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J Weyer

Publications and source records attributed to J Weyer.

18 recordsLinked to original sources

In vitro and in vivo viability assessment of unpurified pancreatic islet tissue.

The viability of porcine collagenase-prepared islet preparations (n = 16) was classified by 31P-NMR spectroscopy, staining by neutral red and trypan blue, and in vitro insulin secretion following glucose challenge. Vital islets exhibited a phosphate diester/phosphate monoester (PDE/PME) ratio of 0.5-0.9, a staining score of 18-30 and an insulin secretion responding well to glucose challenge. Damaged islets performed at a PDE/PME of 0.2-0.49 and a staining score of 9-17 and necrotic islets had 0.0-0.49 and a staining score of 9-17 and necrotic islets had 0.0-0.19 and 0-8, respectively. The islets of the latter two groups did not adequately respond to glucose. The in vivo function following autotransplantation of these islets into the spleen was investigated in five recipients of more than 3000/kg vital islets of which 4 expressed daily normoglycemia (< 200 mg%), normalized intravenous glucose tolerance (K = -2.21), and a prolonged survival (mean +/- SD) of 167 +/- 12 days compared to five recipients of > 3000/kg damaged islets (K = -0.814) (P = 0.0017) and a survival of 86 +/- 21 days (P = 0.0096). It is suggested that 31P-NMR spectroscopy is a valuable and practical method to predict islet graft viability prior to transplantation in order to assure good graft function in the recipient.

Animals

Islet isolation and autotransplantation in pigs.

Despite recent considerable progress in the isolation and purification of porcine pancreatic islets the final proof of functional integrity has not yet been performed. In the present study the feasibility, technical problems and posttransplant metabolic function of islet transplantation in the pig were investigated. Intraductal collagenase perfusion technique for islet preparation was used in 27 landrace pigs and eight minipigs followed by intraportal or intrasplenic transplantation of the islets. Islet purification was performed by dextran gradient in six preparations. Islet quantification, portal vein pressure measurements, intra- and postoperative complications and postoperative graft function were monitored. Between 1.73 x 10(5) and 11.4 x 10(5) islet containing fragments (8.23 x 10(3)-54.28 x 10(3) islet containing fragments/kg recipient body weight) were transplanted. Portal vein thrombosis occurred in 4 animals with significantly elevated portal pressure (p = 0.0001). 11 of 27 landrace pigs died due to postoperative complications. None of the minipigs was lost due to perioperative mortality (p = 0.031). Four of eight landrace pigs with intrasplenic grafts (50%) were normoglycemic and two of eight landrace pigs with intrahepatic transplants (25%) were normoglycemic. In minipigs two out of four (50%) with intrasplenic transplants and two of four (50%) with intraportal transplants were normoglycemic. The results in glucose metabolism as measured with intravenous glucose tolerance tests and calculated by K-values were statistically significantly different between normoglycemic and hyperglycemic animals (landrace pigs p = 0.0002 and minipigs p = 0.0005). Longevity was prolonged in normoglycemic animals as compared to hyperglycemic and apancreatic animals. It is concluded that successful islet isolation and transplantation is feasible in the landrace pig and the minipig while the landrace pig appears to be more susceptable to perioperative mortality.

Animals

Provocation paralysis.

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Diphtheria-Tetanus-Pertussis Vaccine

[The pig--an experimental model for transplantation of isolated islets pancreatic islets].

The authors present results of autotransplantation of the islets of Langerhans of the pancreas in pigs and miniature pigs ("Troll"). Diabetes was induced by total pancreatomy. From the removed pancreas the islets of Langerhans were separated by the method of intraductal perfusion with collagenase and implanted into the spleen or liver via the portal vein. The mortality on operation in pigs was 33%, in miniature pigs 20%. In domestic pigs normal blood sugar levels were achieved in 25% after implantation of the islets of Langerhans into the liver (in 2 of 8 animals) and in 50% after implantation into the spleen (in 4 of 8 animals). In miniature pigs autotransplantation of the islets of Langerhans was equally successful when transplanted into the liver or the spleen -50%. The 50% success of autotransplantations justifies the use of pigs as a model for further investigations of allo- or xenotransplantations of the islets of Langerhans.

Animals

[In vitro and in vivo studies of isolation, transplantation and function of Langerhans islets in the swine].

Limits and possibilities of the transplantation of islets of Langerhans in pigs were studied. 6 x 10(4) to 3 x 10(6) islets and insulin producing fragments per pancreas were obtained by intraductal collagenase digestion of the pancreatic gland following total pancreatectomy. Islets grafted into the spleen or liver rendered normoglycemia to the pancreatectomized animals as demonstrated by normal fasting blood sugars and normal intravenous glucose tolerance tests as compared to not operated animals permitting a survival time of up to one year. Apancreatic controls died of ketoacidosis and diabetic coma 10 to 12 days posttransplant. The number of isolated and transplanted islets correlated well to the normoglycemic state of the animal. Beyond that the in vitro challenge of the islets with glucose and resulting insulin secretion was a very important indicator for the functional status and integrity of the islets after transplantation. Thus the pig appears to be a suitable model for the preclinical studying of islet transplantation especially since immunologic, physiologic and anatomic features of the pig are similar to those in the human regarding pancreas and nutrition.

Animals

31P NMR spectroscopy for in vitro viability testing of porcine pancreatic islets.

The quality of pancreatic islets prepared by an intraductal pancreas collagenase perfusion technique was tested using three independent methods: 31P NMR spectroscopy, an insulin secretion test, and a staining method. The viability of pancreatic islet tissue was evaluated using the ratio of phosphate diester to phosphate monoester (PDE/PME) as a new criterion obtained by 31P NMR spectroscopy. According to this criterion, three types of tissue fragments could be characterized: vital (PDE/PME 0.5-0.9), damaged (PDE/PME less than 0.2), and necrotic (no PDE, no PME). The findings in the three different groups could be correlated to three trends of insulin secretion of the preparations following glucose challenge: good response to the glucose challenge, continuous decrease of insulin production, and no insulin secretion. We feel that 31P NMR spectroscopy offers a rapid and suitable method for classifying the viability of isolated pancreatic islets.

Animals

On the structure of the epidemic spread of AIDS: the influence of an infectious coagent.

The reported AIDS cases in the USA and the Federal Republic of Germany are growing almost exponentially. Considering the epidemiological curves for different risk groups (homosexual men, i.v. drug abusers, heterosexual partners etc.) it is extremely surprising, that nearly exactly the same development occurs in all risk groups. One only has to consider a certain time shift for each group. The conformity of the development for all groups is evident by the fact, that the curves representing the reported AIDS cases for different risk groups are straight lines (in a logarithmic scale) running nearly exactly in parallel. This remarkable parallelism can be understood only if the spread of AIDS is independent of the sexual or drug risk in a certain sense. On the other hand, the drastic overrepresentation of the sexually highly active groups and drug abusers in the number of AIDS cases obviously requires that the transmission of AIDS unequivocally depends on the sexual and drug risk. We present a mathematical model that is suitable to reconcile this apparent contradiction in the interpretation of the epidemiological data: the observed parallel time series for the spread of AIDS in groups with different risk of infection can be realized by computer simulation, if one assumes that the outbreak of full-blown AIDS only occurs if HIV and a certain infectious coagent (cofactor) CO are present. Such a situation is not uncommon, see, e.g. the influenza virus--Staphylococcus aureus system. According to the mathematical model this cofactor would spread independently of the sexual and drug risk--in contrast to HIV. However, due to its analytical properties the simulated cofactor cannot be identified so far with any known infectious agent.

Acquired Immunodeficiency Syndrome

On the mean incubation time of AIDS infections.

Using a nonlinear curve fitting method we calculate the incidence of AIDS cases through a study of reported data on cumulative AIDS cases. The method allows one to estimate the expected value of the incubation time, which happens to be about 11 years, if the intervals of observation are sufficiently large (greater than or equal to 45 years). For smaller intervals of observation the mean observed incubation time will be much shorter in consequence of the overrepresentation of "quick runners". The model predicts a mean observed incubation time of 5.3 years for an infected cohort in the first seven years after infection.

Acquired Immunodeficiency Syndrome