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Biomedical subjects

B Bhogal

Publications and source records attributed to B Bhogal.

At least 19 recordsLinked to original sources
PubMed2005

Discoid lupus erythematosus with secondary amyloidosis.

BACKGROUND: Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes. OBJECTIVES: To characterize the amyloid deposition observed incidentally within lesional biopsies from three patients with discoid lupus erythematosus (DLE), and retrospectively to study the phenomenon within DLE skin samples. METHODS: Localized amyloid deposition was observed in three cases of DLE by immunofluorescence studies, and these cases were further studied by histology and immunohistochemistry using a monoclonal anticytokeratin antibody. Retrospective histological review of DLE tissue specimens archived over 12 months was performed to look for evidence of previously undetected amyloid. RESULTS: Amyloid deposition was confirmed histologically in the three index cases by staining with Congo red and thioflavin T. Positive staining with an anticytokeratin antibody demonstrated the epidermal origin of the amyloid protein. Of the 18 archived cases reviewed amyloid was retrospectively detected in one sample. CONCLUSIONS: Secondary cutaneous amyloidosis of keratinocyte origin can be seen in DLE lesions. It may be a not infrequent occurrence and may remain under-reported. We discuss the possible role of disease chronicity and colloid body degradation in the pathogenesis of amyloidosis.

Amyloid↗
PubMed2004

Paraneoplastic pemphigus secondary to fludarabine evolving into unusual oral pemphigus vegetans.

We report a patient with chronic lymphocytic leukaemia who developed paraneoplastic pemphigus (PNP) soon after the initiation of fludarabine therapy. He presented with severe oral and cutaneous erosions. Initially, he had high titres of circulating autoantibodies as detected by indirect immunofluorescence (IF) on multiple epithelial substrates (normal human skin, monkey oesophagus, and rat bladder) and by desmoglein 1 and 3 enzyme-linked immunosorbent assays (ELISAs). His oral erosions have subsequently progressed into unusual hyperplastic papillomatous lesions affecting the inner aspect of lips and buccal mucosae, histologically consistent with pemphigus vegetans. Desmoglein 1 antibodies and IF on rat bladder substrate have become negative after 18 months of therapy. Several agents had been initiated to bring the disease under control originally, but a partial remission was achieved and maintained with mycophenolate mofetil and low-dose prednisolone.

Aged↗
PubMed2003

Various factors (allergen nature, mouse strain, CpG/recombinant protein expressed) influence the immune response elicited by genetic immunization.

BACKGROUND: Genetic immunization is a very promising therapeutic approach for allergy treatment. In the present study we investigate the influence of the nature of the allergen, the mouse strain, and the relative amount of CpG to expressed recombinant protein on immune responses using two major peanut allergens, Ara h 1 and Ara h 4. METHODS: The cDNA of Ara h 1 and of an isoform of Ara h 4 were cloned and inserted in pcDNA3. Antigen specific IgG1, IgG2a and IgE were followed after genetic immunization with 100 microg of these clones in mouse strain SKH-Hr1 or BALB/c and with 1 microg of the clones+99 blank plasmid in SKH-Hr1. RESULTS: Genetic immunization in SKH-Hr1 with Ara h 1 elicited a classical Th1 type response, but Ara h 4 elicited a mixed Th1/Th2 response with high IgG1 and even IgE in some mice. In BALB/c both plasmids produced a high IgG1 level. Decreasing the amount of plasmid injected did not change the immune response profile. However, increasing the amount of CpG administered relative to the recombinant Ara h 4 protein expressed reversed the Th1/Th2 response pattern in SKH-Hr1 mice. CONCLUSIONS: Immune responses after genetic immunization are strongly influenced by the nature of the allergen, the mouse strain, and the ratio of CpG to recombinant protein expressed.

Allergens↗
PubMed2003

An evaluation of the usefulness of mycophenolate mofetil in pemphigus.

BACKGROUND: Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes requiring management with immunosuppressive therapy. The optimal therapeutic regimen would rapidly induce remission and maintain effectiveness with minimal adverse effects in the long term. OBJECTIVES: The present study describes our experience of the addition of mycophenolate mofetil (MMF) to prednisolone in the management of severe, refractory pemphigus. METHODS: Patients with active, refractory pemphigus were treated with MMF. Our series included 12 cases of pemphigus vulgaris, four cases of pemphigus foliaceous and one case of paraneoplastic pemphigus. All patients were monitored to assess disease control and mycophenolate toxicity. RESULTS: Of the 17 cases, MMF has been of benefit to 12. MMF was well tolerated and there were no treatment withdrawals because of safety concerns. CONCLUSIONS: We found that MMF permitted a reduction in prednisolone dosage without disease relapse.

Adult↗
PubMed2000

Aerosol delivery of robust polyethyleneimine-DNA complexes for gene therapy and genetic immunization.

Aerosol delivery of plasmid DNA to the lungs offers the possibility of direct application of gene preparations to pulmonary surfaces as a means of treating a variety of genetic pulmonary disorders. However, the process of jet nebulization rapidly degrades naked DNA, viral vectors, and many lipid-based formulations. While complexing DNA with cationic lipids has been shown to significantly stabilize plasmid DNA, losses of biological activity often occur during nebulization, severely limiting the efficiency of aerosol delivery of many such complexes. In conjunction with the design of aerosol delivery systems appropriate for DNA delivery, we have developed formulations using polyethyleneimine (PEI, a polycationic polymer) and DNA that result in a high level of pulmonary transfection (10- to 100-fold greater than many cationic lipids) and are stable during nebulization. In addition, these PEI-based formulations exhibit a high degree of specificity for the lungs. The properties of PEI-based formulations that make them resistant to nebulization and efficient as DNA delivery vectors for pulmonary sites have been investigated. Potential applications of this technology, including the use of aerosolized PEI-DNA for genetic immunization, are discussed.

Aerosols↗
PubMed1997

Dermatitis herpetiformis and bullous pemphigoid: a developing association confirmed by immunoelectronmicroscopy.

We report a case of dermatitis herpetiformis associated with bullous pemphigoid in which the clinical, histopathological and immunopathological findings were corroborated by direct immunoelectronmicroscopy performed on normal and peri-lesional skin biopsies. Western immunoblotting detected the 180 kDa BPAG2 consistent with bullous pemphigoid. HLA-typing confirmed the DR3 DQ2 haplotype associated with dermatitis herpetiformis.

Aged↗
PubMed1997

Epidermolysis bullosa acquisita associated with epidermal-binding circulating antibodies.

Epidermolysis bullosa acquisita (EBA) is a rare, immunobullous disease, characterized by circulating and tissue-bound antibodies against type VII collagen (C7) of anchoring fibrils in the cutaneous basement membrane zone. These antibodies localize to the dermal aspect of salt-split skin on indirect and direct immunofluorescence (IMF). We report two patients with clinical features of EBA, in whom circulating IgG antibodies bound to the epidermal aspect of salt-split skin. In both patients direct IMF of salt-split perilesional skin revealed dermal IgG deposits, and direct immunogold immunoelectron microscopy showed antibody deposits in the region of anchoring fibrils. Their serum failed to react with epidermal or dermal extracts on Western immunoblotting. Epidermal-binding antibodies have not been reported previously in association with EBA, and the IMF findings in these cases suggest the development of autoantibodies to additional epidermal-associated antigens. Target antigen heterogeneity has been reported in most other immunobullous diseases, and may be a hitherto unrecognized feature of EBA.

Adult↗
PubMed1996

Characterisation of leucocytic somatic cells in bovine milk.

The mammary gland is of cutaneous origin with stromal leucocytic infiltrates and it excretes leucocytes in the milk. Milk T lymphocytes are highly enriched by sedimenting milk somatic cells in a 43 per cent preformed Percoll gradient. Thirty to 54 per cent of leucocytes, harvested from the upper Percoll band, belong to CD2+ CD3+ T lymphocytes. These milk T lymphocytes are mature CD4+, or CD8+ single positive T cells, expressing CD44, CD26, and beta 1 integrin, but not Lam-1. Milk T lymphocyte subsets may play an important role in regional immunosurveillance of the mammary epithelia and stroma. Selective mechanisms may account for the trafficking of this activated, memory T lymphocyte subset in the gland.

Animals↗
PubMed1995

Cloning and expression of FECV spike gene in vaccinia virus. Immunization with FECV S causes early death after FIPV challenge.

The spike gene of the feline enteric coronavirus (FECV), strain FECV-1683, was PCR amplified from total RNA extracted from FECV-infected cells and its sequence determined. A primary translation product of 1454 amino acids is predicted from the nucleotide sequence, containing a N-terminal signal sequence, a C-terminal transmembrane region and 33 potential N-glycosylation sites. The sequence shares 92% homology with the previously published feline infectious peritonitis virus, strain WSU-1146; however, several regions were identified that distinguished FECV from Feline Infectious Peritonitis virus, FIPV. The full length FECV S gene was cloned and expressed in vaccinia virus. Recombinants produced a 200 kD protein which was recognized by sera from cats infected with FIPV. When kittens were immunized with the vaccinia/FECV S recombinant, neutralizing antibodies to FIPV were induced. After challenge with a lethal dose of FIPV, the recombinant vaccinated animals died earlier than control animals immunized with vaccinia virus alone.

Animals↗
PubMed1995

Immunohistological comparison of granulated cell proteins in induced immediate urticarial dermographism and delayed pressure urticaria lesions.

Urticarial dermographism and delayed pressure urticaria are two forms of physical urticaria which are well defined clinically and histologically. Previous studies have shown eosinophil granule protein deposition in urticarial reactions, including chronic urticaria, solar urticaria and delayed pressure urticaria. To evaluate and compare the involvement of granulated inflammatory cells in urticarial dermographism and delayed pressure urticaria, we studied sequential biopsies of induced lesions of urticarial dermographism and delayed pressure urticaria by indirect immunofluorescence, to detect eosinophil granule major basic protein (MBP) and neutrophil granule elastase. Biopsies from dermographic lesions at time 0, 5 min, 15 min, 2 h and 24 h, showed few infiltrating eosinophils, with minimal extracellular MBP deposition, and a few infiltrating neutrophils, with minimal neutrophil elastase deposition, throughout the evolution of the lesions. Sequential biopsies of delayed pressure urticaria at time 0, 20 min, 6, 12 and 24 h, showed eosinophil infiltration with extensive MBP deposition beginning at 20 min, and neutrophil infiltration with variable elastase deposition beginning at 20 min. Control tissue specimens from normal volunteers showed neutrophil infiltration and slight degranulation, but no eosinophil infiltration or degranulation. Comparison of urticarial dermographism with delayed pressure urticaria showed marked differences in the patterns of infiltration. Delayed pressure urticaria, with eosinophil and neutrophil degranulation, was strikingly similar to the IgE-mediated late phase reaction. In contrast, eosinophil and neutrophil involvement in urticarial dermographism was minimal. Considering the extent of eosinophil granule protein deposition and the biological activities of the eosinophil granule proteins, the findings in delayed pressure urticaria point to an important pathophysiological role of eosinophils in the disease.

Blood Proteins↗
PubMed1995

Staphylococcal enterotoxin is a bovine T cell superantigen.

Different isoforms of soluble staphylococcal enterotoxins (SE): SEB, SEC-1 and SEC-2, were shown to stimulate bovine T cell proliferation, expression of cytokine messages, and IgG production. Intact metabolic function of APC was not required since peripheral blood mononuclear cells (PBMC), UV-irradiated prior to or following incubation with SE, were both capable of presenting SE, while PBMC treated with MAbs against MHC II lost the ability to stimulate T cell proliferation. SE caused approximately two fold increase of CD4+, and CD8+ T cells, but not MHC II+ APC or B cells. This model system suggests that SE transduces not only T cell activation signal, but also a non-proliferative signal for primary B cells to produce polyclonal IgG. We hypothesize that enterotoxin virulence may be in part due to its effect on activating the immune system.

Animals↗
PubMed1994

Acquired bullous diseases of childhood: re-evaluation of diagnosis by indirect immunofluorescence examination on 1 M NaCl split skin and immunoblotting.

Acquired autoimmune bullous diseases of childhood are rare, and can be difficult to distinguish clinically. We have studied 12 children, with an initial diagnosis of bullous pemphigoid (BP) in eight patients, cicatricial pemphigoid (CP) in one, chronic bullous disease of childhood (CBDC) in one, and epidermolysis bullosa acquisita (EBA) in two. All patients had positive indirect immunofluorescence (IIF) of the BMZ with IgG. Using 1 M NaCl split skin, six patients showed epidermal binding of IgG, with additional IgA in three cases, and in five patients IgG antibodies bound a dermal protein. Immunoblotting studies revealed an antibody to type VII collagen (EBA antigen) in three patients who had a dermal pattern on IIF. Six sera reacted with an epidermal protein of 180 and/or 220 kDa, characteristic of BP and CP. One of the three IgA-positive sera detected 220- and 180-kDa epidermal proteins using anti-IgA antibody. Following these studies the diagnosis was changed in three of the children. The diagnosis of CBDC was changed to either BP or EBA because of the presence of circulating IgG autoantibodies. In two children with an initial diagnosis of BP the diagnosis was changed to EBA. We conclude that the clinical picture in bullous disorders of childhood shows considerable overlap, and is often misleading. Additional circulating IgA autoantibodies seem to be more common in BP than has been recognized previously. Indirect immunofluorescence investigation on 1 M NaCl split skin may be helpful in differentiating between BP and EBA, but does not replace immunoblotting studies. EBA is apparently more common in children than in adults. No difference was found between the children with BP and EBA with regard to the duration of disease. The long-term outlook is good, although the course may be protracted.

Adolescent↗
PubMed1991

Chronic bullous dermatosis of childhood--clinical and immunological features seen in African patients.

During the period 1985-88, 30 children with a chronic blistering dermatosis were studied. Of these 25 were found to have chronic bullous dermatosis of childhood (CBDC) and five had bullous pemphigoid (BP). No case of dermatitis herpetiformis (DH) was seen in the same period. Except for the difference in immunofluorescence (IMF) there were no definite clinical, histological or therapeutic differences between the two groups. All the children were Africans with the exception of one Indian girl. Their ages ranged from 1 year to 12 years with a mean of 5 years. The females outnumbered the males in a ratio of 3:2. All children had a generalized eruption consisting of large tense blisters arising on normal skin. The blisters were more profuse on the lower trunk, pelvic region and limbs. Face and scalp were also affected. Histological features of BP and DH were seen. Direct IMF in the CBDC patients showed linear deposits of IgA at the basement membrane zone (BMZ) while linear deposits of IgG were seen in the BP group. Complement and IgM were also seen in some cases in both groups. Sixty per cent of the CBDC patients showed IgA BMZ antibodies by indirect IMF. There were no symptoms or signs of malabsorption. Serum vitamin B12 and folate levels were normal. HLA studies showed the B-8 antigen in five of the 20 patients studied. Therapy was difficult in most cases. All patients haemolysed on therapeutic doses of dapsone, sulphapyridine and/or prednisone had to be added. Follow-up was generally poor as six patients failed to return after discharge from hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1990

Epidermolysis bullosa acquisita antigen and the carboxy terminus of type VII collagen have a common immunolocalization to anchoring fibrils and lamina densa of basement membrane.

In this study a variety of immunoelectron microscopic methods were used to define the precise ultrastructural binding site of epidermolysis bullosa acquisita antibodies (EBA-Ab). We used two EBA sera which immunoblotted with the same skin-extracted protein as that labelled by a monoclonal antibody (LH7.2) which is known to react with the carboxy terminus of type VII collagen. Gold-conjugated antibodies were used in two different immunoelectron microscopic procedures to compare the labelling characteristics of EBA-Ab and LH7.2 in normal human skin. Antibody incubations were performed using ultra-thin cryosections of unfixed skin and thin slices of fresh skin (en bloc technique) before conventional fixation and embedding in Epon. Both methods showed similar labelling features for both EBA-Ab and LH7.2. With ultra-thin cryosections there was labelling of the lamina densa and an undefined component of the sublamina densa region. With the en bloc technique, labelling of dermal ends of anchoring fibrils and of amorphous material recently defined as 'anchoring plaques' was evident. There was no labelling of the central banded portions of anchoring fibrils. We conclude that EBA-Ag is localized to the dermal ends of anchoring fibrils in addition to the lamina densa and possibly anchoring plaques, and thus has the same distribution as the carboxy terminus of type VII collagen.

Antibodies, Monoclonal↗
PubMed1990

Determination of the optimum site for diagnostic biopsy for direct immunofluorescence in bullous pemphigoid.

The distributions in deposition of immunoreactants in bullous pemphigoid before and after initiating treatment were investigated. Punch biopsies of skin were performed on each patient from up to five different sites and studied by direct immunofluorescence (DIF). Both groups showed the highest diagnostic yield for DIF from perilesional biopsies, with positivity of 78% from the pretreatment group and 83% from the post-treatment group. The percentage of positive DIF for remaining sites in the pre-treatment group were as follows: 50% lower back, 62% oral mucosa, 70% flexor aspect of forearm, 70% anterior aspect of thigh. The post-treatment group had positive DIF of other sites biopsied as follows: 59% anterior aspect of thigh, 64% flexor aspect of forearm, 68% back. We conclude that a single perilesional biopsy is usually sufficient to provide positive DIF and more than two biopsies is seldom justified as it is unlikely to increase the yield of positive DIF. If it is not possible to obtain a perilesional biopsy, then the anterior aspect of thigh or flexor aspect of forearm is a suitable alternative site. If a second biopsy is considered after initiating treatment, it should be taken from the oral mucosa as this has been shown in a separate study to have a higher rate of positive DIF than uninvolved skin.

Aged↗
PubMed1989

A timed study of the histopathology, direct immunofluorescence and ultrastructural findings in idiopathic cold-contact urticaria over a 24-h period.

The histopathology, immunofluorescence and ultrastructure of skin in idiopathic cold-contact urticaria have been studied over the 24 h following the application of a cold stimulus sufficient to provoke a confluent weal on the anterior thigh. Biopsies were taken 10 min, 2 h and 24 h after ice removal. Considerable epidermal and dermal oedema was present. Type I and Type II mast-cell degranulation was noted but was not universal. Lymphatics and capillaries were dilated and endothelial cells showed an increase in micropinocytotic activity, without evident vasculitis. In two cases packed platelets were seen within vessel lumina. There was no change in the infiltrating dermal cell population and direct immunofluorescence was negative. The evidence suggests that idiopathic cold-contact urticaria is an exudative rather than an infiltrative process.

Adolescent↗
PubMed1988

Chronic bullous disease of childhood, childhood cicatricial pemphigoid, and linear IgA disease of adults. A comparative study demonstrating clinical and immunopathologic overlap.

Linear IgA disease of adults, chronic bullous disease of childhood, and the rare childhood cicatricial pemphigoid currently are regarded as separate clinical entities despite their many shared features. All are sulfone-responsive subepidermal bullous diseases associated with linear IgA deposition at the basement membrane zone. In this paper we present a long-term study of 25 cases of adult linear IgA disease, 25 cases of chronic bullous disease of childhood, and four cases of childhood cicatricial pemphigoid, which has revealed further similarities among all three groups. The morphology and distribution of the cutaneous and mucosal lesions were similar; mucosal involvement was present in 80% of patients with adult linear IgA disease, 64% of those with chronic bullous disease of childhood, and 100% of those with childhood cicatricial pemphigoid, and ocular scarring affected patients in all groups. Remission occurred in 64% of those with chronic bullous disease of childhood (the disease was active in 12% after puberty), 48% of those with adult linear IgA disease, and in no cases of childhood cicatricial pemphigoid. HLA B8 and circulating IgA anti-basement membrane zone antibody were more common in chronic bullous disease of childhood than adult linear IgA disease. There were no absolute differences among the three groups, and we suggest that adult linear IgA disease, chronic bullous disease of childhood, and childhood cicatricial pemphigoid are the same disease, with childhood cicatricial pemphigoid being a more severe form of chronic bullous disease of childhood.

Adolescent↗