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Biomedical subjects

A R Rabson

Publications and source records attributed to A R Rabson.

At least 19 recordsLinked to original sources
PubMed1996

Clinical, hematologic, and immunologic effects of interleukin-10 in humans.

We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15 +/- 1.1, 208 +/- 20.1, and 505 +/- 22.3 ng/ml) occurred after 2-5 min for 1, 10, and 25 micrograms/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24-63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12-24%) in neutrophil superoxide generation. There was a marked inhibition (60-95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10 micrograms/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72-87%) in interferon-gamma (IFN gamma) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reduces ex vivo production of IL-6, IL-8, and IFN gamma.

Adolescent↗
PubMed1995

A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses.

In vitro, IL-10 inhibits T cell proliferation and LPS-induced monocyte production of IL-1, TNF-alpha, IL-6, and IL-8. We studied the safety and immunomodulatory effects of IL-10 administration in humans. Seventeen healthy volunteers received a single i.v. bolus injection of either human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Routine safety parameters, lymphocyte phenotypes, T cell proliferative responses, and stimulus-induced cytokine production were assessed before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or signs after IL-10 administration. A transient neutrophilia and monocytosis that peaked at 6 h (45-160% above base line) was observed. However, lymphocyte counts fell by 25% 3 and 6 h after the injection (p < 0.01). In particular, lymphocytes expressing the T cell surface markers CD2, CD3, CD4, CD7, and CD8 were significantly decreased. Mitogen-induced T cell proliferation was suppressed by up to 50% (p < 0.01) in the two higher dose groups. Significant dose-dependent inhibition (65-95%) of TNF-alpha and IL-1 beta production from whole blood stimulated ex vivo with endotoxin occurred after each dose of IL-10. In contrast, there was no reduction in the production of their respective antagonists, TNF soluble receptor p55 or IL-1 receptor antagonist. We conclude that a single intravenous injection of IL-10 is safe in humans, has inhibitory effects on T cells, and suppresses production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta.

Adolescent↗
PubMed1994

A search for mycobacterial DNA in sarcoidosis using the polymerase chain reaction.

The etiology of sarcoidosis is unknown, but mycobacteria have been considered as a possible etiologic agent. The authors used the polymerase chain reaction (PCR) to search for mycobacterial DNA in paraffin-embedded granulomatous tissues from patients with sarcoidosis. The target sequence used for PCR amplification is a 383-base pair segment of the gene encoding the 65 kD mycobacterial surface antigen. This assay can detect Mycobacterium tuberculosis and atypical mycobacteria in archival material. Its sensitivity, which is superior to Ziehl-Nielsen staining for acid-fast bacilli, is 1 bacterium per 2500 cells. Ten sarcoidosis blocks and 10 normal controls were negative with mycobacterial PCR but positive with beta-actin PCR, indicating the presence of amplifiable DNA. Mycobacterial PCR gave positive results for six acid-fast bacilli stain/culture-positive blocks from patients with tuberculosis. These results indicate that sarcoidosis probably does not represent an active mycobacterial infection. These data also suggest that mycobacterial PCR is helpful in differentiating tuberculosis and sarcoidosis.

Base Sequence↗
PubMed1994

Flow cytometry in the diagnosis of brain tumors.

Flow cytometry is a useful technique for detecting surface antigens on cells in suspension, particularly lymphoid cells in blood or disaggregated lymphoid tissue. It is eminently suited to the diagnosis of lymphoma, but its use in differentiating brain tumors depends on better definition of tumor cell surface antigens. Flow cytometry's best application is in measuring cellular DNA content and proliferative activity of tumor cells, and, therefore, it can readily detect whether a tumor is diploid or aneuploid. Clinical correlations of aneuploidy in astrocytomas are still controversial, but there is significant evidence relating aneuploidy to a favorable prognosis in patients with neuroblastoma and medulloblastoma. Studies in which the proliferation fraction was assessed by means of BUdR incorporation or using the monoclonal antibody Ki-67 indicate a marked correlation with biological behavior in a variety of brain tumors.

Antigens, Neoplasm↗
PubMed1992

Use of the polymerase chain reaction mismatch technique to identify the HLA-DQw8 allele in patients with insulin-dependent diabetes mellitus.

The allelic forms of the HLA-DQB gene have been recognized as susceptibility markers of type 1 diabetes mellitus. One of these alleles, the DQw3.2 (DQw8), accounts for the well-documented association of the DQw3 locus with the disease. This report describes a method using the polymerase chain reaction mismatch technique to amplify the three different DQw3 allele sequences in 26 insulin-dependent diabetic patients. Primers were designed that differed only at one base at the growing end of their sequences. Using a common oligonucleotide primer located downstream in the first domain of the DQB gene and three other primers located at the other end of the sequence being amplified, it was possible to identify and distinguish the DQw8 allele from the other two closely related alleles (DQw7, DQw9). This method, which could be useful in excluding HLA-related susceptibility to diabetes mellitus, is rapid and nonisotopic, and indeed could be adapted to investigate any DNA sequence polymorphism.

Alleles↗
PubMed1992

Rapid detection and species identification of mycobacteria in paraffin-embedded tissues by polymerase chain reaction.

The sensitivity and specificity of the polymerase chain reaction (PCR) in the detection of mycobacteria in paraffin-embedded tissues and in crude lysates of mycobacterial cultures were assessed. Sections of formalin-fixed, paraffin-embedded tissues were deparaffinized and then subjected to a simple proteinase K and boiling lysis procedure. These preparations were used directly for PCR amplification of the 383 bp segment of the gene encoding the 65 kDa mycobacterial surface antigen. Crude lysates of mycobacteria were used as positive controls. The specificity of the PCR products was confirmed by Southern blot using a region-specific digoxigenin-labeled oligonucleotide probe and chemiluminescent detection. The 383 bp diagnostic fragment was visualized in 11 of 12 acid-fast bacilli (AFB) stain/culture-proven-positive blocks. Crude lysates of mycobacteria were detected to a sensitivity of approximately 80 organisms. Amplified fragments from paraffin-embedded tissues and mycobacterial cultures of M. tuberculosis, M. avium-intracellulare, and saprophytic mycobacteria were distinguished by digestion with Nar 1 restriction endonuclease. These results suggest that PCR amplification followed by restriction enzyme digestion of the PCR product is a rapid, specific, and highly sensitive technique for the detection and speciation of mycobacteria in paraffin-embedded tissues.

Base Sequence↗
PubMed1990

Fruit allergy: demonstration of IgE antibodies to a 30 kd protein present in several fruits.

A patient who had experienced allergic responses to various fruits developed an acute anaphylactic reaction after the ingestion of a local strain of cling peaches. The patient's serum, but not control sera, contained IgE antibodies reactive to extracts from peaches, guavas, bananas, mandarins, and strawberries in an ELISA. The patient's serum, however, did not demonstrate elevated levels of IgE antibodies to extracts from apples, pears, and nectarines. Adsorption of the patient's serum with extracts from peaches, strawberries, and mandarins resulted in a decline of detectable IgE antibodies to these fruits. Adsorption with extracts from apples and pears had no such effect. These results demonstrate the specificity of the patient's IgE antibodies to selected fruits only. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western blotting revealed a 30 kda of protein that was recognized by the IgE antibodies in the patient's serum. This protein was not present in extracts from pears or apples. Our results highlight the importance of specific allergens in considering acute allergic reactions to individuals exhibiting sensitivity to various foods or fruits.

Adult↗
PubMed1989

A 180-kilodalton protein from Mycobacterium tuberculosis defined by a human T cell clone.

A high molecular weight protein from Mycobacterium tuberculosis (M. tuberculosis) has been identified, that is recognized by peripheral blood mononuclear cells from several tuberculous patients and by a T cell clone derived from a patient with tuberculous pleurisy. Purification of this fraction demonstrated biological activity to reside in a 180-kDa protein component. This mycobacterial protein appears to exist in some, but not all mycobacteria as the clone reacts to M. tuberculosis, BCG M. kansasii, M. flavescens and M. fortuitum, but not to M. intracellulare, M. scrofulaceum or a variety of gram-positive or gram-negative bacteria, or to PPD. Specific anti-genic challenge of the T cell clone in the presence of irradiated antigen presenting cells results in proliferation and interleukin-2 (IL-2) production. Proliferation is restricted to HLA Class II antigens as antigenic recognition occurs only in the presence of either one of the two parental DR haplotypes. Peripheral blood mononuclear cells from several other patients with pulmonary tuberculosis also proliferate in response to this antigen, emphasizing the relevance of T cell cloning techniques in identifying important mycobacterial antigens.

Antigen-Presenting Cells↗
PubMed1989

Arthralgias as a presenting manifestation of primary biliary cirrhosis.

Two patients presenting with arthralgias had associated minor elevations in liver enzymes. Each patient's serum had a cytoplasmic pattern of fluorescence on HEp-2 cells which led to the detection of antimitochondrial antibodies. Liver biopsy in both patients revealed primary biliary cirrhosis. Awareness of this limited, articular presentation of primary biliary cirrhosis may result in early treatment and the potential to arrest liver damage in some patients.

Adult↗
PubMed1988

Clofazimine reverses the inhibitory effect of Mycobacterium tuberculosis derived factors on phagocyte intracellular killing mechanisms.

The effects of clofazimine on phagocyte functions associated with antimicrobial activity have been investigated. Clofazimine at a variety of concentrations was capable of enhancing the spontaneous production of hydrogen peroxide and the intracellular killing ability of phagocytes; but had no effect on resting phagocyte lysozyme release, or hexose monophosphate shunt (HMPS) activity. However, when these latter functions were assessed in the presence of a phagocytic stimulus, clofazimine moderately increased both lysozyme release and HMPS activity. A 25 Kd glyco-lipoprotein derived from Mycobacterium tuberculosis has been shown to inhibit these antimicrobial functions. Clofazimine was capable of partially reversing the inhibitory effect of the mycobacterial component in all of the systems assessed. Partial restoration was observed at concentrations of 0.5 mg/l and was maximal at 2 mg/l. These studies indicate important mechanisms operative in the pathogenesis of tuberculosis and suggest that clofazimine may have clinical relevance in the treatment of mycobacterial diseases.

Bacterial Proteins↗
PubMed1988

Low specific IgE, IgG and lymphocyte reactivity in a group of patients developing anaphylaxis following a honey-bee sting.

Ten patients who developed severe generalized reactions following a honey-bee sting were investigated for the presence of specific IgE and IgG antibodies, and for lymphocyte reactivity following in-vitro honey-bee venom (HBV) stimulation. Five of the patients (high responders) showed high HBV-specific IgE and IgG levels, whereas the other five patients (low responders) showed low HBV-specific IgE and IgG levels. Mononuclear cells from the high responder group incorporated significant amounts of 3H-thymidine when activated with pure bee venom, whereas insignificant lymphocyte proliferation was observed in the low-responder group. It is concluded that, amongst HBV-sensitive patients, a group of low responders exists in whom the mechanism of anaphylaxis cannot be explained.

Adolescent↗
PubMed1988

Enzyme-linked immunosorbent assay for the detection of antibodies against Mycobacterium tuberculosis in bronchial washings and serum.

This prospective study evaluates an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies against Mycobacterium tuberculosis when applied to serum and bronchial washings (BW) of patients requiring bronchoscopy for definitive diagnosis. The ELISA employed an adsorbed fraction of mycobacterial sonicates as antigen. Of the 57 patients tested, 12 had tuberculosis (TB), 13 had malignant disease, 14 acute pneumonia or chronic destructive pneumonia, 13 had no demonstrable disease, and five had miscellaneous diseases. The mean optical density (OD) at 492 nm for a 1 in 40 dilution of serum of patients with TB was 0.338 +/- 0.218 and for control subjects was 0.162 +/- 0.098 (p = 0.0323). Values for neat BW were 0.317 +/- 0.122 for TB patients and 0.191 +/- 0.140 for control subjects (p = 0.0084). Using stepwise discriminant analysis, the ELISA on serum gave a sensitivity of 70.0 percent and specificity of 86.4 percent and 83.3 percent correct classification. When applied to BW, there was a 72.7 percent sensitivity, a 82.2 percent specificity, and patients were correctly classified in 80.4 percent of cases. It is concluded that the assay is a useful and reliable adjunct to conventional tests for tuberculosis.

Adult↗
PubMed1988

Differentiation of sarcoidosis from tuberculosis using an enzyme-linked immunosorbent assay for the detection of antibodies against Mycobacterium tuberculosis.

This study evaluates the ability of an enzyme-linked immunosorbent assay (ELISA) using adsorbed mycobacterial sonicates as antigen to differentiate between patients with tuberculosis (TB) and patients with sarcoidosis. The study group consisted of 11 patients with active sarcoidosis, seven patients with sputum-positive tuberculosis, and seven normal control subjects. Serum specimens were subjected to ELISA. Serum anti-TB IgG optical density measured at 492 nm (mean +/- SD); pulmonary TB, 0.291 +/- 0.040; normal control subjects, 0.092 +/- 0.011; and sarcoidosis, 0.064 +/- 0.033 (TB vs sarcoid, p less than 10(-6)). This ELISA is a valuable test for the differentiation between sarcoidosis and TB.

Adult↗
PubMed1988

Defective dendritic cell accessory function in NZB/W F1 hybrid mice.

The proliferative response of NZB/W F1 hybrid mice when activated by sodium periodate (NaIO4) was found to be markedly defective as compared to the response in control NZW mice. This defect was observed in both 4 month old female mice and in 8-10 month old male mice. To determine whether the defect was an intrinsic T cell defect or an accessory cell defect, splenic dendritic cells (DC) were purified and their ability to activate enriched T cells after NaIO4 stimulation was assessed. In mixing experiments it was observed that normal NZW dendritic cells could restore the response of NZB/W F1 hybrid T cells whereas addition of NZB/W F1 dendritic cells to NZW T cells resulted in defective 3H-thymidine incorporation after NaIO4 stimulation. These results indicate that accessory DC of NZB/W F1 mice are defective and unable to support T cell responses to the mitogen NaIO4.

Animals↗
PubMed1987

An enzyme-linked immunosorbent assay using adsorbed mycobacterial sonicates for the serodiagnosis of tuberculosis.

Sera from 123 patients with confirmed tuberculosis and 576 patients with other non-mycobacterial diseases were tested for antibodies to an adsorbed mycobacterial sonicate antigen employing an enzyme-linked immunosorbent assay. The results show significant differences in IgG levels between sera from tuberculosis patients and controls. The results of delayed hypersensitivity skin-test reactions to purified protein derivative in both the patient and control groups were unrelated to antibody levels. The assay was able to detect antibodies for at least 4 months after diagnosis and treatment. Patients diagnosed as having tuberculosis 7 months or more before being tested did not demonstrate increased antibody levels. The assay could be useful not only as a screening technique for diagnosing tuberculosis in an immunised population but also as a means of monitoring antituberculosis treatment.

Antigens, Bacterial↗
PubMed1987

Anaphylactic shock due to cytarabine in a leukemic child.

In a young child with acute promyelocytic leukemia, treatment with a variety of chemotherapeutic agents produced an acute anaphylactic reaction. When cytarabine was removed from the chemotherapeutic regimen, no further anaphylaxis occurred. Employing an enzyme-linked immunosorbent assay with cytarabine coated onto the wells in bovine serum albumin, specific IgE antibodies to this drug could be demonstrated. Similar antibodies could not be demonstrated in the serum of normal controls or of two other patients receiving cytarabine. We therefore document anaphylactic shock mediated by specific IgE antibodies to cytarabine.

Anaphylaxis↗
PubMed1987

Depressed natural cytotoxicity but normal natural killer cytotoxic factor (NKCF) production by mononuclear cells derived from patients with hepatocellular carcinoma.

This study investigated the relation between the production of natural killer cytotoxic factors (NKCF) and the phenomenon of natural killing (NK) activity against target K562 cells. Two different models of defective NK cell activity were employed. In the first instance, cytotoxic activity of mononuclear cells (MN) derived from patients with hepatocellular carcinoma was compared to the ability of these cells to produce NKCF. Although direct cytotoxicity was considerably impaired in these patients, the ability of their MN to produce NKCF when stimulated with K562 cells was found to be normal. In the second model, MN treated with the lysosomotropic drug monensin showed considerably reduced direct cytotoxic activity, although they were capable of producing normal amounts of NKCF when activated by K562 cells. These results therefore indicate that there is no correlation between NK activity and corresponding NKCF release, and suggest that NKCF production and activity is independent of direct NK cytotoxic activity.

Adult↗