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Biomedical subjects

C Svalander

Publications and source records attributed to C Svalander.

At least 37 records · Page 2Linked to original sources

Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis.

The serum concentrations of IgG, IgA, IgM and of the four subclasses of IgG were determined by radial immunodiffusion in 103 patients, mean age 42 (range 16-72), with various types of glomerulonephritis. Forty-nine healthy blood donors, mean age 41 years (range 19-65), served as controls. Kidney biopsies were obtained from all the patients for examination by histopathology and by immunofluorescence. The glomerulopathies were classified according to WHO criteria. The serum immunoglobulin patterns were different for the various clinical groups of patients. Patients with Wegener's granulomatosis, rapidly progressive glomerulonephritis and SLE had a significant increase in total IgG and of IgG4 (P less than 0.05-0.001). Patients with minimal change disease had low concentrations of IgG (P less than 0.001) with a significant decrease in IgG1 and IgG2 (P less than 0.001 and 0.01, respectively). Highly significant increases in IgA were noted for patients with IgA nephritis (P less than 0.001) but high levels were also seen in patients with chronic glomerulonephritis. The findings might have diagnostic implications.

Adolescent

Effect of eicosapentaenoic acid rich menhaden oil and MaxEPA on the autoimmune disease of Mrl/l mice.

The Mrl lpr/lpr (Mrl/l) mouse is a model for systemic lupus erythematosus and rheumatoid arthritis in humans. The diet of Mrl/l mice was supplemented with EPA (see Introduction) in menhaden oil or in the commerical fish oil MaxEPA. The survival of mice was not affected by the dietary manipulations. The addition of menhaden oil decreased the severity of the renal pathology. However, MaxEPA containing the same amount of eicosapentaenoic acid was considerably less effective. A diet deficient in polyunsaturated fatty acids did not ameliorate any manifestations of the disease. Anti-DNA antibody levels in serum were not influenced by the therapy. Myocardial abscesses and/or ulcerating valvular lesions were observed in about one third of the mice, irrespective of the diet given.

Animals

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy.

Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mm Hg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 micrograms/min (geometric mean 688 micrograms/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml.min-1. (1.73 m2)-1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open + occluded) was estimated by combined light-and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r = 0.77, p less than 10(-4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r = -0.78, p less than 10(-5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects. Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.

Adult

Effect of captopril on murine systemic lupus erythematosus disease.

The MRL/1 and New Zealand black-New Zealand white cross (NZB x W) mice spontaneously develop a disease similar to systemic lupus erythematosus in man. The effect of antihypertensive treatment on MRL/1 and NZB x W mice was studied with respect to survival, blood pressure, proteinuria, haematuria and renal histopathology. The treatment consisted of angiotensin converting enzyme (ACE) inhibitors (captopril and enalapril) and bretylium, a sympathetic blocker. Tail systolic blood pressure was measured with a strain gauge technique. All antihypertensive drugs caused a reduction in blood pressure in both strains. In MRL/1 bretylium and both ACE inhibitors improved renal histopathology, but only captopril prolonged survival, and it decreased proteinuria and haematuria. In NZB x W captopril decreased proteinuria but did not influence survival or renal histopathology. Bretylium was without any effect on these parameters. At the doses used captopril improves survival in MRL/1 mice and decreases proteinuria and haematuria in both MRL/1 and NZB x W mice. Since bretylium and enalapril lack this property despite a similar blood pressure reduction, it seems to be a drug-specific action.

Animals

Beneficial effect of captopril on systemic lupus erythematosus-like disease in MRL lpr/lpr mice.

MRL lpr/lpr (MRL/l) mice exhibit a disease similar to systemic lupus erythematosus (SLE) in humans. To investigate the influence of antihypertensive treatment on this disease, four groups of MRL/l mice were treated with the angiotensin-converting enzyme inhibitor captopril (n = 25), with the sympathetic blocker bretylium (n = 15), and with cyclophosphamide (n = 10). Thirty-five mice did not receive any treatment and served as controls. Survival rate, blood pressure, incidence of proteinuria and hematuria, renal pathology, lymphoid hyperplasia and dermatitis were studied. The survival at the age of 36 weeks was significantly improved by captopril as compared to controls (60 vs. 25%, p = 0.035). The cyclophosphamide group showed no mortality at that time and the bretylium group did not differ from the control group. Captopril and bretylium reduced systolic blood pressure significantly while cyclophosphamide was without effect. Captopril and cyclophosphamide diminished significantly the glomerular damage with less proliferative changes and a decreased incidence of proteinuria. The bretylium-treated animals also exhibited an improved renal pathology index but they did not differ from the controls with respect to proteinuria and hematuria. Lymphoid hyperplasia and dermatitis were decreased only by captopril and cyclophosphamide. It is concluded that captopril improves survival in SLE disease of MRL/l mice, counteracting lymphoid hyperplasia, renal disease, dermatitis and decreasing arterial blood pressure.

Animals

Inflammatory cells in transplanted kidneys are infected by human cytomegalovirus.

To determine which cells in kidney grafts are infected with human cytomegalovirus (HCMV) before and after transplantation, kidney specimens were studied by in situ hybridization with 35S-labeled DNA probes representing HCMV immediate-early and late genes. Pretransplantation biopsies and serial posttransplantation biopsies were obtained from 7 renal grafts. All of the transplant recipients were HCMV-seronegative at the time of transplantation and all developed primary HCMV infections. HCMV nucleic acids were not detected in biopsies taken from the healthy donor kidneys before transplantation. However, biopsies taken at various intervals after transplantation showed abundant hybridization with HCMV immediate-early and late gene probes. Virtually all of the hybridizing cells were mononuclear inflammatory cells in the interstitial spaces of the kidney. Occasional hybridization was seen with renal tubular or glomerular cells. No cytomegalic cells were seen. Biopsy specimens taken after systemic anti-HCMV chemotherapy with phosphonoformate showed no uniform reduction in HCMV gene expression. These studies demonstrate that the principal HCMV-infected cells in kidneys of renal transplant patients with primary HCMV infections are infiltrating inflammatory cells.

Biopsy

Macrophages and C3-deposition in early biopsies as a sign of poor prognosis in human kidney graft rejection.

Clinical characteristics such as retransplantation, cytotoxic antibodies, no or delayed graft onset, or early anuria seem to be important factors to define this group of patients. If early biopsies show intravascular presence of macrophages in venulae or capillaries usually combined with a C3-deposition in glomular capillary walls, the prognosis of graft outcome seems to be poor even with rather heavy antirejection therapy.

Adult

Cytotoxic drug treatment of reactive amyloidosis in rheumatoid arthritis with special reference to renal insufficiency.

Twenty-two patients with amyloidosis secondary to rheumatoid arthritis were randomised and followed prospectively in order to determine whether treatment with cytotoxic drugs could postpone the development of end-stage renal failure. The diagnosis of amyloidosis was based on albuminuria, amyloid-positive rectal and/or abdominal fat aspiration and/or renal biopsies. Renal function was followed by repeated 51Cr-EDTA measurements of the glomerular filtration rate (GFR). Urinary albumin and serum-creatinine were found unreliable as predictors of renal function. GFR declined more rapidly in the patient group receiving only symptomatic drugs and no cytotoxic drugs (NT-group). After an initial decline, the GFR in the cytotoxic drug treatment group (T-group), mean treatment quotient 79%, levelled off and remained constant for a considerable time. The mean observation time was 45.7 months in the NT-group and 53.5 months in the T-group. Seven out of eleven patients in the NT-group developed end-stage renal disease, compared to two out of eleven patients in the T-group. The cumulative proportion of survivors in the NT-group at 36 and 60 months was 71% and 27% respectively. The corresponding figures in the T-group were 89% and 89%. The difference in favour of the cytotoxic drug-treated group was significant (p less than 0.04).

Adult

Conditions for the immunohistochemical demonstration of complement factor C3 in formaldehyde-fixed and paraffin-embedded renal tissues.

Paraffin sections of formaldehyde-fixed renal biopsies were labeled for complement C3 by a polyclonal rabbit antibody to human complement C3, by the peroxidase-antiperoxidase complex (PAP) and the avidin-biotin peroxidase complex (ABC) techniques, respectively. All tissues had C3 deposits according to direct immunofluorescence on fresh frozen sections. Staining for muramidase was introduced as an intrinsic control for the degree of tissue proteolysis after the necessary trypsin digestion prior to the immunoenzyme labeling. The results indicated that even minute deposits of C3 could be detected in paraffin sections by the ABC method, which was more sensitive than the PAP technique; the ABC method allowed a maximal dilution of 1:2,400 of the primary antibody as compared to 1:800 for the PAP technique.

Animals

Gastrointestinal carcinoma-associated antigen detected by a monoclonal antibody in dysplasia and adenocarcinoma associated with chronic ulcerative colitis.

Colorectal tissue specimens from 13 patients with chronic ulcerative colitis, of whom all had epithelial dysplasia and 2 had adenocarcinoma, were tested for the presence of gastrointestinal carcinoma-associated antigen (GICA), using an immunoperoxidase technique with a monoclonal antibody (MAb) against this antigen. GICA was present in the formaldehyde-fixed and paraffin-embedded sections of dysplastic and cancer tissue but absent from normal or hyperplastic epithelium. However, the pattern and extent of staining with the antibody did not correlate with the degree of dysplasia, i.e., "mild" dysplasia was often positive, and "severe" dysplasia was sometimes negative. Changes classified as "indefinite for dysplasia but probably negative" were variable in their expression of GICA. The adenocarcinomas were selectively labelled within cell clusters. In contrast, ulcerative colitis (UC) patients with severe inflammatory changes but with no detectable dysplasia were negative for GICA. GICA could be eluted from paraffin blocks of dysplastic tissue and biochemically characterized as a glycolipid. The detection of this antigen might be a useful complement to morphological examination in discriminating between precancerous and benign epithelial lesions of the colon.

Adenocarcinoma

Hydralazine-associated glomerulonephritis.

Nine patients (6 men, 3 women) with rapidly progressive glomerulonephritis developing during hydralazine therapy were seen. Early cessation of hydralazine treatment resulted in improvement in seven patients, while continued hydralazine treatment resulted in permanent renal insufficiency in two. The clinical symptoms of systemic illness associated with the hydralazine syndrome were absent in most patients. Antinuclear antibody test was positive in all, and six investigated patients had antibodies to histones. All patients had anemia, high ESR, and microscopic hematuria. Five of the nine patients were rapid drug acetylators. Renal biopsies from eight patients revealed a uniform histologic picture with segmental necrosis of glomeruli and extracapillary proliferation. Immunofluorescence investigation was positive in all and electron microscopy revealed deposits in the glomerular capillary walls in five of seven specimens. This renal disease may represent a late and monosymptomatic manifestation of the hydralazine syndrome.

Antibodies, Antinuclear

Expression of gastrointestinal carcinoma-associated antigen (GICA) detected in human fetal tissues by monoclonal antibody NS-19-9.

The expression of a gastrointestinal carcinoma-associated antigen (GICA), a monosialoganglioside, was investigated in tissues from human fetuses of various gestational ages (10-40 weeks). Mouse monoclonal antibody NS-19-9, generated in mice immunized with SW1116 human colon carcinoma cells, was used along with a second polyclonal antibody to mouse IgG to detect antigen expression as visualized by means of the biotin-avidin-peroxidase assay. Sections of snap-frozen tissues or tissues fixed in 4% formaldehyde, in mercury chloride-formaldehyde, or in Bouin's solution were used. GICA was consistently detected in the mucosal epithelium of the small intestine. In contrast, the mucosal epithelium of the colon-rectum contained no detectable GICA, nor could the antigen be detected biochemically in extracts from the large intestine. GICA was usually found in the epithelium of the larynx, trachea and main bronchi as well as in the conjunctiva, lacrimal and salivary glands, gall bladder and ductus choledochus, and in the epithelium of the renal pelvis of early and mid-gestation fetuses.

Antibodies, Monoclonal