Both serum studies by indirect immunofluorescence (IIF) tests and skin biopsy examination by direct immunofluorescence (DIF) were performed on 22 cases of pemphigus with clinically active lesions. Twenty cases had pemphigus vulgaris and two, pemphigus foliaceus. The majority of cases (70%) were between 21 and 60 years old; the mean age was 39.5 +/- 12.7 years. There was no sex predilection. DIF showed the positive fluorescence of intercellular cement substance (ICS) of the epidermis in all 22 cases (100%). IgG was positive in 77.2%, followed sequentially by C3C (50%), IgA (45.45%), and IgM (36.36%). Six cases (27.27%) also showed granular immunoglobulin and/or complement deposits at the dermoepidermal junction. IIF detected serum antiepithelial antibodies in 18 cases (81.81%) using human esophagus as substrate. Most of these cases (88.88%) showed IgG type of antibodies; the other 11.11% exhibited IgA and IgM in low concentrations. 1+ titer positivity was observed in 15 cases. This study demonstrates the value of DIF for a definitive diagnosis of pemphigus. However, it is also important to appreciate that immunofluorescence is not a substitute for histopathology, but rather complementary to it.

Adult↗

PubMed1995

Nephropathy in type 1 diabetes: the role of genetic factors.

Diabetic nephropathy affects up to 30% of all patients with Type 1 (insulin-dependent) diabetes and is associated with a high morbidity and mortality. A number of studies have suggested that, unlike retinopathy or neuropathy, the influence of hereditary factors on the development of nephropathy is strong. Much interest has focused on possible genetic markers indicating an increased risk for developing diabetic nephropathy. It is envisaged that patients with Type 1 diabetes may be screened at diagnosis for increased susceptibility to nephropathy and subsequently have intensified follow up and possibly even prophylactic therapy in order to prevent progression to nephropathy. Two groups of candidate genes have so far been of particular interest: those implicated in the aetiology of hypertension, and those involved in the metabolism of glomerular basement membrane proteins. This article aims to review the evidence suggesting a role for hereditary factors, possible genetic models, and the genetic loci thought to be involved.

Aldehyde Reductase↗

PubMed1995

Microalbuminuria in non-insulin dependent diabetes mellitus.

Explore the source record for details and available documents.

Albuminuria↗

PubMed1995

Reproducibility of time and frequency domain analysis of heart rate variability in patients with chronic stable angina.

Before heart rate variability (HRV) can be used to investigate the effects of drugs or other clinical interventions in chronic stable angina, it is important to establish the stability and reproducibility of HRV indices over time. HRV analysis was performed on two consecutive 24-hour ambulatory ECG recordings in 19 patients with chronic stable angina. Time-domain analysis included average heart rate, variance, SDNN, SDANN5, ASDNN5 and PNN50. The power spectral analysis was computed using fast Fourier transformation for the total power (0.003 and 0.40 Hz), low frequency (0.04-0.15 Hz), and high frequency (0.15-0.40 Hz) bands. No statistically significant differences in the time or frequency domains were found between the two ambulatory ECG recordings. HRV indices in the time and frequency domains are consistent and reproducible in patients with chronic stable angina. Thus, cardiac autonomic tone can be evaluated using HRV analyses, and any significant changes that occur after medical therapy or other clinical interventions can be ascribed to the intervention rather than the lability of cardiac autonomic tone.

Adrenergic beta-Antagonists↗

PubMed1995

Surface display compared to periplasmic expression of a malarial antigen in Salmonella typhimurium and its implications for immunogenicity.

Two different expression systems were investigated for the production of an 80 amino acid polypeptide, M3, from the C-terminus of the Plasmodium falciparum blood stage antigen Pf155/RESA in an attenuated Salmonella typhimurium vaccine strain. Upon expression, the malarial polypeptide was targeted either to the periplasm as a soluble fusion protein containing two IgG-binding domains (ZZ) from the staphylococcal protein A or, to the bacterial surface as an insert within a chimeric outer membrane protein A (OmpA) derived from Escherichia coli and Shigella dysenteriae. Both the ZZM3 and the OmpAM3 proteins were stably expressed in the periplasm or on the surface of Salmonella, respectively. The ZZ expression system yielded 10-100 times more malarial immunogen than did the OmpA system. Live recombinant Salmonella expressing ZZM3 or OmpAM3 were used to immunize mice intraperitoneally. Both the ZZM3 and OmpAM3 genes persisted for up to three weeks in bacteria isolated from different lymphoid organs. Bacteria expressing ZZM3 induced antibodies to M3, ZZ and to the Pf155/RESA antigen whereas, bacteria producing OmpAM3 induced similar levels of antibodies reactive with M3 but not with Pf155/RESA. Both recombinants induced a memory response of antibodies reactive with both M3 and Pf155/RESA. The high levels of M3 produced by the ZZ expression system make it suitable for the expression of heterologous antigens in Salmonella. Nevertheless, in spite of the quantitative difference in M3 expression, the ZZ and OmpA constructs elicited comparable immune responses to M3.

Animals↗

PubMed1995

Idiotypic DNA vaccines against B-cell lymphoma.

Idiotypic antigens are clearly defined tumor-associated protein antigens, which can induce protective immunity against lymphoma. Because each patient requires an individual vaccine, idiotypic antigens also provide ideal candidates for exploring the feasibility of replacing protein antigens by DNA vaccines. Component idiotypic variable region genes can be identified in patients' tumor biopsies and rapidly assembled as scFv sequences. These can be used to produce recombinant scFv protein in bacteria, or as direct naked DNA vaccines. A preliminary small trial of DNA vaccines for chemotherapy-resistant patients with lymphoma has begun. Intramuscular idiotypic DNA vaccination in a mouse model induces low levels of anti-idiotypic antibody in serum. Levels can be increased dramatically by coinjection of DNA plasmids encoding either IL-2 or GM-CSF, and specific proliferative anti-idiotypic T cells are induced. However protective immunity remains to be demonstrated, and a possible reason for this may lie in the continued secretion of idiotypic scFv antigen which blocks antibody activity by formation of immune complexes. Methods for regulating secretion of antigen are required before this category of tumor antigen can be fully exploited as a vaccine. The power of DNA technology should allow analysis and manipulation of pathways of antigen presentation to induce maximal therapeutic attack on neoplastic B cells. In addition, lymphoma presents a model for application of DNA technology to the wide range of human tumors known to harbor potential tumor antigens.

Animals↗

PubMed1995

Cellular mechanisms in the immune response to malaria in Plasmodium vinckei-infected mice.

Infection of mice with the malaria parasite Plasmodium vinckei vinckei is 100% lethal. However, after two infections followed by drug cure, BALB/c mice develop a solid immunity which is antibody independent but mediated by CD4+ T cells. To elucidate the mechanisms of this immunity, spleen cells from immune mice were challenged in vitro with lysates of P. vinckei-infected or uninfected erythrocytes. The parasite antigen induced proliferation of T cells from immune mice but not from nonimmune mice. When gamma interferon production by cells from immune mice was assayed at the single-cell level, 1 to 3 cells per 1,000 cells were found to release this cytokine when exposed to antigen. In contrast, the numbers of interleukin 4 (IL-4)-producing cells from both immune and control mice were < or = 4 per 10(6) cells, regardless of antigen exposure. Investigation in a bioassay showed that P. vinckei antigen induced the release of IL-4 from spleen cells of immune mice but not from those of control mice. Nevertheless, that IL-4 is of minor significance in this system is also suggested by the absence of elevation of immunoglobulin E levels in blood samples from these mice, in contrast to what is seen with P. chabaudi infection, in which IL-4-producing Th2 cells are of major importance for immunity during later phases of infection. Taken together, the present results indicate that immunity to P. vinckei is a Th1 response, with gamma interferon being an important protective factor. Whether or not the Th1 response, through overproduction of tumor necrosis factor alpha, is also responsible for pathology and death in this infection remains to be clarified.

Animals↗

PubMed1995

Splenic lymphoma with circulating villous lymphocytes.

This report describes the occurrence of splenic lymphoma with villous lymphocytes (SLVL) in a 56 year old white female with a family history of chronic lymphocytic leukaemia. Other unusual features included a marked lymphocytosis with counts up to 224 x 10(9)/l and marked clumping of lymphocytes in EDTA anticoagulated blood. The neoplastic cells were CD19+, CD20+, CD22+, CD22+, IgM+, lambda+, kappa-, CD5-, and CD10-. The spleen had nodular infiltrates of B lymphocytes in the region of the white pulp with minimal red pulp involvement. Electron microscopy of peripheral blood lymphocytes revealed cells with polar cytoplasmic processes. This report underlines the need for detailed analysis, including morphology and immunophenotyping, for each patient with a small B cell lymphoproliferative disorder.

Aged↗

PubMed1995

Mendenhall's syndrome: clues to the aetiology of human diabetic neuropathy.

The pathogenesis of human diabetic neuropathy remains unclear. Mendenhall's syndrome is characterised by a mutation in the insulin receptor gene with consequent lifelong uncontrolled hyperglycaemia. The sural nerve biopsy from a patient with Mendenhall's syndrome showed a gross loss of myelinated fibres that was comparable with the degree of fibre loss in a case matched diabetic patient with established neuropathy. The biopsy from the patient with Mendenhall's syndrome showed only a very mild degree of microangiopathy, however, which failed to relate to the degree of nerve fibre loss and also did not compare with the advanced degree of microangiopathy seen in the diabetic patient. Thus hyperglycaemia itself did not result in appreciable microangiopathy. Furthermore the presence of severe neuropathy without advanced microangiopathy suggests an important and independent role for metabolic factors in the pathogenesis of neuropathy.

Adult↗

PubMed1995

Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins.

Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation. We investigated the serum activity and concentration of paraoxonase in 78 patients with type 1 diabetes mellitus, 92 with type 2 diabetes, and 82 nondiabetic control subjects. Paraoxonase activity was generally lower in diabetics than in control subjects. This decrease was unrelated to differences in paraoxonase phenotype distribution or its serum concentration. Rather, the difference in paraoxonase activity was explained by its specific activity, which was lower in diabetics, indicating either the presence of a circulating inhibitor or disturbance of the interaction of paraoxonase with HDL affecting its activity. Paraoxonase specific activity was lowest in patients with peripheral neuropathy, suggesting an association of paraoxonase with neuropathy. In control subjects but not patients with diabetes, paraoxonase correlated with HDL cholesterol and apolipoprotein A-1. Our results indicate that the low paraoxonase activity in diabetes is due to decreased specific activity. In other studies low serum paraoxonase activity has been associated with increased susceptibility to atherosclerosis, and the present results also suggest an association with peripheral neuropathy, which could be due to reduced capacity to detoxify lipid peroxides in diabetes.

Adult↗

PubMed1995

Case report: inferior vena caval thrombosis following severe liver trauma and perihepatic packing--early detection by intraoperative ultrasonography enabling treatment by percutaneous mechanical thrombectomy.

Patients with severe liver trauma present a major challenge in management. We report the successful treatment of a patient presenting with a severe liver injury. The detection of major inferior vena caval thrombosis by intraoperative ultrasonography enabled the use of a percutaneous thrombectomy device to facilitate dissolution of the thrombus.

Adult↗

PubMed1995

Symmetric and asymmetric two-handed pull-push strength of young adults.

Forty normal young adults volunteered for an experiment in which they were required to perform two-handed maximal pull-push in isometric and isokinetic modes (50 cm/s linear velocity of the handle) at 50-, 100-, and 150-cm heights of handle in sagittal, 30-deg lateral, and 60-deg lateral planes. Subjects were stabilized on a circular platform that rotated on its axis and allowed fixation in any position to achieve asymmetric settings. The pull-push strengths were applied to a 53-cm wide handle and were measured through the load cell assembly of the Static Dynamic Strength Tester. The peak and average strengths were compared statistically, and an ANOVA and multiple regression were performed. The main effects of gender, activity (pull or push), mode (isometric or isokinetic), plane (sagittal, 30 deg lateral, or 60 deg lateral), and height (low, medium, or high) of activity for both peak and average strengths were highly significant (p < 0.01). All subjects were strongest in pulling activity in the isometric mode in the sagittal plane at medium height. Males were significantly stronger than females for most activities. However, with increased postural asymmetry, the difference between genders declined.

Adolescent↗