Biomedical subjects

R Bohm

Publications and source records attributed to R Bohm.

At least 19 recordsLinked to original sources

PubMed2006

CpG-C ISS-ODN activation of blood-derived B cells from healthy and chronic immunodeficiency virus-infected macaques.

Cytosine-phosphate-guanine class C (CpG-C) immunostimulatory sequence oligodeoxynucleotides (ISS-ODNs) activate human B cells and dendritic cells (DCs), properties that suggest potential use as a novel adjuvant to enhance vaccine efficacy. After demonstrating that the CpG-C ISS-ODN C274 activates macaque DCs, we examined in vitro activation of macaque B cells by C274 as a prelude to evaluation of this molecule as an adjuvant in the testing of candidate human immunodeficiency virus vaccines in the rhesus macaque-simian immunodeficiency virus (SIV) model. C274 induced macaque CD20(+) B cells to proliferate more strongly than CD40 ligand or CpG-B ISS-ODN. C274 enhanced B cell survival; increased viability was most evident after 3-7 days of culture. Increased expression of CD40, CD80, and CD86 by B cells was apparent within 24 h of exposure to C274 and persisted for up to 1 week. C274-stimulated, B cell-enriched and peripheral blood mononuclear cell suspensions from naïve and immunodeficiency virus-infected monkeys secreted several cytokines [e.g., interleukin (IL)-3, IL-6, IL-12, interferon-alpha] and chemokines [e.g., monocyte chemoattractant protein-1/CC chemokine ligand 2 (CCL2), macrophage-inflammatory protein-1alpha/CCL3, IL-8/CXC chemokine ligand 8]. In comparison, exposure of macaque B cells to SIV had minimal impact on surface phenotype, despite inducing cytokine and chemokine production in cells from infected and uninfected animals. These observations emphasize the need to identify strategies to optimally boost immune function, as immunodeficiency viruses themselves only partially activate B cells and DCs. The ability of C274 to stimulate B cells and DCs in healthy and infected monkeys suggests its possible use as a broad-acting adjuvant to be applied in the rhesus macaque model for the development of preventative and therapeutic vaccines.

AIDS Vaccines↗

PubMed2001

Mucosal transmission and induction of simian AIDS by CCR5-specific simian/human immunodeficiency virus SHIV(SF162P3).

Nonhuman primate models are increasingly used in the screening of candidate AIDS vaccine and immunization strategies for advancement to large-scale human trials. The predictive value of such macaque studies is largely dependent upon the fidelity of the model system in mimicking human immunodeficiency virus (HIV) type 1 infection in terms of viral transmission, replication, and pathogenesis. Herein, we describe the efficient mucosal transmission of a CCR5-specific chimeric simian/human immunodeficiency virus, SHIV(SF162P3). Female rhesus macaques were infected with SHIV(SF162P3) after a single atraumatic application to the cervicovaginal mucosa. The disease course of SHIV(SF162P3)-infected monkeys is similar and as varied as natural HIV infection in terms of viral replication, gradual loss of CD4(+) peripheral blood mononuclear cells, and the development of simian AIDS-defining opportunistic infections. The SHIV(SF162P3)/macaque model should facilitate direct preclinical assessment of HIV vaccine strategies in addition to antiviral compounds directed towards envelope target cell interactions. Furthermore, this controlled model provides the setting to investigate immunologic responses and putative host-specific susceptibility factors that alter viral transmission and subsequent disease progression.

Animals↗

PubMed2000

First determination of generalized polarizabilities of the proton by a virtual compton scattering experiment

Absolute differential cross sections for the reaction ep-->epgamma have been measured at a four-momentum transfer with virtuality Q2 = 0.33 GeV2 and polarization epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high-resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.

Journal Article↗

PubMed2000

Partial hepatectomy and laparoscopic-guided liver biopsy in rhesus macaques (Macaca mulatta): novel approach for study of liver regeneration.

BACKGROUND AND PURPOSE: Although valuable information has been gained using a rodent partial hepatectomy model to assess liver regeneration, the ability to apply this research to humans remains uncertain. Thus, liver regeneration was assessed in a non-human primate, the rhesus macaque (Macaca mulatta). METHODS: One animal underwent 60% hepatectomy, a second animal underwent 30% hepatectomy, and control surgery (cholecystectomy) was performed on two separate animals. Laparoscopic-guided liver biopsy was performed on days 1, 2, 7, 14, and 30 after surgery. Changes in hemoglobin concentration and alanine transaminase activity were assessed, and liver regeneration was evaluated by measuring the expression of Ki-67. RESULTS: All animals survived surgery and laparoscopy. Substantial liver regeneration was induced in the animal that underwent 60% hepatectomy. Excellent tissue specimens were obtained via laparoscopic-assisted liver biopsy. CONCLUSIONS: Sixty percent partial hepatectomy in rhesus macaques appears to be an excellent model for the study of hepatocellular regeneration. The procedure was safe, and effectively induced liver regeneration. In addition, laparoscopic-guided liver biopsy allows observation of changes in the liver remnant as regeneration develops, and provides excellent tissue specimens for analysis. Thus, this rhesus macaque partial hepatectomy model will allow further characterization of liver regeneration in a species closer to humans.

Animals↗

PubMed1999

Selective induction of protective MHC class I-restricted CTL in the intestinal lamina propria of rhesus monkeys by transient SIV infection of the colonic mucosa.

The identification of mucosal immune responses required for protection against sexual transmission of HIV is essential for the development of an efficacious vaccine. To gain a better understanding of these responses, we have characterized the immune responses in the lamina propria (LP) and epithelium of the jejunum, the mesenteric lymph nodes, and peripheral blood (PBMC) of 11 rhesus monkeys following colonic exposure to two molecular clones of SIV. Two monkeys had no signs of infection. Three monkeys became persistently infected. Transient infections, characterized by the sporadic detection of virus in the periphery and/or detection of SIV-specific immune responses in either the gut-associated tissues or PBMC, were induced in six of the monkeys. One persistently infected and three transiently infected monkeys had high levels of SIV env-specific MHC class I restricted CTL in the jejunal LP. Another transiently infected monkey had SIV-specific IgA secreting B cells in the LP. Three or six months postexposure, these animals and four naive controls were challenged intracolonically with the heterologous primary isolate, SIV/DeltaB670. All four monkeys with strong SIV env-specific MHC-restricted CTL in the LP were protected, whereas none of the naive controls or the remaining seven monkeys with little or no CTL in the LP were protected. These experiments provide the first direct evidence that transient mucosal infection can induce SIV-specific immunity that remains localized to the gut-associated tissues. Furthermore, a strong correlation between SIV env-specific MHC-restricted CTL in the LP and protection against colonic mucosal challenge was observed.

Animals↗

PubMed1998

A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine.

OBJECTIVE: A clinical definition of a hypertensive emergency is excessively high blood pressure in the presence of symptoms indicating end organ damage. Equally high blood pressure without symptoms is called a hypertensive crisis. Patients with hypertensive crisis or emergency need prompt, effective, and specific therapy and a controlled reduction of blood pressure. METHODS: We performed a randomized, double-blind multi-centre study, to compare the safety, efficacy and tolerability of an intravenous (i.v.) infusion of two dihydropyridine calcium channel blockers (either nifedipine or felodipine) in 122 patients, of whom 63 were diagnosed as hypertensive emergencies and 59 as hypertensive crisis, who had not reacted adequately (diastolic blood pressure <115 mmHg) to 5 mg of nifedipine PO. RESULTS: Both drugs lowered blood pressure adequately in more than 90% of the patients and were well tolerated. Only one patient had to be withdrawn, because of an excessive decrease in blood pressure. CONCLUSION: Patients with excessively high blood pressure who do not react to oral nifedipine can be treated equally effectively with felodipine and nifedipine IV. Felodipine is easier to handle because of its lack of light sensitivity.

Administration, Oral↗

PubMed1997

Thoracoscopic surgery of the oesophagus in rats: a training concept for the treatment of tracheo-oesophageal malformations in preterm infants

In extremely preterm babies with type Vogt III b oesophageal atresia, the primary operative management can be restricted to a gastrostomy and ligation of the fistula. Some of these patients, however, may not even tolerate a thoracotomy or placement on the operating table. We developed a minimally invasive procedure to prepare and ligate the oesophagus thoracoscopically and perform laparoscopic gastrostomy in a rat model. In 15 operations we observed only one complication. This study implies that after adequate practice, thoracoscopic dissection of the oesophagus with ligation of a tracheo-oesophageal fistula could be performed even in every small infants.

Journal Article↗

PubMed1995

Genotypic selection of simian immunodeficiency virus in macaque infants infected transplacentally.

To understand viral and host factors that contribute to transplacental transmission of human immunodeficiency virus, we developed an animal model using pregnant female macaques infected with simian immunodeficiency virus (SIV). Pregnant females were inoculated intravenously during midgestation with either a well-characterized primary isolate of SIV (SIV/DeltaB670) or a combination of SIV/DeltaB670 and the macrophage-tropic molecular clone SIV/17E-Fr. The viral genetic diversity in five infected female macaques and their in utero-infected infants was analyzed. All of the mothers harbored a genetically diverse virus population at parturition, whereas a single genotype from the maternal quasispecies was identified in the infants at birth. Only one of two variants was found in the infants: SIV/17E-Fr (two cases) or a genotype contained within the SIV/DeltaB670 quasispecies (three cases). The macrophage-tropic properties of both transmitted genotypes were suggested by productive replication in primary rhesus macrophage cultures in vitro and the clonal presence in central nervous system tissue of infected monkeys with encephalitis. These observations provide compelling evidence for both genotypic and phenotypic selection in transplacental transmission of SIV and suggest a critical role for macrophages in fetal infection in utero.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Experimental microsporidiosis in immunocompetent and immunodeficient mice and monkeys.

Microsporidia cause opportunistic infections in AIDS patients and commonly infect laboratory animals, as well. Euthymic C57B1/6 mice experimentally infected with intraperitoneal injections of 1 x 10(6) Encephalitozoon cuniculi Levaditi, Nicolau et Schoen, 1923, Encephalitozoon hellem Didier et al., 1991, or Nosema corneum Shadduck et al., 1990 displayed no clinical signs of disease. Athymic mice, however, developed ascites and died 8-16 days after inoculation with N. corneum, 21-25 days after inoculation with E. cuniculi, and 34-37 days after inoculation with E. hellem. All athymic mice displayed hepatomegaly, dilated intestine and accumulation of ascites fluid. Granulomatous lesions are primarily located in the liver, lung, pancreas, spleen, and on serosal surfaces of abdominal organs. The murine microsporidiosis model also was used to examine immune response that inhibit microsporidia growth in vitro. Recombinant murine interferon-gamma (mIFN-gamma, 100 mu/ml) alone or in combination with lipopolysaccharide (LPS; 10 ng/ml) could activate thioglycollate-induced peritoneal murine macrophages to destroy E. cuniculi. The production of the nitrogen intermediate, NO2-, correlated with parasite destruction. Inhibition of NO2- generation by addition of the L-arginine analogue, NG-monomethyl L-arginine (NMMA), inhibited microsporidia killing, as well. Since microsporidiosis is becoming an important opportunistic infection in AIDS patients, a microsporidiosis model is being developed using SIV/DeltaB670-infected rhesus macaque monkeys (Macaca mulatta). SIV-infected immunocompetent monkeys given E. cuniculi or E. hellem per os developed specific antibodies, and microsporidia could be detected sporadically by calcofluor or antibody fluorescence staining of stool and urine sediment smears. As immunodeficiency progressed, monkeys developed diarrhoea, cachexia, and anorexia, and organisms were detected in urine and stool with greater frequency. Immunodeficient SIV-infected monkeys died approximately 27 days after receiving E. hellem by intravenous inoculation, and approximately 110 days after receiving E. hellem per os. Lesions typical for SIV-infection were observed in both groups of monkeys and microsporidia were detected in kidney and liver of the intravenously-injected monkeys. The murine microsporidiosis model provides an efficient means for studying protective immune responses to microsporidiosis, and may prove useful for screening immunological and chemotherapeutic agents. The pathogenesis of Encephalitozoon microsporidiosis in SIV-infected monkeys appears to parallel encephalitozoonosis in AIDS patients, suggesting that simian microsporidiosis may provide a useful model for evaluating diagnostic methods and therapeutic strategies during various stages of progressing immunodeficiency.

Animals↗

PubMed1993

Efficacy of (-)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine in African green monkeys infected with simian varicella virus.

(-)-9-[4-Hydroxy-2-(hydroxymethyl)butyl]guanine was evaluated for its efficacy in African green monkeys infected with simian varicella virus. Treatment by intramuscular injection was initiated 48 h after virus inoculation and was continued for 10 days; the treatment showed therapeutic effects on rash and viremia at dosages down to 1 mg/kg of body weight per day.

Acyclovir↗

PubMed1991

Evaluation of infrequent dosing regimens with (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]-cytosine (S-HPMPC) on simian varicella infection in monkeys.

(S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (S-HPMPC) was able to prevent simian varicella infection in African green monkeys inoculated intratracheally with virus. A dose of 50 mg/S-HPMPC/kg administered intravenously was shown to prevent the development of rash, reduce viremia and protect the monkeys from death. The 50 mg/kg dose was effective when treatments initiated on day 2 post-infection (p.i.) was given as ten daily doses of 5 mg/kg, as 10 mg/kg administered on five days on an alternate-day schedule, as two 25 mg/kg doses given on day 2 and on day 7 p.i., or as a single injection of 50 mg/kg on day 2. The single 50 mg/kg dose was also effective when treatment was delayed until four days p.i., but was ineffective when treatment was delayed until six days p.i. The 50 mg/kg dose was not effective when given orally by gavage. No evidence of toxicity was noted in daily clinical examinations, or in frequent hematology and clinical chemistry tests performed during the clinical evaluation of the infection.

Administration, Oral↗

PubMed1989

[General, non-medicamentous treatment of arterial hypertension].

This review focuses on the following aspects of nonpharmacological management concerning elevation of blood pressure: historical development, highlights and theses, possibilities of intervention, as well as favorable observations, advantages (in early diagnosis), disadvantages, fields of application, and integration of this form of treatment into a comprehensive strategy of hypertension control at a population level. A selection of detailed results is elaborated including: possible failure in primary classification of elevated blood pressure and its consequences, the reducibility of the hypertension problem if nonpharmacological measures are generally used, risk factor prevalences in medical and non-medical university cadres, blood pressure reduction in a spa, and hemodynamic changes induced by nonpharmacological or combined antihypertensive treatment simultaneously with drugs. Finally, reference is made to international results, as well as to the importance of the relation between diagnosing and treating blood pressure elevation concomitantly with a simultaneous management of other main risk factors that must be influenced in order to reduce the cardiac risk in hypertensives.

Adult↗

PubMed1988

Hypertension and social factors in a developing country.

A coronary heart disease prevention study, implemented in and near Havana (Cuba), evaluated the correlation of social factors with major cardiovascular risk factors, including elevations in blood pressure, in order to improve treatment strategies and compliance. The protocol consisted of questionnaires, standardized measurements of blood pressure and cholesterol determination at a central laboratory. The assessment of social aspects was carried out as previously described in comparable preventive studies in the German Democratic Republic. Around 1200 people aged 30-50 years had been screened by home visits. Correlations were found between blood pressure elevation (as well as smoking and hypercholesterolaemia, at least in part) and education, but in the opposite direction compared with experience in the United States and Europe. The prevalence of hypertension (and mean blood pressure) was higher in qualified than unqualified people (especially in younger males). Sex was a more important factor than age. No conclusion can be drawn from the variations between urban and rural subjects because the observations were not complete.

Adult↗

PubMed1987

Comparative studies in hypertension under different continental conditions.

Preventive studies were undertaken according to the same protocol (questionnaire, blood pressure and cholesterol assay standardized) integrated in the Public Health Services of the GDR and Cuba. In a German community (Cottbus-Land) 5,377 people (2,340 males/3,037 females) and in the Havana region 1,179 people (437 males/742 females), all aged 30-50 years, were followed up. The Germans revealed higher proportions of hypertension and hypercholesterolemia, the Cubans those of (heavy) smoking. Conditioning factors, such as overweight, physical inactivity and psychic stress, were found to be quite differently distributed, explaining however only in part prevalence differences between the continental regions even when both sex and localization of living were considered separately.

Adult↗

PubMed1987