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Biomedical subjects

K Behbehani

Publications and source records attributed to K Behbehani.

At least 55 records · Page 3Linked to original sources

Echinococcus multilocularis: the non-specific binding of different species of immunoglobulins to alveolar hydatid cysts grown in vivo and in vitro.

Alveolar hydatid cysts (AHC) were isolated from C57BL/6J and BALB/c mice at 8 and 12 weeks post-infection from subcutaneous and intraperitoneal foci and cultured in vitro. Freshly isolated as well as in vitro-grown cysts were incubated with Fc or F(ab')2 fragments of human, rabbit, mouse, goat or sheep immunoglobulins, then washed and incubated with a fluorescein-conjugated rabbit or goat F(ab')2 fraction of antisera to each of the above primary sera. Significant fluorescence on the surface of AHC was detected when they were incubated with human, rabbit or mouse Fc fractions followed by the addition of goat or rabbit fluorescein-conjugated antiserum. No fluorescence was detected when the AHC were incubated with the F(ab')2 fragments and fluorescein-conjugated antiserum, except when the primary antiserum was mouse F(ab')2 fractions. Cysts grown in vitro retained their binding ability to human, rabbit or mouse Fc fractions. However, the intensity of fluorescence decreased proportionally with time. The maximum intensity of staining was observed with small cysts. Large cysts showed diminished fluorescence. The non-specific binding of human, mouse or rabbit immunoglobulins (Fc fractions) to AHC was also confirmed by rosetting with sheep erythrocytes (SRBC) which suggests that the larvae of Echinococcus multilocularis may utilize the presence of Fc receptors on their surface in order to elude immune destruction by the host.

Animals↗

Type 2 diabetes in Arab patients in Kuwait.

We describe the characteristics of 75 Arab Type 2 diabetic patients in Kuwait. Their age (+/- SD) at onset was 41 +/- 10 years, and fasting serum C-peptide concentration was 0.32 +/- 0.23 nmol/l (n = 51). Fifty-three percent (37/70) possessed HLA-DR3 or -DR4 epitopes, and 64% (47/73) had a family history of diabetes. Data review suggested that they could be segregated into two groups, those under 40 years old at onset (32 +/- 6 years, n = 37), and the remainder (48 +/- 6 years, n = 38) (p less than 0.001). Those in the former group had a significantly higher frequency of a family history of diabetes than those in the latter group (92% vs 38%, p less than 0.001) suggestive of a greater genetic influence on the development of Type 2 diabetes in those with early onset disease.

Adult↗

Effect of recombinant IL-1 isomers on fetal and adult islet cell function and replication.

Natural human interleukin and the recombinant human IL-1 alpha and beta isomers were tested for effects on both fetal and adult rat isolated pancreatic islets. IL-1 alpha inhibited both replication and insulin secretion and decreased the insulin content of both islets. In contrast, the beta isomer did not affect fetal islets. It is concluded that the two isomers may have different avidities for the same receptors, or that receptors are expressed at different stages of differentiation.

Animals↗

The effect of adjuvants on immune function in the multi-low-dose streptozotocin model of murine diabetes.

The effect of various adjuvants has been investigated on the multi-low-dose (mld) streptozotocin (STZ) model of diabetes in C57BL/6 and CBA mice; diabetes was severe in the former strain. Diabetic levels of glycaemia were not attained in either strain using half the mld STZ dose (sub-mld-STZ). The adjuvants were found to affect the levels of glycaemia variously. Thus, in C57BL/6 mice at mld-STZ, CFA and saponin had no effect, whereas MDP and LPS respectively decreased and increased glycaemia; at sub-mld-STZ, each of the adjuvants increased glycaemia. In CBA mice, at both mld- and sub-mld-STZ, CFA and saponin increased glycaemia; at mld-STZ, MDP caused an initial increase but a later decrease in glycaemia, whereas with sub-mld-STZ only a decrease in glycaemia occurred; at mld-STZ, LPS was toxic in this strain, and had no effect on glycaemia at sub-mld-STZ. In both C57BL/6 and CBA mice, STZ caused a decrease in both spontaneous and PHA-stimulated blastogenesis. This persisted until day 14 in the C57BL/6 strain and until day 28 in the CBA strain. CFA reversed the anergy by day 7 in C57BL/6 mice and by day 14 in CBA mice, but did not improve beta-cell function, since further increments in glycaemia followed, except in mld-STZ C57BL/6 mice. Islet-cell surface antibodies (ICSAs) and cytotoxic islet-cell antibodies (CxICAs) occurred in both strains of mouse. ICSAs were persistent (still present at day 67), but CxICAs were detected only until day 23. The presence of ICSAs and CxICAs during the development of the diabetic state, and of ICSAs during its perpetuation, suggests that they may have a role in its aetiopathology. The lack of a correlation of non-specific T-cell anergy with glycaemia does not exclude a role for antigen-specific T-cell pathogenic processes.

Adjuvants, Immunologic↗

Antibody levels to mycobacteria in relation to HLA type: evidence for non-HLA-linked high levels of antibody to the 65 kD heat shock protein of M. bovis in rheumatoid arthritis.

We previously reported DR2 and DR7-associated regulation of antibody binding to mycobacteria in rheumatoid arthritis sera (RA), but not in tuberculosis (Tb). An extensive analysis of antibody to mycobacteria in matched normal sera, in relation to both HLA class I and class II has revealed no class II correlations, confirming that the original findings were due to RA. There was however a very strong association between IgM binding to M. tuberculosis and Cw1 (P = 0.0004). RA patients have strikingly raised levels of IgG (but not of IgA or IgM) binding to the 65 kD heat shock protein of M. tuberculosis, recently implicated in the pathogenesis of adjuvant arthritis in the rat. Remarkably, levels in RA were significantly higher even than in tuberculosis. Levels of this antibody showed no HLA associations. Thus the 65 kD antigen does not account for the DR7, and DR2 associations of IgM and IgA binding to mycobacteria reported previously, but does suggest a role for cross-reactive autoimmunity in RA.

Adolescent↗

HLA-DR-associated isotype-specific regulation of antibody levels to mycobacteria in rheumatoid arthritis.

Using sera from 75 healthy donors, 68 rheumatoid arthritis (RA) patients, and 85 tuberculosis (TB) patients, we have examined the level of antibody of the three major classes binding to seven mycobacterial species, and to three control antigens. The major findings are that IgM binding to mycobacteria is reduced in RA patients who have HLA-DR7 (P = 0.008 for M. tuberculosis antigen), and that IgA binding to mycobacteria is reduced in RA patients who have HLA-DR2 (P = 0.007 for M. tuberculosis; P = 0.0004 for M. nonchromogenicum). These associations were not seen in TB, and were restricted to these antibody isotypes. We believe this is the first report of isotype specific Class II MHC-associated regulation of antibody levels in man. A possible interpretation of our data is that patients bearing these haplotypes are recognizing suppressor epitopes common to all the mycobacterial species tested. Since DR2 and DR7 have recently been shown to be associated with a significantly reduced risk of RA, our findings are compatible with the view that changes in immune responsiveness to mycobacterial antigens, or to autoantigens which cross-react with them, are relevant to RA.

Adolescent↗

Induction, in vivo and in vitro, of macrophage membrane interleukin-1 by adjuvant-active synthetic muramyl peptides.

Recent evidence has shown that a membrane form of interleukin-1 (IL-1) serves as a necessary signal for antigen presentation, leading to T-cell activation. The synthetic immunostimulant muramyl dipeptide (MDP) is known to induce secretion of IL-1 and its adjuvant effect was found to be mediated through enhancement of T-helper cells. We have investigated the ability of MDP and 19 other adjuvant-active or -inactive MDP analogs and derivatives to induce membrane IL-1 in mouse peritoneal macrophages. Enhancement in vitro of membrane expression and secretion of IL-1 in fresh or aged cultures of macrophages was observed after stimulation with MDP or with adjuvant-active but not with adjuvant-inactive muramyl peptides. Administration in vivo of adjuvant-active doses of MDP or of any of 12 other active analogs induced high levels of macrophage membrane IL-1 detected by the lymphocyte-activating factor assay. This effect was not observed when 7 other adjuvant-inactive derivatives were used. Moreover, under conditions where MDP did not exert an adjuvant effect, this immunomodulator was found to be incapable of inducing the expression of macrophage membrane IL-1. These results demonstrate a very high correlation between the ability to induce membrane IL-1 and the adjuvant activity of muramyl peptides. The correlation was observed irrespective of other biological effects of the synthetic adjuvants such as pyrogenicity and/or anti-infectious activity.

Acetylmuramyl-Alanyl-Isoglutamine↗

Induced malaria and antibody titres in acute infections and in blood donors in Kuwait.

Concurrent with the increase in the number of imported cases of malaria into non-endemic Kuwait during the past 5 years, induced infections have been identified for the first time. We report 10 such cases over a 4-year-period. Of 8 transfusion-induced infections, 4 were due to Plasmodium falciparum and 4 to P. vivax. The mean incubation period for P. falciparum patients was 13 d and for P. vivax, 17 d. An accidental syringe-needle transmission and a congenital infection were due to P. falciparum and P. vivax respectively. Malarial antibody levels were assayed on commercially-available cultured P. falciparum schizonts by the indirect fluorescent antibody (IFA) test. To establish a base line, the sera of patients with blood film-confirmed P. falciparum and P. vivax were assayed. 96% of the P. falciparum sera were positive, the geometric mean titre (GMT) being 10,280. However, all sera from P. vivax patients were reactive but the GMT was lower at 505. 28% of sera from Kuwaitis and 45% of sera of a consecutive group of blood donors were also reactive, the respective GMTs being 38 and 51. The risk of transfusion malaria was calculated as 79 per million units drawn, an unacceptably high figure for a non-endemic country. We suggest a revised blood donor policy.

Adolescent↗

Unexpected findings amongst the skin test responses to mycobacteria of BCG vaccinated Kuwaiti school children.

A multiple skin test survey was carried out in Kuwait on 1200 school children aged 8-11 years, and on 1228 children aged 12-16 years. With only 15 exceptions, all these children had received vaccination with Japanese BCG just before they started school, 5 years and 9 years earlier respectively. Tuberculin positivity was almost 90% in both groups, with a mean response size of 8.7 mm. This was associated with remarkably high responsiveness to many of the other mycobacterial species investigated. Since this high reactivity was also to Mycobacterium ulcerans, a species most unlikely to be present in Kuwait, it is proposed that this might be due to responsiveness to group ii antigen which is present in all slow growing species. Only M. flavescens and M. rhodesiae amongst the fast growing species, were absent as sensitising organisms. After correction for the supposed reactivity to group ii antigen, M. avium B, M. gordonae, M. ulcerans and M. xenopi amongst the slow growing species, also appeared to be absent from the Kuwait environment. The species most commonly encountered were M. leprae, M. chitae, M. neoaurum, M. diernhoferi, and M. vaccae in this order. This was a remarkable finding for a country assumed to be poor in contact with environmental species, and known to have a very low prevalence of leprosy. As previously reported from Iran, but not confirmed in other places, there was a 95% correlation between responsiveness to Leprosin A and Vaccin. Amongst the slow growing species M. avium A, M. intracellulare, and M. kansasii appear to be frequent sensitising agents, in common with many other places.

Adolescent↗

Gastric alpha heavy chain disease.

Clinicopathological and immunohistological features of 4 cases of gastric lymphomas with alpha-heavy chain disease (AHCD) are described. Clinically there were no reliable features that could distinguish them from the 'western' types of gastric lymphomas (WGL). Two of the 4 had diffuse mucosal involvement reminiscent of the more common intestinal form of AHCD. Histologically, all 4 were low-grade follicular-centre cell lymphomas with plasmacytic differentiation. The diagnosis of gastric AHCD and its implications are discussed.

Adult↗

Complete Freund's adjuvant has a differential amplification action on the induction of diabetes by streptozotocin in various murine strains: CFA amplifies STZ in murine diabetes.

The effect of complete Freunds Adjuvant (CFA) has been investigated on the multi-low-dose streptozotocin (STZ) model of diabetes in mice of the H-2b (C57Bl/6) and of the H-2k (A/J, CBA) genotypes. Physiological (glycemia and body weight) and morphological (insulitis) parameters were monitored. STZ was used at standard and sub-diabetogenic dose levels (45 and 22.5 mg/kg STZ, for five consecutive days respectively) and CFA was given as a single dose (0.1 ml) on the first dosage day. In H-2k mice, CFA was synergistic with STZ at 45 mg/kg but did not cause the 22.5 mg/kg dose to raise glycemia to diabetic levels. By comparison, CFA was not synergistic with STZ at 45 mg/kg in H-2b mice, but did convert the subdiabetogenic dose to a diabetogenic action in these animals. Histologically, it was noted that insulitis was a more prominent and persistent feature of the H-2k mice. It occurred at the subdiabetogenic dose level of STZ in H-2k mice, in the absence of increased glycemia, suggesting that these two phenomena are not related. CFA, either alone, or with STZ, caused severe persistent perilobular inflammation of the exocrine pancreas. It did not increase the incidence or severity of insulitis. A possible mechanism whereby CFA is synergistic with STZ at different doses in H-2b and H-2k mice is suggested.

Animals↗

Counterimmunoelectrophoresis using an arc 5 antigen for the rapid diagnosis of hydatidosis and comparison with the indirect hemagglutination test.

A modified counterimmunoelectrophoresis and a conventional indirect hemagglutination test were compared for routine diagnosis of human hydatid disease in an endemic area in the Middle East. Counterimmunoelectrophoresis was performed on a cellulose acetate membrane with dilutions of a commercially available antigen which interacts with sera of patients with confirmed hydatid disease to produce the arc 5 precipitin line. The test was performed with unconcentrated human sera and the lines stained in an aqueous solution of Ponceau red. Sensitivity (95.5% vs. 93.2%) and specificity (99.2% vs. 89.9%) were higher with counterimmunoelectrophoresis than with indirect hemagglutination. Cross-reactivity with sera of patients with other parasitic infections was noted with indirect hemagglutination but not with counterimmunoelectrophoresis. There was no cross-reactivity with sera of patients with autoimmune disorders by either test.

Antibodies↗

HLA associations in an Arab type 1 diabetic population.

We have studied HLA-A, -B, -C, -DR, and -DQ antigen frequencies in 63 Type 1 diabetic Arab patients resident in Kuwait. Both HLA-DR3 (relative risk (RR) = 5.80) and -DR4 (RR = 2.87) showed positive associations with Type I diabetes mellitus in these patients whilst -DR2 (RR 0.16) and -DR5 (RR = 0.15) were negatively associated. The strong positive association with both HLA-DR3 and -DR4 was confirmed in Non-Gulf Arabs (RR = 12.55 and 4.29, respectively) whereas the Gulf Arabs had a significant positive association with HLA-DR3 (RR = 4.41) only. The disease was negatively associated with HLA-DR2 (RR = 0.05) in Gulf Arab patients only and with HLA-DR5 (RR = 0.10) in Non-Gulf Arabs only. HLA-DRw52 and -DRw53 were increased in Non-Gulf Arabs only (RR = 3.14 and 4.63, respectively). In both groups there was strong association with HLA-DQ3 (Gulf, RR = 28.11; Non-Gulf, RR = 6.25). Amongst HLA-A, -B, and -C loci, there was a positive association with HLA-B8 (RR = 19.06).

Diabetes Mellitus, Type 1↗

Autosomally inherited recessive spastic ataxia, macular corneal dystrophy, congenital cataracts, myopia and vertically oval temporally tilted discs. Report of a Bedouin family--a new syndrome.

A Bedouin family is described with an unusual form of spinocerebellar degeneration. Spastic ataxia was found to be associated with congenital cataracts, macular corneal dystrophy and non-axial myopia, in the absence of retardation of somatic or mental maturation. Immunological abnormalities were common. Genetic analysis revealed that the pedigree is expressing the transmission and segregation of a single mutant autosomal recessive gene.

Cataract↗

Detection of antibodies to muramyl dipeptide, the adjuvant moiety of streptococcal cell wall, in patients with rheumatic fever.

The presence of antibodies to muramyl dipeptide (MDP), an adjuvant structure of streptococcal peptidoglycan, was investigated in patients with acute rheumatic fever (ARF). The detection of these antibodies was done by an enzyme-linked immunosorbent assay with a synthetic multivalent MDP conjugate as an antigen. Sera from 33 of 54 children with ARF had detectable levels of antibodies to MDP at the time of diagnosis. Such antibodies could only be detected in sera from two of 52 healthy children and one of 21 children with acute poststreptococcal glomerulonephritis. The specificity of the antibodies to MDP was demonstrated by inhibition, with free MDP, of binding of the sera to the MDP conjugate. The possible use of these antibodies in the diagnosis of ARF and in screening for safe synthetic muramyl peptides in immunization of humans is discussed.

Acetylmuramyl-Alanyl-Isoglutamine↗

Association between HLA-D region epitopes and multiple sclerosis in Arabs.

We have studied the HLA associations of MS patients in Arab patients from two regions. Those patients from the Mediterranean area showed an association of MS with HLA-DR2 (p less than 0.001) and -DQw1 (p less than 0.05), whilst in those from the Gulf there was an association with -DRw53 (p less than 0.02). In the Mediterranean patients -DRw52 was negatively associated with MS (p less than 0.05). In the control populations from the two regions there was a considerable variation in the incidence of HLA antigens. Thus, Gulf Arabs had an increased incidence of -DR1 (p less than 0.05), -DR2 (p less than 0.02), -DR6 (p less than 0.05) and decreased incidence of -DR5 (p less than 0.05), -DRw52 (p less than 0.02) and -DQw3 (p less than 0.01) compared to the Mediterranean control population. These findings are discussed in relation to the aetiology of the disease.

Alleles↗

Imported malaria in Kuwait.

The number of imported malaria cases in Kuwait rose from 87 in 1980 to 504 in 1983, an increase of 579%. The continued resurgence of malaria in endemic zones, improved diagnostic techniques and a heightened awareness of imported malaria have contributed to the increase in the number of microscopically proved cases. Thick blood films fixed in acetone and stained in Giemsa proved a rapid method of diagnosis; species identification on the basis of a thin film on the same slide was performed with ease. Malaria was acquired in 38 countries. Most patients were young male adults. Most of the cases were due to Plasmodium vivax originating from India, although an increasing number of P. falciparum cases are also now being diagnosed from there. P. falciparum infections were evenly distributed throughout the year and most cases presented within 14 days of their arrival in the country. The highest number of P. vivax cases were diagnosed between May and October, when heat stress might have been a factor in precipitating a clinical attack of an infection previously acquired in the endemic zone. Attention is drawn to the importance of delayed attacks of P. vivax and, in semi-immunes, of P. falciparum. The time interval involved in establishing a history of "recent" travel in clinically suspected cases of malaria needs to be more clearly defined in each geographical area. Cases of induced malaria due to transfusion, accidental and congenital infections were identified. The fatality rate due to P. falciparum infections was low. In terms of the risk of renewed transmission, Kuwait may be considered a vulnerable area.

Adolescent↗