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Biomedical subjects

B E Persson

Publications and source records attributed to B E Persson.

33 records · Page 2Linked to original sources

CA-50 as a tumour marker for monitoring colorectal cancer: antigen rises in patients postoperatively precede clinical manifestations of recurrence.

Using a monoclonal antibody-based radioimmunoassay inhibition method we have determined preoperative serum levels of the carcinoma-associated carbohydrate antigen CA-50 in 266 patients with primary colorectal cancer. CA-50 levels exceeding the mean value for blood donor sera by more than 2 standard deviations (greater than or equal to 17 U/ml) were found in 47% of these patients, with 15%, 43% and 31% being elevated in patients with Dukes' A, Dukes' B and Dukes' C cancer, respectively, and 63% and 66% being elevated in patients with more advanced localized or disseminated cancer. Only 5% of patients with benign colorectal disease had elevated CA-50 level and these were patients with ulcerative colitis of a duration of more than 10 years. Among patients who had developed a recurrence after operation for a primary Dukes' A-C colorectal cancer 66% had elevated levels, and 25% of resected patients with no clinical evidence of disease at corresponding times after operation also had CA-50 levels above the normal concentrations. From 139 patients operated for a Dukes' A-C colorectal cancer a definitive rise in CA-50 levels from the pre- to a 6-9 months postoperative sample was demonstrated in 12 cases in the absence of any clinical evidence for a recurrence. On prolonged follow-up a clinically manifest recurrence later developed in all of these cases with lead times of CA-50 titre rises ranging from 5 to 40 months. Our findings suggest that a rise in CA-50 levels after resection of a Dukes' A-C primary colorectal cancer is indicative of a recurrence and may precede any clinical evidence of disease by many months or years. Thus CA-50 may be a clinically useful tool for monitoring of patients with colorectal cancer.

Adenocarcinoma↗

Juxtaglomerular interstitial hypertonicity in Amphiuma: tubular origin-TGF signal.

One of the mechanisms mediating renal vascular autoregulation in mammals senses tubular flow rate-dependent changes in luminal NaCl concentrations and signals renal arterioles to change diameter. A similar mechanism operates in the salamander, Amphiuma means. To trace the signal, we measured chloride activity in juxtaglomerular interstitial spaces in Amphiuma during perfusion of the early distal tubule belonging to the same nephron. Interstitial Cl- activity exceeded systemic levels and increased when perfusion rate in the adjacent early distal tubule was increased, reaching values more than five times isotonic. Bumetanide, which inhibits NaCl transport by the early distal tubule, eliminated the hypertonicity. Regions of the interstitial space not a part of the juxtaglomerular apparatus (JGA) were not hypertonic. The Cl- concentration was 80% greater than isotonic in the JGA of nephrons studied under free-flow conditions. Single-nephron blood flow, measured by counting the flux of erythrocytes labeled with a fluorescent molecule, showed typical feedback inhibition with maximum sensitivity to the same rates of tubular perfusion that caused the maximum change in JGA interstitial hypertonicity. Juxtaglomerular interstitial hypertonicity could be an important part of the signal for renal autoregulation.

Animals↗

Treatment of ulcer and nonulcer interstitial cystitis with sodium pentosanpolysulfate: a multicenter trial.

The effect of sodium pentosanpolysulfate (Elmiron) in the treatment of interstitial cystitis was observed in an open controlled multicenter trial. We studied 87 patients with symptoms for more than 2 years at 17 centers in Finland and Sweden. Patient selection was based on the typical chronic symptomatology but the material subsequently was stratified according to objective cystoscopic findings. The medication (400 mg. daily in 2 oral doses) was discontinued after 6 months. The response was evaluated every 4 weeks during treatment and every 3 months thereafter. Most patients responded favorably, many with diminution of pain within only 4 weeks from the start of treatment. The frequency of micturition decreased significantly and the mean volume per void per 24 hours increased in the patients without bladder ulceration but such changes were not found in the patients with ulcer. The bladder capacity was smaller in the ulcer group. In these patients the pre-treatment intensity of pain was somewhat greater than in those without bladder ulcer but the pain was alleviated in both groups and this effect was stable at the 3-month followup. The differences in responses in the 2 groups indicate a probable fundamental difference between ulcerative and nonulcerative interstitial cystitis. Side effects of the drug were few, slight and transient. Therefore, the study indicates that a significant number of patients with interstitial cystitis can be expected to benefit from treatment with sodium pentosanpolysulfate.

Adult↗

GFR regulation and flow-dependent electrophysiology of early distal tubule in Amphiuma.

Tubuloglomerular feedback (TGF) in mammals and amphibians senses flow-dependent concentration changes in tubular fluid of the distal tubule and signals to arterioles to initiate changes in glomerular filtration rate. The distal tubules and afferent arterioles are situated on the surface of the kidney of Amphiuma means. Micropuncture techniques were used to measure luminal and intracellular chloride concentrations and the associated electrical potential differences, while tubular perfusion rate was varied. Transepithelial potential difference (PDte) and basolateral potential difference (PDbl) became more positive at increased tubular flow rates. Intratubular and intracellular chloride concentrations also increased significantly with perfusion rate. Single-nephron glomerular filtration rate decreased when perfusion rate was increased but this response was eliminated by the inclusion of furosemide in the perfusion solution; the drug also inhibited the flow dependence of PDte. The results suggest that local changes in PD and Cl- activity result from flow-dependent changes in the rate of hypertonic NaCl transport propagated along the length of the perfused segment; they establish a correlation between the rate of transport and the magnitude of the TGF inhibition; and, because transport and TGF can be jointly inhibited, they suggest a causal link between the two.

Animals↗

Carbonic anhydrase inhibition and cell volume regulation in Necturus gallbladder.

Gallbladder epithelial cells transport salt and water isotonically as the renal proximal tubule. The cells also have the property of regulating their cell volume in response to osmotic stress (Fisher et al. 1981, Persson & Spring 1982, Fisher & Spring 1984, Foskett & Spring 1985). The volume-regulating phenomenon is the result of a balance between cell uptake of salt and water at the luminal membrane and exit at the basolateral membrane. Different properties regarding volume regulatory increase and decrease have been found (Eriksson & Spring 1982 and Larson & Spring 1983). The present study links fluid transport and volume regulatory increase of the cell. First we concluded from histological techniques that carbonic anhydrase is present in the cell membrane or in the vicinity of the epithelial cells. Then we measured a decreased net fluid transport in the presence of increasing concentrations of the carbonic anhydrase inhibitor acetazolamide. We showed that the volume regulatory increase is substantially slowed down and that the steady-state volume of the cells changed when carbonic anhydrase was inhibited. Our conclusion is that the rate of CO2 hydration was a limiting step, at carbonic anhydrase inhibition, in both the net transfer of salt and water and also in the ability of the cells to efficiently regulate their volume.

Acetazolamide↗

Permeability properties of the subepithelial tissues of Necturus gallbladder.

The permeability properties of the subepithelial connective tissue of Necturus gallbladder were evaluated by measurement of electrical resistance, dilution potentials and hydraulic water permeability. The gallbladder epithelial cells were removed by scraping and the underlying connective tissue placed in an Ussing chamber. The electrical resistance was 2.2 +/- 0.8 omega X cm2; the tissue was slightly cation selective relative to free solution. The subepithelial tissues restricted the rate of diffusion of small solutes to 50% of the free solution value. The hydraulic water permeability averaged 2.1 X 10(-2) cm/s per atm. We conclude that limitations of the area of subepithelium available for fluid movement are the most important factors in determining the restrictions to solute and water flow offered by the subepithelial tissues.

Animals↗

Acidification in the distal tubule of the Amphiuma kidney.

The acidification of the urine within the distal tubule of Amphiuma means was studied with micropuncture techniques. Antimony microelectrodes calibrated in vivo were used for measuring the intratubular pH and samples were taken for the determination of Na+- and Cl- -concentrations and for determining buffer lines within the HCO-3-CO2 buffer system. The TF/P Na+ was used as a relative length determinator and a significant acidification along the length of the tubule was found. The pH in the tubule was more acid than samples equilibrated at blood PCO2. This disequilibrium can be described in terms of an imbalance within the Henderson-Hasselbach formula or/and as a PCO2-gradient across the tubular wall. The calculated PCO2-gradient was found to be correlated to the arterial PCO2 and the acidification to the arterial pH. The greatest pH-gradient is generated in the collecting duct and in the bladder.

Acid-Base Equilibrium↗

Gallbladder epithelial cell hydraulic water permeability and volume regulation.

The hydraulic water permeability (Lp) of the cell membranes of Necturus gallbladder epithelial cells was estimated from the rate of change of cell volume after a change in the osmolality of the bathing solution. Cell volume was calculated from computer reconstruction of light microscopic images of epithelial cells obtained by the "optical slice" technique. The tissue was mounted in a miniature Ussing chamber designed to achieve optimal optical properties, rapid bath exchange, and negligible unstirred layer thickness. The control solution contained only 80% of the normal NaCl concentration, the remainder of the osmolality was made up by mannitol, a condition that did not significantly decrease the fluid absorption rate in gallbladder sac preparations. The osmotic gradient ranged from 11.5 to 41 mosmol and was achieved by the addition or removal of mannitol from the perfusion solutions. The Lp of the apical membrane of the cell was 1.0 X 10(-3) cm/s . osmol (Posm = 0.055 cm/s) and that of the basolateral membrane was 2.2 X 10(-3) cm/s . osmol (Posm = 0.12 cm/s). These values were sufficiently high so that normal fluid absorption by Necturus gallbladder could be accomplished by a 2.4-mosmol solute gradient across the apical membrane and a 1.1-mosmol gradient across the basolateral membrane. After the initial cell shrinkage or swelling resulting from the anisotonic mucosal or serosal medium, cell volume returned rapidly toward the control value despite the fact that one bathing solution remained anisotonic. This volume regulatory response was not influenced by serosal ouabain or reduction of bath NaCl concentration to 10 mM. Complete removal of mucosal perfusate NaCl abolished volume regulation after cell shrinkage. Estimates were also made of the reflection coefficient for NaCl and urea at the apical cell membrane and of the velocity of water flow across the cytoplasm.

Animals↗

Epithelial cell volume regulation: bicarbonate dependence.

When Necturus gallbladder epithelial cells are osmotically shrunken, they rapidly return to their original volume despite the continued presence of a hypertonic bathing solution. This volume-regulatory process requires bicarbonate ions in the bathing solutions and is associated with the uptake of chloride ions. Volume-regulatory increase by epithelial cells in probable due to the parallel operation of sodium-hydrogen and chloride-bicarbonate exchangers in the apical cell membrane.

Animals↗

The existence of a tubulo-glomerular feedback mechanism in the Amphiuma nephron.

A single nephron tubulo-glomerular feedback control of the glomerular filtration rate, which is known in mammalian animals, could be one way by which amphibians regulate the glomerular filtration rate (GFR). To investigate whether the Amphiuma means shows any sign of a tubulo-glomerular feedback control, micropuncture experiments were carried out. Six different series of experiments were performed. In the first series, tubular stop-flow pressure (SFP) was measured during distal tubular perfusion with amphibian Ringer solution at a rate of 10, 25 and 50 nl/min. A significant decrease of SFP was found at the three perfusion rates compared to the controls. In the second group, single nephron glomerular filtration rate (SNGFR) was measured, while the distal tubule was perfused at 10, 25 and 50 nl/min. At a perfusion rate of 10 nl/min the SNGFR did not decrease, whereas at 25 and 50 nl/min it decreased significantly. In the third group the perfusion pipette was located in the proximal tubule and the nephron was perfused at 10, 25 and 50 nl/min, while at the same time the proximal tubular stop-flow pressure was measured. No reduction of SFP was found at a perfusion rate of 10 nl/min, while significant reductions were noted at rates of 25 and 50 nl/min. In the fourth group the SNGFR was measured in the distal tubule beyond the macula densa and in Bowman's space of the same nephron. No significant difference was found. In the fifth group, the glomerular capillary pressure (GCP) was measured before and after blockade of the tubular fluid flow. No significant difference was found between these two measurements. The sixth series deals with the changes occurring at the single nephron level by the tubulo-glomerular feedback control. The single nephron filtration fraction (FF) was determined from efferent arteriolar protein concentration with and without a feedback-induced reduction of the SNGFR. The FF values were not significantly different from one another. From these results and data from the other series, the afferent (Raff) and efferent (Reff) arteriolar resistances were calculated. Reff did not change, while Raff increased significantly when a feedback stimulus was applied. These experiments indicate the existence of a tubulo-glomerular feedback control which depresses the SNGFR and SFP by contracting the afferent arteriole.

Animals↗

Dynamics of glomerular ultrafiltration in Amphiuma means.

To study renal function in Amphiuma means, the hydrostatic pressures in vascular and tubular structures and the glomerular filtration rate were determined at different arterial blood pressures. In the arterial blood pressure range studied no evidence of autoregulation of the glomerular capillary pressure of the hydrostatic pressure gradient over the capillary membrane was found. The glomerular filtration ceases at an arterial blood pressure below 12 cm H2O. No significant difference between tubular free flow pressure and peritubular capillary pressure was noted. Furthermore, it was found that the glomerular capillary pressure could be estimated by measuring the intratubular stop-flow pressure and arterial colloid osmotic pressure at an arterial pressure above 15 cm H2O. It was also found possible to measure the glomerular capillary pressure at the very end of the afferent arteriole. The protein concentrations in afferent and efferent arteriolar blood were determined and the colloid osmotic pressures were calculated according to a new formula derived for Amphiuma plasma. The dynamics of glomerular ultrafiltration was evaluated. A filtration equilibrium across the glomerular membrane was reached, since the efferent colloid osmotic pressure was not significantly different from the hydrostatic pressure gradient across the glomerular capillary membrane.

Animals↗

Glucose-induced insulin response is reduced and proinsulin response increased in healthy siblings of type 1 diabetic patients.

Glucose-stimulated insulin and proinsulin responses, and insulin sensitivity, were studied in 30 HLA identical, 38 HLA haplo-identical, and 25 HLA non-identical, healthy islet-cell-antibody negative siblings of Type 1 diabetic patients. The results were compared with 41 age- and sex-matched healthy subjects with no diabetes in the family. The proinsulin-corrected insulin response to an intravenous glucose infusion test was significantly lower among siblings when insulin sensitivity was taken into account (1.65 (inter-quartile range 1.20-2.64) vs 2.18 (1.65-3.28) nmol mmol-1 min, p = 0.04). Proinsulin values were consistently higher among siblings than among control subjects (peak values 50.0 vs 38.0 pmol l-1 (p = 0.004)). When proinsulin release was corrected for individual insulin sensitivity this difference remained. The results suggest disturbed islet B-cell function, unrelated to HLA identity or the presence of circulating islet cell antibodies.

Adolescent↗

Structural and functional studies of gap junctions in human myometrium.

Gap junctions are of importance in the coordinated contraction of uterine smooth muscle during labor. There are indications that in the human myometrium, gap junctions are much more numerous in the period immediately surrounding parturition. The presence and the functional state of gap junctions in human myometrium was studied by electron microscopical morphometry and by studying the distribution of an injected fluorescent dye. Electron microscopy showed that the number and size of gap junctions was significantly higher during the active phase of labor than during the pre-labor phase. Pressure injection of Lucifer Yellow into myometrial cells in vitro showed only weak coupling in the pre-labor stage. These data support the notion that coupling between myometrial cells develops in immediate association with parturition.

Female↗