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C Kramer

Publications and source records attributed to C Kramer.

12 recordsLinked to original sources

An upstream activating sequence from the Aspergillus nidulans gpdA gene.

Introduction of a previously identified promoter element of the Aspergillus nidulans gpdA gene (encoding glyceraldehyde-3-phosphate dehydrogenase), the so-called gpd box, into the upstream region of the highly regulated A. nidulans amdS gene (encoding acetamidase), significantly increased (up to 30-fold) the expression of the lacZ reporter gene fused to these expression signals. This increase was dependent on the orientation of the gpd box and on the site of introduction into the amdS upstream region. The presence of additional gpdA sequences which flank the gpd box reduced or even extinguished positive effects of the gpd box. omega-Amino acid and carbon catabolite regulation of the amdS promoter were retained after introduction of the gpd box, indicating that the gpd box does not abolish interactions of the regulatory proteins, AmdR and CreA, with the amdS transcription control sequences. Based on the results, it is suggested that the gpd box comprises at least two separate activities: one being orientation dependent, but relatively independent of position of the gpd box in the upstream region, and the other is only functional near other sites of transcriptional control. Most likely, both activities are not involved in regulation of the amdS promoter.

Aspergillus nidulans

p-aminophenol nephrotoxicity: biosynthesis of toxic glutathione conjugates.

p-Aminophenol causes necrosis of the pars recta of the proximal tubules in rats, and its nephrotoxicity may be due to glutathione-dependent bioactivation reactions. We have investigated the hepatic metabolism of p-aminophenol in Wistar rats and the cytotoxicity of formed glutathione S-conjugates in rat renal epithelial cells. After ip application of p-aminophenol (100 mg/kg), the following metabolites were identified in rat bile: 4-amino-2-(glutathion-S-yl)phenol, 4-amino-3-(glutathion-S-yl)-phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol, an aminophenol conjugate (likely a sulfate or glucuronide), acetaminophen glucuronide, and 3-(glutathion-S-yl)acetaminophen. 4-Amino-3-(glutathion-S-yl)phenol, 4-amino-2,5-bis(glutathion-S-yl)phenol, and 4-amino-2,3,5(or 6)-tris(glutathion-S-yl)phenol induced a dose- and time-dependent loss of cell viability in rat kidney cortical cells. Cell killing was significantly reduced by inhibition of gamma-glutamyl transpeptidase with Acivicin. p-Aminophenol was also toxic to renal epithelial cells. Coincubation of p-aminophenol with tetraethylammonium bromide, a competitive inhibitor of the organic cation transporter, and with SKF-525A, an inhibitor of cytochrome P450, protected cells from p-aminophenol-induced toxicity. p-Aminophenol would thus be accumulated in the kidney mainly by organic cation transport systems, which are concentrated in the S-1 segment of the proximal tubule. However, p-aminophenol toxicity in vivo is directed toward the S-2 and S-3 segments, which are rich in gamma-glutamyl transpeptidase. These results and the observation that biliary cannulation and glutathione depletion reduce p-aminophenol nephrotoxicity suggest that the biosynthesis of toxic glutathione conjugates is responsible for p-aminophenol nephrotoxicity in vivo. The aminophenol glutathione S-conjugates formed induce p-aminophenol nephrotoxicity by a pathway dependent on gamma-glutamyl transpeptidase.

Aminophenols

Otitis media.

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Child

Multifunctional nature of P fimbriae of uropathogenic Escherichia coli: mutations in fsoE and fsoF influence fimbrial binding to renal tubuli and immobilized fibronectin.

P fimbriae of the F7(1) serotype of Escherichia coli are composed of a major subunit, FsoA, and of three minor proteins named FsoG, FsoE, and FsoF. FsoG is the Gal alpha(1-4)Gal-specific lectin. We assessed mutated recombinant strains each deficient in one fimbrial component for adhesion to frozen sections of rat cortical kidney and to fibronectin immobilized on glass. Rat kidney lacks the Gal alpha(1-4)Gal-containing glycolipids. The fsoG mutant strain was as adhesive to sections of rat kidney and to fibronectin-coated glass as was the recombinant strain expressing the complete fso gene cluster. The fsoA mutant strain was highly adhesive to fibronectin and to kidney sections. In the rat kidney, the adhesion of these strains was predominantly localized to sites of basolateral membranes of tubuli. The fsoE and the fsoF mutant strains were slightly less adhesive to kidney structures and failed to adhere to fibronectin. The fsoE, fsoF double mutant strain adhered neither to fibronectin nor to kidney sections. None of the fso recombinant strains reacted with soluble fibronectin, suggesting that the interaction is dependent on the conformation of the fibronectin molecules. Recombinant strains expressing the F7(2), F8, F11, F13, and F14 serovariants of the P fimbria also showed adherence to immobilized fibronectin. The results show that in addition to binding to globoseries of glycolipids via the G protein, the P fimbriae of uropathogenic E. coli exhibit a tissue-binding property influenced by fsoE and fsoF gene products and with affinity for basolateral membranes and fibronectin.

Amino Acid Sequence

Mediastinal irradiation in combined modality therapy for Hodgkin's disease.

Patients with Hodgkin's disease who present with large mediastinal masses in the setting of either early or advanced stage disease are frequently treated with combined modality therapy. Policies for radiation dose to the mediastinum in these settings range from no radiation to doses in the 3600-4000 cGy range. We reviewed the charts of 50 patients treated with radiation therapy following remission induction with chemotherapy between 1979 and 1983 to determine whether the dose of radiation to the mediastinum could be correlated with mediastinal control, relapse-free, and overall survival. Patients were divided into groups with small (SM, 30 pts.) and large (LM, 20 pts.) mediastinal masses and analyzed according to whether they had received low dose (LD, less than or equal to 2500 cGy) or high dose (HD, greater than 2500 cGy) radiation to the mediastinum. The 5-year relapse-free survival (RFS) for all 50 patients was 84% (+/- 8%, 95% confidence limits). For the patients with small mediastinal masses, 5-year RFS was 81% +/- 20%, and for the patients with large mediastinal masses, 89% +/- 16%. No clear dose-response effect was observed when the outcomes of the low dose and high dose patients were compared. This was true even in the patients with large mediastinal masses although the high dose subset of this group included patients felt to be at a higher risk for relapse following chemotherapy. Nine of eleven patients with large mediastinal masses treated with chemotherapy and low dose radiation remain disease-free. There was only one isolated mediastinal relapse in the entire group of patients. Treatment was well tolerated with no acute treatment-related deaths. Two patients developed second malignancies. We conclude that combined modality therapy using low dose radiation results in excellent 5-year relapse-free survival for most small and many large mediastinal mass patients, and that it is not necessary to treat all chemotherapy patients who present with mediastinal disease with high dose radiation to achieve these relapse-free survival rates.

Adult

[Measuring quality of life in weekly assessment of the disease course in myocardial infarct patients--initial results of methodology].

In a quality-of-life study in the first year after successful in-patient rehabilitation following first infarct, a questionnaire method for daily and weekly evaluation of subjective life quality was carried out. The questionnaire presents varying aspects in particular processes concerning the assessment and valuation of life quality. Errors in measurement resulting from processes of memory and revaluation as they are possible in methods with longer intervals of data collection are avoided. An investigation of the reliability of this method revealed good reliability. To definitely assess the validity of this evaluation, further inquiries will be necessary. However, the correlation analysis points to a great significance of the collected weekly data.

Adult

Radiation treatment of FIGO stage IVA carcinoma of the cervix.

Forty-eight patients with FIGO stage IVA cervix cancer were treated with radiation therapy at the Hunter Radiation Therapy Center, Yale--New Haven Hospital from 1966 to 1985. Nine of the 48 patients are alive without recurrence (NED) and the 5-year actuarial survival rate is 18% (+/- 6%, standard error). There was a substantial difference in outcome based on treatment technique. Thirty-five patients were treated with external beam (EB) plus intracavitary (IC) and 8 of these patients (23%) are NED. None of the 12 patients treated with EB alone are alive. One patient treated with preoperative EB plus exenteration is NED. The severe complication rate was 22% and most complications were vesicovaginal fistulas due to successful treatment for bladder involvement. There was a significant difference in survival for patients with minimal parametrial disease (stage IVA1) versus patients with significant parametrial disease (stage IVA2) which was defined as fixation to one or both pelvic sidewalls or hydronephrosis on IVP. The 5-year survival for stage IVA1 disease was 46% (+/- 14%) versus only 5% (+/- 4%) for stage IVA2 disease. Our results indicate that superior survival for stage IVA cervix cancer patients is associated with two factors: minimal parametrial disease and radiation treatment which combines EB plus IC.

Adenocarcinoma

Implementation of the NCA modified assessment instrument with a population of intoxicated drivers in two Wisconsin counties 1982-1985.

Upon completion of a 3-yr. research project which assessed the effects of Wisconsin's mandatory testing program for drunk drivers, the evaluation showed that a disproportionate number of repeated offenders who were being rearrested had been assessed initially as social drinkers. While there are several possible causes for this finding, the most probable one seems to be that of under-assessment by the testing instrument.

Accidents, Traffic

Respiration during sleep in Huntington's chorea.

In view of recent reports on lower brainstem dysfunction in Huntington's chorea, we studied respiration during sleep in 12 patients with Huntington's chorea (HC) and in controls. There were no statistically significant differences between patients and controls with respect to apnea periods, respiratory frequency and time elapsed between minimal and maximal value of the respiratory curve. No statistically significant differences in respiratory variability were observed between patients and controls. In the present study, no indication was found for dysfunction of lower brainstem structures involved in respiration in HC.

Adult

Inhibition of neutrophil activation by p-bromophenacyl bromide and its effects on phospholipase A2.

In an effort to elucidate the nature of the inhibitory effects of p-bromophenacyl bromide (pBPB) on neutrophil stimulation, we have examined its effects on several stages of stimulus-response coupling. Pretreatment of rat neutrophils with pBPB resulted in a dose- and time-dependent irreversible inhibition of both N-formylmethionyl-leucylphenylalanine (fMet-Leu-Phe)-induced lysosomal enzyme release and change in transmembrane potential. Inhibition of the biological responses to the chemotactic peptide fMet-Leu-Phe was not due to receptor inactivation since fMet-Leu-[3H]-Phe binding to the formyl peptide receptor was not significantly altered by pBPB pretreatment. Inhibition by pBPB of phorbol myristate acetate (PMA)-induced changes in transmembrane potential and the generation of superoxide (0-2) was also observed. pBPB treatment appeared to inhibit activation of the NADPH oxidase without a direct effect on the oxidase itself. This inhibitory effect was not accompanied by cell death or decrease in cellular titratable sulphydryl groups (at least at doses less than 20 microM). There was, however, significant inhibition of a membranous fraction of fMet-Leu-Phe-induced phospholipase A2 activity by pretreatment with 10 microM pBPB, although total cellular phospholipase A2 was only minimally (less than 20% inhibition) affected. These data would indicate that pBPB inhibits an early event associated with stimulus-response coupling in rat polymorphonuclear leukocytes (i.e. change in transmembrane potential). The inhibitory effects of pBPB may be secondary to the inhibition of a critical membranous fraction of cell bound phospholipase A2 activity or its activation, necessary for the initiation of cell activation.

Acetophenones

Nucleotide sequence of the genes coding for minor fimbrial subunits of the F1C fimbriae of Escherichia coli.

F1C fimbriae allow uropathogenic Escherichia coli to adhere to specific epithelial surfaces. This adhesive property is probably due to the presence of minor fimbrial components in F1C fimbriae. The foc gene cluster encoding F1C fimbriae has been cloned, as described previously. Here we present the nucleotide sequence (2081 bp) coding for the F1C minor fimbrial subunits. The structural genes code for polypeptides of 175 (FocF), 166 (FocG), and 300 (FocH) amino acids. The deduced amino acids of the F1C minor subunits were compared with the reported sequences of the minor subunits of other types of fimbriae. The data show that the Foc minor subunits are highly homologous to the corresponding Sfa proteins, whereas homology to the minor subunits of type 1 and P fimbriae is much lower.

Bacterial Adhesion