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Biomedical subjects

E Borgström

Publications and source records attributed to E Borgström.

At least 19 recordsLinked to original sources

The prevalence of loss of heterozygosity in chromosome 3, including FHIT, in bladder cancer, using the fluorescent multiplex polymerase chain reaction.

OBJECTIVE: To determine some of the genetic alterations involved in the pathogenesis and progression of transitional cell carcinoma of the bladder. Materials and methods In a population-based study, freshly frozen tissue was collected from all patients newly diagnosed with urinary bladder cancer in the Stockholm region during 1995-1996. The prevalence of loss of heterozygosity (LOH) was assessed at seven sites on chromosome 3, analysed in 151 patients, using a fluorescent multiplex polymerase chain reaction based on DNA from the tumour and peripheral blood. RESULTS: LOH was detected in 12.1% (at 3q25-26.2) to 22.1% (at 3p11-12) of the informative cases. Relatively frequent LOH was detected at 3p22-24.2 (21.6%), at 3p14.2 within FHIT (21.5%), and at 3p11-12 (22.1%). Of 151 tumours, 72 (47.7%) showed LOH at one or more loci on chromosome 3. LOH on chromosome 3 was weakly associated with tumour grade (P = 0.095), but not with tumour stage (P = 0.701). However, when the frequency of LOH was analysed individually at each site, the prevalence of LOH at 3p11-12 was closely correlated with higher tumour stage (P = 0.011). Replication errors were detected in only four of 151 (2.6%) tumours. Conclusion These findings suggest that the 3p11-12 locus may involve a putative candidate tumour-suppressor gene which might be associated with bladder tumour invasiveness. The FHIT gene locus showed a relatively high frequency of LOH even in Ta tumours.

Acid Anhydride Hydrolases↗

Bladder cancer: allelic deletions at and around the retinoblastoma tumor suppressor gene in relation to stage and grade.

Inhibition of the retinoblastoma tumor suppressor gene (RB) is probably important in the pathogenesis of urinary bladder cancer. Little information is available concerning allelic loss on 13q11 to 13q32 and its relation to grade and stage. In a population-based study, freshly frozen tissue was collected from all new cases of urinary bladder cancer in the Stockholm region during 1995-1996. Here we report the occurrence of loss of heterozygosity (LOH) at seven sites in 13q11 to 13q32 as analyzed in 236 cases by a fluorescent multiplex PCR-based on tumor DNA and peripheral blood. For each site, about 30% of the cases were not informative because of homozygosity. Replication errors were detected in 4% (17 cases). LOH was found in 21 (at 13q11-12.1) to 32% (at 13q14.3 in RB) of the informative cases. A correlation was found between the prevalence of LOH at all observed loci and stage and grade, respectively, and it was statistically significant for 13q14.3. LOH at RB was found in Ta as well as grade 1 tumors. Also, a statistically significant correlation was found between the number of loci with LOH at 13q and tumor stage and grade, respectively. Typically an altered RB function is related to the expected clinical course of urinary bladder cancer, but allelic loss including the gene also occurs in low grade and low stage tumors. An altered RB function probably is not necessary for a malignant transformation of urothelial cells. The causal direction of the relation between the quantity of the deleted DNA and tumor aggressiveness is not clear.

Alleles↗

Prophylactic instillation therapy of superficial bladder cancer. A randomized study comparing mitomycin C and adriamycin with special reference to DNA ploidy.

Sixty patients with Ta and T1 bladder cancer were randomized between treatment with resection only and resection and instillations with either Adriamycin or Mitomycin C. Treatment lasted for one year and patients were evaluated after a mean follow-up of 35 to 47 months if progression had not occurred. Mitomycin C was superior in reducing the recurrence rate. Progressive disease was observed in 17 patients regardless of therapy but in all patients DNA aneuploidy could be identified at a risk factor.

Administration, Intravesical↗

Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial.

In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma-concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment.

Adult↗

Penile ulcer as complication in self-induced papaverine erections.

We report on penile ulcus as a complication of self-induced papaverine erections in 2 patients. The ulcers which occurred after inadvertent subcutaneous injection of the drug healed in four to six weeks. The patients resumed papaverine injections without subsequent adverse effects.

Humans↗

ABH isoantigens, histology and DNA ploidy in 36 consecutive patients with transitional cell bladder cancer. Status of tumor and biopsies taken from visually normal urothelium.

Tumors and biopsies from visibly normal urothelium in 36 consecutive patients with transitional cell bladder carcinoma were analysed for histological pathology, DNA ploidy and ABH isoantigens. Tumor isoantigen deletion correlated strongly with malignant histology (p = 0.016) and aneuploidy (p = 0.005). In 4/12 patients with ABH isoantigens present on the tumor, and in 6/8 with isoantigens absent, isoantigen changes were found in normal looking urothelium, usually with normal histology and ploidy. It was concluded that the ABH isoantigen change was an early event in bladder carcinoma.

ABO Blood-Group System↗

ABH isoantigens in bladder carcinoma patients grouped according to DNA changes over time.

Eighteen patients with transitional cell bladder carcinoma and increasingly abnormal ploidy were assembled to evaluate the relation over time between ploidy and ABH isoantigen deletion. Fifteen patients with diploid recurrent tumors and 16 with aneuploid tumors over time were used as controls. ABH isoantigen deletion at diagnosis was closely related to cancer death, while isoantigen assessments on recurrences gave less prognostic information. Aneuploidy at diagnosis also indicated an adverse prognosis, as did recurrent bladder carcinoma with deteriorating ploidy. Patients with tumors deleted of isoantigen expression at diagnosis but with normal ploidy had as bad a prognosis as patients with deleted tumors and aneuploidy, indicating that isoantigen deletion may occur earlier than ploidy changes.

Adult↗

Clinical significance of A, B, H isoantigen deletion of urothelial cells in bladder carcinoma.

The occurrence and/or deletion of A, B, H isoantigens in cytologic specimens was compared to a number of other clinical parameters commonly used for prediction of prognosis or monitoring of bladder carcinoma. Isoantigens were better preserved by our preparation for cytologic than for histologic specimens. Patients with isoantigen present on urothelial cells were more likely to have small or no visible tumors than large tumors. A strong correlation was found between isoantigen status and cytologic diagnosis (P less than 0.001), but not with ploidy (P = 0.059). For short-term prognosis of recurrence, tumor size appeared to be highly significant, whereas A, B, H isoantigen determinations had no predictive value. Intravesical chemotherapy did not per se influence expression/deletion of isoantigens.

ABO Blood-Group System↗

Fluorescence methods for measuring the A, B, and H isoantigens on cytological material from bladder carcinoma.

Fluorescence methods for determining ABH isoantigens on transitional cells were developed for the study of cytologic material. Indirect immunofluorescence was used for A- and B-antigens, fluorescein-labeled Ulex Europaeus lectin for the H-antigen. Isoantigens of 151 patients with bladder carcinoma were studied. Patients with a malignant cytology showed deletion in 31/65 cases compared to 12/62 cases when the cytology was benign. Cyto-flow ploidy determinations were abnormal in 41/120 cases measured; cells from 21 of these 41 had isoantigen deletion compared to 25/79 cases with a diploid pattern. The ABH isoantigen deletion shows some relation to malignant cytology, abnormal ploidy and a visible tumor, but is probably an independent parameter.

ABO Blood-Group System↗

Urinary modified nucleosides as tumor markers in cancer of the urinary organs or female genital tract.

Using a sensitive and specific method involving high-performance liquid chromatography, urinary levels of four modified nucleosides--pseudouridine (psi), 1-methylinosine (m1I), 1-methyladenosine (m1A), and 1-methylguanosine (m1G)--were investigated before and after treatment in 31 patients with cancer of the urinary organs or the female genital tract. Before treatment m1I was the most frequently elevated nucleoside (77%). Pretreatment urinary levels of psi, m1I, and m1A in patients with stage 2-4 cancer of the female genital tract were significantly elevated compared to human healthy volunteers (p less than 0.005). Compared with the other nucleosides, psi appeared to correlate more closely with the clinical outcome (progression or regression) of patients with cancer of the female genital tract. In the case of patients with cancer of the urinary organs, m1I followed the clinical outcome better than the other nucleosides measured. Therefore psi and m1I seem to be useful for monitoring genito-urinary cancers.

Adenosine↗

Pseudouridine and uridine in normal kidney and kidney cancer tissues.

The tissue concentrations of a modified nucleoside, pseudouridine, and a normal nucleoside, uridine, were measured with high-performance liquid chromatography. Human kidneys were obtained from five patients with renal cell carcinoma and divided into a noncancerous part and a cancerous part. The pseudouridine concentration in the cancerous part of the kidneys ranged between less than 2-2.8 nmoles/g and in the noncancerous part 4.3-19.4 nmoles/g (mean 10,9 nmoles/g). The uridine concentration in the cancerous and noncancerous parts of the kidney ranged between 19.6-179.1 nmoles/g (mean 110.7 nmoles/g) and 117.5-235.6 nmoles/g (mean 191.5 nmoles/g), respectively. The pseudouridine concentration appeared to be approximately seven times higher in the noncancerous part as compared to the cancerous part of the kidney. In the case of uridine, the difference was less pronounced.

Carcinoma, Renal Cell↗

Alcohol occlusion of segmental renal arteries as alternative to kidney resection.

Treatment of postoperative urine leakage after a lower pole resection by embolic occlusions of segmental arteries using pure ethanol in a thirty-four-year-old man is described. There were no postoperative complications, and follow-up examination at two years showed a functioning but small kidney in a patient without symptoms.

Adult↗

Quantitative analysis of the A, B and H isoantigens in single transitional carcinoma cells.

To obtain objective data on deletion of the ABH isoantigens in bladder carcinoma, microfluorometry was used. Slides were scanned in phase contrast to lessen fading of the immuno- or lectin-fluorescence stained cells. The fluorescence intensity was measured in relation to an external uranyl standard. Staining was most intense in the peripheral and cytoplasmic parts of the cells. The intra specimen fluorescence intensity varied as 1 to 10. In nondeleted cell populations fluorescence intensity means ranged from 1025 to 12,550 and in deleted populations from 304 to 510. Microfluorometry accurately separates deleted cell populations from those with a normal ABH antigen content.

ABO Blood-Group System↗

Use of prophylactic antibiotics in orthopedic surgery.

The use of prophylactic antibiotics was studied prospectively in 2371 consecutive clean orthopedic operations. The infection rates for operations with obvious selection for antibiotic prophylaxis were twice as high (7.2%) as compared with operations with planned prophylaxis (3.4%) and with operations without such prophylaxis (3.7%). Sixteen per cent of all clean operations received antibiotics for prophylaxis and 85 per cent of all prophylactic courses lasted at least 8 days or longer. Fifty-one per cent of all antimicrobial drugs used during the study were administered for prophylaxis in clean orthopaedic operations. The length of the hospital stay was the only factor closely related to the length of antibiotic prophylaxis. The drugs most often used for prophylaxis were penicillinase-resistent penicillins. Significant increase of gram-negative pathogens was observed in cultures from wounds of patients on antibiotic prophylaxis.

Humans↗

On the presence of prostatic secretion protein in rat seminal fluid.

The copulating plug collected from the tip of the penis from rats immediately after decapitation contains a protein very similar and probably identical to PSP (prostatic secretion protein); this protein has earlier been purified from rat prostatic cytosol and characterized. The protein present in the copulating plug interacts with [3H]estramustine and binds to the antibody raised against rat PSP. The concentration of the protein in the copulating plug is 400 ng/mg of total protein, when measured using the radioimmunoassay technique developed earlier for measurement of PSP in rat prostate. The [3H]estramustine-protein complex formed in a preparation of the copulating plug has an apparent molecular weight of about 50,000 and a sedimentation coefficient of about 3S when analyzed using sucrose density gradient centrifugation. The complex was retained on Concanavalin-A Sepharose indicating that the protein is a glycoprotein. Binding of the complex was also observed on hydroxylapatite and DEAE-Sephadex columns, from which it was eluted at 0.18 M KCl. Light microscope autoradiograms of rat sperms incubated with 125I-labeled PSP indicated that PSP is bound to all parts of the sperms. A macromolecule interacting with the PSP-antibodies is also present in human seminal fluid but at a concentration considerably lower than in rat seminal fluid. The present study shows that a macromolecule probably identical to prostatic secretion protein is present in the copulating plug from the rat. The biological role of this protein in normal male fertility is discussed.

Animals↗