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Biomedical subjects

S Pettersson

Publications and source records attributed to S Pettersson.

At least 19 recordsLinked to original sources

Identification of Ets-like lymphoid specific elements within the immunoglobulin heavy chain 3' enhancer.

Recently we identified an additional enhancer in the 3' end of the immunoglobulin heavy chain (IgH) locus. To identify individual regulatory elements within the rat IgH 3' enhancer, deletion analysis was performed. Transfection experiments using reporter constructs suggest that the enhancer contains three functionally distinct domains, two of which are lymphoid specific and one domain is active in both lymphoid and in nonlymphoid cells. The three domains together contribute to enhancer function and act synergistically. Further analyses suggest that a putative mu E1 site, octanucleotide motif, mu E3 site, and mu B/Ets-like motif are important for the overall transcriptional activity of the IgH 3' enhancer. Moreover, we provide evidence that an additional Ets-like element, micro A, is involved in the tissue specific regulation of enhancer activity and that binding of a protein to this element correlates with the transcriptional activity of one of the lymphoid restricted domains.

Animals

The influence of pH and urine composition on urease enzymatic activity in human urine.

It is reasonable to assume that the rate of pH increase in urine induced by urease-producing microorganisms is one of the factors which determine whether crystallisation with subsequent stone formation will occur or not. To evaluate how the time needed to increase urine pH varies between different urine samples and how it depends on urine composition, a standardised amount of urease was added to different human urine samples. The incubations were performed in a pH-stat. This allowed simultaneous study of how urease enzymatic activity depends on urine pH and how it varies between different urines. The enzymatic activity was found to be negatively correlated to urine pH and to vary between different urines. The rate of the pH increase varied markedly between different urines. Small pH increases depended on the native urine pH and urease enzymatic activity. Higher pH increases up to the levels of phosphate crystallisation depended more on urine phosphate, the major urine buffer. The results presented show that urine composition influences the urease-induced pH increase. This might have clinical implications.

Adult

Effect of substance P on detrusor muscle in rats with diabetic cystopathy.

Diabetic cystopathy (DCP) is a well known complication in diabetes mellitus (DM). In the present experimental study, DM was induced in rats by streptozotocin and DCP was confirmed on cystometry. In vitro studies on detrusor strips from diabetic rats showed an increased contractile response to substance P (SP) compared with controls, indicating denervation supersensitivity. A decreased response to capsaicin in diabetic detrusor strips indicated a decreased neuronal content of SP or a diminished number of SP-containing sensory nerves. This suggests that DM induces alterations in nerves containing SP which may be at least partly responsible for sensory loss and the development of DCP.

Animals

ESR-measurement of production of oxygen radicals in vivo before and after renal ischaemia in the rabbit.

This study describes a spin trap technique to determine production of oxygen radicals in rabbit kidneys after ischaemia and reperfusion. OXANOH was infused intra-arterially. When exposed to oxygen free radicals OXANOH is oxidized to the stable radical OXANO(.). The concentration of OXANO. in samples of renal venous blood was determined by ESR. Production of oxygen radicals was calculated from the amount of OXANO. in the venous blood and the blood flow which was determined by an ultrasound technique. The radical production at reperfusion after ischaemia was expressed as a per cent of the pre-ischaemic value. A drastic increase in radical production was observed during (60 min) reperfusion after 60 min of ischaemia. Pretreatment with oxypurinol (20 mg kg-1) before ischaemia and before recirculation almost completely abolished the rise in radical production at recirculation. Similar results were obtained when oxypurinol was given before recirculation only.

Anesthesia

Skeletal metastases in 102 patients evaluated before surgery for renal cell carcinoma.

During a 3-year period a consecutive series of 102 patients were treated for renal cell carcinoma at one urological unit. Thirty-three patients (32.4%) had metastatic spread, but bone metastases were found in six patients only, i.e. 5.9% of the whole series and 18.2% of the patients with metastases preoperatively. The bone metastases had in all six patients given local symptoms first indicating radiography, and thereafter radionuclide scintigraphy of the entire skeleton. Bone scintigraphy performed merely by routine in 70 patients did not reveal one single case of bone metastasis. Only one patient had a solitary bone metastasis, and this metastasis was considered inoperable because of its location and size and the patient's age. The decision about nephrectomy was not in any case altered by the finding of bone metastases. Solitary bone metastasis must be diagnosed early since they may be radically removed. Routine scintigraphy of the skeleton in symptomless patients, however, has a low yield. Screening for skeletal metastases may therefore be best performed by careful physical examination and history-taking.

Adult

Bilateral asynchronous renal cell carcinoma. Computed tomography of the contralateral kidney 10-43 years after nephrectomy.

Computed tomography (CT) was carried out in 31 patients 10-43 years after surgery for renal cell carcinoma, 10 belonging to a consecutive series of patients operated upon at one urological department 10 years previously. Twenty-eight patients were symptomless, and 3 had flank pain, severe fatigue and hematuria, respectively. Cancers in the remaining kidney were found 13-21 years after nephrectomy in 4 of 31 patients (12.9%). The 3 patients with symptoms were among these 4. An adenoma was found in 1 patient 10 years after nephrectomy. The cancers were treated by renal resection in 2 patients, multiple tumors made nephrectomy necessary in 1 patient and 1 patient was not operated upon because of disseminated disease. The adenoma indicated future checkup by CT. Three of the 4 new cancers had a dismal outcome. The renal parenchyma was found to be essentially normal in all the other 26 patients, irrespective of the widely varying time interval between nephrectomy and CT. Asynchronous bilateral renal cell carcinoma has a poor outcome which presumably can be improved by early diagnosis and aggressive treatment. CT is the method of choice for early detection and follow-up of renal tumors. It should be carried out every other year after nephrectomy for renal cell carcinoma.

Adult

The mouse IgH 3'-enhancer.

A lymphoid-specific transcription enhancer element has recently been identified at the far 3' end of the rat immunoglobulin heavy chain (IgH) locus. Sequence analysis presented here reveals that this enhancer is flanked by a 350-bp invert repeat, giving a structure reminiscent of a transposable element. We therefore screened for the equivalent enhancer in the mouse to determine whether its presence was conserved during evolution. A mouse homologue was indeed identified and is located 16 kb downstream of the C alpha 1 exon. It is also flanked by invert repeats and these are not repeated throughout the genome. The mouse and rat enhancers retain high sequence homology. As regard activity, the IgH 3'-enhancer is lymphoid specific. However, this activity was detected in two plasmacytoma lines tested but not in two B cell lymphomas nor in HeLa cells suggesting that the enhancer may only play a stage-specific role during lymphocyte differentiation. As regards function within the IgH locus, we found that inclusion of the mouse IgH 3'-enhancer (in addition to the intron-enhancer) on mu gene expression plasmids effected a small increase in mu mRNA levels in stable plasmacytoma transfectants.

Animals

Urease-induced precipitation of phosphate salts in vitro on indwelling catheters made of different materials.

The urease-induced precipitation of phosphate salts on indwelling catheters was studied in an experimental in vitro model. The precipitation was strongly pH-related and was much higher in synthetic urine than in human urine. In the latter, it was significantly lower on silicone catheters than on latex catheters, including those with a hydrophilic coating. The precipitation on silicone catheters that had been in situ was not increased as compared with that on unused catheters, in contrast to latex catheters with a hydrophilic coating, among which the precipitation on used catheters was higher.

Catheters, Indwelling

Studies of urease-induced crystallisation in undiluted human urine using the Coulter counter technique.

Urease-induced crystallisation was studied in different human urine samples after urease incubation. The studies were performed using the Coulter counter technique, which enables determination of the number and size of particles in a solution and calculation of the total particle volume. The crystallization took place in three consecutive but overlapping steps: (1) nucleation, (2) growth and (3) aggregation. The maximal number of particles obtained in the different samples varied little, but there was a great variation in particle size and total particle volume. The variation in particle size appeared to be mainly due to differences in particle growth, a factor that might be of importance for stone formation.

Adult

Influence of indomethacin on the adherence of urease-induced crystals to rat bladder epithelium.

The mucous coat lining the urinary tract has a barrier function which prevents bacteria and crystals from adhering to the uroepithelium. The mucous coat of the gastric mucosa is sensitive to prostaglandins, and prostaglandin synthetase inhibitors induce gastric erosions and disrupt the continuity of the mucous lining. To determine whether prostaglandin synthetase inhibitors also exert a similar effect on the uroepithelium, rats were given indomethacin intraperitoneally or orally. The effect of this treatment on the adhesion of urease-induced crystals to rat bladder mucosa was studied using a previously developed in-vivo method. Both when given intraperitoneally and orally in a dose of one mg. per kg. b.w. for six weeks, indomethacin significantly increased crystal adherence. This constitutes indirect evidence for the concept that prostaglandins influence the mucous coat of the rat urinary tract and reduce its antiadhesive properties.

Adhesiveness

Transitional cloacogenic carcinoma of the female urethra treated with external irradiation and afterloading with cobalt-60.

A case of transitional cloacogenic carcinoma of the urethra in a 70-year-old woman is reported. Due to incomplete removal of the tumor and reluctancy to undergo extensive surgery, the patient also received external radiation and afterloading with cobalt-60. The patient is alive with no evidence of disease 7 years after the diagnosis, which may suggest that postoperative radiation as outlined should be considered in elderly women with urethral carcinoma.

Aged

Use of a tamponade catheter in the bleeding nephrostolithotomy track.

Bleeding from the nephrostomy track, which is the most common major complication of percutaneous extraction of renal stones, was treated in 5 patients with the Kaye double-lumen nephrostomy tamponade catheter. This treatment was effective in all cases. The procedure eliminates the need for more invasive measures like embolisation and open surgery with renal resection, both of which cause loss of functioning renal parenchyma.

Adult

Outpatient-based extracorporeal shock wave lithotripsy using EDAP LT-01.

Between March 1988 and March 1990, 751 patients were treated with shock wave lithotripsy using EDAP LT-01. Six hundred and eight patients had renal stones while 143 patients had stones located in the ureter. Because of difficulties in locating ureteric stones with ultrasound 92% of them were pushed back to the kidney before treatment. The mean stone size was 10 mm, range 4-30 mm. Patients with stones bigger than 15 mm had a double J-stent placed before treatment. The mean number of treatments per patient was 1.7 (range 1-8). Sixty-six per cent of the patients with renal stones were completely stone-free after ESWL monotherapy. Another 5% became stone-free after auxiliary procedures in the ureter, because of retained fragments. Fragments equal to or less than 4 mm were retained in 14% of the patients with the renal stones. Of the patients with ureteric stones mobilised back to the kidney 95% were rendered stone-free after ESWL. Most patients experienced no or very little discomfort during the treatment and only 29% of them received analgesics. General of epidural anaesthesia was given to 1% of the patients. Because of the low demand for analgesia or anaesthesia, 99% of the patients with renal stones were treated on an outpatient basis. During the second year, 74% of the patients with ureteric stones were treated on an outpatient basis.

Adolescent

A second B cell-specific enhancer 3' of the immunoglobulin heavy-chain locus.

The expression of immunoglobulin heavy-chain (IgH) genes is generally thought to be regulated by the combination of the VH promoter with the enhancer element which is located in the JH-CH intron. This is probably an oversimplification: there are cell lines that transcribe IgH genes despite the deletion of the intron-enhancer. These findings could imply that other enhancer element(s) exist in the IgH locus. Here we show that a strong B-cell-specific enhancer is indeed located at the 3'-end of the rat IgH locus, 25 kilobases downstream of C alpha. This enhancer should be retained downstream of all rearranged IgH genes, regardless of the VH or CH segment used. Taken together with analogous findings for the mouse kappa locus, the results prompt a re-evaluation of the mechanism of regulation of immunoglobulin gene transcription. Furthermore, unlike the intron-enhancer, the IgH 3' enhancer would become linked to a c-myc that rearranges into an IgH switch region. The IgH 3' enhancer could therefore play a part in the activation of the translocated c-myc genes in rat immunocytomas, mouse plasmacytomas and Burkitt lymphomas.

Animals

Effects of serum, albumin and immunoglobulins on urease-induced crystallization in urine.

The effects of serum, albumin and gammaglobulins on urease-induced crystallization have been studied in synthetic and in human urine. Serum and the studied proteins increased urease enzymatic activity in synthetic urine. In human urine only serum had this effect. In synthetic urine, the proteins and serum markedly decreased the precipitation attached to glass surfaces, while the intraluminal precipitation was increased. In human urine, similar but weaker effects on the precipitation were found for serum and albumin. These findings suggest that the proteins studied, in the concentrations in which they are present in human urine, have profound effects on urease-induced crystallization and may be physiological crystallization inhibitors.

Crystallization

How variations in the composition of urine influence urease-induced crystallization.

To Study how the composition of urine influences urease-induced crystallization, human urine samples were incubated with urease and the subsequent precipitation measured. Beside the pH increase, the urinary content of magnesium and calcium had profound effects on the precipitation of magnesium ammonium phosphate and calcium phosphate, respectively. Urine phosphate, ammonium and osmolarity had no direct effects on the precipitation. Among the urine components with potential inhibitory properties, only albumin was found to be correlated with such an effect. This inhibitory activity was especially influential in urines with high calcium and magnesium levels. These findings suggest that the composition of urine could also influence the formation of stones consisting of magnesium ammonium phosphate and calcium phosphate.

Calcium Oxalate

Bacteriology of upper urinary tract stones.

Extensive cultures of stones and urine were performed in 215 patients who underwent an operation for upper urinary tract calculi. Microorganisms could be cultured from the stone in 1 of every 3 patients. Despite the extended culture technique urease-producing microorganisms could be cultured from the stone in only 48% of the patients with calculi that contained magnesium ammonium phosphate. This finding suggests that an infection with urease-producing microorganisms is not obligatory for the formation of this type of stone. Of the patients with calcium oxalate phosphate stones 32% had positive stone cultures, which distinguished them from patients with pure calcium oxalate stones, only 8% of whom had a positive stone culture (p less than 0.001).

Adolescent