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Biomedical subjects

J Kuhn

Publications and source records attributed to J Kuhn.

At least 109 records · Page 6Linked to original sources
PubMed1987

Factors affecting outcome of coronary reperfusion with intracoronary streptokinase in acute myocardial infarction.

Aggressive interventional therapy in acute myocardial infarction (AMI) is expensive, time-consuming and not without significant risk. To determine which patients are most likely to benefit from such therapy, the effects of patient age, reperfusion success, admission left ventricular (LV) function, infarct location, admission clinical class, time from onset of pain to reperfusion and admission electrocardiographic findings on the outcome of coronary reperfusion in AMI were assessed in 292 prospectively studied, sequential patients from August 1980 to January 1984. Two hundred ten patients received intracoronary streptokinase (SK) therapy on admission and 82 patients, who either refused the protocol or met exclusion criteria, served as control subjects. Patients older than 65 years showed little improvement in 1-year mortality risk and no significant improvement in LV function during hospitalization after treatment with intracoronary SK. The remaining patients, 178 treated with SK and 48 control, were well matched and served as the basis for further comparisons. In this subgroup of patients, reperfusion success was associated with improved survival and LV function (mortality rate 3%, vs 17% in control subjects; increase in ejection fraction [EF] 18% vs 4%). Patients with an EF of less than 45% on admission showed a 21 +/- 30% increase in EF, compared with an increase in control subjects of 8 +/- 19%, and a lower 1-year mortality rate than controls (6% vs 21%, p = 0.01). Patients with anterior AMI had a significant increase in EF in the SK group (22 +/- 31%) and lower mortality compared with control subjects (5% vs 25%, p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Use of bacterial luciferase to establish a promoter probe vehicle capable of nondestructive real-time analysis of gene expression in Bacillus spp.

We report the construction and use of a new promoter probe vehicle capable of allowing extremely sensitive measurements of transcriptional activity promoted from random, chromosomal DNA fragment inserts. Coupled with the advantage of sensitivity, the detection system is noninvasive, nondestructive, and provides real-time reportage of expression potential. These latter aspects make it an especially valuable system for a continuing analysis of the complex transcriptional regulation patterns now recognized as a dominant control feature during the differentiation and morphogenesis characteristic of the sporulation cycle in Bacillus species. In this respect we describe the isolation of DNA fragments from B. megaterium and B. subtilis capable of initiating transcription in both the respective parent organisms and, in certain instances, also in Escherichia coli. Detailed luminescence studies showed that several promoter regions which are entirely or substantially developmentally controlled were isolated.

Bacillus↗
PubMed1987

Characterization of Vibrio fischeri rRNA operons and subcloning of a ribosomal DNA promoter.

Analysis of rRNA genes in Vibrio fischeri indicates the presence of eight rRNA gene sets in this organism. It was found that the genes for 5S rRNA, 16S rRNA, and 23S rRNA are organized in operons in the following order: 5' end 16S rRNA 23S RNA 5S rRNA 3' end. Although the operons are homologous, they are not identical with regard to cleavage sites for various restriction endonucleases. A DNA library was constructed, and three ribosomal DNA clones were obtained. One of these clones contained an entire rRNA operon and was used as a source for subcloning. The promoter region which leads to plasmid instability was successfully subcloned into pHG165. The terminator region was subcloned into pBR322.

Chromosome Mapping↗
PubMed1986

Autoimmunity induced by HgCl2 in Brown-Norway rats. I. Production of monoclonal antibodies.

Mercuric chloride (HgCl2) induces in Brown-Norway rats (BN) a B cell polyclonal activation resulting in autoimmune disease. Spleen cells from BN rats injected with HgCl2 were fused with IR983F, a nonsecreting rat myeloma cell line, in order to obtain monoclonal antibodies reacting with autoantigens or IgE-producing hybridomas. After screening for immunoglobulin-producing clones, we found 5% clones with anti-tissue activity, 8% with anti-TNP activity, and 41% secreting IgE. Among the anti-tissue monoclonal antibodies, one recognizes both TNP and mesangial structures of rat normal glomeruli, which could be an as yet unrecognized mechanism of nephrotoxicity. These experiments 1) confirm that HgCl2 induces polyclonal activation, 2) show that the mercury model is of interest to obtain monoclonal IgE and various autoantibodies, and 3) suggest a new possible mechanism of antibody-mediated renal injury.

Animals↗
PubMed1986

Autoimmunity induced by HgCl2 in Brown-Norway rats. II. Monoclonal antibodies sharing specificities and idiotypes with mouse natural monoclonal antibodies.

Spleen cells derived from BN rats receiving HgCl2 were fused with the nonsecreting rat myeloma cell line IR983F. We screened 59 supernatants from immunoglobulin-secreting hybrids for antibody activity against actin, tubulin, autologous and heterologous myosin, myoglobin, dsDNA, peroxidase, and the haptens TNP, NIP, NNP, and NBrP. Six monoclonal antibodies (mAb) were found to react with antigen(s) of the panel. At least three groups of antibody specificities were identified: clones reacting with TNP (1 IgM, 1 IgE); clones reacting with horseradish peroxidase (1 IgM); and clones possessing widespread reactivity for several antigens as found for mouse natural autoantibodies (2 IgM, 1 IgE). We also analyzed the idiotypic (Id) determinants of the 59 mAb by using anti-Id antibodies described elsewhere prepared in rabbits against the BALB/c D23 natural monoclonal autoantibody and recognizing a BALB/c recurrent Id (Id D23) of natural polyspecific autoantibodies. We found that all rat mAb that possessed widespread reactivities bore this Id. We performed similar studies in sera from normal and mercury-stimulated rats. The results indicate a role for HgCl2 in the stimulation of natural antibodies producing cells and the existence of interspecies cross-reactive Id among mouse and rat natural antibodies.

Animals↗
PubMed1986

pHG165: a pBR322 copy number derivative of pUC8 for cloning and expression.

During the construction of the Messing pUC plasmid series, the rop(rom) gene of pBR322 which mediates the activity of RNAI was deleted. This has resulted in an elevated copy number for the pUC plasmids which makes the expression of beta-galactosidase activity constitutive in a host containing the Iqtss lac repressor. We describe the construction of a new series of vectors which retain the pUC multiple cloning site (MCS) but in which copy number control has been recovered. In addition, the lac alpha/lac promoter expression region has been inserted into a HpaI cassette. This facilitates the movement of recombinant DNA clones within the MCS. It also increases the complementation activity of the lac alpha peptide by an order of magnitude, allowing selection of recombinants by their Lac- phenotype on MacConkey agar.

Bacterial Proteins↗
PubMed1986

pHG276: a multiple cloning site pBR322 copy number vector expressing a functional lac alpha peptide from the bacteriophage lambda PR promoter.

The bacteriophage lambda early promoter PR has been used to direct the synthesis of lac alpha in a plasmid containing the multiple cloning site of pUC8. The copy number of the plasmid is controlled by the rop(rom) gene and the plasmid incorporates the cI857 gene for temperature regulation of lac alpha expression. Isolation of recombinant derivatives with DNA inserts in the multiple cloning region can be identified by insertional inactivation of lac alpha and consequently, a Lac- phenotype in a host carrying the M15 deletion of lac. The potential of pHG276 as a fully regulated expression vector is examined.

Bacteriophage lambda↗
PubMed1984

Electron-microscopic immunohistochemical study of the localization of immunoglobulin G in the choroid plexus of the rat.

The localization of autologous antiperoxidase immunoglobulin G (IgG) was studied in the choroid plexus of Lewis rats immunized against horseradish peroxidase (HRP). This experiment was performed to study the permeability of the choroid plexus to intravascular IgG. It was shown that autologous IgG was present in the extravascular spaces. The transendothelial transfer appeared to occur mainly via the fenestrations and some interendothelial junctions. No transfer of IgG at the level of epithelial cells toward the cerebrospinal fluid was demonstrated. Interstitial spaces in contact with the connective-tissue cells of the choroid stroma were strongly labeled. The significance of these spaces remains hypothetical and raises the question of the fate of IgG from the interstitial space.

Animals↗
PubMed1984

IgG Fc membrane receptor on normal human glomerular visceral epithelial cells.

This study demonstrates that human glomerular epithelial cells are able to bind heat aggregated immunoglobulins and antigen-antibody complexes. This has been observed on kidney cryostat sections, on whole glomeruli and on cultured visceral epithelial cells. Binding depends on the presence of the Fc portion of IgG and occurs in the absence of complement, showing that the IgG Fc receptor is different from the C3b receptor. The use of heat aggregated anti-peroxidase IgG and of peroxidase anti-peroxidase complexes allowed us to demonstrate, at the ultrastructural level, that the binding of the reagents at the plasma membrane was followed by their internalization within coated pits of vesicles. These observations strongly suggest that glomerular visceral epithelial cells are capable of receptor mediated endocytosis. The role of this process in glomerular diseases remains to be established.

Antigen-Antibody Complex↗
PubMed1984

Phase I clinical investigation of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887), a new purine antimetabolite.

9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887) is a new purine antimetabolite that has been evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. infusion over a period of 30 min once each day for 5 consecutive days, repeated at 4-week intervals. Thirteen patients received 30 courses of the drug in a dose range of 18 to 40 mg/sq m/day. Granulocytopenia and thrombocytopenia were dose limiting. Repeated courses produced similar degrees of granulocytopenia, but in 7 of 7 patients receiving 2 or more courses, the degree of thrombocytopenia was less severe during the first than during subsequent courses. Myelosuppression in humans was more severe than predicted from the mouse model. Lymphopenia was profound at all dose levels, but reversed within 3 weeks. Somnolence occurred during infusion in 8 of 13 patients, but quickly cleared after the infusion was completed. The infused drug was rapidly dephosphorylated in plasma and then cleared so there was no cumulation of drug in plasma when it was rapidly infused once each day in these doses. Phase II studies of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate are planned at a starting dose of 18 mg/ sq m/day for patients with prior chemotherapy or radiotherapy and 25 mg/sq m/day for those without prior therapy, as a single dose on each of 5 consecutive days repeated at 21- to 28-day intervals.

Adenocarcinoma↗
PubMed1983

Phase I investigation of ametantrone.

Ametantrone is the third of a family of anthracene derivatives to undergo a phase I trial in man. Sixteen patients received 33 courses of drug as a single iv dose given every 3 weeks. Escalations proceeded from 120 to 180 mg/m2. Predictable and reversible leukopenia was the dose-limiting toxic effect. Four patients developed thrombocytopenia. Nonhematologic toxic effects included a marked cumulative blue discoloration of the skin seen in all patients receiving more than three courses of the drug. This cumulative cosmetic effect may also be dose-limiting. Other nonhematologic toxic effects included: blue urine (all patients), nausea (two), vomiting (one), a blue stool (one), and reversible elevations of either SGOT or alkaline phosphatase (two). No objective responses were seen in this study. A dose of 140-160 mg/m2 is recommended as the starting dose for phase II trials in patients who have received prior chemotherapy or radiotherapy.

Aged↗
PubMed1982

Permeability of the blood-air barrier to antiperoxidase antibodies and their fragments in the normal rat lung.

The permeability of the blood-air barrier to antiperoxidase (HRP) IgG antibodies (160,000 daltons), F(ab')2 fragments (100,000 daltons) and Fab fragments (50,000 daltons) was studied in the normal rat. The use of isologous and heterologous immunoglobulin G or IgG fragments injected intravenously allowed a sequential study. It was shown that these proteins transfer from the vascular bed towards to interstitium. Evidence was obtained that these proteins crossed the endothelium through interendothelial spaces or structures suggesting transendothelial channels. The alveolar epithelium was found to be an efficient barrier for heterologous and isologous proteins, raising the question of the origin of serum proteins found in the alveolar surface material. Heterologous anti-HRP IgG antibodies and their Fab fragments were also administered intraalveolarly. The alveolar epithelium was found permeable to Fab fragments but not to IgG molecules, suggesting that some serum proteins present in the alveolar lining fluid can be transepithelially reabsorbed.

Animals↗
PubMed1982

Trapping of circulating proteins in immune deposits of Heymann nephritis.

The renal distribution of autologous and heterologous albumin and IgG was studied by electron microscopy using peroxidase-labeled conjugates in rats with Heymann nephritis. In addition, the renal distribution of autologous and heterologous antiperoxidase IgG and their F(ab')2 and Fab fragments was detected using peroxidase alone. All of these proteins crossed the glomerular lamina densa and passed into the urinary space by an extracellular pathway through the epithelial slits and the sites of epithelial detachment. The proteins were trapped in subepithelial immune deposits irrespective of the degree of proteinuria and regardless of the molecular weight, the autologous or heterologous origin, and the electric charges of the protein studied. The trapping was transient and easily reversed. These findings suggest that circulating proteins are able to modify the composition of immune deposits, thereby altering the course of immune complex disease.

Animals↗