Biomedical subjects

E Hilme

Publications and source records attributed to E Hilme.

5 recordsLinked to original sources

PubMed1994

Functional autoimmune epitope on alpha 1-adrenergic receptors in patients with malignant hypertension.

Because of the growing evidence that hypertensive disease is accompanied by immunological dysfunction, we have investigated autoimmunity in patients with malignant hypertension. Peptides corresponding to the sequence of the second extracellular loops of the human alpha 1-adrenergic receptor and the M2-muscarinic receptor were used as antigens in an ELISA. Serum from 4 (12%) of 33 healthy controls, 3 (20%) of 15 patients with malignant essential hypertension, and 7 (64%) of 11 with secondary hypertension showed positive responses in the ELISA for the alpha 1-adrenergic receptor peptide. Positive responses were significantly more common among the patients with secondary hypertension than in the other two groups (p < 0.01). By contrast, no autoantibodies against the M2-muscarinic receptor peptide were detected in either hypertensive group. Autoantibodies against the alpha 1-adrenergic receptor, affinity-purified from patients with positive responses, specifically recognised bands with molecular masses of 68, 40, and 37 kDa on immunoblotted membrane proteins of rat ventricles. The patients' autoantibodies caused a decrease in tritiated prazosin binding sites and an increase in heart beating frequency of neonatal cultured rat cardiomyocytes; antibodies purified from the controls had no effect. Circulating autoantibodies against the alpha 1-adrenergic receptor are present in a subgroup of patients with malignant hypertension. These autoantibodies have pharmacological activity in vitro, which suggests that they may be involved in the pathogenesis of malignant hypertension.

Adult↗

PubMed1993

Abnormal immune function in malignant hypertension.

OBJECTIVE: To investigate the extent to which the immune system is influenced in patients with previous malignant hypertension. DESIGN: Twenty-three patients with malignant hypertension (fundus hypertonicus grades III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had been instituted they were investigated to establish the function of the cellular immune system (number of T lymphocytes and the proliferative response to T-cell mitogens), human leucocyte antigens A, B and C and frequency of autoantibodies. METHODS: The numbers of T lymphocytes were quantified as erythrocyte rosettes. Lymphocyte-stimulation tests were carried out using the T-cell mitogens phytohaemagglutinin and concanavalin-A. Autoantibodies were determined with immunoassay techniques and leucocyte A, B and C antigens with a lymphocytotoxicity test. RESULTS: The frequency of T lymphocytes and their baseline thymidine incorporation were significantly depressed in patients with previously malignant hypertension compared with control subjects. The group with malignant hypertension also had a decreased proliferative response to concanavalin-A but not to phytohaemagglutinin, and they had an increased frequency of antinuclear antibodies. Human leucocyte antigen B15 tended to occur more frequently in patients with malignant and non-malignant hypertension than in control subjects, especially if a family history of hypertension was taken into consideration. CONCLUSION: The results from the present study indicate that immune mechanisms are involved in malignant hypertension, either secondary to the vascular damage or as a primary abnormality.

Antibody Formation↗

PubMed1992

Urinary kallikrein excretion is low in malignant essential hypertension.

OBJECTIVE: To determine whether the urinary excretion of kallikrein is altered in patients with previously malignant hypertension. DESIGN: Twenty-two patients with malignant hypertension (fundus hypertonicus III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had begun they were investigated for blood pressure control, family history of hypertension, renal function and urinary kallikrein and plasma prekallikrein concentrations. Twenty-two patients with treated non-malignant hypertension and 36 control subjects were investigated concomitantly. The two hypertensive groups were also separated into subgroups of essential and secondary hypertension. METHODS: Prekallikrein was activated and kallikrein determined by a spectrophotometric assay using a synthetic chromogenic substrate. Renal function was estimated by serum creatinine and 51Cr-ethylenediaminetetraacetic acid clearance. RESULTS: Prekallikrein levels tended to be elevated in all groups of hypertensive patients compared with controls whilst urinary kallikrein was significantly decreased in malignant hypertensives. The most pronounced suppression of urinary kallikrein was seen in the group of patients with essential malignant hypertension. The differences persisted when urinary kallikrein was related to the degree of renal impairment or when urinary volume was taken into account. There was no relation between family history of hypertension and low levels of urinary kallikrein. CONCLUSION: Decreased urinary kallikrein could indicate depressed activity in the renal kallikrein-kinin system, which may be associated with the initiation of essential malignant hypertension.

Antihypertensive Agents↗

PubMed1990

Erythrocyte sodium transport in malignant hypertension.

Twenty-three patients with treated malignant hypertension (MH), 23 patients with treated non-malignant hypertension (NMH) and 46 normotensive control subjects were investigated with regard to intraerythrocyte sodium (Na) and potassium (K) levels, as well as transmembrane fluxes of sodium (Na-influx and Na-efflux rate constant). Intraerythrocyte Na and K concentrations were determined by flame photometry. The Na-influx and Na-efflux rate constant were calculated from uptake values for 22Na in vitro. In NMH the Na-influx and Na-efflux rate constant were significantly higher while intraerythrocyte Na and K levels did not differ from the controls. Patients with MH tended to have an elevated intraerythrocyte Na concentration, but an unchanged Na-influx and Na-efflux rate constant relative to controls. The increased rate of erythrocyte membrane transport of Na in treated NMH could be due to a stimulatory effect of antihypertensive treatment on cellular Na transport. Patients with treated MH do not show this effect, and in addition, tend to have an elevated intraerythrocyte Na concentration, which is compatible with the existence of a more pronounced abnormality of cellular ion transport in MH.

Biological Transport↗

PubMed1989

Increased secretion of immunoglobulins in malignant hypertension.

Recent evidence suggests that immunogenic factors may be of importance for development and maintenance of severe hypertension. Twenty-three patients with a previously malignant phase of hypertension (MH) were investigated with respect to serum levels as well as actual production of immunoglobulins (lgs) and compared with a group of 22 patients with non-malignant hypertension (NMH) and 45 matched normotensive control subjects (C). Patients with MH had a significantly elevated secretion of IgG and IgA as compared with C. Total serum concentration of lgs did not differ between the groups, but a raised level of the subclass IgG3 was found in MH. There was a significant positive correlation between systolic blood pressure (SBP) and secretion of IgA and IgG when all hypertensive patients were studied. Six patients were subjected to repeated investigations during the first year after malignant phase. If examined in an early phase of MH (within 4 months) the secretion of IgG, IgA and IgM was enhanced compared with later stages (after 5-12 months). The results suggest that an immunological process is involved in MH. This could either be a primary immunological disturbance or more plausibly secondary effects due to the vascular damage caused by the very high blood pressure.

Antihypertensive Agents↗