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Biomedical subjects

D Fink

Publications and source records attributed to D Fink.

At least 73 records · Page 4Linked to original sources
PubMed1996

The role of DNA mismatch repair in platinum drug resistance.

Loss of DNA mismatch repair occurs in many types of tumors. The effect of the loss of DNA mismatch repair activity on sensitivity to cisplatin and a panel of analogues was tested using two pairs of cell lines proficient or deficient in this function. HCT116+ch2, a human colon cancer cell line deficient in hMLH1, was 2.1-fold resistant to cisplatin and 1.3-fold resistant to carboplatin when compared to a subline complemented with chromosome 3 expressing a wild-type copy of hMLH1. Likewise, the human endometrial cancer cell line HEC59, which is deficient in hMSH2, was 1.8-fold resistant to cisplatin and 1.5-fold resistant to carboplatin when compared to a subline complemented with chromosome 2 with a wild-type hMSH2. In contrast to cisplatin and carboplatin, which form the same types of adducts in DNA, there was no difference in sensitivity between the DNA mismatch repair-proficient and -deficient cell lines for oxaliplatin, tetraplatin, transplatin, JM335, or JM216. The formation of protein-DNA complexes that contained hMSH2 and hMLH1 was documented by mobility shift assay when nuclear extracts were incubated with DNA platinated with cisplatin but not with oxaliplatin. These results demonstrate a correlation between failure of the DNA mismatch repair proteins to recognize the platinum adduct and low-level resistance, suggesting a role for the DNA mismatch repair system in generating signals that contribute to the generation of apoptotic activity. They also identify the use of drugs whose adducts are not recognized as a strategy for circumventing resistance due to loss of DNA mismatch repair.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Loss of DNA mismatch repair in acquired resistance to cisplatin.

Selection of cells for resistance to cisplatin, a well-recognized mutagen, could result in mutations in genes involved in DNA mismatch repair and thereby to resistance to DNA-alkylating agents. Parental cells of the human ovarian adenocarcinoma cell line 2008 expressed hMLH1 when analyzed with immunoblot. One subline selected for resistance to cisplatin (2008/A) expressed no hMLH1, whereas another (2008/C13*5.25) expressed parental levels. Microsatellite instability was readily demonstrated in 2008/A cells but not in 2008 and in 2008/C13*5.25 cells. In addition, the 2008/A cells were 2-fold resistant to methyl-nitro-nitrosoguanidine and had a 65-fold elevated mutation rate at the HPRT locus as compared to 2008 cells, both of which are consistent with the loss of DNA mismatch repair in these cells. To determine whether the loss of DNA mismatch repair itself contributes to cisplatin resistance, studies were carried out in isogenic pairs of cell lines proficient or defective in this function. HCT116, a human colon cancer cell line deficient in hMLH1 function, was 2-fold resistant to cisplatin when compared to a subline complemented with chromosome 3 and expressing hMLH1. Similarly, the human endometrial cancer cell line HEC59, which expresses no hMSH2, was 2-fold resistant to cisplatin when compared to a subline complemented with chromosome 2 that expresses hMSH2. Therefore, the selection of cells for resistance to cisplatin can result in the loss of DNA mismatch repair, and loss of DNA mismatch repair in turn contributes to resistance to cisplatin.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Coronary artery bypass surgery during pregnancy.

A 32-year-old woman, in the 22nd week of pregnancy, underwent emergency coronary artery bypass grafting to the left anterior descending artery (LAD). She had suffered an acute myocardial infarction 10 days previously, and continued to suffer from intractable angina pectoris afterwards. Cardiac catheterization revealed spontaneous dissection of the LAD. The left internal mammary artery was used to bypass the LAD, and the operation was performed on a beating heart without the use of cardiopulmonary bypass. The patient's recovery was uneventful, and ultrasound examination and pulse monitoring of the fetus were both normal. She subsequently gave birth to a healthy term baby. To our knowledge this is the second report of coronary artery bypass surgery performed successfully in a pregnant woman. We believe the unique surgical approach avoided the risk of cardiopulmonary bypass to the fetus and placenta.

Adult↗
PubMed1996

[Comparison of gynecologic and perineal ultrasound examination of women with stress incontinence].

UNLABELLED: A COMPARISON AIM: To determine how well results of gynecological and perineal sonographic examinations of the urethrovesical junction correlate. METHOD: 186 women with urodynamically verified stress incontinence underwent a perineal ultrasound and then a gynecologic examination. Standardised procedures were used for both. The findings of the gynecological examination were compared with measurement values and morphological findings from perineal ultrasound. RESULTS: There was agreement on the cystocele grade in 69% of the cases. The position of the bladder neck as assessed by the ultrasound image revealed typical measurement values for this disorder. The expected bladder neck funneling was detected in 49% of these women. CONCLUSION: In stress-incontinent women there is good correlation between the findings of the gynecological and perineal sonographic examinations. Bladder neck funneling-a morphological sign of stress incontinence-can be detected with perineal ultrasound in nearly one-half of the cases.

Adult↗
PubMed1996

[Stewart-Treves syndrome after breast carcinoma].

The Stewart-Treves syndrome is an angiosarcoma that occurs due to chronic lymphoedema which in most cases is a complication after mastectomy with axillary node dissection and postoperative radiation. Prognosis for this rare tumour is poor. The best therapy is early and radical excision. Chronic lymphoedema seems to be an important pathogenetic factor. We report on a 70-year old patient with early stage lymphangiosarcoma who had a lumpectomy with axillary node dissection and postoperative radiation five years ago.

Aged↗
PubMed1996

[Ovarian metastasis of extragenital tumors at the Zurich University Gynecologic Clinic 1978-1990].

37 cases of extragenital tumours metastatic to the ovaries are analysed from a clinicopathological viewpoint. In 25 out of 334 patients who were operated on between 1978 and 1990 because of a palpable malignant ovarian tumour, ovarian involvement from extragenital cancer was diagnosed. The most frequent primary sites were the stomach (n = 7), colon (n = 6) and breast (n = 6). 4 of the 6 patients with metastatic colon carcinoma had previously documented diagnosis of colon cancer with a time interval between diagnosis of primary tumours and secondary ovarian tumour ranging up to 11 years. Only one patient had a previously known stomach cancer, operated on 32 months earlier. All our patients with gastrointestinal primary tumour died within 1 year (gastric origin) of detection of metastases and 2 years (colon carcinoma) except for one patient with metastasis of colon carcinoma, who is still living after more than 4 years and one patient with gastric carcinoma who survived 34 months after oophorectomy. Surprisingly, ovarian metastases of breast cancer were detected before the primary tumour in 2 out of 6 cases. The other 4 patients were operated on because of an ovarian tumour but had a known and previously operated breast cancer. 27 patients had therapeutic ovarian ablation in metastatic breast cancer without a palpable pelvic mass. None of these patients had symptoms related to the ovaries. In 12 (40%) patients we found microscopic metastases which were bilateral in 9 cases. Metastases to the ovary may not infrequently mimic primary ovarian tumour and are difficult to diagnose preoperatively. We hope that some clinical features described by us (nationality, patient's history, bilateral ovarian tumours in young women) will alert the clinician to investigate further in order to achieve the best possible therapeutic management, because some patients may benefit from adequate treatment and survive for a long time.

Adult↗
PubMed1996

Identification of nitric oxide synthase in human and bovine oviduct.

Nitric oxide synthase (NOS) is responsible for the biological production of nitric oxide (NO) in several organs. NOS activity has also been localized in the reproductive tract, although direct evidence for its presence in the human or bovine oviduct is still lacking. In the present study, four different techniques were used to identify the presence of NOS activity in human (n = 11) and bovine (n = 9) oviduct: (i) conversion of [3H]-L-arginine to [3H]-L-citrulline; (ii) production of nitrite/nitrate (NO2/NO3; stable NO metabolites); (iii) identification of NADPH-diaphorase activity; and (iv) immunostaining with antiserum to endothelial NOS. Cytosolic extracts from human ampullary segments of the Fallopian tube, obtained from post-partum patients (n = 4), converted [3H]-L-arginine to [3H]-L-citrulline (21.0 +/- 8.8 fmol/mg protein/min). This conversion rate was significantly (P < 0.05) reduced in the presence of either EDTA or N-monomethyl-L-arginine monoacetate (L-NMMA), an inhibitor of NOS activity. When bovine (n = 3) ampullary segments were incubated for 36 h in Hanks' balanced salt solution, the concentration of NO2/NO3 in the medium was increased (P < 0.05) if segments were pretreated with lipopolysaccharide (LPS; an inducer of inducible NOS), but not after treatment with LPS + L-NMMA. Additionally, epithelial cells cultured from ampullary segments showed positive staining both for NADPH-diaphorase activity and with antiserum to endothelial NOS. The results of the present study provide direct evidence for the presence of both the Ca(2+)-dependent constitutive form of NOS, as well as the inducible form of NOS activity in human and bovine oviduct. Since the oviduct plays a key role in the reproductive process, it is possible that the two forms of NOS may be involved in the physiological regulation of oviduct function.

Animals↗
PubMed1996

Differential expression of Na,K-ATPase isoforms in oligodendrocytes and astrocytes.

Using Western blot and immunocytochemistry to detect protein, and in situ hybridization and Northern blot to detect RNA, we studied the expression of Na,K-ATPase subunit isoforms in cultured astrocytes and oligodendrocytes in vitro, and in glial cells in the brain. We found that astrocytes in culture express alpha 1 and alpha 2 isoforms of the catalytic subunit and both beta 1 and beta 2 isoforms of the regulatory subunit. Oligodendrocytes in culture express only alpha 1, but in vivo high levels of alpha 2 are seen in oligodendrocytes of white matter tracts. These results suggest that expression of the alpha 2 isoform in mature oligodendrocytes may be regulated by axonal contact and related to myelination.

Animals↗
PubMed1996

Incorporation of nuclear matrix attachment regions into the herpes simplex virus type 1 genome does not induce long-term expression of a foreign gene during latency.

The nuclear matrix plays a critical role in DNA replication, gene transcription and RNA processing. Transcriptionally active genes are usually associated with the nuclear matrix through DNA sequences, matrix attachment regions or MARs, which tether looped DNA to the matrix. In stable transfection and in transgenic mice MAR elements placed at the flanks of genic constructs may enhance expression and insulate against position effect variability, suggesting that independent units of transcription are established insulated from the regulatory controls of their neighbors. Herpes simplex virus type 1 (HSV-1) establishes lifelong latency in the infected host. Latency repression of viral genes extends to foreign genes incorporated into the viral genome. We report here a test of the hypothesis that MAR elements, flanking a foreign gene in the HSV-1 genome, would act to insulate it from latency repression, achieving long-term expression. A recombinant virus was produced which has an expression construct inserted into the HSV-1 genome at the Us3 locus. The expression construct consists of the A MAR element on one flank, an HIV-LRT driving the lacZ gene and the B MAR element on the other flank. The A MAR element is a 3 kb pair fragment of the 5' portion of the chicken lysozyme gene and the B MAR element is a 2.6 kb pair fragment from the 5' end of the human beta-globin gene locus control region. The LTR is derived from a human immunodeficiency virus isolated from the brain of an AIDS patient. Virus was stereotactically injected in the hippocampus, olfactory bulb and striatum of rat brains. Intense blue reaction product indicating beta-galactosidase activity was found in cells in each injected area at 2 days after injection. At 14 days after injection beta-galactosidase activity was no longer detected at any of the injected sites. We conclude that the MAR element construct did not escape latency repression.

Animals↗
PubMed1995

[Female incontinence: work-up and therapy].

Female incontinence is a more frequent disorder than sometimes realized. The patient should be asked about urinary incontinence symptoms. Depending on her degree of suffering, the appropriate diagnostic examinations and therapy can be chosen. With simple procedures, such as anamnesis, gynecological examination with testing, Valsalva maneuver with a full bladder, and a review of miction diaries, the kind of incontinence can be reliably determined, and first therapeutic steps can be initiated. For stress incontinence this would be pelvic floor reeducation or physical therapy with electric stimulation and bio-feed-back; only if these conservative measures fail, one should operate. For urge incontinence, it is important to strive for a change in drinking and miction habits (bladder training), i.e., to increase the amount of liquid intake and the miction volume (checked by miction diaries). This therapy can be further supported by medication. Urodynamic diagnostic examinations are indicated when primary therapy (pelvic floor reeducation, bladder training) fails, before any incontinence operation and when the type of incontinence is not clear.

Adult↗
PubMed1995

[Evaluation of perineal ultrasound examination--are the results reproducible?].

UNLABELLED: Perineal ultrasound was used with a new measurement method that locates the urethrovesical junction. The aim of this study was to test the reproducibility of this examination. Two different investigators examined 40 patients at rest and during Valsalva's manoeuvre. Using a rectangular coordinate system, the bladder neck was located by means of distance measurements. In addition, the retrovesical angle beta was measured as described by Green, and certain anatomical signs were noted. There was a good inter-examiner correlation (r values 0.77-0.92) both at rest and during Valsalva for the distances and angle beta. There was good agreement in the analysis of the anatomical signs. CONCLUSION: Perinatal ultrasound, together with the measurement method described in this paper, is a reliable technique for determining the bladder neck position, for measuring angle beta and for analysing anatomical signs. This method permits a quantitative evaluation and quality control of therapeutic procedures.

Female↗
PubMed1995

[Multivariate analysis of clinico-pathologic predictors of axillary lymph node metastasis in invasive breast carcinoma].

UNLABELLED: The aim of this study was to find both predictors of axillary lymph node involvement and predictors of level II or III involvement. With these predictors patients should be selected who can be spared axillary lymph node dissection or who qualify for removal of only first-level lymph nodes. 239 consecutive patients with invasive breast cancer stage I-III treated with total axillary dissection were evaluated. In multiple logistic regression analysis 17 clinical and histopathological variables were included. We found 4 multivariate significant predictors for metastatic axillary involvement: Clinically positive axilla, peritumoural lymphatic vessel invasion, multicentric or multifocal tumours and a large number of past pregnancies. Multivariate significant predictors of involvement of level II or III were peritumoural lymphatic vessel invasion, younger age, larger tumour size, multicentric or multifocal tumours and postmenopausal patient. The metastatic involvement of more than 3 nodes was associated with young age and clinically positive axilla. With these easily available predictors a reliable assessment of risk of metastatic involvement of the upper levels of the axillary nodes could be defined. The binary logistic regression model to axillary node involvement had a rather unsatisfactory predictive value. CONCLUSIONS: The risk calculation of level II or III involvement with these predictors may help the surgeon to find the adequate extent of axillary clearance needed in the individual patient. Multiparity proved to be an independent predictor of metastatic axillary node involvement.

Adult↗
PubMed1995

[Systemic methotrexate therapy of persistent trophoblast after tube saving surgery for extrauterine pregnancy].

Is single-drug methotrexate therapy for persistent trophoblastic tissue after conservative laparoscopic surgery an effective medical treatment? Here we report and discuss a case of apparent persistent trophoblastic tissue after salpingotomy and removal of an ectopic pregnancy treated with methotrexate and review the published cases. Single drug-therapy with methotrexate is an alternate approach to a persistent trophoblast after conservative surgery for ectopic pregnancy. Having recently undergone surgery, these women suffer when operated again due to anesthesiologic, surgical and psychological stress. The current case and the published data demonstrate that methotrexate is a simple, efficacious, successful and by now established therapy.

Adult↗