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J Frick

Publications and source records attributed to J Frick.

At least 37 records · Page 2Linked to original sources
PubMed1996

Fluorescence-optical measurements of chloride movements in cells using the membrane-permeable dye diH-MEQ.

Fluorescence-optical measurements of the intracellular chloride concentration facilitate identification of chloride movements across the cell membrane of living cells. The two main dyes used for this purpose are 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ) and 6-methoxy-quinolyl acetoethyl ester (MQAE). The use of both substances is impaired by their poor membrane permeability and therefore limited loading of the cells to be studied. Here we report the use of 6-methoxy-N-ethylquinolinium iodide (MEQ), a chloride-sensitive dye for which a membrane-permeable form is easily prepared. This makes the loading procedure as easy as with the acetoxymethyl (AM) forms of other dyes for sensing intracellular ions. In addition, the original method, which described absolute concentration measurements of chloride in the cytosol, was modified in so far as only relative measurements were made. This avoids the known limitations of single wavelength excitation and emission dyes with respect to exact concentration measurements. Moreover, to enhance the signal-to-noise ratio the driving force for chloride was considerably increased by changing the original direction of the anion flux in the cells under investigation. We verified the method by using fibroblasts and activating ICln, a putative chloride channel cloned from epithelial cells and of paramount importance in the regulatory volume decrease in these cells. In the presence of SCN- the MEQ quench measured in NIH 3T3 fibroblasts is dramatically enhanced in hypotonically challenged cells compared with cells under isotonic conditions. Antisense oligodeoxynucleotides sensing ICln considerably impeded the swelling-induced chloride current (ICl) in NIH 3T3 fibroblasts. Accordingly, the chloride movement measured by the SCN- quench of the MEQ signal was significantly reduced. Similar results can be obtained in the presence of 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) or 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), two known blockers of chloride transport in the plasma membrane of a variety of cells. In conclusion, fluroscence-optical measurements using MEQ as the chloride-sensitive dye provide a reliable and easy-to-use method for measuring changes of the chloride flux across the cell membrane of living cells.

3T3 Cells↗
PubMed1996

Quality of life in patients undergoing bacille Calmette-Guérin therapy for superficial bladder cancer.

OBJECTIVE: To determine the impact of post-operative education about bladder cancer and topical immunotherapy on the physical, psychological and social well-being of patients with superficial bladder cancer. PATIENTS AND METHODS: Eighty-five patients (mean age 59 years, range 26-85, 64 men and 21 women) receiving topical immunotherapy were questioned during the initial cycle of treatment and during maintenance therapy with bacille Calmette-Guérin (BCG). Patients completed a questionnaire on their quality of life when they commenced treatment and twice more during maintenance therapy. RESULTS: Psychological distress and physical symptoms were intense when the diagnosis of bladder cancer was revealed to the patients, despite the knowledge that this cancer is usually curable. The overall quality of life, condition of health and sexual activity were mostly only moderate, were poor during initial therapy and better during 3-monthly maintenance therapy. CONCLUSION: In general, the quality of life of these patients is characterized by the disruption of their lifestyle and marked by change in their circumstances. It is the responsibility of the urologist to take the necessary time to educate, comfort and motivate such patients with superficial bladder cancer.

Adult↗
PubMed1996

Blockade of swelling-induced chloride channels by phenol derivatives.

1. In NIH3T3 fibroblasts, the chloride channel involved in regulatory volume decrease (RVD) was identified as ICln, a protein isolated from a cDNA library derived from Madin Darby canine Kidney (MDCK) cells. ICln expressed in Xenopus laevis oocytes gives rise to an outwardly rectifying chloride current, sensitive to the extracellular addition of nucleotides and the known chloride channel blockers, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and NPPB (5-nitro-2-(3-phenylpropylamino)-benzoic acid). We set out to study whether substances structurally similar to NPPB are able to interfere with RVD. 2. RVD in NIH3T3 fibroblasts and MDCK cells is temperature-dependent. 3. RVD, the swelling-dependent chloride current and the depolarization seen after reducing extracellular osmolarity can be blocked by gossypol and NDGA (nordihydroguaiaretic acid), both structurally related to NPPB. 4. The cyclic AMP-dependent chloride current elicited in CaCo cells is less sensitive to the two substances tested while the calcium-activated chloride current in fibroblasts is insensitive. 5. The binding site for the two phenol derivatives onto ICln seems to be distinct but closely related to the nucleotide binding site identified as G x G x G, a glycine repeat located at the predicted outer mouth of the ICln channel protein.

3T3 Cells↗
PubMed1996

Treatment of prostate cancer with gonadotropin-releasing hormone analogue: effect on lipoprotein[a].

Because of its association with cardiovascular disease, lipoprotein[a] (Lp[a]) has attracted the interest of the medical community. Even though serum concentrations of Lp[a] are mainly controlled by the apolipoprotein[a] gene locus, hormonal and metabolic factors, including manipulations of sex hormone levels, have been associated with changes in Lp[a] levels. We report here that the GnRH analog buserelin reduced concentrations of Lp[a] by 48% in elderly males suffering from cancer of the prostate. In contrast, apolipoprotein B levels increased during treatment, whereas other lipid factors, including serum cholesterol, triglyceride, high and low density lipoprotein cholesterol, and apolipoprotein A-I, were not affected. Although the study does not exclude a specific Lp(a)-lowering effect of buserelin, our results suggest that GnRH analogs may reduce Lp[a] levels in the circulation.

Aged↗
PubMed1996

[Pathophysiology of benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is primarily a anatomical diagnosis. The prepubertal weight of the gland is about 1.6 g and at the end of the third decade around 20 g. With histological evidence for BPH there is an increase of weight and volume with aging. The human prostate is divided into zones which form, however, a fairly regular gland. The prostate is organized similar to a grape, these parts are surrounded with the epithelial cells which express different compounds and proteins and finally disappear by apoptosis. The stromal compartment is kind of a skeleton, both compartments (epithelial and stromal part) present manifold interactions based on androgens, androgen receptors and growth factors.

Adolescent↗
PubMed1996

ICln: a chloride channel paramount for cell volume regulation.

Cell volume regulation is a ubiquitous cell regulatory mechanism based on meticulously controlled ion transport mechanisms. Keeping the absolute volume constant seems to be of the highest priority for most cells and is achieved at the expense of altered intracellular ion concentrations. We have been able to demonstrate that ICln, a chloride channel cloned from epithelial cells, is paramount for the ability of swollen cells to regulate their volume back to that under resting conditions. A unique feature of ICln is the distinct sensitivity of these channels for nucleotides and nucleoside analogues added to the extracellular fluid. In addition, cromolyn sodium and nedocromil sodium, drugs used by patients with asthma, are able to impede the function of these channels.

Animals↗
PubMed1995

Five-year results of a phase II study with low-dose bacille Calmette-Guerin therapy in high-risk superficial bladder cancer.

OBJECTIVES: Numerous studies have shown bacille Calmette-Guérin (BCG) to be an effective prophylactic and therapeutic agent for superficial transitional cell carcinoma of the bladder. The high-grade T1 lesion treated by transurethral resection alone is reported to progress to muscle invasion in 30% to 50% of the patients. Until now, optimal treatment schedule and optimal dose have not been defined. As suggested by Pagano's group, we used BCG in a lower dose than hitherto usual in our high-risk cancer patients. METHODS: Five years ago, we treated 32 Stage T1 cancer patients who were described as at high risk based on the criteria of histologic grade 3 in 21 patients, grade 2, but multiple in 11 patients, and with carcinoma in situ in 17 patients. Follow-up ranged from 51 to 63 months, with a mean of 57 months. We used BCG strain Pasteur Paris 75 mg weekly for 6 weeks and then maintenance therapy monthly for the first year and every 3 months for the second year. Complete remission was defined as negative cystoscopy, biopsy, and cytology. RESULTS: After a single 6-week course of BCG, 25 patients had negative cytology and biopsy findings after 3 months; 2 other patients needed a second 6-week cycle of BCG, for an overall response rate of 80%. Five patients underwent cystectomy because of multiple recurrences and tumor progression. After 2 years of follow-up, but under continuing maintenance therapy, 3 additional patients had tumor recurrences and also underwent cystectomy. Now, after 5 years' follow-up, the overall progression rate to cystectomy was 25% (8 of 32 patients), but none of the patients had progression to metastasis. Treatment-related toxicity did not appear to be lower at a lower dose of BCG. CONCLUSIONS: Low-dose BCG therapy is also an effective treatment in high-risk T1 bladder cancer (especially with maintenance therapy and short-term evaluations of the patients always by the same controlling physician) to prevent progression and recurrence and to preserve bladder function.

Aged↗
PubMed1995

Low-dose bacille Calmette-Guérin (BCG) therapy in superficial high-risk bladder cancer: a phase II study with the BCG strain Connaught Canada.

OBJECTIVE: To evaluate low-dose bacille Calmette-Guérin (BCG) therapy, with the Connaught Canada strain, in patients with superficial transitional cell carcinoma (STCC) of the urinary bladder. PATIENTS AND METHODS: Between September 1990 and December 1992 25 patients were entered into a phase II study to evaluate the feasibility, response and toxicity of BCG immunotherapy for patients with high-risk STCC. Therapy consisted of six, weekly instillations of 27 mg (3 x 10(8) colony-forming units) of the BCG strain Connaught Canada. Maintenance therapy was administered monthly for 1 year with the same dosage. RESULTS: Of 25 eligible patients, 84% had complete responses after the initial cycle with low-dose BCG and had stable disease. Four patients had no response, three of whom subsequently underwent radical cystectomy. The mean length of follow-up was 30.8 months (25-36). Toxicity included profound local reactions such as severe dysuria, frequency and gross haematuria. No systemic infections, except fever, were seen; none of the patients needed isoniazid. All reactions were treated symptomatically. CONCLUSIONS: The results of this study suggest that low-dose BCG with the strain Connaught Canada can be successfully used in the treatment of patients with high-risk STCC. Toxicity was not reduced substantially by the lower dosage of BCG used.

Administration, Intravesical↗
PubMed1994

The effect of active immunization against gonadotropin-releasing hormone on the ultrastructure of the rat ventral prostate.

To evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on the ultrastructure of the rat ventral prostate, male Sprague-Dawley rats received three consecutive intramuscular injections of 10 micrograms/100 g body weight (D-Lys6)-GnRH-diphtheria toxoid conjugate (GnRH-DT vaccine). Following immunization, test animals developed sufficiently high antibody titres to block the pituitary gonadal axis. Consequently testosterone values dropped to the levels in castrates. This therapy leads to atrophy of the prostate. Following immunization a strong immunological response, indicating the presence of considerable amounts of a GnRH-like peptide, was observed in the ventral prostates as early as 14 days after the first injection of GnRH-DT. Immunoneutralisation of GnRH-like activity may contribute to the effects observed.

Animals↗
PubMed1994

Diagnostic problems of urine cytology on initial follow-up after intravesical immunotherapy with Calmette-Guérin bacillus for superficial bladder cancer.

After transurethral resection or biopsy, patients with recurrent bladder cancer or in situ carcinoma were given topical immunotherapy with low-dose Calmette-Guérin bacillus (BCG). In the recurrence-free interval they were treated with BCG monthly for 1 year and then every 3 months for the next year. Cytological analysis was always performed concomitant with the administration of immunotherapy. In order to evaluate the therapeutic success, cystoscopy and biopsy were performed after the first cycle of BCG and then every 3 months. At the start of topical therapy with BCG, a great increase in the number of inflammatory cells was seen. In urothelial cells the nuclei were enlarged; they were hyperchromatic with sometimes increased and prominent nucleoli, anisocaryosis and a distorted nucleus-plasma ratio. These cytological findings were also made 1 year after initial therapy and slowly diminished in the 2nd year during immunotherapy at 3-month intervals. The accuracy of urine cytology for carcinoma in situ is 80%. Interpretation of cytology in the recurrence-free interval was impaired. When doubtful, the recurrence of a carcinoma in situ under maintenance therapy with BCG must be proved by biopsy.

Administration, Intravesical↗
PubMed1994

Mediastinal tumor and Klinefelter's syndrome.

Klinefelter's syndrome with karyotype 47,XXY in patients with primary extragonadal germ cell tumors rarely occurs. The endocrinology of Klinefelter's syndrome is changed; elevated beta-human choriomic gonadotropin levels are present. Chemotherapy and thoracic surgery brought complete remission in a patient with lung metastases.

Adolescent↗
PubMed1993

LHRH and cryptorchidism.

This paper is a historic review of two studies of the treatment of cryptorchidism. One was concluded 20 years ago with native LHRH, while the other took place 14 years ago and involved one of the potent LHRH analogues. The first study was initiated at the end of 1971-at a time when the different modes of action of the decapeptide were by far not evaluated to the full extent they are now-and included ten prepubertal boys with undescended testes aged five to ten years. The treatment consisted of intramuscular application of 20 micrograms LHRH once daily for three weeks. Additionally, three boys, five, seven and nine years of age, also presenting undescended testes underwent an LHRH test with intravenous bolus application of 200 micrograms. In all three subjects, a 2.5-fold increase in plasma testosterone was observed 20 min after the bolus. The treatment group showed neither a rise in LH nor in testosterone at the end of therapy. Testicular descent was achieved in six out of six boys with bilateral and in 2/4 with unilateral undescended testes. These good results might be based on the fact that six boys had retractile rather than actually undescended testes. In the second study started in 1978, 18 boys, three to 12 years of age with either unilateral or bilateral cryptorchidism, were treated with a synthetic LHRH analogue ("D-Leu 6, Des-Gly-10 LHRH ethylamide") applied intranasally. The peptide prepared in an aqueous solution was administered in the form of nose drops.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1993

[Endocrinology and fertility in stage I testicular tumor].

The situation of endocrinology and fertility of patients suffering from testicular cancer stage I (Peckham) with good survival rates were evaluated before semicastration. The value of beta-hCG is of great importance. According to this criteria 3 groups were formed. beta-hCG positive tumors, beta-hCG positive tumors out of the blood sample of the vena spermatica after ablation of the testis tumor and beta-hCG negative tumors. The histology is of secondary importance. 54 patients with testicular cancer were evaluated in this study. From 37 patients it was possible to get a spermiogram before semicastration. For the analysis of the spermiogram the values of LH, FSH, Testosterone and E2 are responsible. The values of beta-hCG in the serum from the periphery is of great importance, while a single elevation of beta-hCG in the serum out of the v.spermatica does not change the endocrinology. The question of kryosperm conservation is according to these parameters better evaluable.

Adult↗