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Biomedical subjects

L Jansson

Publications and source records attributed to L Jansson.

At least 217 records · Page 12Linked to original sources

Glucose stimulation of pancreatic islet blood flow by redistribution of the blood flow within the whole pancreatic gland.

Whole pancreatic blood flow (PBF) and islet blood flow (IBF) were measured 5 min after administration of glucose at serum glucose concentrations ranging between 8.5 and 25 mM. The serum insulin concentration increased proportionally (p less than 0.01) to the serum glucose concentration. PBF was unaffected by i.v. glucose administration at 5 min, while IBF increased in proportion to the serum glucose concentration of the animals in the range of 8.6-16.7 mM. No further increases in IBF could be seen at higher glucose concentrations. It is concluded that glucose preferentially stimulates IBF and that this increase, to a major extent, is due to a redistribution of flow within the gland.

Animals↗

Large-scale production of fetal porcine pancreatic isletlike cell clusters. An experimental tool for studies of islet cell differentiation and xenotransplantation.

A recently described method for the preparation of isletlike cell clusters (ICC) from human fetal pancreas has been applied to the fetal pig with the ultimate aim of large-scale production of ICC. Fetuses ranging in age from 51 to 77 days were used, and after a brief collagenase-incubation the pancreatic digest was plated into culture dishes containing medium RPMI 1640 supplemented with either 10% fetal calf serum (FCS) or human serum (HS). HS seemed to increase the number of ICC formed as compared to that obtained with FCS. A total of more than 100,000 ICC were produced from each of 3 litters, ages 67-77 days, after culture in the presence of HS. The DNA content of such ICC was reduced by about 50% as compared to those maintained with FCS supplementation. Immunocytochemical staining revealed insulin- and glucagon-positive cells scattered among a majority of nonstained cells within the cell clusters. ICC maintained in either FCS or HS displayed significant rates of (pro)insulin biosynthesis in vitro and an increased insulin release when exposed to 16.7 mM glucose plus 5 mM theophylline. Four weeks after implantation, ICC grafted under the kidney capsule of nondiabetic nude mice contained frequent insulin- and glucagon-positive cells. In 2 nude mice transplanted with ICC, the functional capacity of the graft was tested by perfusing the graft-bearing kidney. When the perfusion fluid was changed from one containing 2.8 mM glucose to one containing 16.7 mM glucose +/- 5 mM theophylline, the secretion of insulin increased within a few min. It is concluded that the fetal porcine pancreas can be used for large-scale production of ICC, which have a very consistent, but immature functional capacity. Because of their inherent growth and differentiation properties, fetal porcine ICC constitute a potential source of xenogenic islet grafts intended for human diabetics.

Animals↗

Intermittent protein-calorie malnutrition in the young rat causes long-term impairment of the insulin secretory response to glucose in vitro.

The effect of a limited period of protein-calorie malnutrition in young rats on insulin secretion in the adult has been studied. Three-week-old rats were weaned onto diets containing 5% protein (low protein; LP) or 15% protein (control; C) and maintained for 3 weeks on their respective diets. A third experimental group was weaned onto standard rat chow (18% protein; normal diet; N). From 6 weeks of age onwards all rats were fed the standard rat chow. Pancreatic islets were isolated from rats aged 3, 6 and 12 weeks and their insulin secretory response to glucose or arginine was tested. At 12 weeks the effects of the secretagogues were also tested using perfusion of isolated pancreatic glands. In islets from 6-week-old LP rats the glucose-stimulated insulin release was only 25% of that of C and N rats of the same age. Islets from C and N rats responded to arginine in the presence of a low glucose concentration with a small increase in insulin secretion, whereas no such response could be demonstrated in islets from 6-week-old LP rats. Islets from 6- and 12-week-old N rats responded to glucose and arginine. Islets from 12-week-old C rats had a similar response to glucose but did not respond to arginine in the presence of a low glucose concentration. In islets from 12-week-old LP rats the secretory response to glucose remained only 40% that of C and N rats and there was no response to arginine in the presence of a low glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunogenetics of type II collagen autoimmunity and susceptibility to collagen arthritis.

The MHC restriction of the antibody response and development of arthritis after immunization with autologous or heterologous type II collagens in mice have been investigated. Mice from three different H-2q-carrying strains (DBA/1, NFR/N and B10.G) with different non-MHC genes, as well as B10-congenic strains carrying wild type H-2q-related or H-2r haplotypes, were susceptible for collagen arthritis. All strains tested developed an antibody response cross-reacting with autologous type II collagen after immunization with heterologous type II collagen; H-2q predisposes for a high response against chick, rat and bovine type II collagen, H-2r and H-2b for a high response against bovine type II collagen. Only mouse strains with H-2q, H-2r, H-2w3 or H-2w17 were responders to mouse type II collagen, and only these strains developed arthritis after immunization with heterologous or autologous type II collagens. These findings indicate that the ability to mount an immune response against autologous type II collagen is a prerequisite for the susceptibility to collagen arthritis. A cross-reactive autoimmune response after immunization with various heterologous type II collagen may enhance further the development of arthritis.

Animals↗

Haemorrhagic gastritis. Incidence, etiological factors, and prognosis.

Etiological factors and prognosis were analyzed in 78 patients with haemorrhagic gastritis admitted to an intensive care unit during 8 years. These patients constituted 11.4% of a total of 684 cases with massive upper gastrointestinal haemorrhage admitted during the same time period. The annual incidence of haemorrhagic gastritis was 6.5/100,000 inhabitants. Most frequently, the bleeding episode was associated with intake of alcohol (35%) or anti-inflammatory drugs (23%). Only 4 patients (5%) had classical stress ulcers. Due to massive bleeding, surgery was necessary in 5 patients. Non-resectional surgery was carried out with no postoperative mortality. Six patients (8%) died (age 72-92 years), one as a direct cause of bleeding and five in severe associated disease, haemorrhagic gastritis being more or less a terminal event. Thus, in the great majority of unselected patients with haemorrhagic gastritis bleeding ceases on conservative treatment. In a minor fraction surgical treatment is a last resort but the method of choice is debatable. We propose that gastric resection should be avoided.

Adult↗

A method for the analysis of a large number of specific and multispecific B cell hybridomas derived from primary immunized lymph nodes.

A previously described efficient short term immunization protocol enables analysis of the specificities of large numbers of monoclonal antibodies in murine lymph nodes. In this paper we measure the B cell responses against two highly immunogenic antigens, rat type II collagen (NRC) and chick ovalbumin (OVA), as well as against the poorly immunogenic denatured rat type II collagen (DRC). We found that relatively large numbers of specific B cell hybridomas could be produced after immunization with NRC (28%) and lower numbers with OVA (6%) and DRC (3%). However, in all immunizations there were also generated large numbers of hybridomas producing multispecific antibodies (5-15%). The multispecificity was sustained when the hybridomas were subcloned. These results show that large numbers of immunogen-reactive hybridomas can easily be obtained with the present method. They also show that different immunogens differ in their immunogenicity. The very high efficiency of native type II collagen to induce an antibody response, which is widely crossreactive with autologous type II collagen, could possibly be explained if it is assumed that the natural occurring repertoire is based on stimulation of autoantigens.

Animals↗

An increased number of mast cells in the sclerae of alloxan-diabetic mice.

The number of mast cells in the sclerae and retinae has been investigated in alloxan-diabetic mice, in obese-hyperglycaemic mice and in non-diabetic, lean control animals. In contrast to the alloxan-diabetic mice the obese-hyperglycaemic animals have increased circulating inulin levels. In the sclerae of alloxan-diabetic mice the number of mast cells was significantly (P less than 0.05) increased. No increase in mast cell content could be observed in the sclerae of the obese-hyperglycaemic mice. No mast cells could be observed in the retina in any of the experimental groups. It is concluded that lack of insulin may be of importance for the accumulation of mast cells in the sclerae of mice with hyperglycaemia.

Animals↗

Blood flow measurements in autotransplanted pancreatic islets of the rat. Impairment of the blood perfusion of the graft during hyperglycemia.

No information is available on the rate of blood flow in transplanted islets. In this study, adult rats were partially depancreatized, and islets from the excised pancreas were then isolated, maintained for 7 d in tissue culture, and subsequently transplanted back to the animal, beneath the renal capsule. Some rats were rendered diabetic with streptozotocin before transplantation. A month after transplantation the blood flow of the grafts was measured by a microsphere technique. Autotransplantation to streptozotocin-diabetic rats of approximately 500 islets did not revert the hyperglycemia, and the blood flow of these grafts was approximately 25% of that in the normoglycemic-transplanted rats. However, in insulin-treated diabetic rats the blood flow of the pancreatic graft was similar to that in the normoglycemic rats. The present results suggest that the blood flow in transplanted islets is markedly diminished by hyperglycemia and that this can be enhanced by insulin administration.

Animals↗

Intrinsic regulation of the blood flow to the endocrine and exocrine parts of the rat pancreas.

To evaluate possible differences in the local regulation of blood flow between the endocrine and exocrine pancreatic parenchyma, the blood perfusion of the pancreas and the pancreatic islets has been measured after a 90-second period of anoxia or a 5-min period of increased venous pressure. After anoxia, caused by interruption of arterial blood flow, there was a significant increase (P less than 0.01) in islet blood flow (IBF) while whole pancreatic blood flow (PBF) remained unchanged. Arterial occlusion also increased the serum glucose (P less than 0.01) and serum insulin concentrations (P less than 0.001). Vagotomy prevented the increase in IBF but did not affect the increase in serum glucose or serum insulin concentration, which suggests that the increase in IBF was due to the increased serum glucose concentration. An increased venous pressure in the portal vein did not affect IBF, PBF, serum glucose or serum insulin concentrations. It is concluded that, in the rat pancreas, the local control of PBF and IBF is of minor importance in the regulation of blood flow.

Animals↗

The blood flow to the islets of Langerhans in different regions of the rat pancreas.

Pancreatic blood flow (PBF) and islet blood flow (IBF) have been determined separately in two different regions of the rat pancreas, namely, that perfused by the superior mesenteric artery (SMA) and that perfused by the coeliac artery (CA). Although there were no differences in either the PBF or the IBF between these two regions, the IBF, when expressed as a percentage of PBF, was significantly higher in the region perfused by the SMA. It is concluded that glucose regulation of the blood flow to the islets and exocrine parenchyma is similar in the two regions perfused by SMA and CA. In the SMA region the percentage of blood supply to the islets, in relation to the acinar part, is, however, somewhat higher than in that of the CA region.

Animals↗

Oestrogen induced suppression of collagen arthritis: I. Long term oestradiol treatment of DBA/1 mice reduces severity and incidence of arthritis and decreases the anti type II collagen immune response.

Experimental animal models can be used to help understand how oestrogen modulates autoimmune arthritis. We have previously shown that castration of female DBA/1 mice exaggerates arthritis induced with type II collagen. This report shows that treatment of castrated DBA/1 mice with low doses (0.2 micrograms twice a week) of beta-oestradiol reduces the incidence (37% vs 78% in controls) and severity (3.9 vs 5.6 mean scores) of arthritis. Levels of IgG anti type II collagen antibodies are decreased whereas levels of IgM antibodies are increased in the beta-oestradiol treated mice. The T cell response, as measured by a 3H-thymidine assay, is reduced in the beta-oestradiol treated mice. The results suggest that treatment with low doses of beta-oestradiol exerts a suppressive effect on both development of collagen arthritis as well as T cell dependent immune reactivity towards type II collagen.

Animals↗

Evaluation of cimetidine as an aid in the management of non-variceal massive upper gastrointestinal haemorrhage.

In order to evaluate the effect of H2-receptor blockade as an adjunct to antacid treatment in non-variceal massive upper gastrointestinal haemorrhage, 106 patients were randomized to treatment with either antacid (n = 54) or cimetidine and antacid (n = 52). One patient (antacid group) died as a direct cause of bleeding. Acute surgery was carried out in 8 patients (14.8%) in the antacid group and in 4 patients (7.7%) in the cimetidine-antacid group. Continuous bleeding or re-bleeding occurred in 11 patients (20.4%) in the antacid group and in 10 patients (19.2%) in the cimetidine-antacid group. Neither these differences, nor any differences related to specific source of bleeding, were statistically significant. It is concluded that, according to the regimen applied in the present study, treatment with cimetidine does not to any significant extent influence the immediate outcome for patients with non-variceal massive upper gastrointestinal haemorrhage.

Adult↗

Homologous type II collagen induces chronic and progressive arthritis in mice.

Native mouse type II collagen was used for immunization of DBA/1 mice. Arthritis developed exclusively in male animals and was characterized by a variable and delayed onset, a slow and progressive development, and frequent exacerbations of disease in several joints including those that were previously affected. Titers of anti-type II collagen autoantibodies were found not to correlate well with arthritis development. It appears that experimental arthritis induced with homologous type II collagen resembles rheumatoid arthritis in humans, both in certain clinical features and in the lack of correspondence between anti-type II collagen autoantibody titers and disease symptoms.

Animals↗

Female sex hormones suppress development of collagen-induced arthritis in mice.

We have previously reported that male DBA/1 mice are more susceptible to collagen-induced arthritis than are females. Here we report that oophorectomy makes female mice as susceptible to collagen arthritis as are normal males. Induction of collagen-induced arthritis in mice is a T cell-dependent process. The role of female sex hormones in modulating T cell-dependent autoimmune diseases is discussed.

Animals↗

Alloxan-induced diabetes in the mouse: time course of pancreatic B-cell destruction as reflected in an increased islet vascular permeability.

The extent to which injections of the pancreatic B-cytotoxin alloxan in C57BL/Ks mice induced an increase in islet vascular permeability, and the time course of this increase, were studied. The vascular permeability was monitored by administration of the dye Monastral blue B, which is entrapped in leaky blood vessels with intact basement membranes. The islets were visualized by a freeze-thawing technique which allows identification of stained islets. Not until four hours after the alloxan injections was there an increase in islet uptake of Monastral blue B when compared with saline-treated control animals. Thereafter the islet staining increased further. The process was accompanied by gradual development of hyperglycaemia and a reduction of number of the islets identified in the pancreatic preparations. It is concluded that alloxan causes an increase in islet vascular permeability, which appears to become manifest at a later stage than the cytotoxic B-cell degeneration.

Alloxan↗