animals inoculated on either anagen or telogen skin, and the rate of clearance of the organisms was equivalent for infections on the 2 types of skin. Some of the animals inoculated on anagen skin developed foci of Candida infection in the well-developed hair follicles, below the skin surface. Deep foci of infection were not found after inoculation of the telogen areas. The infections resulted in increases in epidermal thickness and sensitization of the animals to Candida antigens, but these responses were not different between animals inoculated on the 2 types of skin. The results of these experiments indicate that although Candida albicans can infect skin containing either active or resting hair follicles, foci of infection below the skin surface occur only when well-developed hair follicles are present. These findings may have relevance to the consequences of human cutaneous candidiasis.

Animals↗

Transmission of bovine leukemia virus (BLV) to immunocompromised monkeys: evidence for persistent infection.

Splenectomized or irradiated adult and untreated baby macacques were infected with bovine leukemia virus from continuously virus producing fetal lamb kidney cell cultures. Persisting high antibody titers were followed for 4 years in the adult and 16 months in the baby monkeys, using an ELISA technique. With the exception of a persistent leukocytosis in one adult monkey, the animals remained healthy throughout the observation period. Transfer of lymphocytes from this animal to a seronegative recipient led to anti-BLV seroconversion with a lag of 5 months. All other transfer experiments showed a negative result. Virus could be recovered from the newly infected baby macacques by means of lymphocyte/fetal lamb kidney cell cocultivation for up to 4 weeks after inoculation. All other attempts to recover virus from the infected animals at a later point were unsuccessful.

Animals↗

[Postpartum hemophilia A with factor VIII inhibitor].

An abnormal life-threatening haemorrhagic diathesis occurred 6 weeks after delivery in a 25-year-old female. The reason was a spontaneously acquired factor VIIIC inhibitor haemophilia. The clinical presentation was characterised by extensive deep-seated soft-tissue haemorrhages of the extremities, a retroperitoneal haemorrhage, haematuria and recurrent joint bleedings. The activity of factor VIIIC decreased to below 1% of normal. The factor VIII inhibitor reached a maximum of 122 Bethesda units. The recurrent knee joint haemorrhages responded well to treatment with an activated prothrombin complex concentrate (Feiba). Repeated Feiba administration did not lead to an increase of the factor VIII inhibitor. It disappeared completely within 16 months and did not recur during a second pregnancy. The pregnancy was without complications and delivery on time resulted in a healthy child. Six months after the second pregnancy both mother and child showed no evidence of a disorder of haemostasis.

Adult↗

Etiology of AIDS: biological and biochemical characteristics of HTLV-III.

The newly identified human HTLV-III virus, the etiologic agent for AIDS, shares many of the biological and physicochemical properties common to a family of retroviruses named human T-cell leukemia (lymphotropic) viruses, or HTLV. Because of the similarities, and because of the uniform nomenclature for human T-cell leukemia (lymphotropic) viruses adopted at the first Cold Spring Harbor Meeting on HTLV (19, 79), this newly discovered virus associated with AIDS as HTLV-III was named HTLV-III. Other investigators making independent isolations of virus have suggested naming the virus lymphadenopathy virus or LAV (3, 16), immunodeficiency associated virus or IADV (48), AIDS-related virus (41). Immunological and nucleic acid comparison has now demonstrated that these viruses are, not surprisingly, very similar to HTLV-III (55, 63, 78). In view of the wide range of disease manifestations caused by the virus, and previous discussions concerning a uniform nomenclature for human T-lymphotropic retroviruses, it would seem ill-advised to restrict the name of this virus to one clinical manifestation of one disease. The frequent isolation of HTLV-III from patients with AIDS and ARC, the detection of antibodies specific for HTLV-III in nearly all patients with these diseases and in a high proportion of individuals at risk, and finally its effect on cells in vitro, leaves little doubt that HTLV-III is causatively involved in the development of these diseases. This etiologic association is further strengthened by the detection of HTLV-III infection in many instances where a direct cause-and-effect association can be made, e.g., hemophiliacs and children with AIDS, and blood from HTLV-III infected donors and the otherwise normal recipients of this blood who subsequently develop AIDS.

Acquired Immunodeficiency Syndrome↗

Stressor invoked exacerbation of amphetamine-elicited perseveration.

The provocation of stimulus preservation induced by amphetamine in a Y-maze was appreciably enhanced in animals that had been exposed to uncontrollable shock, whereas controllable shock did not influence performance. The enhancement of the stimulus perseveration was evident irrespective of whether the stressor was applied immediately or 72 hr prior to the perseveration test, provided that the stimulus complex in which shock was delivered was similar to that in which the perseveration test was conducted. When the two environments were distinctively different from one another the enhancement of stimulus perseveration was evident immediately after shock exposure, but not 72 hr after shock. It is suggested that stressors may have long-term effects of amphetamine-elicited perseveration, but the expression of such an effect is dependent upon the stimulus context in which the behavior is examined. Moreover, it is suggested that evaluation of amphetamine-induced behavioral changes, and possibly amphetamine-elicited and idiopathic psychosis, should consider the stress history of the organism.

Amphetamine↗

Nucleotide sequence analysis of a variant human T-cell leukemia virus (HTLV-Ib) provirus with a deletion in pX-I.

A variant of human T-cell leukemia virus subgroup I (HTLV-I), designated HTLV-Ib, has been isolated from a transformed T-lymphocytic cell line established from a Zairian patient with adult T-cell lymphoma. A recombinant phage clone of the variant provirus, denoted lambda MC-1, hybridizes under high stringency to HTLV-I DNA probes, but 17 of 43 restriction enzyme sites differ from those of HTLV-I, 10 of them clustering within 1.5 kilobases in the env-pX region. Since this variant virus retains its capacity to transform T-cells in vitro, and since a pX product is suspected to be important in transformation, we have determined the nucleotide sequence of the entire pX region of this virus for comparison to the prototype HTLV-I. In addition, the region between the gag and pol genes, parts of the pol and env genes, and a portion of the U3 region of the long terminal repeat sequence were also analyzed. We noted 141 single-base-pair changes among 3,897 base pairs, which were relatively well distributed over those portions of the provirus that were examined. In addition, an 11-base-pair deletion was found which included the potential initiator ATG codon of the first open reading frame of pX (pX-I). The next potential initiator codon predicted by the sequence is followed by 10 codons and then a termination codon. An identical deletion was also demonstrated in the only provirus present in another cell line established from the same patient on a different occasion after transformation in vitro of normal human umbilical cord blood cells. These results indicate that pX-I is not required for transformation.

Amino Acid Sequence↗

Molecular biology of human T-lymphotropic retroviruses.

The generic name for a family of human T-lymphotropic retroviruses is HTLV. Two of the three members in this family have been linked etiologically to human diseases: HTLV-I with adult T-cell leukemia and HTLV-III with the acquired immunodeficiency syndrome. In addition to their T-cell tropism and a number of other common biological and biochemical properties, the most unique common features of these viruses from a molecular biological point of view are the presence of the x-lor gene towards the 3' end of the genome and the phenomenon of a virus-induced trans-acting factor in activation of transcription initiated in the viral long terminal repeat. These features may not only be key in understanding the mechanism of transformation or cell killing by these viruses, but they also provide a basis for new classification of retroviruses. In spite of these similarities among HTLV-I, -II, -III, and bovine leukemia virus, the genome of HTLV-III is only distantly related to these other viruses. Instead, it shows greater homology to members of the Lentivirus family. Therefore, all these viruses may have a common progenitor. Two other salient features arose from the analyses of HTLV-III and acquired immunodeficiency syndrome. (a) HTLV-III frequently infects the brain of acquired immunodeficiency syndrome patients who suffer from central nervous system disorders. This not only identifies HTLV-III as the direct candidate in these central nervous system disorders but also poses the problem of crossing the blood-brain barrier in therapy strategies to eradicate the virus. (b) Different HTLV-III isolates comprise a spectrum of related viruses, with the degree of divergence varying from virtual identity to 10-15% difference. The most divergent region resides in the envelope gene. Whether this finding has implications in the development of an effective vaccine for acquired immunodeficiency syndrome remains to be determined.

Acquired Immunodeficiency Syndrome↗