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Biomedical subjects

J Metzger

Publications and source records attributed to J Metzger.

At least 109 records · Page 6Linked to original sources
PubMed1989

Interaction of the lymphoid cell line BCL1 with lipopeptide analogues of bacterial lipoprotein: electron energy loss spectroscopy (EELS) as a novel method to detect the distribution of the activator within the cells.

The lipopeptide Pam3Cys-Ser, a synthetic analogue of the N-terminal part of bacterial lipoprotein, constitutes a potent activator for B lymphocytes, monocytes/macrophages and several lymphoid cell lines. We applied the novel method of electron energy loss spectroscopy (EELS) to determine, after stimulation, the distribution of the activator within the cell compartments of the lipopeptide sensitive cell line BCL1. Our results show that the lipopeptide, 20 min after the addition to the cell culture, was found at different locations within the cell: A major amount of the mitogen was found in the plasma membrane. Remarkably, considerable amounts of the activator were also found on the cytoplasm, the nuclear membrane, and the nucleus. After 24 h, a substantial amount of the lipopeptide was still present within the cells. These findings should help to elucidate the molecular mechanism of lymphocyte stimulation by lipopeptides. The novel method of EELS, which was demonstrated here using lipopeptides as examples, constitutes a valuable tool of localizing any given compounds such as growth factors or drugs within cells.

Amino Acid Sequence↗
PubMed1989

Lipopeptide derivatives of bacterial lipoprotein constitute potent immune adjuvants combined with or covalently coupled to antigen or hapten.

Lipopeptide analogues of the N-terminus of bacterial lipoprotein consisting of N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteine (Pam3Cys) attached to one to five further amino acids [Pam3Cys-Ser-Ser-Asn-Ala, Pam3Cys-Ser-(Lys)4, Pam3Cys-Ala-Gly, and Pam3Cys-Ser] were investigated for biological activity. In vitro, the compounds proved to be potent activators for Balb/c splenocytes as determined by proliferation assays. When given in vivo in combination with SRBC, Pam3Cys-Ser and Pam3Cys-Ala-Gly acted as immunoadjuvants enhancing the antigen specific IgM response after 7, and the IgG response after 14 days. In combination with dinitrophenylated bovine serum albumin (BSA(Dnp)), especially the amphiphilic and water-soluble lipohexapeptide Pam3Cys-Ser-(Lys)4 constituted a potent immune adjuvant. The lipopeptide was able to fully replace Freund's complete adjuvant (FCS) enhancing both anti-Dnp IgM and IgG in Balb/c mice. The hapten Dnp was also coupled directly--or via the spacer molecule 1,6-diaminohexane (HMD)--to the synthetic lipopeptides. The chemically defined low-molecular-mass conjugates obtained were capable of inducing anti-hapten-specific IgM and IgG without further adjuvants or carriers. The anti-hapten responses induced by these chemically uniform lipopeptide-hapten conjugates were, however, less pronounced than the response to the conventional heterogeneous hapten-protein conjugate BSA(Dnp), and only a weak boost effect was observed. Our results show that defined lipopeptides are novel immunoadjuvants either combined with or covalently linked to antigens or haptens.

Adjuvants, Immunologic↗
PubMed1989

Induction of tumor cytotoxicity in murine bone marrow-derived macrophages by two synthetic lipopeptide analogues.

Lipoprotein from the outer membrane of Escherichia coli and the synthetically prepared lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 derived from the N-terminus of lipoprotein constitute potent macrophage and polyclonal B-lymphocyte activators. The compounds have also been shown to induce tumor cytotoxicity in murine bone marrow-derived macrophages (BMDM). Bone marrow stem cells were cultured in the presence of colony-stimulating factor 1 to yield BMDM of 98 to 99% purity at day 8. After stimulation with the lipopeptides on days 4, 6, 8 and 10 of bone marrow culture, the cytotoxic effect of BMDM on the tumor cell line L929 was determined in a [3H]thymidine release assay. Maximum tumor cytotoxicity was found on day 8 with an optimal effector/target-cell ratio of 10:1, and a duration of lipopeptide stimulation of 4 h. The supernatants of lipopeptide stimulated BMDM also showed cytotoxic activity that could be inhibited by antiserum against tumor necrosis factor alpha. The effects of the lipopeptides Pam3Cys-Ala-Gly and Pam3Cys-Ser-[Lys]4 were comparable or superior to those exerted by lipopolysaccharide. Our results demonstrate that synthetic lipopeptides are potent activators for murine BMDM and may therefore prove to be an important tool for the elucidation of the role of macrophages in the host defence mechanisms against tumor cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

[Successful separation in 1974 of craniopagus twins united at the vertex. Indications, technics, follow-up after 14 years].

On July 22, 1974, 55 days after delivery, the separation of female craniopagus twins united at the vertex was performed. This case was very similar to the case published by Voris in 1957 after separation in 1955. Surgery was decided because the neurological examination was normal in both twins, because there was no body malformation, because the angiogram as well as isotopic scintigraphy showed two normal brains, two superior sagittal sinuses and two torcular areas with a short venous union in the middle of the bone defect. In addition, Sophie and Sonia were suffering from respiratory disturbances due to their position. Surgery was easy (90 min) using the operative microscope; intubation and placing intravascular tubes for hemodynamic monitoring were difficult and lasted 4 hours. After all it took 14 years and 23 operations to complete the reconstructive surgery of the bone and skin. Cranioplasty was finally performed using vitallium plates. On their 14th birthday a neuropsychological investigation was performed with an IQ of 94 in Sophie and 76 in Sonia. Both girls are nubile and enjoy a normal school attendance.

Adolescent↗
PubMed1988

Postischemic ATP levels predict hepatic function 24 hours following ischemia in the rat.

Hepatic function was assessed by the aminopyrine breath test (ABT) in male Sprague Dawley rats 24 h after partial hepatic ischemia. ABT decreased progressively to 26.3 (p less than 0.05) and 19.7% of dose (p less than 0.05) after 90 and 120 min of ischemia, respectively. ABT at 24 h after injury was correlated to the concentration of ATP in the ischemic lobes 1 h after the onset of reperfusion (r2 = 0.971) but not to ALT activity in plasma at 1 h (r2 = 0.391). We conclude that postischemic ATP levels are a better index of subsequent hepatic function than ALT.

Adenosine Triphosphate↗
PubMed1988

Lactitol: gastrointestinal absorption and effect on blood lactate in healthy volunteers and patients with cirrhosis.

The gastrointestinal absorption of lactitol has been studied in 6 healthy volunteers and 8 patients with cirrhosis. Following administration of lactitol 0.5 g/kg, no lactitol was found in serum. The urinary excretion of lactitol over 24 h ranged from 0.1 to 1.4% of the administered dose (0.46% in cirrhotics and 0.35% in healthy volunteers). Blood D- and L-lactate and plasma glucose did not increase following lactitol. The data indicate that lactitol was poorly absorbed from the gastrointestinal tract in healthy volunteers and patients with cirrhosis, and that the disaccharide did not disturb glucose or lactate homeostasis.

Adult↗
PubMed1988

Effect of allopurinol on oxidant stress and hepatic function following ischemia and reperfusion in the rat.

Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. Therefore, the effect of allopurinol, an inhibitor of xanthine oxidase, on the oxidant stress associated with reperfusion and on hepatic function 24 h after ischemia was assessed in a model of partial hepatic ischemia in rats. The increase in circulating glutathione disulfide (GSSG) was used as an index of oxidant stress. Hepatic function was assessed using a breath test to quantitative the demethylation of aminopyrine in vivo. In control animals the plasma concentration of GSSG 1 h after onset of reperfusion increased from 0.9 mumol/l in sham-operated controls to 4.2, 5.5, and 8.0 mumol/l following 45, 90 and 120 min of ischemia, respectively. The percent of the administered dose of (dimethylamine-14C)-aminopyrine appearing in breath as 14CO2 was not significantly different from sham-operated controls (40.2%) 24 h after 45 min of ischemia (34.1%), but decreased progressively to 26.0% (p less than 0.05) and 20.6% (p less than 0.05) after 90 and 120 min of ischemia, respectively. Allopurinol, administered at a dose of 50 mg/kg 18 h and 1 h prior to ischemia, did not prevent the rise in plasma GSSG, did not alleviate the release of transaminases, and did not improve the demethylation of aminopyrine 24 h after ischemia, suggesting that reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver do not contribute significantly to ischemic injury.

Allopurinol↗
PubMed1988

Effects of plasma administration on gram negative shock in granulocytopenic dogs.

We studied the effect of an infusion of citrated plasma on the hemodynamic response and bacterial clearance of acutely septic dogs rendered severely neutropenic with cyclophosphamide. Two hours after a 5 X 10(9)/kg intravenous injection of E. coli, neutropenic control dogs infused with 20 ml/kg of normal saline became hypotensive and remained so for the next 2 hr. In contrast, the infusion of 20 ml/kg of citrated plasma after the initiation of bacteremia was followed by a significant (P less than .01) improvement in the mean arterial pressure (MAP), compared to saline-treated animals. The effect of citrated plasma administration on MAP was unrelated to bacterial clearance or to improvement in cardiac output but was associated with an increase in total peripheral resistance that was sustained for 2 hr after plasma infusion. The infusion of hyperimmune plasma from dogs previously immunized to core glycolipid antigen appeared to have no important advantage over normal plasma. At the doses of plasma that were given, a relatively higher arterial pH was the only observed significant difference (P less than .05) when immune plasma was compared to normal plasma. Resuscitation of septic neutropenic dogs with large volumes of plasma deserves further study with respect to the specific mechanisms responsible for its beneficial effect.

Agranulocytosis↗
PubMed1987

Effects of granulocytopenia on the hemodynamic responses of dogs during E. coli bacteremia.

In both neutropenic and normal dogs a significant and sustained fall in mean arterial pressure (MAP) occurred within 2 h (P less than .01) of the onset of E. coli bacteremia. The MAP remained depressed (P less than .001) in the neutropenic dogs while it increased to normal by 4 h in the control dogs. The fall in MAP was primarily related to a fall in total peripheral resistance (TPR). Although myocardial performance curves declined in both groups over the 4-h period, cardiac index (CI) and left ventricular stroke work index (LVSWI) were not significantly different from baseline in either group; nor was LV filling as assessed by the pulmonary artery wedge pressure (PAWP). No significant differences between groups were demonstrated between the mean pulmonary vascular resistance (PVR), dead space, shunt, or oncotic pressure for either group. A significant (P less than .01) percent reduction of arterial PO2 (PaO2) occurred in the neutropenic dogs. The pH of both groups fell during the course of the experiment and was significantly lower (P less than .02) in the neutropenic dogs at the termination of the study. A similar percent fall in platelet count, factor VIII, and fibrinogen levels was observed in both groups. Circulating endotoxin levels were paradoxically higher in normal animals and did not correlate with any hemodynamic alteration in either group--except that the earlier, higher endotoxin levels in the normal animals were associated with a more rapid decline in myocardial performance. However, the vasodilation of the neutropenic group was clearly related to the higher level of E. coli circulating since the concentration of E. coli in both groups at 4 h was significantly inversely correlated with the MAP (P less than .001).

Agranulocytosis↗
PubMed1987

Transfusion and long-term hemodialysis.

We analyzed the transfusion practice at a large regional renal dialysis center. More than half of all long-term dialysis patients received at least one transfusion annually, and the average transfused patient received 10 U of blood. A review of data on 318 dialysis patients over one year showed there is a sizable group (15.0%) who require greater than ten transfusions of blood. This group of intensely transfused dialysis (ITD) patients account for a disproportionate 67% of all units transfused. The majority of these patients (73%) were women, which may have been related to the relatively small proportion (12.5%) of women undergoing dialysis who were treated with synthetic androgens. These ITD patients were older and underwent dialysis longer than others in the population studied. One year mortality in the ITD group was 27%; more than twice that of the entire group (12.8%). A retrospective examination of transfusion practice in the five years preceding the present study showed that the number of transfusion recipients was essentially a constant fraction of the dialysis population. However, there was a significant trend to less intense transfusion of each transfused patient. Most of the ITD group had significant iron overload, and attending physicians indicated that concern about transfusion related hemosiderosis outranked other reasons including acquired immunodeficiency syndrome, that would account for the more conservative transfusion practice of recent years.

Blood Transfusion↗
PubMed1986

Aneurysm of the circle of Willis. Comparison between computed tomography and angiography.

The authors report their experience in 13 patients with unruptured non-giant aneurysms diagnosed at computed tomography (CT), who were without clinical deficits but who complained of chronic headache or cranial nerve palsy and had other members in their families with a cerebral vascular malformation. Screening with contrast-enhanced CT is discussed with respect to certain social groups. Surgical management before rupture of aneurysms could be envisaged in view of the bad prognosis when rupture has occurred.

Cerebral Angiography↗