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Biomedical subjects

P Ohman

Publications and source records attributed to P Ohman.

17 recordsLinked to original sources
PubMed1995

Chimeric macaque/human Fab molecules neutralize simian immunodeficiency virus.

A collection of simian immunodeficiency virus (SIV) neutralizing recombinant Fab fragments was generated using the combinatorial antibody library approach. Functional antibody fragments efficiently expressed in Escherichia coli were identified only in the form of chimeric macaque heavy chain gamma 1 and human light chain kappa. The gamma 1 and kappa chains were derived from a clinically healthy long-term surviving SIVsm-infected cynomolgus macaque and from an asymptomatic HIV-2 seropositive individual, respectively. The combinatorial library was constructed on the surface of filamentous phage using the pComb3 phagemid vector and screened against purified SIVsm surface glycoprotein (gp148). Twelve chimeric clones reacting with the antigen were isolated. Six of these clones showed a pronounced neutralizing activity against SIVsm with effects at concentrations of 0.01-0.1 micrograms/ml. All neutralizing Fab fragments were clonally unrelated as demonstrated by nucleic acid sequencing. These potent neutralizing reagents will be used for prophylactic and therapeutic immune intervention of lentivirus infection in macaques and to map neutralizing determinants of SIV.

Amino Acid Sequence↗
PubMed1994

Stable biological and antigenic characteristics of HIV-2SBL6669 in nonpathogenic infection of macaques.

The purpose of the present study was to investigate if the biological and antigenic properties of human immunodeficiency virus type 2 change over time in cynomolgus macaques (Macaca fascicularis) experimentally infected with HIV-2SBL6669. Sequential virus isolates and serum samples were obtained during a 2-year period and studied in autologous neutralization assays. All six macaques studied seroconverted shortly after infection and remained healthy during the observation period. Virus could be isolated from all six animals during the first 100 days postinfection. Thereafter four monkeys became virus isolation negative, either permanently or transiently (two macaques each), whereas two macaques remained virus isolation positive during the entire observation period. Sequential reisolates from the macaques invariably replicated in HUT-78, U937-2, and Jurkat-tat cell lines, similarly to the HIV-2SBL6669 inoculum virus. The ability to produce neutralizing antibodies correlated with positive virus isolations, hence four macaques produced neutralizing antibodies against inoculum virus and sequential reisolates. Once the neutralizing antibody appeared, sequential reisolates obtained at both early and late time after infection were neutralized, indicating that the neutralizing epitopes of the virus are conserved in the infected animals over time. This is different from the pathogenic SIVsm infection in macaques or HIV-1 infection in humans, where emergence of neutralization resistant variants seems to be the rule. In contrast, in HIV-2-infected macaques the biological properties of the virus are stable and the neutralizing antibody response shows extensive cross-reactivity.

Animals↗
PubMed1993

Autologous neutralizing antibodies to SIVsm in cynomolgus monkeys correlate to prognosis.

Sequential virus isolates from eight cynomolgus monkeys experimentally infected with SIVsm were studied for susceptibility to neutralization by autologous antibodies. The biological and antigenic characteristics of sequential reisolates differed both from the inoculum virus and from each other. Five monkeys developed neutralizing antibodies to the inoculum virus and the 12-day reisolate at 4 months postinfection, while the remaining three monkeys produced very little, if any, neutralizing antibodies. Strikingly, the two long survivor monkeys developed neutralizing antibody response to a second or third autologous reisolate and to 12 reisolates obtained from other monkeys. Thus the neutralizing antibody response of the long survivor monkeys showed a relatively broad specificity, whereas the neutralizing antibody response of the monkeys with early disease, if at all present, was specific for the infecting strain only and lost over time. Our results show that the pattern of virus neutralization in SIVsm-infected monkeys is similar to human immunodeficiency virus type 1-infected humans. In both cases, variant viruses resistant to neutralization by autologous sera emerge during the entire course of infection. In addition, the ability to produce autologous neutralizing antibodies to sequential virus reisolates appeared to correlate with the degree of immunodeficiency in the host.

Animals↗
PubMed1985

Long-term effects of captopril and atenolol in essential hypertension.

Fifty patients with mild or moderate essential hypertension were randomized (double-blindly) to treatment with either captopril (n = 26) or atenolol (n = 24). Their mean supine diastolic blood pressure after placebo was 100-125 mmHg. The study included an initial dose finding phase (12 weeks) during which the dosages of captopril and atenolol were increased stepwise every second week in order to obtain normotension (supine diastolic blood pressure less than 95 mmHg). Hydrochlorothiazide was added when necessary. During the second phase of the study the patients were followed on active treatment for 2 years. After the initial 12 weeks of active treatment, recumbent and standing blood pressures had fallen significantly both in the captopril group (by 31/20 and 33/19 mmHg, p less than 0.001) and in the atenolol group (by 24/18 and 30/20 mmHg, p less than 0.01 (systolic), p less than 0.001 (diastolic)). The antihypertensive effect was maintained in both groups during long-term treatment. The antihypertensive effect of both agents was potentiated to the same extent by addition of hydrochlorothiazide. Side-effects were few and mild. It can be concluded that both captopril and atenolol are safe and effective antihypertensive drugs.

Adult↗
PubMed1984

A long-term follow-up of patients with essential hypertension treated with captopril.

Seventy-four patients from four short-term studies of captopril in mild-moderate essential hypertension continued in a cooperative long-term efficacy and tolerance program. The duration of observation is 2- greater than 4 years, the total treatment time being 2434 months. No development of resistance to therapy was observed. The total daily dose of captopril has been gradually decreased and in 20 patients changed from t.i.d. to b.i.d. regime. The drug has been well tolerated and only few and mild side-effects have been observed after the initial titration period. The drop-outs (n = 19) were mostly due to non-medical causes (n = 14). Except for one case of proteinuria, no laboratory abnormalities were detected and there were no signs of long-term toxicity.

Adult↗
PubMed1984

Patients compliance in hypertension--the importance of number of tablets.

The importance of number of tablets for patient compliance was investigated in 160 patients with mild-moderate essential hypertension treated with a beta-adrenoceptor blocker and a thiazide diuretic. Mean BP at entry 146 +/- 16/92 +/- 8 mm Hg. All patients were given pindolol 10 mg and clopamide 5 mg in one combination tablet or in separate tablets for 4 months respectively. Approximately 90% of the patients took greater than 90% of the prescribed dose throughout the study. Mean BP decreased progressively and heart rate increased slightly. Side effects were more frequently reported during the first month of the study than previously, and 30 patients discontinued the treatment. No differences in this respect were seen between 1 and 2 tablets daily. Approximately 75% of the patients preferred 1 tablet daily, but combining two drugs in one tablet had no effect upon compliance.

Adult↗
PubMed1984

Initial clinical experience with ICI 141,292 (Visacor), a new selective beta 1-adrenoceptor blocker with ISA--a multicentre trial in 59 patients.

The objective of this placebo controlled double-blind multicentre (six centres) trial was to investigate the safety and efficacy of ICI 141,292 (Visacor), a new selective beta 1-adrenoceptor antagonist with modest intrinsic sympathomimetic activity (ISA), in hypertensive patients. Fifty-nine patients with mild essential hypertension were randomized to two of five treatment alternatives (placebo, 50 mg, 100 mg 200 mg or 300 mg of ICI 141,292) each given once daily for 2 weeks with a 4 week placebo period before (run in) and in between (wash out) active periods. Thus, each of the five treatments was evaluated in 20-24 patients. After 2 weeks (24 h after last dose) the reduction in recumbent blood pressure for all doses except 50 mg of ICI 141,292 was statistically significant and in the order of 6/4 mm Hg. Standing systolic blood pressure was reduced in a dose-dependent way but only significant for 200 mg of ICI 141,292 (8 mm Hg). Heart rate changes (delta) less than 4 beats/min) were not statistically significant for any dose. It is concluded that ICI 141,292 was well tolerated and had a significant but weak antihypertensive effect which might be explained by too much beta 1-adrenoceptor ISA.

Adrenergic beta-Antagonists↗
PubMed1983

Evaluation of once daily hydralazine in inadequately controlled hypertension.

Despite the short plasma half-life of hydralazine, once daily Slow Apresoline has been shown to maintain blood pressure control in well controlled hypertension. In the present investigation of 118 inadequately controlled hypertensives, we have shown that 50-150 mg Slow Apresoline once daily induces a significant blood pressure reduction and is well tolerated. Normotension, i.e. supine diastolic blood pressure less than 95 mmHg, was reached in 53% of the patients. Normotension or a supine diastolic blood pressure reduction of greater than or equal to 10 mmHg was achieved in 72% of the patients, the hydralazine responders. Sixteen patients discontinued treatment due to symptoms probably related to hydralazine. Acetylator phenotyping showed that slow acetylators predominated in the group of patients discontinuing hydralazine due to side-effects. In contrast, 90% of the phenotyped non-responders were rapid acetylators, which suggests a suboptimal use of hydralazine in some rapid acetylators.

Adult↗
PubMed1982

Captopril and atenolol combined with hydrochlorothiazide in essential hypertension.

1 Fifty-seven patients with mild or moderate essential hypertension, mean age 50 (range 31-69) were randomised to treatment with either captopril or atenolol. Twenty-six patients in each group completed the study. 2 Captopril (25-50 mg three times daily) and atenolol (50-100 mg once daily) caused a highly significant fall in blood pressure both supine and standing. 3 When hydrochlorothiazide (25-50 mg once daily) was added a further fall in blood pressure was observed in both groups. 4 Captopril as single drug caused no significant change in heart rate, while atenolol significantly reduced heart rate both supine and standing. 5 Two patients were excluded from the captopril group, one because of a reversible loss of taste and the other because of dizziness. Three patients were excluded from the atenolol group, two because of bradyarrhythmias and one because of inadequate blood pressure response. 6 Both captopril and atenolol were found to be effective antihypertensive agents, suitable for the treatment of essential hypertension.

Adult↗
PubMed1981

Metoprolol administered once daily in the treatment of hypertension. A double-blind crossover comparison between conventional tablets and metoprolol Durules.

The effect of metoprolol, a beta1-selective receptor blocking agent without intrinsic stimulating activity, on blood pressure, pulse and plasma concentration 2 and 24 h after dose intake and on working capacity and perceived exertion 2 h after dose intake was investigated when given as 100 mg and 200 mg conventional tablets or 200 mg slow-release tablets (Durules) once daily, long-term, to 20 patients with primary (essential) hypertension. Metoprolol 100 mg and 200 mg once daily effectively lowers blood pressure over a 24-h period, and 200 mg Durules once daily gives beta-receptor blockade for 24 h. Peak plasma concentration 2 h after dose intake and individual variations in plasma concentrations are reduced on 200 mg Durules compared with 200 mg conventional tablets. Working capacity is not reduced, though perceived exertion and leg fatigue seem to be slightly increased with metoprolol, especially 200 mg conventional tablets.

Adult↗