Glucose tolerance in overweight babies and infants of diabetic mothers.
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Biomedical subjects
Publications and source records attributed to B Persson.
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Two different strategies for scanning and screening of mutations in polymerase chain reaction (PCR) products by hybridization analysis are described, employing real-time biospecific interaction analysis (BIA) for detection. Real-time BIA was used to detect differences in hybridization responses between PCR products and different 17-mer oligonucleotide probes. For the analysis using a biosensor instrument, two different experimental formats were investigated based on immobilization of either biotinylated PCR products or oligonucleotide probes onto a sensor chip. Applied on the human tumour suppressor p53 gene, differences in hybridization levels for full-match and mismatch situations employing both formats allowed the detection of point mutations in exon 6 PCR products, derived from a breast tumour biopsy sample. In addition, a mutant sample sequence could be detected in a 50/50 background of wild type exon 6 sequence. The suitability of the different formats for obtaining a regenerable system and a high throughput of samples is discussed.
Diurnal profile studies have been used to define the fetal carbohydrate and lipid substrate environment in normal and diabetic women during late pregnancy. In women with normal glucose tolerance the diurnal plasma glucose concentration was maintained within close limits (mean +/- S.D., 4.70 +/- 0.38 mmol/l) but in chemical and insulin-dependent diabetics there was a marked increase in both the mean diurnal glucose value and in the variability of the plasma glucose levels observed through the day (mean +/- S.D., 5.61 +/- 5.61 +/- 1.03 and 6.02 +/- 1.26 mmol/l respectively, P less than 0.01). No difference was observed between the peripheral insulin activity of the normal and chemical diabetic women, and the impaired glucose tolerance of the latter group was due to a deficient insulin response to goucose. The diurnal glucose variability, expressed as the standard deviation of the mean, was found to be inversely correlated with the residual C-peptide response in insulin-requiring diabetics. The mean diurnal plasma free fatty acid (FFA) concentration was slightly raised in chemical diabetic subjects compared to normal women (mean +/- S.D., 0.77 +/- 0.34 and 0.68 +/- 0.20 mmol/l respectively) but this difference was not significant. Insulin treatment produced a marked reduction in circulating FFA concentration, with a mean value in the insulin-dependent diabetic group of 0.45 +/- 0.11 mmol/l (P less than 0.001). Neonatal glucose assimilation during the first two hours of life correlated strongly with several functions of maternal carbohydrate tolerance. This was associated with higher plasma insulin concentrations at birth, and a marked tendency to hypoglycaemia in the infants of untreated chemical diabetic women. Impaired mobilization of triglyceride stores was also observed during the two hours after birth in the infants of diabetic women. This, however, appears to be due not to impaired lipolysis but to rapid re-esterification of FFA. These findings all indicate a state of functional hyperinsulinism in the infant of the diabetic women secondary to maternal hyperglycaemia.
A real-time biospecific interaction analysis (BIA) was performed to study the specific interaction between the Fc portion of human immunoglobulin G1 (Fc1) and a one domain analogue (designated Z) of staphylococcal protein A, in monovalent (Z) and divalent (ZZ) forms, and five different single amino acid substituted Z variants (L17D, N28A, F30A, I31A, K35A). Experimental BIA data were used to calculate association rate constants (kon), dissociation rate constants (koff) and affinity constants (Kaff). The divalent form (ZZ) showed a higher affinity for Fc1 mainly because of a slower off rate. Out of the five mutant Z proteins, four (L17D, N28A, I31A, K35A) showed a decreased affinity to Fc1 compared to the parent Z molecule. Surprisingly, two (L17D, I31A) of these four had the major effect of a decreased binding energy as a lowered kon while the other two (N28A, K35A) mutant proteins showed an increased koff as the major kinetic difference from Z in their binding to Fc1. For five of the six different Z variants, as well as for the ZZ molecule, calculated Kaff and calculated differences in binding free energies relative to the parent Z molecule (delta delta G), are in good agreement with the corresponding values obtained in a competitive displacement assay using radioactively labeled Z as a tracer (Cedergren et al., (1993) Prot. Eng. 6, 441-448). However, the I31A variant, with a measured kon that was more than three orders of magnitude lower than that of Z in the BIA assay, showed a significantly weaker affinity to Fc1 when calculated from the BIA data compared to the competitive displacement assay. The discrepancy between these two methods for Z(I31A) is discussed as well as possible explanations for the unexpected large effect of lowered kon for two of the mutant Z proteins.
Neuroendocrine liver metastases are rare, yet they represent an entity that has attracted much attention lately. The protracted course of neuroendocrine tumors and the hormone origin of their typical incapacitating symptoms constitute a logical basis for well founded and bespoke treatment. Demonstration of the liver secondaries is best done by ultrasonography (US) and contrast-enhanced computed tomography (CT), which on the whole have replaced the invasive angiography techniques. By use of histochemical and molecular biologic methods the exact nature of the tumor can be typified in tissue samples obtained percutaneously, laparoscopically, or surgically. Localization of nonpalpable metastases of the liver is best done by intraoperative US. Surgical removal of liver metastases is curative in some cases and is usually effective in relieving the symptoms. Also, palliative debulking or cytoreductive surgery is often worthwhile as it offers a chance of prolonged survival and symptom relief. Similar benefits are achieved by ischemic therapy preferably by temporary dearterialization, which in our department is done on an outpatient basis using a specially designed (externally controlled) occluder applied during a single laparotomy that includes debulking when appropriate as well as cholecystectomy. Hormonal therapy with somatostatin analogs may be used as a single treatment or in combination with ischemic therapy. It has an ensured symptom-reducing effect, whereas its influence on tumor growth is unsettled. Lately similar effects have been ascribed to human leukocyte interferon. In conclusion the specific characteristics of neuroendocrine tumors and the available treatment arsenal favor an active treatment approach in patients who have developed liver metastases.
PURPOSE: To develop a method for isolated perfusion of the liver using radiological methods. METHODS: Twenty-one pigs, weighing about 20 kg, were divided into three groups. By transjugular and transfemoral approaches two occlusion balloons were placed in the inferior vena cava cranial and caudal, respectively, to the origin of the hepatic veins. One occlusion balloon was placed transfemorally in the common hepatic artery. Another occlusion balloon was inserted in the main branch of the portal vein via the transjugular-transhepatic approach in 11 pigs (groups 1 and 2), and in 10 pigs (group 3) by a percutaneous transhepatic route. After inflation of the balloons, patency of the isolated liver circulation was evaluated by recirculation of 99Tcm-labelled human albumin during 30 min. Blood tests were obtained after 1, 3, 5, 10, 15, and 30 min to evaluate leakage from the liver to the systemic circulation. RESULTS: Increasing leakage to the systemic circulation from the isolated liver circulation was observed in groups 1 and 2. In the third group the leakage was less than 10%. CONCLUSION: In an experimental animal model, isolated perfusion of the liver with minor leakage to the systemic circulation may be achieved using radiological methods.
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A method for the assay of lipoprotein lipase activity (LPLA) in heparin eluates of needle biopsies of adipose tissue is presented. A serum activated phosphatidestabilized emulsion of labelled triolein has been used as substrate. This method and a previously described method using heparin eluates as enzyme source and a commercial triglyceride emulsion, Ediol, as substrate, showed a high degree of correlation (correlation coefficient = 0.94) when parallel determinations were performed on biopsies from 16 subjects. Further, the Ediol method similarly correlated well with a method for LPLA assay, previously described by Nilsson-Ehle and Belfrage, on acetone-ether extracts of adipose tissue (correlation coefficient = 0.88; 19 subjects).
An optimization procedure for the separation of 24 PTH-amino acids by high-performance liquid chromatography on an inexpensive Merck Superspher Si 60 RP-8, (4.0 x 250 mm) column with PTH-Nle as an internal standard is described. The effects of pH, ionic strength, temperature and gradient were investigated. Using conventional HPLC equipment, the practical detection limit is about 5 pmol.
Two polypeptides, eristocophins I and II, have been characterized from leaf-nosed viper (Eristocophis macmahoni) venom. They contain 10 half-Cys residues of a total of 61/62 residues, have 72% residue identity, and exhibit similarities to platelet aggregation inhibitors and segments of adhesive proteins. Eristocophin I contains the sequence Arg-Gly-Asp, known to inhibit fibrinogen interaction with the platelet receptor. Eristocophin II has Met instead of Arg in this sequence, and an adjacent Trp-Asn-Asp segment. The latter is also typical of adhesive proteins, thus linking two potentially functional segments in one molecule. Exchanges are maximal in these segments, suggesting that the polypeptides exhibit functional divergence with isoform differences in important regions.
The characteristics of gastric mucosal patterns in the polyp-bearing stomach were investigated by the endoscopic Congo red test and systemic four-points biopsy in 46 patients with hyperplastic polyps and 21 patients with gastric adenomas. In addition, function of the stomach in these patients was assessed by determination of gastric acidity and fasting serum gastrin level and by gastrin response test to a beef extract. In the investigation of the gastric mucosal pattern in hyperplastic polyp patients, Type A gastritis (involving the corpus but sparing the antrum) was most frequently found. On the other hand, extensive intestinal metaplasia from the pyloric antrum to the corpus was most often noted in the adenoma-bearing stomach. Hypergastrinemia was more marked in hyperplastic polyp patients, and may be involved in the pathogenesis of hyperplastic polyps. Attention should be paid to the detection of cancer in areas without polyps during endoscopic observation and reexamination of patients. On these occasions, the characteristics of the background mucosa for each type of polyp should be kept in mind.
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