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Biomedical subjects

B Gerdin

Publications and source records attributed to B Gerdin.

At least 73 records · Page 4Linked to original sources
PubMed1993

Interconnection of integrins alpha 2 and alpha 3 and structure of the basal membrane in colorectal cancer: relation to survival.

The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA-ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator.

Adenocarcinoma↗
PubMed1992

Selective expression of interleukin 10, interferon gamma, and granulocyte-macrophage colony-stimulating factor in ovarian cancer biopsies.

The variable clinical response seen with most cancer immunotherapy suggests that there is a large interindividual variation in immunologic response to tumors. One of the key functional parameters of an immune response is the local production of cytokines. As a method to survey the immune status of tumor-infiltrating cells, we have investigated the constitutive expression of cytokine mRNA in biopsies from epithelial ovarian carcinomas by using a PCR-assisted mRNA amplification assay. Using a set of cytokine-specific primers for 10 different cytokines, we have found selective expression of interleukin 10 (IL-10), granulocyte-macrophage colony-stimulating factor, and interferon gamma mRNA in ovarian tumor tissue as compared to normal ovaries and ovarian tumor cell lines. Such differences could not be explained by the extent of T-cell infiltration, since comparing samples with the same intensity of T-cell receptor (TCR) constant region alpha-chain product from the tumor and normal biopsies demonstrated different cytokine patterns. No IL-2 gene expression was detected in the tumor biopsies. IL-2 mRNA, however, became expressed after stimulation of the tumor-derived cells via the CD3 molecule but not after growth in recombinant IL-2 alone. Using the same methodology, we also analyzed the TCR variable region beta-chain gene repertoire. No restriction or biased expression of these genes was observed.

Base Sequence↗
PubMed1992

Effect of LS-2616 on the graft protection achieved by cyclosporin A, prednisolone, and 15-deoxyspergualin in heart-transplanted rats.

The immunostimulator LS-2616 abolishes the effect of cyclosporin A in a rat cardiac transplantation model. The present paper compares the characteristics of rejection obtained under different immunosuppressive regimens with and without additional LS-2616 application in the same model. Cyclosporin A (CyA, 10 mg/kg daily), prednisolone (15 mg/kg daily), or 15-deoxyspergualin (2, 5, or 10 mg/kg daily), all given from the day of transplantation until day 9, protected the grafts during the treatment period. The addition of LS-2616 (160 mg/kg, day -1 until stop) resulted in a total abrogation of the immunosuppressive effect of CyA and prednisolone. However, LS-2616 could only partially or not at all reverse the effect of 15-deoxyspergualine. These results show a certain drug selectivity of LS-2616 in promoting rejection of immunosuppressed allografts. Further studies with LS-2616 may be of benefit in evaluating the mode of action of different immunosuppressive compounds and, thus, contribute to finding more effective antirejection therapies.

Adjuvants, Immunologic↗
PubMed1992

Hyaluronic acid accumulation; the mechanism behind graft rejection edema.

Hyaluronic acid (HA) is an important stabilizing consistuent of the loose connective tissue and regulates water homeostasis. Thus, excessive accumulation of HA in interstitial tissue immobilizes water and may thereby contribute to interstitial tissue edema. By the use of biotin labelled core protein and an avidin-enzyme system, we visualized HA in grafted rat kidney, rat heart, rat small bowel and also in human kidneys. By an extraction procedure the tissue amounts of HA were measured in the experimental grafts. Simple techniques for measuring water content were also employed. The extracellular amounts of HA increased between 100% and 350% in rejecting tissues as compared to syngeneic controls. The relative water content also increased and correlated well with the HA accumulation. The clinical value of these experimental observations was confirmed in human transplantation where rejecting kidney allografts demonstrated a highly significant increase in HA staining in the interstitium as compared to non-rejecting biopsy specimens. We therefore concluded that transplantation edema--a key features of graft rejection--is regulated by the accumulation of HA not only under experimental conditions but also in the clinical setting.

Animals↗
PubMed1992

Enhancement of the effect of low-dose cyclosporin A by sulphasalazine in prevention of cardiac allograft rejection in the rat.

Sulphasalazine (SASP) is an immunomodulatory compound with disease-modifying activity in ulcerative colitis and in other autoimmune disorders. SASP was previously shown to prolong the survival of heart allografts in rats treated with cyclosporin A (CyA) for 9 days after transplantation. We have now evaluated whether SASP also exerts a beneficial effect under continuous treatment with CyA, when CyA is discontinued after 14 days, or alone if given 10 days prior to transplantation. Cardiac grafts were transplanted from PVG donors to Wistar/Kyoto recipients using an accessory cervical heart transplantation technique. Rejection was defined as the absence of palpable contractions and occurred in the control group in a very reproducible manner on day 8 or 9. SASP alone was given orally (100 mg/kg body weight) starting 10 days before transplantation and resulted in a minor prolongation of graft survival. When SASP was given in addition to oral CyA (1 mg/kg or 2 mg/kg from day 0 to rejection) there was a significant prolongation in graft survival [from medians of 8 (range 6-11) and 9 (range 8-11) days, respectively, to medians of 10 (range 8-15) and 12 (range 11-15) days, respectively]. When SASP was given from day 0 to rejection, in addition to a schedule of oral CyA (10 mg/kg) for 15 days, there was no prolongation of graft survival [median of 30 (range 26-42) days vs median of 32 (26-38) days]. The data show that SASP acts as a weak immunosuppressive agent which enhances the effect of CyA given at a low dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat.

Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF-AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA-treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF-AA is effective in vitro but it is clearly less effective in vivo.

Animals↗
PubMed1992

Sodium hyaluronate as an adjunct in adhesion prevention after flexor tendon surgery in rabbits.

Topical application of sodium-hyaluronate (NaHe) has been proposed to decrease the formation of adhesions after tendon surgery, but reports published thus far have been contradictory. A new test instrument capable of simultaneous registration of tensile load, tendon excursion, and joint motion was therefore developed and used to evaluate the effect of locally administered NaHe of different concentrations and molecular weights on the outcome after tenorrhaphy of rabbit hindlimb flexor tendons. Immediately after tenorrhaphy, NaHe or saline solution was deposited into the tendon sheath. The functional characteristics of the digits were evaluated 15 days after surgery. NaHe with a concentration of 19 mg/ml and a molecular weight of 6 x 10(6) significantly limited the strength of the adhesions formed without impairment of tensile strength. These results suggest that the efficacy of NaHe is affected by both the concentration and the molecular weight of the NaHe preparation used.

Animals↗
PubMed1992

Efficacy of the 21-aminosteroid U74006F in improving neurological recovery after spinal cord injury in rats.

The efficacy of three different regimens of the 21-aminosteroid U74006F in counteracting the neurological damage after spinal cord compression causing paraparesis in rats was investigated. Three groups of ten animals each were given totally 6 mg/kg of U74006F in different regimens beginning one hour after injury (A: bolus doses of 1.5 mg/kg at 1, 4, 7 and 10 hours; B: bolus of 1.5 mg/kg at 1 hour and 4.5 mg/kg as an infusion over the next 9 hours; and C: infusion alone, 6 mg/kg, given between 1 and 10 hours after trauma). Two groups of ten animals each received vehicle alone in administration modes comparable to those of the U74006F treated animals. The motor function was assessed daily on the inclined plane. On day one, the capacity angle had decreased from about 62 degrees preoperatively to 28-30 degrees in the two vehicle-treated groups and in group C. In these groups there was a similar improvement in neurological function and on day 9 the capacity angles were 49-55 degrees. In groups A and B, both of which received a bolus dose of U74006F at 1 hour, the neurological outcome improved on day one with capacity angles of 38-40 degrees. The difference in neurological function between the animals given U74006F as bolus doses and those given vehicle alone persisted over the entire observation span until day 9. The data suggest that early treatment with a bolus dose seems to be required in order to obtain an effect of U74006F on neurological recovery.

Animals↗
PubMed1992

Increased luminal release of hyaluronan in uninvolved jejunum in active Crohn's disease but not in inactive disease or in relatives.

Recently obtained data suggest that there is a subclinic inflammatory activity in the apparently uninvolved intestinal mucosa in Crohn's disease (CD). As CD is characterized by an activation of connective tissue and fibrosis, we investigated the extent to which hyaluronan (HA), an essential component of the connective tissue, was released into the lumen of an isolated jejunal segment in CD patients and in relatives. Patients with active CD of the terminal ileum (CD activity index, CDAI, > 150; n = 14), patients with CD in remission (CDAI < 150 n = 10), first-degree relatives of the CD patients (n = 21) and healthy controls (n = 43) were orally intubated with a catheter allowing occlusion and perfusion of a segment of the proximal jejunum. The jejunal fluid concentration of HA was 65 +/- 45 micrograms/l in patients with active CD in the terminal ileum, significantly higher than the value for 43 healthy controls (42 +/- 23 micrograms/l; p < 0.05), and the corresponding values for patients in remission (42 +/- 23 micrograms/l) and for first-degree relatives of the CD patients (53 +/- 52 micrograms/l), were not increased compared to the control group. To localize HA in the tissue, small bowel biopsies were taken during surgery from patients with CD and from controls and affinity stained for HA. There was an intense staining for HA in the lamina propria of the villi, both in biopsies from patients with CD and from controls, but no staining in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Viability, prostaglandin E2 production, and protein handling in normal and inflamed human colonic mucosa cultured for up to 48 h in vitro.

Human colonic mucosa obtained from colon cancer resections ('normal') and from colectomies owing to ulcerative colitis (inflamed) were cultured for up to 48 h in vitro. The 3H-leucine incorporation in normal tissue decreased to 52% (p less than 0.001) at 48 h compared with 24 h. The protein synthesis in normal but not in inflamed explants was significantly (p less than 0.01) improved at 48 h, reaching 72% of the 24-h value, on additions of insulin and the protease inhibitors aprotinin, soyabean trypsin inhibitor, and N alpha-tosyl-L-lysine chloromethyl ketone to the culture medium. Inflamed tissue had significant protein losses of 15% after 24 h and 29% after 48 h in culture, and the excretion of precipitable 3H-leucine-labelled proteins could be as high as 20%/24 h. A slight protein loss was observed in normal tissue after 48 h in culture, but the excretion of labelled proteins was very low (3%). The prostaglandin E2 (PGE2) production in both normal and inflamed tissue displayed an increasing non-linear pattern with time in culture, with higher values for inflamed tissue. The PGE2 release profiles and the differences in basic protein metabolism between normal and inflamed human colonic biopsy specimens in culture might reflect important characteristics of the inflammatory process.

Animals↗
PubMed1992

Dependence of traumatic vasospasm on blood flow in the central artery of the ear in rabbits.

The effect of total obstruction of blood flow on traumatically induced vasospasm was studied in the central arteries of rabbits' ears. All side branches were ligated along a 7 cm segment of the artery. Obstruction of blood flow was achieved by ligation of the central artery distal to this segment. The inner diameter of the artery was measured microscopically after transillumination. A standardised injury was induced with a clip applying forceps. The duration, intensity (reduction of diameter) and severity (integrated change in diameter over time) of the resulting spasm were assessed. Spasm induced after cessation of blood flow lasted significantly less time (mean (SEM), 6.0 (2.0) minutes compared with 18.1 (2.5) min) and was less severe than spasm induced when the blood flow was intact (1.6 (0.6) mm/min compared with 6.2 (0.6) mm/min). The results may be explained by local accumulation of vasodilating substances in the injured segment of the vessel in the absence of blood flow.

Animals↗
PubMed1992

Effects of prostaglandin E2 (PGE2) and drugs affecting PGE2 degradation on acute rejection of rat cardiac allografts.

Systemic administration of prostaglandin E2 (PgE2) has been reported to prolong graft survival of heart transplants. We investigated the influence of systemic injection of two compounds which inhibit the endogenous degradation of PgE2 (CL42A and CL68A) and of local infusion of PgE2 into the transplant on the survival time of rat cardiac allografts. Both CL42A and CL68A gave increased graft survival time in two rat strain combinations, though this was not predictable in individual rats. Locally infused PgE2 gave slight, but not significant prolongation of graft survival in some recipients. Combined PgE2 and cyclosporin A, however, gave significant prolongation of graft survival time compared with cyclosporin A treatment alone. When local PgE2 treatment was begun 5 days after transplantation, graft survival time was prolonged in almost all the rats. Manipulation of the local PgE2 concentration thus seemed to have a positive effect on graft survival, possibly due to down-regulation of certain cells of the immune system by PgE2.

Acute Disease↗
PubMed1992

Delorme's operation for rectal prolapse in elderly or unfit patients.

OBJECTIVE: To evaluate the results after Delorme's operation for rectal prolapse in elderly and unfit patients. DESIGN: Retrospective analysis and telephone interview. SETTING: Akademiska sjukhuset, Uppsala, Sweden. SUBJECTS: A consecutive series of 14 women (median age 82, range 32-92) operated on for rectal prolapse 1987-1992 and followed up after a median of 18 months. RESULTS: There were no serious postoperative complications. Continence was improved in 6/11 incontinent patients. The recurrence rate was 3/14 (21%). CONCLUSION: Delorme's operation is an attractive alternative in elderly or unfit patients, but is not recommended for younger and low risk patients because of the recurrence rate.

Adult↗
PubMed1992

A technique for segmental rectal and colonic perfusion in humans.

To enable a better characterization of pathophysiologic processes in colon and rectum, we have developed a perfusion technique for collection of soluble substances and cells from standardized intestinal segments. A tube with balloons attached to its outer wall was endoscopically introduced into the rectum and sigmoid colon, and its position ascertained fluoroscopically. The balloons delimited two segments, one in the sigmoid colon and one in the rectum. The segments were simultaneously perfused by a buffer at 37 degrees C. After a 30-min rinsing period, perfusate and cells were collected at 20-min intervals. Of 51 attempted perfusions, 45 were successfully completed. Recovered volumes equaled those infused. Leakage from the proximal intestine to the segments was negligible. In 18 healthy volunteers, the mean perfusate concentration from the rectal segment was 57.5 (27.5-120.2) mg/L for albumin, 1.3 (1.0-1.7) micrograms/L for eosinophil cationic protein, 5.1 (2.8-9.5) ng/L for prostaglandin E2, and 61.7 (41.7-89.1) micrograms/L for hyaluronan, and all values were lower in the sigmoid segment. Steady state conditions were achieved from the second perfusion period. The perfusate contained 4-80 x 10(4) cells, more than 95% of which were epithelial cells. The technique is safe, has a good subject compliance, and seems to be a valuable tool in investigations on quantitative release of soluble substances and cells in, e.g., colorectal inflammation.

Adult↗
PubMed1992

Prognosis of surgically treated radiation-induced damage to the intestine.

A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the intestinal tract were retrospectively reviewed and clinical and surgical factors were related to the ultimate prognosis by multivariate analysis. The first operation was performed on the small intestine in 47 patients, the large intestine in 32 patients or both in nine patients. Postoperative complications occurred in 35 patients (40%), with fatal outcome in 12 (13%). Thirty-one patients (35%) required further surgery and altogether 19 patients (22%) ultimately died from RID. Negative prognostic factors after the first operation were postoperative intestinal leak (P < 0.05) and operation for fistula or perforation (P < 0.01). The outcome after the last operation was negatively influenced by intestinal leak (P < 0.001) by the choice of bypass as operative procedure (P < 0.01) and by operation for fistula or perforation (P < 0.01). In addition, 43% of the patients in whom the disease had progressed between two explorations died from RID. Thus, the severity of the RID as diagnosed at laparotomy, and progression of the disease between two subsequent explorations were related to the prognosis. Care should be taken to avoid intestinal leak. Resections should be preferred to bypass of injured intestine whenever possible.

Adult↗
PubMed1991

Elimination of exogenously injected sodium-hyaluronate from rabbit flexor tendon sheaths.

To obtain information about the elimination of Na hyaluronate (NaHe) deposited in flexor tendon sheaths in rabbits, two flexor tendon sheaths from each hind limb were operatively exposed in 15 animals and each filled with one of four different NaHe preparations, namely: 10 mg/ml, MW 2.6 x 10(6); 10 mg/ml, MW 6.3 x 10(6); 19 mg/ml, MW 3.0 x 10(6); and 19 mg/ml, MW 6.5 x 10(6). One, 3, and 7 days after surgery, the NaHe concentration was measured in frozen specimens from the tendon sheaths. One day after surgery, NaHe concentration in the tendon sheath fluid was close to 10 mg/ml in all groups. Three and 7 days after surgery it was higher in tendon sheaths in which NaHe preparations with a high (19 mg/ml) rather than with a low concentration (10 mg/ml) had been deposited. At 3 days, NaHe concentration was also higher in sheaths that had received a preparation with a high MW (6.5 x 10(6)) than those with a lower MW (2.6 or 3.0 x 10(6)). The findings suggest that within the first 24 h, a dilution of concentrated NaHe preparations takes place, probably as a result of their hyperoncotic properties. After 24 h, there was a slower decline in NaHe concentration when more concentrated solutions (19 mg/ml) and solutions with high MWs (6.5 x 10(6)) were administered. Development of pharmaceutical NaHe preparations with slow elimination from tendon sheaths should reasonably be focused on a solution with a high MW and high concentration.

Animals↗