Biomedical subjects

R W Jansen

Publications and source records attributed to R W Jansen.

At least 73 records · Page 4Linked to original sources

PubMed1990

Molecular epidemiology of human hepatitis A virus defined by an antigen-capture polymerase chain reaction method.

We describe an immunoaffinity-linked nucleic acid amplification system (antigen-capture/polymerase chain reaction, or AC/PCR) for detection of viruses in clinical specimens and its application to the study of the molecular epidemiology of a picornavirus, hepatitis A virus (HAV). Immunoaffinity capture of virus, synthesis of viral cDNA, and amplification of cDNA by a polymerase chain reaction (PCR) were carried out sequentially in a single reaction vessel. This approach simplified sample preparation and enhanced the specificity of conventional PCR. AC/PCR detected less than one cell culture infectious unit of virus in 80 microliters of sample. Sequencing of AC/PCR reaction products from 34 virus strains demonstrated remarkable conservation at the nucleotide level among most strains but revealed hitherto unsuspected genetic diversity among human isolates. Epidemiologically related strains were identical or closely related in sequence. Virus strains recovered from epidemics of hepatitis A in the United States and Germany were identical in sequence, providing evidence for a previously unrecognized epidemiologic link between these outbreaks.

Animals↗

PubMed1990

In vivo replication and reversion to wild type of a neutralization-resistant antigenic variant of hepatitis A virus.

Six seronegative owl monkeys were intravenously inoculated with an antigenic variant (S18) of hepatitis A virus that is highly adapted to growth in cell culture and resists neutralization by monoclonal antibodies due to replacement of aspartic acid 70 of capsid protein VP3 with histidine. Each developed hepatitis 22-33 days after inoculation. Virus in feces, serum, and liver was quantified by radioimmunofocus assay. Viremia developed 7-11 days after inoculation, in parallel with fecal shedding of virus, and persisted for a mean of 20.5 days. Although the antigenic variant was recovered from feces or liver of three animals, virus in liver at the time of enzyme elevations was predominantly wild-type antigenic phenotype. Virus was not recovered from liver 96 days after challenge. These studies further define virologic events in hepatitis A and show that in vivo replication of an antigenic variant was restricted compared with that of wild-type virus.

Animals↗

PubMed1990

The effect of oral glucose, protein, fat and water loading on blood pressure and the gastrointestinal peptides VIP and somatostatin in hypertensive elderly subjects.

In elderly subjects blood pressure (BP) may fall after a meal. It can be reproduced by oral glucose, but the effect of fat and protein ingestion on postprandial BP has not been reported. Furthermore, we hypothesized that vasoactive gastrointestinal peptides are involved in this phenomenon. We studied 10 hypertensive elderly subjects (mean age 74 +/- 3 years) for the effects of oral glucose, fat, protein and water loading on BP in relation to plasma concentrations of vasoactive intestinal polypeptide (VIP), somatostatin and insulin. Glucose loading resulted in a decrease of mean arterial pressure by 14 +/- 2 mmHg (P less than or equal to 0.001). In contrast, the ingestion of fat, protein or water had no significant effect on BP. Somatostatin increased after fat and protein loading, whereas VIP increased only after fat loading. These data indicate that postprandial BP reduction in the elderly is related to glucose-related factors. The gut peptide VIP does not seem to play a role in this phenomenon.

Aged↗

PubMed1990

Immunogenic domains of hepatitis delta virus antigen: peptide mapping of epitopes recognized by human and woodchuck antibodies.

Hepatitis delta virus (HDV) is a defective RNA virus which is dependent on hepatitis B virus for essential helper functions. Only a single highly basic phosphoprotein, HDV antigen (HDAg), is expressed by the HDV genome during infection in humans. Antibody directed to HDAg is important in the diagnosis of HDV infection, and it is likely but not yet proven that the immune response to HDAg provides significant protection against subsequent exposures to HDV. In an effort to map the antigenic domains of HDAg, 209 overlapping hexapeptides, spanning the entire 214 amino acid residues of the protein, were synthesized on polyethylene pins and probed by enzyme-linked immunosorbent assay with sera containing high titers of anti-HD antibodies. Domains recognized by antibodies present in serum from human chronic carriers of this virus included residues 2 to 7, 63 to 74, 86 to 91, 94 to 100, 159 to 172, 174 to 195, and 197 to 207. Antibody from an acutely superinfected woodchuck recognized similar epitopes, as well as a domain spanning residues 121 to 128. Together, residues in these antigenic domains constitute 41% of the HDAg molecule. Oligopeptides 15 to 29 residues in length and representing epitopes of HDAg found to be dominant in humans (residues 2 to 17, 156 to 184, and 197 to 211) were synthesized in bulk and found to possess significant antigenic activity by microdilution enzyme-linked immunosorbent assay. The reactivity of peptide 197-211 with human sera confirms that the entire 214 amino acids of HDAg are expressed during infection in vivo. In addition, these results suggest that synthetic peptides may be useful reagents for development of new and improved diagnostic tests for HDV infection.

Amino Acid Sequence↗

PubMed1990

The influence of glycyrrhetinic acid on plasma cortisol and cortisone in healthy young volunteers.

Based on studies in laboratory animals and on measurements of the urinary metabolites (allo)tetrahydrocortisol and tetrahydrocortisone in human volunteers it has been claimed that liquorice-induced mineralocorticoid excess is caused by a unique defect in the conversion of cortisol to cortisone. To further evaluate this hypothesis we have investigated the influence of glycyrrhetinic acid (GA), the mineralocorticoid-active constituent of liquorice, on plasma cortisol and cortisone in 10 healthy young normotensive volunteers. Pure GA (500 mg/day), administered orally from days 3-10 of the study, exerted pronounced mineralocorticoid activity. Ingestion of GA resulted in an elevated urinary excretion of free cortisol and virtually unchanged plasma cortisol levels in the presence of markedly decreased levels of both plasma cortisone and urinary free cortisone. These results provide direct clinical support for the hypothesis that GA induces an inhibition of the activity of 11 beta-dehydrogenase, resulting in a blockade in the conversion of cortisol to cortisone.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1990

Postprandial blood pressure reduction.

Recently it has been shown that, after a meal, blood pressure may fall in the elderly, in patients with autonomic failure and in patients on haemodialysis. This review deals with the available data on postprandial blood pressure reduction, the clinical significance and some pathophysiological hypotheses. The mechanism is not fully understood, but postprandial blood pressure reduction seems to be related to glucose related factors, since blood pressure only falls after oral glucose loading, but not after oral fructose, fat or protein loading. Vasoactive gastrointestinal peptides may play a role in the glucose induced vasodilation of splanchnic vasculature, but attempts to identify such peptides have been unsuccessful. The role of insulin in postprandial blood pressure reduction remains to be elucidated, but it does not appear to have any influence on systemic vasodilation or baroreflex response. Although the clinical significance of postprandial blood pressure reduction remains uncertain, patients can be advised in several ways on how to avoid this symptom. Treatment of hypertension, small carbohydrate meals, caffeine and treatment with the somatostatin analogue SMS 201-995 may have a beneficial effect. Patients on haemodialysis with symptomatic hypotension should not consume meals during the procedure.

Eating↗

PubMed1989

Nitrendipine versus hydrochlorothiazide in hypertensive patients over 70 years of age.

The effects of nitrendipine and hydrochlorothiazide were studied in hypertensive elderly patients. Blood pressure was reduced (p less than 0.01) by both nitrendipine (13/10 +/- 4/3 mm Hg [n = 15], mean +/- SE) and hydrochlorothiazide (25/11 +/- 4/2 mm Hg [n = 16]). After hydrochlorothiazide, plasma glucose, uric acid, and renin activity increased and plasma potassium levels decreased. Edema and flushing were the main adverse reactions during nitrendipine. The response of blood pressure and heart rate to head-up tilt were not significantly different under both treatments. However, the effects of both drugs on diastolic blood pressure and norepinephrine responses to head-up tilt differed significantly. We conclude that, in the elderly, hydrochlorothiazide lowers systolic blood pressure more effectively than nitrendipine. However, nitrendipine does not have any of the potentially harmful metabolic side effects that were found during hydrochlorothiazide therapy. The clinical significance of a lower vasoreactivity during nitrendipine, as was found with the head-up tilt test, has to be established.

Aged↗

PubMed1989

The influence of age and blood pressure on the hemodynamic and humoral response to head-up tilt.

It has been reported that postural hypotension in the elderly is common. However, these studies included institutionalized and more or less disabled persons. Furthermore, postural hypotension may be related to baseline blood pressure. In this study, the influence of age and blood pressure on the hemodynamic and plasma catecholamine responses to orthostatic stress was investigated in young and old normotensive and hypertensive healthy subjects. In normotensive and hypertensive elderly persons, the percentage blood pressure responses during tilt were not significantly different from that seen in young normotensives. We measured a slight decrease of systolic blood pressure and a slight increase of diastolic blood pressure. The hypertensive young patients showed an enhanced diastolic blood pressure response with no fall in systolic blood pressure, in contrast to the normotensive young subjects. Both elderly groups had a lower increase of heart rate than the young subjects. The percentage increase in norepinephrine after tilting was significantly lower in elderly hypertensives than in elderly normotensives and young hypertensives. The presence of hypertension was associated with a decrease in blood pressure, but age had no influence on the change in blood pressure during tilt. In this group of healthy elderly subjects, there was no significant orthostatic hypotension when the blood pressure course of the entire tilt test was taken into account.

Adult↗

PubMed1989

Influence of octreotide (SMS 201-995) and insulin administration on the course of blood pressure after an oral glucose load in hypertensive elderly subjects.

Pretreatment with a somatostatin analogue, octreotide (SMS 201-995), prevents postprandial blood pressure reduction in the elderly. We hypothesized that this beneficial effect on blood pressure is caused by an octreotide-induced suppression of insulin secretion. We studied the effects of octreotide and insulin administration on the course of blood pressure after oral glucose loading in 10 healthy hypertensive old persons (mean age 73 +/- 3 years). Octreotide was given in a dose of 50 micrograms subcutaneously (sc) (time = -30 minutes). Insulin was given sc in a dose of 0.3 U/kg body weight (time = -10 minutes) and glucose was given orally in a dose of 75 g in 300 mL water (time = 0 minutes). Plasma insulin concentrations remained essentially unchanged after placebo and rose to a maximum level of 58 +/- 6 mU/L following insulin administration. The course of blood pressure was not different following glucose loading with high or low plasma insulin levels. These data indicate that the effects of octreotide on postprandial blood pressure reduction in the elderly are unrelated to the inhibition of insulin secretion.

Administration, Oral↗

PubMed1989

The influence of oral glucose loading on baroreflex function in the elderly.

Blood pressure in the elderly may decrease after a meal or after oral glucose loading. It has been suggested that eating may affect blood pressure homeostasis through an insulin-induced blunting of baroreflex sensitivity. We investigated the effects of oral glucose loading on baroreflex sensitivity in young normotensives and in elderly normo-and hypertensive subjects. Blood pressure was measured by a new noninvasive device, Finapres, which measures blood pressure continuously in the finger. Baroreflex sensitivity was estimated with the phenylephrine and nitroglycerin method. In both elderly groups mean arterial pressure fell significantly after the glucose load (11 +/- 1 mm Hg, P less than .001 in the hypertensives, and 8 +/- 2 mm Hg, P less than .01 in the normotensive subjects), whereas no change in blood pressure was found in the young group. Baroreflex sensitivity was lower in both elderly groups than in young normotensives. Glucose loading had no influence on baroreflex sensitivity in the three groups. Therefore, we conclude that other factors are involved in the phenomenon of postprandial hypotension in the elderly.

Administration, Oral↗

PubMed1989

Characterization of a simian hepatitis A virus (HAV): antigenic and genetic comparison with human HAV.

PA21, a strain of hepatitis A virus (HAV) recovered from a naturally infected captive owl monkey, is indistinguishable from human HAV in polyclonal radioimmunoassays and cross-neutralization studies. However, cDNA-RNA hybridization has suggested a significant difference at the genomic level between PA21 and a reference human virus, HM175. Further characterization of this unique HAV was undertaken in an effort to determine the extent of genetic divergence from human HAV and its relation to the conserved antigenic structure of the virus. The close similarity between PA21 and HM175 antigens was confirmed with an extended panel of 18 neutralizing murine monoclonal antibodies: a reproducible difference in binding to the two viruses was detected with only one antibody (B5-B3). The nucleotide sequence of the P1 region of the PA21 genome had only 83.2% identity with HM175 virus, a difference approximately twice as great as that found between any two human strains. Most nucleotide changes were in third base positions, and the amino acid sequences of the capsid proteins were largely conserved. Amino acid replacements were clustered in the carboxy terminus of VP1 and the amino-terminal regions of VP2 and VP1. These data indicate that PA21 virus represents a unique genotype of HAV and suggest the existence of an ecologically isolated niche for HAV among feral owl monkeys.

Amino Acid Sequence↗

PubMed1989

Somatostatin analog octreotide (SMS 201-995) prevents the decrease in blood pressure after oral glucose loading in the elderly.

In elderly subjects blood pressure (BP) may fall after a meal. The mechanism of this phenomenon is unknown, but it has been suggested that it may be mediated by insulin and/or vasoactive gut hormones. We studied in normo- and hypertensive elderly subjects the effects of the synthetic long-acting somatostatin analog octreotide (SMS 201-995) on the BP reduction that follows oral glucose administration in subjects who are recumbent and on their postglucose plasma vasoactive intestinal polypeptide (VIP) and insulin concentrations. After placebo treatment, mean arterial pressure fell by 15 +/- 1 mm Hg (P less than 0.001) in the 10 hypertensive subjects and by 7 +/- 2 mm Hg (P less than 0.01) in the 10 normotensive subjects. In contrast, when 50 micrograms octreotide were given sc, BP did not change significantly in either group. Oral glucose did not induce a rise in plasma VIP after either octreotide or placebo administration. The postglucose rises in plasma glucose concentrations were similar after octreotide and placebo treatments in both groups. After placebo administration the postglucose plasma insulin levels increased from 79 to 519 pmol/L in the hypertensive subjects and from 63 to 464 pmol/L in the normotensive subjects, whereas after octreotide treatment plasma insulin increased little in either group. These data indicate that treatment with octreotide holds promise for patients with symptomatic postprandial hypotension, and that VIP does not seem to play a role in this phenomenon.

Administration, Oral↗

PubMed1989

[Reduction in blood pressure after meals in the elderly. A review article].

It has been known for several years that blood pressure in the elderly may fall after a meal. Although the mechanism is not fully understood, postprandial blood pressure reduction seems to be related to glucose related factors, since blood pressure only falls after oral glucose loading, but not after oral fructose, fat or protein loading. Vasoactive gastrointestinal hormones may play a role in the glucose induced vasodilation of splanchnic vasculature, but attempts to identify such hormones were unsuccessful. Therefore we suggest that interference of insulin with a sympathetic response diminished by age or disease to splanchnic vasodilation, may be responsible for the postprandial fall in blood pressure in the elderly. However, vasodilator effects of insulin or a baroreflex response diminished by insulin do not seem to be involved. Although the clinical significance of postprandial blood pressure reduction remains uncertain, several advises can been given. Treatment of hypertension, small carbohydrate meals, use of caffeine before a meal or treatment with the somatostatin analogue SMS 201-995 may have a beneficial effect.

Aged↗

PubMed1988

Complete nucleotide sequence of a cell culture-adapted variant of hepatitis A virus: comparison with wild-type virus with restricted capacity for in vitro replication.

To determine the molecular changes associated with adaptation of hepatitis A virus (HAV) to growth in cell culture, the genome of a cell culture-adapted variant of HM175 strain HAV (p16 HM175, 16th in vitro passage level) was molecularly cloned and the complete nucleotide sequence of the virus was determined. Compared with wild-type virus, p16 HM175 replicates efficiently in monkey kidney (BS-C-1) cells (approximately 58 RNA-containing particles per one infectious unit, compared with 2.4 x 10(5) for wild-type HM175). The nucleotide sequence of p16 HM175 revealed a total of 19 mutations from the wild-type genome, including 5 mutations in the 5' nontranslated region, 1 mutation in the 3' nontranslated region, and 13 mutations predicting 8 changes in the amino acid sequences of HAV proteins. Only one amino acid substitution occurred among the capsid proteins (VP2), while others involved proteins 2A, 2B, 2C, VPg, and 3Dpol. When the sequence of p16 virus was compared with that reported previously for an independently isolated, cell culture-adapted variant of HM175 virus (J.I. Cohen et al., (1987). Proc. Natl. Acad. Sci. USA 84, 2497-2501), there were three identical mutations in nontranslated regions of the RNA, and four mutations involving identical amino acids in proteins VP2, 2B, and 3Dpol. The distribution of these mutations within the genome suggests that changes in RNA replication may be of primary importance in adaptation of the virus to growth in vitro. These data are thus helpful in understanding the molecular basis of adaptation of HAV to cell culture and, since attenuation frequently accompanies adaptation of virus to growth in cell culture, may be of benefit in planning for attenuated vaccine development.

Amino Acid Sequence↗

PubMed1988

Identification of an immunodominant antigenic site involving the capsid protein VP3 of hepatitis A virus.

Hepatitis A virus, an hepatotropic picornavirus, is a common cause of acute hepatitis in man for which there is no available vaccine. Competitive binding studies carried out in solid phase suggest that neutralizing monoclonal antibodies to hepatitis A virus recognize a limited number of epitopes on the capsid surface, although the polypeptide locations of these epitopes are not well defined. Neutralization-escape mutants, selected for resistance to monoclonal antibodies, demonstrate broad cross-resistance to other monoclonal antibodies. Sequencing of virion RNA from several of these mutants demonstrated that replacement of aspartic acid residue 70 of capsid protein VP3 (residue 3070) with histidine or alanine confers resistance to neutralization by monoclonal antibody K2-4F2 and prevents binding of this antibody and other antibodies with similar solid-phase competition profiles. These results indicate that residue 3070 contributes to an immunodominant antigenic site. Mutation at residue 102 of VP1 (residue 1102) confers partial resistance against antibody B5-B3 and several other antibodies but does not prevent antibody attachment. Both VP3 and VP1 sites align closely in the linear peptide sequences with sites of neutralization-escape mutations in poliovirus and human rhinovirus, suggesting conservation of structure among these diverse picornaviruses. However, because partial neutralization resistance to several monoclonal antibodies (2D2, 3E1, and B5-B3) was associated with mutation at either residue 3070 or residue 1102, these sites appear more closely related functionally in hepatitis A virus than in these other picornaviruses.

Alanine↗

PubMed1988

SMS 201-995 prevents postprandial blood pressure reduction in normotensive and hypertensive elderly subjects.

The mechanism of postprandial blood pressure reduction in the elderly is unknown but it has been suggested that insulin and/or vasoactive gut hormones play a role in this phenomenon. The increase in insulin and other gut hormones induced by the glucose loading can be blocked by a synthetic long-acting somatostatin analogue. SMS 201-995. We carried out a double-blind randomized study on the effects of SMS 201-995 on the responses of blood pressure, heart rate, insulin and plasma noradrenaline to oral glucose loading in normotensive and hypertensive elderly subjects. After placebo was administered, mean arterial pressure fell by 15 +/- 1 mmHg (P less than 0.001) in hypertensive elderly and by 7 +/- 2 mmHg (P less than 0.01) in normotensive elderly subjects. In contrast, when SMS 201-995 was administered, blood pressure remained essentially unchanged in both groups. These data indicate that treatment with SMS 201-995 might be of value in patients with symptomatic postprandial hypotension.

Aged↗

PubMed1988

Effects of nitrendipine and hydrochlorothiazide on postprandial blood pressure reduction and carbohydrate metabolism in hypertensive patients over 70 years of age.

Recently, it has been recognized that blood pressure (BP) in the elderly may decrease after a meal or oral glucose loading. Calcium antagonists and diuretics have been advocated as first-line drugs for the treatment of hypertension in the elderly. It is not known whether these antihypertensive drugs may further deteriorate or improve BP homeostasis after a meal. Therefore, we studied in a double-blind parallel study the effects of a 12-week treatment with nitrendipine, 20 mg once daily, and hydrochlorothiazide, 50 mg once daily, on BP homeostasis after an oral glucose loading. In addition, the effects of both agents on carbohydrate metabolism were studied. Before treatment, mean BP decreased by 13 +/- 1 mm Hg (SEM) (10%, p less than 0.001) 60 min after the glucose loading in the nitrendipine group [n = 9, age 73 +/- 3 (SD) years] and by 9 +/- 2 (SEM) mm Hg (7%, p less than 0.01) in the hydrochlorothiazide group [n = 13, age 76 +/- 4 (SD) years]. After 12 weeks of treatment, oral glucose loading resulted in mean BP reductions of 7 +/- 2 mm Hg (6%, p less than 0.01) and 4 +/- 2 mm Hg (4%, not significant) in the nitrendipine and hydrochlorothiazide groups, respectively. In the hydrochlorothiazide group, the area under the curve of plasma glucose was significantly higher after treatment than before (p = 0.03). We conclude that antihypertensive treatment with nitrendipine or hydrochlorothiazide improves BP homeostasis after an oral glucose loading. In contrast to nitrendipine, 12 weeks of treatment with hydrochlorothiazide slightly impairs carbohydrate metabolism.

Aged↗

PubMed1987

Blood pressure reduction after oral glucose loading and its relation to age, blood pressure and insulin.

Recently it was shown that blood pressure (BP) in the elderly may decrease after a meal. The pathophysiologic mechanism of this phenomenon is unknown. It has been suggested that a failure of insulin-mediated sympathetic nervous system activation plays a role. To evaluate the role of endogenous insulin, the effects of oral glucose and oral fructose loading on BP, heart rate and norepinephrine levels were studied in 10 young normotensive volunteers (YN), 10 young hypertensive patients (YH), 10 elderly normotensive volunteers (EN) and 10 elderly hypertensive patients (EH). Fructose, 75 g/300 ml of water, elicited--in contrast to the same amount of glucose--only a small increase in insulin and glucose levels. After glucose loading, mean arterial BP decreased by 17 mm Hg in the EH group (p less than 0.001), 6 mm Hg in the EN group (p less than 0.01) and 7 mm Hg in the YH group (p less than 0.001), and did not change in the YN group. After oral fructose loading, BP did not change in any group. In all groups except the YN group, the increases in norepinephrine level and heart rate after both tests were not significantly different. These findings suggest that the BP reduction after glucose loading is related to glucose-mediated factors. A failure of insulin-mediated sympathetic nervous system activation does not appear to play a major role.

Administration, Oral↗