PubMed Health⌕ Search

Biomedical subjects

K Wassermann

Publications and source records attributed to K Wassermann.

At least 73 records · Page 4Linked to original sources
PubMed1993

Chronic Pneumocystis carinii pneumonia in AIDS.

The clinical and radiologic presentation as well as the macroscopic and histologic characteristics of lung parenchyma in three HIV-infected patients with Pneumocystis carinii pneumonia (PCP) are detailed. The distinguishing clinical feature in these patients was a prolonged stable clinical course of the disease over at least 4 to approximately 24 months. Serial chest radiographs in two patients demonstrated persistent focal radiographic lesions. In one patient blebs in both upper lobes were not recognized until thoracoscopy/thoracotomy was performed. Biopsy specimens of affected areas revealed extensive interstitial fibrosis, occasional giant cell reactions, and honeycombing. In view of the combined clinical, radiologic, macroscopic, and histologic patterns, it is suggested that these patients had a chronic productive form of PCP rather than the well-known acute presentation of the disease. Data from the literature confirm the impression that atypical histologic lesions of PCP, either of a productive or destructive nature, are frequently related to a prolonged clinical course. It is unlikely that prophylactic pentamidine contributes to this entity. Coinfection with other pathogens may have a role. Given the recent evidence on augmented release of tumor necrosis factor a (TNFa) in HIV-associated pulmonary complications, it is speculated that TNFa may be of importance in producing focal fibrosis in Pneumocystis infection of the lung.

AIDS-Related Opportunistic Infections↗
PubMed1992

Overexpression of metallothionein in Chinese hamster ovary cells and its effect on nitrogen mustard-induced cytotoxicity: role of gene-specific damage and repair.

Overexpression of metallothionein in mammalian cells has been associated with protection from cytotoxic chemicals and acquired resistance of tumors to cytotoxic drugs. The mechanism of this effect, however, remains unclear. We have explored whether cytotoxicity of the bifunctional alkylating agent nitrogen mustard was correlated with the extent of DNA damage formation and repair in the metallothionein gene regions in Chinese hamster ovary cells. The DNA damage and repair were examined in metallothionein-overexpressing, cadmium-resistant Chinese hamster ovary cells, Cdr200T1, with or without zinc-induced transcriptional activation, and in the parental CHO-met- cell line. The zinc-induced Cdr200T1 cells tolerated significantly higher doses of nitrogen mustard than did the uninduced Cdr200T1 variant. The parental CHO-met- cells, which did not have any detectable metallothionein expression, were even more resistant to nitrogen mustard than the zinc-induced Cdr variants. Nitrogen mustard-induced N-alkylpurines were formed with a higher frequency in inactive genomic regions than in the active genes. The removal of N-alkylpurines was similar in the active MT I gene region in Cdr200T1 and the silent MT I gene region in the parental cells, and the expression of these genes was determined by Northern assay. The MT II gene-containing region was repaired less efficiently than the MT I gene, independently of zinc induction. Further, preferential repair of nitrogen mustard-induced N-alkylpurines were detected in a single copy of the essential active dihydrofolate reductase gene as compared to a downstream noncoding region. This preferential repair was unaffected by the presence of zinc. Neither damage formation nor repair kinetics in the MT gene regions seemed to parallel the observed spectrum of sensitivity to HN2.

Alkylation↗
PubMed1992

Biomonitoring of genotoxic exposure among stainless steel welders.

A biosurvey in the Danish metal industry measured the genotoxic exposure from stainless steel welding. The study comprised measurements of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environmental monitoring of welding fumes and selected metal oxides, biomonitoring of chromium and nickel in serum and urine and mutagenic activity in urine, and evaluation of semen quality were also done. Manual metal arc (MMA) welding and tungsten inert gas (TIG) welding were the dominant welding processes. A higher frequency of chromosomal aberrations, classified as translocations, double minutes, exchanges and rings, was observed in stainless steel welders than in non-welders. SCE was lower in welders working with both MMA and TIG welding than in reference persons. N-Acetoxy-N-acetylaminofluorene (NA-AAF)-induced UDS was lower in 23 never-smoking welders than in 19 unexposed never-smokers. Smoking was a confounding factor resulting in significantly higher CA, SCE, NA-AAF binding to DNA and mutagenic activity in urine. Age was also a confounder: CA, SCE, NA-AAF binding to DNA and UDS increased significantly with age. No significant correlation between SCE and CA or between CA and UDS was found. UDS decreased significantly with increasing lymphocyte count and a higher lymphocyte count was seen in MMA welders than in reference persons and in smokers than in non-smokers. Differences in the composition among lymphocytes in exposed persons compared with non-exposed are suggested. MMA welding gave the highest exposure to chromium, an increased number of chromosomal aberrations and a decrease in SCE when compared with TIG welding. Consequently improvements in the occupational practice of stainless steel welding with MMA is recommended.

Acetoxyacetylaminofluorene↗
PubMed1992

Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells.

Using methodology recently developed to assess gene-specific DNA repair, we have demonstrated that it is possible not only to study mitochondrial DNA repair, but also directly to compare mitochondrial and nuclear DNA repair in the same biological sample. Complex enzymatic mechanisms recognize and repair nuclear DNA damage, but it has long been thought that there was no DNA repair in mitochondria. Therefore, in an attempt to delineate more clearly which DNA repair mechanisms, if any, are functioning in mitochondria, we have investigated the repair of several specific DNA lesions in mitochondrial DNA. They include cyclobutane dimers, cisplatin intrastrand adducts, cisplatin interstrand crosslinks and alkali-labile sites. We find that pyrimidine dimers and complex alkylation damage are not repaired in mitochondrial DNA, and that there is minimal repair of cisplatin intrastrand crosslinks. In contrast, there is efficient repair of cisplatin interstrand crosslinks as evidenced by approximately 70% of the lesions being removed by 24 h. Additionally, there is efficient repair of N-methylpurines following exposure to methylnitrosourea with approximately 70% of the lesions being removed by 24 h. The results of these studies reveal that repair capacity of mitochondrial DNA damage depends upon the type of lesion produced by the damaging agent. We speculate that a process similar to the base excision mechanism for nuclear DNA exists for mitochondrial DNA but that there is no nucleotide excision repair mechanism to remove more bulky lesions in this organelle.

Animals↗
PubMed1992

Induction of DNA repair synthesis in human monocytes/B-lymphocytes compared with T-lymphocytes after exposure to N-acetoxy-N-acetylaminofluorene and dimethylsulfate in vitro.

We have explored the induction of DNA repair synthesis in monocyte/B- and T-lymphocyte enriched cell fractions from 12 different human mononuclear blood cell populations. Unscheduled DNA synthesis was measured in monocyte/B- and T-cells after exposure to the DNA-damaging agents dimethylsulfate (DMS) and N-acetoxy-N-acetylaminofluorene in vitro. Also, the binding of DMS to DNA was measured. An increased DNA repair synthesis was measured in monocyte/B-lymphocytes after induction of the two different types of DNA lesions, whereas no induction of unscheduled DNA synthesis was observed in T-lymphocytes. A significantly higher DMS-DNA binding was also observed in monocyte/B-lymphocytes when compared with T-lymphocytes. Specific characterization of mononuclear blood cell populations used in biomonitoring of DNA adducts and repair is recommended.

Acetoxyacetylaminofluorene↗
PubMed1992

Reversible volume changes of trapped gas in nonspecific bronchoprovocation tests.

Thirty patients with a history of asthma and ten patients with suspected bronchial hyperreactivity underwent nonspecific provocation testing. The control group consisted of ten normal volunteers without a history of lung disease. The patients' baseline FEV1 (percent predicted) revealed mild obstructive disease (72.9 +/- 8.9 percent and 74.6 +/- 7.7 percent) compared with controls (87.2 +/- 8.5 percent, p less than 0.001). The mean volume of trapped gas (D) (ie, TLCB-TLCHe) was not significantly different between groups (0.11 +/- 0.49 L vs 0.15 +/- 0.4 L vs 0.18 +/- 0.45 L), and no correlation was established with any of the remaining lung function data. Bronchial hyperreactivity in response to inhaling acetylcholine could be observed in the asthma group only. Their mean D increased significantly from 0.11 +/- 0.49 L to 0.62 +/- 0.66 L (p less than 0.001), and returned to baseline (0.26 +/- 0.55, NS) subsequent to inhaling salbutamol. D changes induced by acetylcholine correlated weakly with concurrent changes of FEV1 (r = -0.44, p = 0.01), RV (r = 0.59, p less than 0.001), and Rs (r = 0.59, p less than 0.001). In response to bronchodilating doses of salbutamol, however, D was changed in close correlation with FEV1 (r = -0.82, p less than 0.0001), RV (r = 0.85, p less than 0.0001), and Rs (r = 0.76, p less than 0.0001). Provided that D is a valid parameter of small airways function, these data may give a clue to the site of action of both drugs. Acetylcholine affects small and large airways alike with no clear-cut preference, whereas salbutamol's predominant target appears to be the small airways. These conclusions are only partially supported by the pertinent literature.

Acetylcholine↗
PubMed1992

[Transesophageal echography in staging of bronchial cancers].

The kind of relation of central lung cancer (c) to the walls of the central pulmonary arteries (PA) and the aorta is an important information prior to operative or interventional (laser/afterloading) therapy. As computed tomography (CT) and angiography are often inaccurate in the assessment of PA-infiltration, we assessed the diagnostic value of transesophageal echography (TEE) in the staging of LC. 16 patients (pts.) were investigated using TEE in addition to CT or magnetic resonance imaging (MRI). Eleven pts. had central LC, 3 peripheral LC, 1 anterior mediastinal mass and 1 central pneumonia (cancer excluded). 2 pts. with central LC were unable to swallow the probe. In 9/9 pts. with central LC, 1/3 pts. with peripheral LC and 1 pt. with enlarged anterior mediastinum the tumour mass could be visualized. In the pt. with a centrally located infiltrate on chest radiogram TEE demonstrated enlarged hilar lymph nodes, but excluded a central tumour. Main PA branches could be identified in all 14/14 pts. Central left or right PA were compressed slightly in 3 pts. and severely in 2 pts., with a near total occlusion in one (confirmed by MRI/CT). TEE revealed PA-infiltration in 2 pts. and aortic wall infiltration in 2 other pts. Despite adjacent tumour mass aortic wall infiltration was excluded in 2 pts. Enlarged hilar lymph nodes could be demonstrated in 2/9 pts. with central LC, whereas CT/MRI showed enlarged mediastinal lymph nodes in 7/9 pts. In conclusion, TEE is able to visualize central lung cancer and gives useful additional informations about the kind of relation to central PA and the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Pulmonary function tests after pneumocystis carinii pneumonia in HIV infected patients].

UNLABELLED: Significant impairment of lung volumes and gas exchange in HIV-infected patients with acute Pneumocystis carinii pneumonia (PCP) has been reported, whereas little is known about lung function compromise following successful therapy. In 9 patients with acute PCP and 9 patients 1-5 month after PCP lung function testing including spirometry, diffusing capacity for carbon monoxide and exercise blood gas analysis were performed serially at monthly intervals. The results were summarized in a total score. The mean period of follow-up for each patient was 7.2 +/- 2 months. A decrease in lung volumes (FEV1 67 +/- 14.2% pred.norm., VC 72.7 +/- 11.9% pred.norm.) and gas exchange (CO-transfer factor 53.2 +/- 18.5% pred.norm., CO-transfer coefficient 67.8 +/- 14.2 pred. norm.) was observed in all 9 patients with acute PCP. Post-PCP lung volumes normalized within 1 month, whereas disorders in gas exchange persisted for 1-3 months. The total score normalized in 16/18 patients. One of the remaining patients with persisting functional impairment had chronic obstructive airway disease, whereas in the other dysfunction was even observed prior to PCP and no diagnosis could be obtained. 2-6 months following acute disease a second period of decreased lung function occurred in 6 pts. In 3 of the 6 there were no clinical signs of infection (rebronchoscopy refused), in 1 patient infection with cytomegalovirus was suspected. In the other 2 patients a relapse of PCP was diagnosed by bronchoscopy. CONCLUSIONS: Acute PCP compromises lung mechanics and gas exchange. During recovery deficits in gas exchange persist longer than diminished lung volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies↗
PubMed1991

Relationship between DNA cross-links, cell cycle, and apoptosis in Burkitt's lymphoma cell lines differing in sensitivity to nitrogen mustard.

We surveyed 11 Burkitt's lymphoma cell lines for chemosensitivity to nitrogen mustard (HN2) in order to determine whether any simple correlates to cytotoxic response might be revealed. The lines tested varied over a 5-fold range in concentration of HN2 required to inhibit tumor cell growth by 50%. Drug sensitivity correlated neither with continental origin of tumor, growth fraction, presence of Epstein-Barr virus, nor with the precise locations of (8;14) translocation breakpoints. Furthermore, contrary to experience with other cell lines, no simple correlation was found between the HN2 sensitivity of the four most divergent lines (low sensitivity, CA46 and MC116 cells; high sensitivity, Namalwa and JLP119 cells) and exposure to DNA cross-links (area under the DNA cross-linking-versus-time curve). In addition, we found similar extents of gene-specific HN2-induced damage in the native and translocated c-myc alleles of CA46 and JLP119 cells. At equimolar HN2 treatment, CA46 cells exhibited a profound arrest in G2M phase, while JLP119 cells exhibited prolonged S-phase delay. This suggested that despite similar DNA cross-link exposure, JLP119 cells were less able to complete DNA replication while repair was in progress. As cell cycle distribution returned to near normal, JLP119 cells exhibited DNA degradation characterized by oligonucleosome-sized DNA fragments prior to cell membrane disintegration. Our findings indicate that HN2-sensitive Burkitt's lymphoma cells may be more susceptible to delay in S phase for a given frequency of DNA cross-links and that prolongation of S phase correlated with apoptotic cell death.

Alkylation↗
PubMed1991

Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II.

The effect of combinations of the anthracyclines aclarubicin and daunorubicin was investigated in a clonogenic assay using the human small cell lung cancer cell line OC-NYH and a multidrug-resistant (MDR) murine subline of Ehrlich ascites tumor (EHR2/DNR+). It was found that the cytotoxicity of daunorubicin in OC-NYH cells was antagonized by simultaneous exposure to nontoxic concentrations of aclarubicin. Coordinately, aclarubicin inhibited the formation of daunorubicin-induced protein-concealed DNA single-strand breaks and DNA-protein cross-links in OC-NYH cells when assayed by the alkaline elution technique. Aclarubicin had no influence on the accumulation of daunorubicin in these cells. In contrast, the accumulation of daunorubicin in EHR2/DNR+ cells was enhanced by more than 300% when the cells were simultaneously incubated with the MDR modulator verapamil, aclarubicin, or the two agents combined. Yet the cytotoxicity of daunorubicin was potentiated significantly only by verapamil. The increased cytotoxicity of daunorubicin in the presence of verapamil was completely antagonized when aclarubicin was used together with the MDR modulator. Finally, the effect of daunorubicin on the DNA cleavage activity of purified topoisomerase II in the presence and absence of aclarubicin was examined. It was found that daunorubicin stimulated DNA cleavage by topoisomerase II at specific DNA sites. The addition of aclarubicin completely inhibited the daunorubicin-induced stimulation of DNA cleavage. Taken together, these data indicate that aclarubicin-mediated inhibition of daunorubicin-induced cytotoxicity is due mainly to a drug interaction with the nuclear enzyme topoisomerase II. This antagonism at the nuclear level explains why aclarubicin is a poor modulator of daunorubicin resistance even though aclarubicin is able to increase the intracellular accumulation of daunorubicin in a MDR cell line.

Aclarubicin↗
PubMed1991

Pentamidine aerosol increases the number of alveolar macrophages in HIV-infected patients.

In order to determine the possible effect of aerosolized pentamidine on the cellular composition of the bronchoalveolar lavage fluid in HIV-infected patients, differential counts of 22 consecutive patients who had been rebronchoscopied after 3-19 months were reviewed. Eleven patients were started on pentamidine prophylaxis subsequent to their first presentation. Eleven patients had never taken pentamidine or had discontinued the prophylactic regimen. Compared to first bronchoscopy, the bronchoalveolar lavage (BAL) from patients on regular prophylaxis revealed a significant increase in absolute alveolar macrophage (AM) counts at second presentation (20.8 +/- 11.2 to 50.3 +/- 39.4 x 10(5) cells/100 ml BAL; P less than 0.01). The AM counts of those without pentamidine remained essentially unchanged. Lymphocytes, including CD4 and CD8 subtypes, and neutrophils did not change over time in either group. The results of this retrospective analysis suggest that, in addition to its antimicrobial action, pentamidine may modulate local lung defence mechanisms, particularly by increasing the absolute number of AM.

Administration, Inhalation↗
PubMed1990

[Acute pneumocystosis during polychemotherapy following the MACOP-B protocol].

Four out of eleven patients--none of them HIV positive--who received treatment for non-Hodgkin lymphoma by the MACOP-B protocol between June 1989 and February 1990 were taken ill during or shortly after the conclusion of the course with fulminant pneumonia necessitating artificial ventilation. In three cases Pneumocystis carinii was identified as the pathogen, and in one patient the diagnosis of pneumocystosis seemed probable. The mean cumulative doses given before the outbreak of pneumonia were as follows: cyclophosphamide 2753 +/- 1161 mg, methotrexate 1590 +/- 667 mg, bleomycin 36 +/- 16.8 mg and prednisone 4378 +/- 1734 mg. The mean haemoglobin concentration was 10.7 +/- 0.5 g/dl, leucocyte count 5250 +/- 2100/microliters, lymphocyte count 1300 +/- 300/microliters and lactate dehydrogenase 227 +/- 34 U/l. The cumulative doses and laboratory findings in the seven patients not affected by pneumocytosis were not significantly different. The patients with pneumonia were supported by mechanical ventilation for 6-26 days and treated with large doses of corticosteroids and co-trimoxazole. One patient died after 17 days' ventilation. Three patients were successfully weaned from the ventilator. Chemotherapy protocols such as MACOP-B predispose to acute Pneumocystis pneumonia. The risk of infection is independent of the cumulative doses of the drugs employed. For this reason, prophylaxis with co-trimoxazole is normally mandatory.

Antineoplastic Combined Chemotherapy Protocols↗