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Biomedical subjects

F Hartmann

Publications and source records attributed to F Hartmann.

At least 73 records · Page 4Linked to original sources
PubMed1994

Cure of xenografted human tumors by bispecific monoclonal antibodies and human T cells.

Tumor immunotherapy should increase both the number of T cells that kill the tumor and the likelihood that those cells are activated at the tumor site. Bispecific monoclonal antibodies (Bi-mAbs) were designed that bound to a Hodgkin's tumor-associated antigen (CD30) on the tumor and to either CD3 or CD28 on the T cell. Immunodeficient mice were cured of established human tumors when mice were treated with both the CD3-CD30 and the CD28-CD30 Bi-mAbs and then given human peripheral blood lymphocytes that had been incubated with the CD3-CD30 Bi-mAb and cells that expressed CD30. The enrichment of human T cells within the tumor and the fact that established tumors can be cured may indicate in situ activation of both the T cell receptor and the costimulatory pathway.

Animals↗
PubMed1994

Administration of vancomycin for treatment of ascending bacterial cholangiohepatitis in a cat.

A 12-year-old neutered male domestic shorthair cat, being treated with methimazole for hyperthyroidism, developed chronic cholangitis with portal fibrosis and chronic cholecystitis. The common bile duct was not patent, which necessitated cholecystojejunostomy. Four days after surgery, the cat developed suppurative cholangio-hepatitis caused by a beta-lactam resistant Enterococcus. The cat's condition was further complicated by the concurrent development of hypokalemic polymyopathy. On the basis of minimum inhibitory concentrations, the Enterococcus was determined to be susceptible to vancomycin and resistant to numerous antibiotics commonly used for treatment of infections caused by Enterococcus spp. The cat recovered without evidence of adverse effects attributable to vancomycin.

Animals↗
PubMed1994

Recognition of HLA-A1 by murine monoclonal antibodies.

Balb/c mice were immunized with cells from the mouse mastocytoma line P815 transfected with an HLA-A1 gene. The splenocytes of the immunized mice were fused with cells from the murine myeloma NS-1. In an initial screening, supernatants of growing cultures were tested for their binding capacity to the immunizing P815/A1+ cells as well as to P815/A2+ cells. Three out of 756 hybrids produced antibodies which bound to P815/A1+ cells only. They were cloned and further analyzed for their binding reactivity to reference B-lymphoblastoid cells from the Tenth International Histocompatibility Workshop. One monoclonal antibody, designated 6B11, reacted only with HLA-A1+ cells, while the two other antibodies, 3G3 and 7F10, appeared to detect antigenic determinants shared by HLA-A1, A3, A11, A26, and A30 (3G3) and by HLA-A1, A3, A11, A26, A28 and A30 (7F10). Flow cytometric studies on B-lymphoblastoid cell lines as well as on a series of tumor cell lines, including melanoma and colon carcinoma lines, confirmed the specificity of these antibodies. Monoclonal antibodies 7F10 and 6B11 were found to be of the IgM class and 3G3 of the IgG1 class. By complement-dependent 51Cr release experiments it was further shown that the two IgM antibodies 7F10 and 6B11 were able to lyse all cell lines of the HLA-A1 haplotype tested.

Animals↗
PubMed1994

Lactulose or paromomycin do not affect ammonia generation in the isolated perfused rat small intestine.

It has been hypothesized that the beneficial effect on hepatic encephalopathy of lactulose or neomycin might be exerted by their effect on intermediary glutamine metabolism and ammonia generation within enterocytes. We examined glutamine consumption and the production of alanine and ammonia (net substrate exchange in nmol min-1 g-1) in isolated vascularly and luminally perfused small intestine from rats with and without pretreatment with lactulose (2.0 g/kg) or paromomycin (60 mg/kg). Without pretreatment, 50 mM lactulose or 1 mM paromomycin were equally ineffective to significantly reduce the consumption of arterial glutamine (-92 +/- 5 vs. -80 +/- 6 vs. -71 +/- 6 for controls, lactulose, or paromomycin; mean +/- SEM, n = 6 each, n.s. by analysis of variance), and the production of alanine (41 +/- 3 vs. 44 +/- 3 vs. 61 +/- 7, n.s.) or ammonia (42 +/- 6 vs. 42 +/- 6 vs. 38 +/- 6, n.s.). Similarly, glutamine utilisation, and the release of alanine and ammonia were not different after pretreatment for 10 days. Also, both agents did not reduce glutamine absorption from the lumen (-170 +/- 9 vs. -171 +/- 6 vs. -219 +/- 25, n = 5 each) or the concomitant vascular release of metabolic products alanine (92 +/- 7 vs. 78 +/- 10 vs. 77 +/- 10 vs. 77 +/- 7, n.s.) and ammonia (73 +/- 6 vs. 69 +/- 7 vs. 65 +/- 8, n.s.). Our results do not support the hypothesis, that lactulose or paromomycin reduce ammonia generation by small intestinal mucosa through a specific effect on intermediary glutamine metabolism.

Amino Acids↗
PubMed1993

Non-amine based analogues of lavendustin A as protein-tyrosine kinase inhibitors.

The fermentation product lavendustin A (1) is a protein-tyrosine kinase (PTK) inhibitor whose active pharmacophore has previously been shown to reside in the more simplified salicyl-containing benzylamine 2. Amine 2 bears some structural resemblance to two other natural product PTK inhibitors, erbstatin (3) and piceatannol (4). Non-amine containing analogues of 2 were therefore synthesized which incorporated additional aspects of either erbstatin or piceatannol. Examination of these inhibitors in immunoprecipitated p56lck, epidermal growth factor receptor (EGFR), and c-erb B-2/HER 2/neu PTK preparations showed that compound 12 (IC50 = 60 nM) was one of the most potent p56lck inhibitors reported to date. These results demonstrate that nitrogen is not an essential component of the lavendustin A pharmacophore 2 and that 1,2-diarylethanes and -ethenes bearing a salicyl moiety appear to be valuable structural motifs for the construction of extremely potent PTK inhibitors.

ErbB Receptors↗
PubMed1993

Inter-organ communication between intestine and liver in vivo and in vitro.

The maintenance of body homeostasis requires a finely tuned system of interorgan communication. The intimate metabolic interrelation between intestine and liver is characterized by the unique anatomic position of both tissues using the portal vein as a private channel with the pancreas in optimal position to modulate hepatic metabolism. Gut-derived peptides (such as glucagon-like peptide-1) appear to be involved in the process of liver regeneration by regulating the release of pancreatic hormones (e.g. insulin). Extensive bowel resection or functional exclusion of small intestine may lead to severe liver dysfunction and even cirrhosis, which may be due to the lack of some intestine-derived and as yet unknown factor(s). Here a close cooperation between small intestinal mucosa and hepatocytes is demonstrated leading to the concept of a metabolic gut-liver unit. This metabolic interaction forms a wide spectrum ranging from the secretion of peptide hormones to changes in (portal-venous) substrate availability or hepatocyte cell volume. Further investigation and identification of the mechanisms of such regulatory processes may be facilitated by combined perfusion of isolated rat intestine and liver. Using this in vitro approach we could demonstrate the presence of metabolic interorgan communication between isolated perfused tissues independent of plasma borne hormones or extrinsic neural control.

Animals↗
PubMed1993

[Social medicine: why--how--what for? (Social medicine and anthropology)].

The speech held on the occasion of the Salomon Neumann Medal Award 1992 describes with biographical pointers how an internistic clinician (for outpatients) developed towards taking up social medicine as his specialty. The starting point was the management and care of patients suffering from chronic diseases. This was an important step in the direction towards "successful conditional healthiness". The conditions included in the concept are both of a personal and of a sociological nature, i.e. shared by many. They are dealt with by social medicine and also by medical sociology, the separation of which constituted an painful disappointment. Arguments against a dichotomy of social medicine and medical sociology are also supplied by looking back on the history of ideas with emphasis on ancient dietetics and ecology, the early Age of Enlightenment (Leibniz) and the 19th century (Virchow, Neumann). It is suggested to create an active link between social medicine as the overriding concept and epidemiology, social hygiene and medical sociology as subsumptions.

Anthropology↗
PubMed1992

In vivo validation of image-directed Doppler measurement of superior mesenteric artery blood flow.

Image-directed Doppler measurement of superior mesenteric artery blood flow in volunteers was validated in two artificial models with either a venous or an arterial flow profile. In the "venous" model, the Doppler device overestimated the real flow velocity by 86 +/- 7%, and in the "arterial" model by 24 +/- 9%. The areas under the time-frequency curves (AUCs) from the arterial model were measured by planimetry. A correction factor of 1.47 between flow velocities calculated after planimetry and real flow was established. Correction for this factor resulted in a flow velocity of 19.5 +/- 4.7 cm/s and a blood flow rate of 377 +/- 166 ml/min in the volunteers.

Adult↗
PubMed1992

Nitrogen absorption from isonitrogenous solutions of L-leucyl-L-leucine and L-leucine: a study in the isolated perfused rat small intestine.

1. We assessed the efficacy of nitrogen absorption from luminal L-leucine (1.2 and 12 mmol/l) and from isonitrogenous L-leucyl-L-leucine (0.6 and 6.0 mmol/l) in a preparation of vascularly and luminally perfused rat small intestine by measuring luminal leucyl-leucine disappearance and venous leucine appearance. 2. No intact dipeptide was found in the vascular perfusate. Leucine-nitrogen absorption, as judged by venous leucine appearance, was as efficient from free leucine (29 +/- 3 and 245 +/- 19 ng-atom min-1 g-1) as from leucyl-leucine (27 +/- 4 and 211 +/- 58 ng-atom min-1 g-1). It was not reduced in the presence of glycyl-L-proline or of the brush-border dipeptidase inhibitors alanine-beta-naphthylamide and cilastatin. 3. After one passage of the whole small intestine, only trace amounts of dipeptide, but large amounts of free leucine, were detected in the luminal effluent. Peptidase activity in the luminal effluent was demonstrated in 100,000 g supernatant and was inhibited by p-hydroxy-mercuribenzoate, but not by brush-border dipeptidase inhibitors. 4. We propose that nitrogen absorption from luminal leucyl-leucine may proceed predominantly via intraluminal peptide hydrolysis and subsequent transport of free leucine. Nevertheless, our findings and conclusions are at variance with previous observations and current opinion on intestinal handling of dipeptides, which may be due, in part, to the different methodological approach.

Animals↗
PubMed1992

Microbic superinfection in relapse of inflammatory bowel disease.

To assess the association between symptomatic relapse of inflammatory bowel disease (IBD) and superinfection with enteropathogenic microorganisms, we determined prospectively the incidence of infections with enteropathogenic bacteria, protozoa, and helminths in patients with confirmed longstanding IBD. Sixty-four patients with IBD (49 with Crohn's disease [CD] and 15 with ulcerative colitis [UC]) were consecutively enrolled in the study when relapse occurred. Multiple biopsies for histological and microbiological investigations were taken from all patients who were evaluated by colonoscopy. Parallel stool specimens were investigated for the presence of enteropathogenic bacteria, protozoa, and helminths. In six patients, we detected Clostridium difficile or toxin B (five CD, one UC), in one patient Campylobacter jejuni (CD), and in another patient Salmonella typhimurium (UC). Enteropathogenic Escherichia coli were isolated from three patients. Investigation of biopsies for Mycobacteria, microscopic examination of stool samples for helminths, and immunofluorescence for chlamydia were negative in all patients. In summary, as we found enteropathogenic microorganisms so infrequently in patients with relapse of IBD, despite intensive microbiological screening by tissue sampling for detection of gut adherent bacteria, we believe that microorganisms play only a minor role in the exacerbation of IBD.

Adult↗
PubMed1991

Serratia infections in patients with neutropenia.

We report on six cases of sepsis caused by Serratia marcescens in patients with neutropenia. Four cases showed an additional involvement of the upper respiratory and digestive tract with oral and pharyngeal mucositis, haemorrhagic laryngo-tracheo-bronchitis, and oedematous swelling of the face. One patient showed a Serratia marcescens carrier state in the pharynx over a period of months without neutropenia. The isolated strains showed a broad spectrum of resistance against antibiotics; only aztreonam and amikacin were effective in vitro against all isolates.

Adolescent↗
PubMed1991

Use of an artificial oxygen carrier in isolated rat liver perfusion: first demonstration of net glucose uptake at physiological portal glucose concentrations using a hemoglobin-free perfusate.

A defect in isolated perfused rat-liver (IPRL) preparations has been proposed to explain discrepancies between in vivo and in vitro findings regarding hepatic glucose metabolism. The aim of the present study was to investigate whether a preparation of IPRL using a synthetic hemoglobin-free perfusate was capable of net glucose uptake and glycogen deposition at physiological portal substrate concentrations. Livers from fed anaesthetized rats were perfused in a recirculating system using a fluorocarbon emulsion as artificial oxygen carrier. Depending on the prevailing glucose concentration, livers exhibited net glucose uptake or release with a threshold value of 5.5-6.0 mM glucose. Net glucose uptake was associated with net glycogen deposition (+0.23 to +0.59 mumol C6 min-1 g-1). From 5.8 mM (n = 3) and 10.0 mM (n = 8), initial concentration glucose levels fell to 5.3 +/- 0.2 mM after 210 min (n = 3) and 6.3 +/- 0.9 mM after 120 min (n = 8), respectively. This was equivalent to a net glucose uptake of -0.16 and -0.45 mumol min-1 g-1. Anoxia reversibly switched hepatic glucose balance from net uptake (-0.42 mumol min-1 g-1) to release (+0.69 mumol min-1 g-1) followed by net uptake (-0.50 mumol min-1 g-1) after reinstitution of aerobic conditions. We conclude that the composition of perfusion media might play a pivotal role for studies of glucose metabolism in the isolated perfused rat liver. In our experimental model, using a hemoglobin-free synthetic medium, net glucose uptake was readily demonstrated at physiological portal substrate concentrations similar to the in vivo situation.

Aerobiosis↗
PubMed1991

Effects of dexamethasone on glutamine metabolism in the isolated vascularly perfused rat small intestine.

Post-stress metabolism is associated with a large glutamine (Gln) efflux from muscle and an increased Gln utilization by the small intestine. Both appear to be modulated by corticosteroids. The present investigation was performed to better characterize the mechanism of corticoid action on Gln metabolism in an isolated preparation of vascularly perfused rat small intestine. In all perfusions, a synthetic perfusate free from blood components was used with only 0.6 mM Gln and 10 mM glucose as substrates. Irrespective of dexamethasone concentrations in the vascular perfusate (none, 0.25 mg l-1, or 2.5 mg l-1, isolated intestines from normal rats exhibited unchanged extraction rates of Gln (-85 +/- 8, -89 +/- 10, and -87 +/- 16 nmol min-1 g-1) and unchanged production rates of alanine (43 +/- 9, 40 +/- 7, and 51 +/- 5 nmol min-1 g-1) and ammonia (49 +/- 15, 45 +/- 13, and 54 +/- 13 nmol min-1 g-1). Similarly, when intestines were vascularly perfused 2 or 9 days after dexamethasone injection (0.45 mg kg-1 BW), net Gln uptake also remained unchanged (-88 +/- 16 and -84 +/- 11 nmol min-1 g-1). There was, however, a shift in nitrogenous products of Gln metabolism from ammonia (-31% and -38%) to alanine (+16% and +64%). Thus, the failure of dexamethasone to increase Gln uptake in the isolated rat intestine may indicate that rather than acting directly on the mucosa, dexamethasone could regulate intestinal Gln consumption in vivo by indirect mechanisms possibly involving extramucosal tissues. Dexamethasone pretreatment may modulate the pattern of nitrogenous products in portal venous blood presented to the liver and thus support enhanced nitrogen loss through ureagenesis by metabolic cooperation between gut and liver.

Alanine↗