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Biomedical subjects

A Basten

Publications and source records attributed to A Basten.

At least 91 records · Page 5Linked to original sources
PubMed1987

Australian hemophiliac recipients of voluntary donor blood products longitudinally evaluated for AIDS. A clinical and laboratory study, 1983-1986.

One hundred and sixty-one Australian patients with hereditary bleeding disorders comprising hemophilia A (120), hemophilia B (18), von Willebrand's disease (16), and seven symptomatic female hemophilia A or B carriers were screened for clinical and serological evidence of exposure to HTLV-III/LAV/ARV/HIV infection. During the previous five years (1979-1984) they had been treated almost exclusively with blood products derived from Australian voluntary donors. The prevalence of HTLV-III antibodies in 1985 was 45%, with the highest frequency being in those with severe hemophilia A (78%) and the lowest in patients with hemophilia B (6%). Antibody positivity correlated with a reduced absolute T helper (T4) cell numbers and/or an inverted T4:T8 ratio. Lymphadenopathy was detected in 23 subjects but only 13 had an abnormal T cell ratio. Comparison of seropositivity and T4:T8 ratios in 32 patients studied in 1983 and again in 1985 suggested that T4 cell deficiency reflected HTLV-III exposure rather than being a predisposing factor for infection with the virus. Individual patients showed considerable fluctuation in T cell subsets over a 12 month period of follow-up, but as a population there was a slight trend with time towards diminishing T4:T8 ratio only in the antibody positive hemophilia A patients of mild to moderate severity. Three (2%) of the 161 patients screened to date have developed confirmed AIDS with fatal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1987

The serological response to the phenolic glycolipid of Mycobacterium leprae in Australian and Nepali leprosy patients.

Antibodies to the species-specific phenolic glycolipid (PGL-1) of Mycobacterium leprae and a crude M. leprae sonicate were measured by ELISA in sera from newly diagnosed and treated leprosy patients from Sydney and Nepal. IgM anti-PGL-1 antibodies were present in 88-90% of untreated patients at the lepromatous pole of the clinical spectrum and 35-55% of those at the tuberculoid pole. In treated patients with either form of the disease, IgM anti-PGL-1 antibodies were within the normal range or minimally elevated. In contrast, high levels of IgG anti-PGL-1 antibodies were detected in both treated and untreated patients. Neither IgM nor IgG anti-PGL-1 antibodies were elevated in sera from Mantoux negative controls and only one out of 15 sera from patients with untreated tuberculosis contained significant amounts of antibody. Comparison of the data from the anti-PGL-1 assay with the antibody response to a crude M. leprae sonicate revealed that the latter assay yielded more variable results and discriminated less well between lepromatous and tuberculoid subjects and between untreated patients and those on therapy. Thus the IgM anti-PGL-1 response signifies the presence of active disease, particularly in multi-bacillary cases, and has the potential to be used not only to monitor the response of these patients to therapy, but also to detect subclinical leprosy in high-risk groups such as the relatives of patients with lepromatous disease.

Antibodies, Bacterial↗
PubMed1987

Clinical significance of changes in serum proteins, immunoglobulins, and autoantibodies in leprosy.

Changes in the level of acute phase reactants such as C-reactive protein (CRP), serum globulins, and autoantibodies have been reported previously in patients with leprosy, particularly at the lepromatous end of the spectrum. The clinical significance of these findings was investigated by comparing the same parameters of humoral immune function in populations of Australian Aboriginals with stable treated leprosy and relevant contact groups including a) noninfected European sporadic contacts and b) healthy Aboriginal relatives of patients with confirmed leprosy. Raised levels of CRP and immunoglobulins and the higher frequency of autoantibodies seen in leprosy patients compared with sporadic contacts are probably related to differences in the incidence of nonleprous infection rather than to leprosy per se. Comparable results were obtained in the leprosy patients and their family contacts. The data highlight the need to use antigen-specific assays for determining the significance of changes in acute phase reactants and for distinguishing between the primary and secondary effects of Mycobacterium leprae infection.

Alpha-Globulins↗
PubMed1987

Dominant cell wall proteins of Mycobacterium leprae recognized by monoclonal antibodies.

A cell wall fraction of Mycobacterium leprae has enhanced potency in activating immune T cells. By using a panel of monoclonal antibodies (MoAb), the dominant immunogen in this preparation was shown to be a complex of proteins of apparent molecular weight (Mr) 65 to 50 kD with a major antigen of 65 kD. Antigen capture assays supported the results of immunoblots and ELISA that this protein was concentrated in the cell wall. By varying the MoAb used as capture or tracer antibody, one of the three MoAb-defined epitopes on the 65 kD protein proved to be unique to M. leprae while the other two were shared by M. bovis (BCG) and M. tuberculosis. The cross-reactive epitope defined by MoAb L22 was present on a protein of Mr 12 kD as well as the 65 kD protein. The 12 kD protein was strongly radiolabelled with 125I and was immunoprecipitated by L22 but not by two other MoAb, L12 or L14. By contrast the higher molecular weight forms were only weakly precipitated by the three MoAb. Competitive inhibition assays with lepromatous leprosy sera demonstrated that the MoAb-defined epitopes were recognized by human B cells. The proteins bearing one of the cross-reactive determinants was purified from M. bovis (BCG) sonicate by affinity chromatography with MoAb L22 coupled to Sepharose 4B. This antigen fraction stimulated proliferation in peripheral blood mononuclear cells from BCG vaccinated, mantoux positive individuals indicating that the cell wall protein has cellular as well as humoral reactivity. The three MoAb defined epitopes are encoded by the DNA clone Y3178 recently isolated from M. leprae.

Antibodies, Monoclonal↗
PubMed1986

Immunoreactivity of a 70 kD protein purified from Mycobacterium bovis Bacillus Calmette-Guerin by monoclonal antibody affinity chromatography.

The protein antigens from Mycobacterium bovis (BCG), M. tuberculosis, and M. leprae share a number of common determinants. We have used a murine mAb (L7) recognizing such a determinant on a protein of Mr 70,000 to purify this antigen from M. bovis sonicate by affinity chromatography. Enrichment of the protein in column eluates was confirmed by immunoblotting and in antigen inhibition assays. After radiolabelling with 125I, the protein could be immunoprecipitated with human lepromatous leprosy sera. Stimulation of peripheral blood mononuclear cells from BCG-vaccinated and naturally mantoux-positive individuals induced proliferation and IFN-gamma secretion, while intradermal injection of purified antigen into the same subjects resulted in a delayed-type hypersensitivity reaction. Thus, the 70,000 molecule carried epitopes capable of reacting with B cells, and eliciting a potentially protective T cell response. The first 15 N-terminal residues were sequenced using a gas-phase sequenator.

Amino Acid Sequence↗
PubMed1986

A rat model system for radioimmunodetection of kappa myeloma antigen on malignant B cells.

A novel experimental model was established in normal rats for studying the localisation and tissue distribution of a murine monoclonal antibody directed against kappa light chain B cell malignancies. The antibody, K-1-21 was raised against human kappa Bence Jones Proteins and reacts with a cell membrane antigen KMA which is restricted to some kappa myeloma and lymphoma cells. In the rat model, kappa or lambda Bence Jones protein-conjugated sepharose was implanted subcutaneously on either flank 24 h before the injection of 131I-labelled K-1-21 or its F(ab')2 fragment. Gamma camera imaging and tissue distribution studies showed specific localisation of the K-1-21 antibody in the kappa sepharose. Injection of F(ab')2 antibody fragments resulted in faster background clearance, earlier delineation of the specific image and significantly higher target to blood ratios than those obtained with the intact antibody. These results suggest that the model may provide an alternative system to tumour xenograft bearing nude mice for studying localisation of antibodies with therapeutic potential.

Animals↗
PubMed1986

Separate antigenic determinants on cell wall associated carbohydrate antigens of Mycobacterium leprae defined with monoclonal antibodies.

Monoclonal antibodies (Mabs) raised against Mycobacterium leprae sonicate defined two different determinants on related, cell-wall-associated, carbohydrate antigens common to M. leprae, M. bovis (BCG), and M. tuberculosis. Antigen inhibition ELISA and antigen capture assays demonstrated that the two antigens were present in a cell-wall fraction, M. leprae resonicate. There was species variation in the distribution of the antigens; the 4.5-6 kD antigen was more abundant in M. tuberculosis and M. bovis, while the 30-40 kD antigen was more concentrated in M. leprae preparations. Although both were present in the cell wall, only determinants on the 30-40 kD antigen were accessible on intact bacilli. The results from capture assays and Mab affinity chromatography with both L9 and L4 indicated that the 4.5-6 kD antigen was probably a fragment of the larger molecule. Both antigens are significant immunogens in the human B-cell response to M. leprae.

Antibodies, Bacterial↗
PubMed1986

Transfer factor as a therapy for multiple sclerosis: a follow-up study.

The result of a two year, double blind, controlled trial of Transfer Factor (TF) in the treatment of multiple sclerosis (MS) were reported in 1980. It was demonstrated that TF significantly reduced the rate of progression of the disability but the benefit of therapy was not apparent until 18 months after its commencement. After the completion of the trial, TF treatment was offered to all the trial participants. Forty-five of these people accepted TF as treatment and have been followed for the subsequent three years. The twenty-three people who had received TF during the trial, and continued on TF after the trial, consistently had a slower rate of progression of their MS. Although the twenty-two patients initially on placebo had a significantly faster rate of progression during the trial, this slowed with commencement of TF treatment. After 3 years of TF, the rate of progression of disease was similar to that of the group receiving TF continuously for 5 years. In addition, 470 patients with clinically definite MS are being treated in New South Wales in an open study of TF. The rate of progression of the disease is being monitored by neurological assessments and appears to be similar to that of patients who had received TF in the original trial. The follow-up study of the 1980 TF trial patients and the open study of 470 MS patients confirm the original observation that TF has some effect on slowing the course of MS.

Clinical Trials as Topic↗
PubMed1985

Antigen-specific suppression of anti-influenza antibody production in man. Possible role of a membrane-antigen complex.

E rosette-forming (E+) cells from human secondary lymphoid tissue were incubated with high dose influenza A virus (Mem-Bel) in an attempt to generate suppressor T cells. Suppression was assayed by transferring the antigen-pulsed E+ cells into effector cultures consisting of E+ and E- cells stimulated with immunogenic amounts of either the inducing virus Mem-Bel) or the non-cross-reacting influenza B virus (B/HK). The transfer resulted in marked inhibition of IgG, IgA and IgM antibody production to Mem-Bel but not to the control antigen, B/HK virus. The suppressive effect was specific at the level of induction as well as expression since E+ cells exposed to high dose Mem-Bel could provide help to an effector culture containing E- cells and optimal dose of B/HK virus. However, metabolically active cells did not appear to be required for suppression. Thus, it could be elicited (a) after only 15 min incubation of E+ cells with high-dose virus and (b) by E+ cells exposed to irradiation, incubated in the presence of metabolic inhibitors, or disrupted by repeated freeze thawing. In contrast, treatment of E+ cells with pronase reversed the suppressive effect. Interestingly, virus heated to 70 degree C failed to induced suppression, while retailing the ability to elicit a normal helper response. Suppression induced by exposure to standard amounts of high-dose antigen was mediated by T cells of both helper/inducer (Leu-3a+) and suppressor/cytotoxic subsets (Leu-2a+), but not by B cells. Two groups of observations pointed to the B cell as the target of suppression. First, suppression could still be transferred to effector cultures in which helper T cells had been replaced by T cell-replacing factor or suppressor T cells removed by irradiation. Second, significant inhibition of antibody production was obtained when the transfer of antigen-pulsed E+ cells was delayed for up to 120 h after initiation of the effector culture. Taken together the results suggest that suppression in this system is due to the formation of an antigen bridge between specific receptor sites on the T cell membrane and the target. Although not dependent on triggering of metabolically active suppressor T cells the phenomenon highlights the need for care in interpreting the mechanism of suppression by high-dose antigen and could, in addition, represent a biologically important control mechanism capable of rapid inhibition of effector T cells and B cells in sites of high antigen concentration.

Antibodies, Viral↗
PubMed1985

A role for suppressor T cells in induction of self-tolerance.

The potential role of suppressor T cells (Ts) in the induction of self-tolerance was investigated by eliminating I-J+ cells during ontogeny (I-J antigens are encoded by the I-J subregion of the murine major histocompatibility complex). To achieve this, F1 mice were exposed to anti-I-J antibodies via the transplacental route by mating B10.A(3R) females, preimmunized with B10.A(5R) cells, with CBA males. At 6 weeks of age, the offspring were injected with rat erythrocytes (RRBC) to induce erythrocyte autoantibodies. By comparison with age-matched controls, Ts-depleted mice produced significantly higher titers of autoantibody, whereas there was no difference in the antibody response of the two groups to the foreign determinants on the RRBC. The selective increase in autoantibody production was mirrored at the clonal level by the appearance of self-reactive B-cell hybridomas after fusion of RRBC-immune spleen cells with the NS-1 cell line. On the other hand, when helper cell function of RRBC-primed cells was measured in a T-cell proliferative assay, Ts depletion in utero resulted in enhanced T-cell activity to nonself (RRBC) but not to self (mouse erythrocyte) determinants. Thus, helper T cells recognizing nonself determinants on RRBC appeared to be responsible for activating self-specific B cells, presumably through linked recognition of different epitopes on mouse erythrocytes. Taken together, these findings indicate that elimination of I-J+ cells during ontogeny can lead to the appearance and activation of "forbidden" B-cell clones and points to a central role for Ts in induction as well as maintenance of self-tolerance.

Age Factors↗
PubMed1985

An exhaustive tree-searching algorithm for high-resolution computer-assisted nucleotide sequence analysis.

A new computer search strategy has been devised for high-resolution nucleotide sequence analysis. The strategy differs from those used by earlier sequence analysing programs in that it is exhaustive and capable of detecting all possible homologies and other types of relationships between or within sequences irrespective of the pattern of matches and mismatches encountered. The implementation of this strategy into a working algorithm is described.

Algorithms↗
PubMed1985

The SEQANAL and SEQTALK programs: a new method of access to high-resolution nucleotide sequence comparison and analysis programs from a remote laboratory mini- or microcomputer.

A new method of access has been devised for biologists requiring the use of computer programs offering high-resolution analysis and comparison of nucleotide sequence data. The strategy involves the development of a pair of computer programs, called SEQANAL and SEQTALK, designed to operate in tandem. SEQANAL is a large and complex program intended to be used to discover regions of internal repeats and dyad symmetries within one sequence, or regions of homology, complementarity or optimal alignment between two sequences. Three algorithms are supported: those of Staden (1977, 1978); of Korn et al. (1977); Queen and Korn (1980); and the newly-described exhaustive tree-searching algorithm of Burnett et al. (1985, 1986). The SEQTALK program is a small, portable, interactive, front-end program with which the user can specify the instructions to control the SEQANAL program. Together, the SEQANAL and SEQTALK programs permit analyses to be performed at a remote facility on a mainframe computer under the complete control of a distant user equipped with minimal computing facilities, and without needing networking facilities.

Algorithms↗
PubMed1985

Infantile complete heart block associated with maternal Ro(SS-A) ribonucleoprotein autoantibodies: report of two cases.

Two cases of congenital complete heart block arising during pregnancy were observed in association with a circulating maternal autoantibody to the soluble ribonucleoprotein Ro(SS-A). Neither mother had clinical evidence of Sjögren's syndrome or systemic lupus erythematosus usually associated with anti-Ro. However, both had a previous history of first-trimester abortion and laboratory evidence of autoimmunity, and one gave a history of sialadenitis. Maternal anti-Ro antibodies may be predictive of infantile heart block when present in pregnant women with overt or suspected multisystem autoimmune disease.

Adult↗