Search PubMed⌕ Search

Biomedical subjects

J Kuhn

Publications and source records attributed to J Kuhn.

At least 127 records · Page 7Linked to original sources
PubMed1982

Phagocytosis of heat-aggregated immunoglobulins by mesangial cells: an immunoperoxidase and acid phosphatase study.

It has been demonstrated previously that mesangial cells (MC) phagocytose particulate material and nonimmune proteins, but that cells are able to engulf aggregated immunoglobulins (Igs) has not been proven so far. To investigate this cell function, heat-aggregated antiperoxidase (HRP) Igs were injected intravenously into Lewis rats. Sequential immunoelectron microscopic studies revealed that the injected material accumulates progressively in the extracellular compartment from 10 minutes to 5 hours and disappear afterward. This disappearance was related in part to the incorporation of aggregated anti-HRP Igs within phagosomes and phagolysosomes by MC. Quantitation of the phagocytic process showed that it starts as early as 10 minutes after injection and reaches its peak at 2.5 hours. Endocytosis seems to be associated with the sequestration of injected Igs within large cytoplasmic invaginations and with micropinocytosis. To further support these observations, ultrastructural cytochemistry for acid phosphatase activity was performed. Quantitative studies showed that the number of acid phosphatase-labeled lysosomes in MC was up to 7-fold greater in rats receiving aggregated anti-HRP Igs than in noninjected ones. In conclusion, our combined immunoperoxidase and acid phosphatase studies show that MC possess a vacuolar (lysosomal) apparatus capable of handling heat-aggregated Igs. Whether these cells are also operational in the disposal of soluble immune complexes in spontaneous and experimental conditions remains to be proven. In addition, observations suggesting the drainage of macromolecules from mesangium to the juxtaglomerular apparatus and from mesangium to the urinary space are presented.

Acid Phosphatase↗
PubMed1982

Immune complex-mediated lung injury produced by horseradish peroxidase (HRP) and anti-HRP antibodies in rats.

Horseradish peroxidase (HRP) was administered intratracheally to rats with circulating autologous or heterologous anti-HRP antibodies. Intrapulmonary immune complexes containing HRP, anti-HRP antibodies, but no C3, were detected by immunofluorescence from 1 hour to 48 hours with a maximum of 6 hours after antigenic challenge. The concomitant hemorrhagic alveolitis characterized by fibrin deposits and infiltration by polymorphs and macrophages was also maximal after 6 hours. At the ultrastructural level, HRP was easily detected, and HRP-containing immune deposits were demonstrated along the basement membrane in subepithelial and subendothelial localization and in interstitial spaces. These findings suggest a C3 independent mechanism for lung injury mediated by immune complexes formed in situ.

Animals↗
PubMed1982

Detection of human Bhanja virus-specific antibodies in Czechoslovakia.

Blood sera from 185 Czechoslovak citizens, residents of South-Moravia (Znojmo district: 107, Breclav district: 13) and East-Slovakia (Roznava district: 65) regions, were examined for the presence of neutralizing antibodies to Bhanja arbovirus, using PS and Vero cell lines, constant dose of virus and serial serum dilutions. Specific antibody titres greater than or equal to 1:10 were detected in the sera of 10 persons (i.e. 5.4% of all examined), of which 5 men and 4 women were from district of Roznava (13.8% of all examinees in this district) and 1 woman (forest worker) was from district of Znojmo (0.9% of all examinees in this district), but she could not be excluded to get infected while staying abroad (USSR) for a certain period prior to examination. Striking prevalence of seropositivity among the inhabitants of the Roznava district is apparently linked with two circumstances: this area is infested with Haemaphysalis punctata and Dermacentor marginatus ticks (Bhanja virus vector) and all the seroapositive subjects there in contact with goats and sheep. Detection of the human Bhanja virus-specific antibodies is the first one made on the territory of Czechoslovakia; linked with the previously reported seropositivity of goats and sheep in this area it indicates the presence of this arbovirus in the East-Slovakia region.

Adult↗
PubMed1981

Immunoenzymatic study of the protein pathway through the glomerular barrier in rat glomerulonephritides.

Circulating anti-horseradish peroxidase (HRP) IgG antibodies were used in the rat to study the glomerular leakage of proteins in glomerulonephritis (GN) induced by aminonucleoside (AN) and in glomerulonephritis induced by mercuric chloride to produce anti-glomerular basement membrane (GBM) antibodies. In ANGN, autologous albumin and fibrinogen were also detected by immunoperoxidase techniques. In both types of GN, the proteins studied were observed in the glomerular urinary space and proximal tubular cells. No channels were visible in the lamina densa. No accumulation of proteins was seen under the epithelial slits that were not closed. In ANGN, accumulation of proteins was observed in the subepithelial space where the podocytes act as a barrier (closed slits, subepithelial blind pockets, areas covered by broad sheets of cytoplasm), but no accumulation was seen in the lamina rara externa under normal or enlarged slits and areas of large epithelial cytoplasm detachment. Statistical analysis showed that in ANGN, at the time of maximal proteinuria, the number of "micropinocytotic" vesicles in the GBM-embedded part of podocytes was not increased as compared with controls. Such vesicles were not labeled. We conclude that in both types of GN, the permeability of the GBM is diffusely increased and that the plasma proteins pass into the urinary space via an extracellular pathway.

Animals↗
PubMed1981

Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942).

9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942) is a new anthracene bishydrazone derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection repeated at 4-week intervals. Twenty-eight patients received a total of 61 courses of the drug in a dose range of 20 to 280 mg/sq m. Leukopenia was the dose-limiting toxicity. It was of short duration and reversible. A drug-induced hypotension was noted at higher doses in three patients. The hypotension was not dose limiting, it was reversible, and it could largely be avoided by prolonging the drug infusion time to 1 hr. One patient with unsuspected severe coronary artery disease died of complications of myocardial infarction subsequent to a hypotensive episode. Significant phlebitis was also noted at higher doses of drug. This degree of phlebitis could be lessened by diluting the drug in larger volumes of fluid. Three patients experienced diaphoresis, nausea, palpitations, and chest discomfort at the conclusion of the infusions. None of the patients had electrocardiographic changes. Mild fever, alopecia, and nausea and vomiting were noted occasionally. One patient with a hypernephroma and one patient with hepatocellular carcinoma experienced partial responses of their tumors secondary to the drug. Phase II studies of CL216,942 are planned at a starting dose of 260 mg/sq m as a single dose repeated at 21- to 28-day intervals.

Adult↗
PubMed1980

[Results of long-term therapy in hypertension].

Two groups of patients with hypertension ( n = 16 and 20) with comparable average age and degree of severity of clinical hypertension were controlled in an ambulatory long-term investigation for 18 months. While one group was treated with an antihypertensive standard therapy, the other group got a fixed combination of dihydralazin and propranolol. In both groups a significant decrease of the systolic and diastolic initial blood pressure was seen, which was more pronounced in the second group. Side-effects of drugs more frequently appeared in the first group. On the other hand, the total cost were higher in the second group. Nevertheless, the stronger effect, the smaller number of tablets as well as the lower rates of side-effects pleads for the combination dihydralazin-propranolol.

Blood Pressure↗
PubMed1980

Phase I clinical investigation of 1,4-dihydroxy-5,8-bis (( (2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride (NSC 301739), a new anthracenedione.

1,4-Dihydroxy-5,8-bis(( (2-[(2-hydroxyethyl)amino]ethyl)-amino))-9,10-anthracenedione dihydrochloride is a new anthracenedione derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection, repeated at 4-week intervals. Twenty-five patients received a total of 41 courses of the drug in a dose range of 1.2 to 14 mg/sq m. Leukopenia and thrombocytopenia were dose limiting but were of short duration and rapidly reversible. Mild degrees of phlebitis were observed in 10% of courses, and a green discoloration of the urine was noted with doses of greater than or equal to 10 mg/sq m. One patient with adenocarcinoma of the lung experienced a partial response of his tumor secondary to the drug. Phase II studies of 1,4-dihydroxy-5,8-bis(( (2-[(2-hydroxyethyl)amino]ethyl)amino))-9,10-anthracenedione dihydrochloride are planned at a starting dose of 12 mg/sq m as a single dose repeated at 21- to 28-day intervals.

Adult↗
PubMed1979

Relief of polarity in E. coli depleted of 30S ribosomal subunits.

Escherichia coli was depleted of ribosomes by a thermal shock at 47 degrees C which quantitatively destroyed the 30S ribosomal subunits. During recovery in minimal medium at 30 degrees C RNA is synthesized while protein synthesis resumes only after about 90 min. It is shown that lac mRNA is synthesized in the complete absence of ribosomal activity and hence RNA synthesis is not coupled to protein synthesis. Lac mRNA from a series of lac nonsense mutants was examined in both heated and untreated cells. It was found that the polar effect of nonsense mutation is relieved in the absence of ribosomes and that this relief is due to the synthesis of larger mRNA molecules. Since Rho remained active in thermally treated cells, premature termination at secondary signals within the lac operon must also depend on the presence of active ribosomes.

Escherichia coli↗
PubMed1979

Synthesis and degradation of lac mRNA in E. coli depleted of 30S ribosomal subunits.

Escherichia coli was depleted of active ribosomes by a thermal shock at 47 degrees C which quantitatively destroyed the 30S ribosomal subunits. During recovery, RNA is synthesized while protein synthesis resumes only after about 90 minutes. It is shown that lac mRNA is synthesized in the complete absence of ribosomal activity and hence RNA synthesis is not coupled to protein synthesis. Transcription time and average transcript length were slightly less than in untreated cells. lac mRNA was degraded much more slowly in bacteria depleted of ribosomes. In E. coli W both functional half life (T 1/2 = 28 min vs. 2.25 in untreated cells) and chemical stability. The analysis of rna and pnp mutants showed that polynucleotide phosphorylase is involved in lac mRNA degradation in heat treated cells but that RNase I is not. The functional T 1/2 was increased in pnp mutants and was 95 min during the recovery period. The rate of chemical decay is so slow that the half-life cannot be accurately determined.

Bacterial Proteins↗
PubMed1979

Experimental immune glomerulonephritis induced in the rabbit with streptococcal vaccine.

Heavy C3 glomerular deposits were observed in rabbits injected intravenously with C5 streptococcal vaccine. Immunoglobulin deposits appeared later in a few rabbits. Although some data favour the presence of circulating immune complexes during the course of this glomerulonephritis, no evidence for their initiating role could be demonstrated. Streptococcal components are known to activate the alternative pathway of complement. It is suggested that complexes made of streptococcal components and activated C3 might deposit in glomerular tufts.

Agglutinins↗
PubMed1977

Detection of antimetabolite activity: effects and transport of tryptophan analogs in Escherichia coli.

Simple and rapid techniques were developed that allow detection of the effects of a wide range of tryptophan analogs in Escherichia coli. (i) By using certain supersensitive mutant strains, analogs that were without effect on a wild-type strain were shown to be inhibitory. (ii) Many other analogs could inhibit the utilization of d-tryptophan when present as l-tryptophan replacements in a trp dadR strain. (iii) Another approach was to test the ability of a given analog to reverse the inhibition caused by an inhibitory analog. These combined approaches revealed activities in 26 analogs out of a total of 40 that were inactive by testing solely on a wild-type strain. The route of entry of inhibitory analogs was determined unambiguously by comparing their effect on aroP(+) (aromatic permease) and aroP strains. Uptake studies were also performed to determine whether various analogs compete for entry via the aromatic permease system. Many tryptophan analogs enter the cell via this system. The methods developed here should have general applicability to the testing of analogs of a variety of other metabolites.

Escherichia coli↗