A long-term functioning human pancreatic islet allotransplant.
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Biomedical subjects
Publications and source records attributed to E Kolb.
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The entire amino acid sequence of the protein subunit of phosphofructokinase from Bacillus stearothermophilus has been established mainly by sequence analysis of cyanogen bromide fragments and of peptides derived from these fragments by further digestion with proteolytic enzymes. Overlaps of the cyanogen bromide fragments as well as peptide sequences necessary to complement and to confirm tentative assignments within the larger peptide fragments were obtained from the sequences of selected peptides isolated from tryptic and chymotryptic digests of the intact S-[14C]-carboxymethylated protein. Sequence information was also provided by automated sequence analysis of the intact protein subunit and of some of the larger peptide fragments. The sequence is as follows: (See Text).
Local cellular and extracellular (acid mucopolysaccharide) reactions in human lung cancers and metastases - prognostic parameters? The role of immunologic reactions in human malignant tumors is still unsettled. In the work presented, 72 primary lung cancers and 17 pulmonary metastases of 8 different organs of origin were studied with histochemical techniques for cellular infiltrates (eosinophils and macrophages) and extracellular acid mucopolysaccharides (AMPS). The results showed a positive correlation between eosinophils and macrophages and a negative correlation between cellular reactions and the deposition of AMPS. The clinical course of radically operable patients with primary lung cancer 2 to 3 1/2 years after operation showed that patients with the reactive pattern "strong local eosinophilia, no AMPS deposition" had the best prognosis with 12 of 14 patients free of tumor. Of the patients with the same tumor stage, but lacking local eosinophilia, more than half died from the tumor or had generalized metastases within the same period. The most frequent pattern in patients with pulmonary metastases was "no local eosinophilia, strong AMPS reaction". These observations suggest that cellular reactions in radically operable primary lung cancer express immunologic responses. These are often absent in metastases.
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The influence of local irradiation of the spleen and immunosuppressive drugs (cyclophosphamide and azathioprine) on the rejection of intrasplenic pancreatic allotransplants was studied. Fractional splenic irradiation (once 4000-5000 rad before, twice 500-1000 rad after transplantation) prolonged transplant function from 4,1 to 6,5 days, in combination with immunosuppressive therapy to 8,5 days.
Average sorbite half-life values were 11.8 minutes in two fasting calves, 18.7 minutes in three calves after drinking, 16.4 minutes in five heads of young cattle, and 16.6 minutes in two heads of adult cattle, following intravenous injection of 0.5 g/kg live weight of sorbite solution. Sorbite conversion thus proved adequate and better than glucose conversion. Fructose levels in the blood plasma of fasting calves as well as of young and adult cattle underwent statistically significant rises, following sorbite infusion, the steepest rise being recorded from adult cattle. Significant glucose and insulin increases following sorbite infusion were recordable only from blood plasma of adult cattle. Concentrations of free fatty acids in blood plasma were quite irregular.
The glucose, free fatty acid, and insulin levels in the blood plasma of young cattle underwent temporary but considerable rises, following intravenous infusion of adrenalin, doses being 2.5 or 5.0 micrograms/kg body weight. The average weight of these animals was 106.3 kg. The same findings were obtained from adult cattle, weighing 419.3 kg on average. A temporary but unambiguous rise of lactate in the blood was additionally recorded from young cattle. Adult cattle exhibited a temporary rise of fructose in the blood plasma. Regulation causing reflux of the analysed blood components and their return to their original levels or even below those was faster in cattle than it had been in sheep. Administration of insulin to cattle caused, within 45 minutes, decline of glucose in blood plasma from 8 mg/100 ml to 10 mg/100 ml. Intravenous application of adrenalin (5.0 micrograms/kg) increased the glucose level to 45 mg/100 ml or even 57 mg/100 ml, within five minutes. The lipolytic action of adrenalin was low under those conditions. Noradrenalin (5.0 microgram/kg body weight) exhibited merely medium glycogenolytic action but no lipolytic action at all.
Three lambs, aged between four and five weeks, and four sheep, aged one year, received infusions of galactose solutions (0.5 g galactose/kg body weight). The average half-life values were 28.7 minutes in the lambs and 59 minutes in the sheep. Average galactose concentrations, five minutes from mid-infusion, were 61 +/- 1.2 mg/100 ml of blood plasma in the lambs and 71 +/- 3.3 mg/100 ml in the sheep. The infusions caused statistically significant rises of glucose in the blood plasma of both lambs and sheep and an additional rise of fructose in the blood plasma of the sheep. In sheep galactose infusion resulted in rise of insulin in the blood plasma, within ten minutes from mid-infusion, the latter rise being statistically significant, from 53 +/- 26 microE/ml to 96 +/- 23.3 microE/ml. The lambs exhibited, as a result of the infusions, statistically significant rises of blood-borne lactate from 6.7 +/- 2.3 mg/100 ml to 16.7 +/- 1.2 mg/100 ml on average, within five minutes from mid-infusion.
The average iron level in the blood plasma of six gilts, weighting between 120 kg and 130 kg, was 103. 3 micrograms/100 ml, prior to early-morning feeding. The iron fixation capacity, measured at the time, was 673 micrograms/100 ml. Average iron levels went up to 121.3 micrograms/100 ml after 1.5 to two hours and to 130.3 micrograms/100 ml in the course of 3.5 to four hours. An average level of 124.3 micrograms/100 ml had been reached after another 1.5 to two hours. The iron fixation capacities first declined and then went up again. The average iron level recorded from eight adult sows, weighing between 180 kg and 210 kg, was 75 micrograms/100 ml, when measured seven weeks from piglet weaning. The average iron fixation capacity was 488.3 micrograms/100 ml at the same time and for the same animals. The iron level did not change throughout testing. The average copper level was 230.9 micrograms/100 ml, at the beginning, but individual differences in behaviour occurred during the day. No difference was recorded, at the beginning, between gilts and adult sows for blood plasma protein, levels being 7.73 or 7.81 g/100 ml, and for haemoglobin in the blood, levels being 12.8 or 12.5 g/100 ml. Individual variations, however, with no clear-cut direction, occurred over the testing period.
Blood tests were applied to five gilts and twelve adult sows, prior to insemination as well as in the sixth, ninth, twelfth, and 15th weeks of pregnancy. Average haemoglobin values in both groups dropped from 14.0 g/100 ml or 11.3 g/100 ml, at first measurement, to 9.5 g/100 ml in the ninth week of pregnancy. Then regrowth occurred to 12.6 g/100 ml or 12.2 g/100 ml up to the 15th week. The average blood plasma iron levels were 142 micrograms/100 ml or 117 micrograms/100 ml, at first measurement and went up in both groups, between the twelfth and 15th weeks, from 110 micrograms/100 ml to 161 micrograms/100 ml or from 105 micrograms/100 ml to 149 micrograms/100 ml. The original iron fixation capacity values for both groups were 673 micrograms/100 ml or 645 micrograms/100 ml and dropped to 524 micrograms/100 ml or 492 micrograms/100 ml by the 15th week of pregnancy. The copper levels grew from 221 micrograms/100 ml to 305 microgram/100 ml for gilts and from 200 micrograms/100 ml to 236 micrograms/100 ml for adult sows, from the twelfth to 15th weeks. The average blood plasma protein levels had been 7.7 g/100 ml or 8.1 g/100 ml, at the beginning, and went up to 8.5 g/100 ml in either group by the 15th week.
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Combined renal and pancreatic transplantation in patients with juvenile diabetes mellitus, diabetic nephropathy and renal insufficiency is designed to improve the poor prognosis observed with hemodialysis or renal transplantation alone. Interest has recently shifted from pancreatic organ to islet transplantation, in view of the absence of complications with the latter. However, no permanent success with islet transplants in diabetic patients has so far been reported. In the series presented, one patient with juvenile diabetes and subsequent renal failure was successfully treated with simultaneous kidney and intrasplenic pancreatic islet allotransplants. One year after the operation the patient has normal blood glucose levels without exogenous insulin, despite treatment with prednisone.
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Local free cell (eosinophils and macrophages) and extracellular (acid mucopolysaccharides) reactions were studied by histochemical techniques in 72 primary lung cancers (Group A), 17 pulmonary metastases and 5 lung tumours of unknown origin (Group B). Strong cellular reactions were more frequent in Group A than in Group B, whereas extracellular reactions were more frequent in Group B than in Group A. In both groups the degrees of eosinophilic infiltration and accumulation of acid mucopolysaccharides tended to be negatively correlated. In contrast, macrophages and eosinophils showed a positive correlation in the primary cancers, but none in the other tumours. The extracellular material had physical and chemical properties (solubility, affinity to stains and degradability by enzymes) of the sulphated acid mucopolysaccharides. From its distribution it appeared to be derived from fibroblasts and/or tumour cells.
Local infiltrates of eosinophilic leucocytes and macrophages and the deposition of acid mucopolysaccharides (AMPS) in 72 operable primary lung cancers and 17 isolated pulmonary metastases of known origin were correlated to tumour stage (radically or non-radically operable) and clinical course, by following the patients for 2-3 1/2 years. Half of the primary lung cancers showed strong local eosinophilia which, in combination with either strong macrophage infiltration or absence of AMPS reaction, characterized a very good prognosis in radically operable patients. No eosinophils, together with a strong AMPS reaction, indicated a very poor prognosis, irrespective of tumour stage. 16/17 metastases (7 different histologies) had either no local eosinophilia (13), strong AMPS deposition (12) or both (9). This suggests that malignant clones with great metastatic potential in general are characterized by absence of local eosinophilia and/or a strong AMPS reaction. These observations taken together indicate that local eosinophilia expresses an immune reaction which is, houl metastatic clones. It if does, metastatic success may be due to an escape mechanism based on the elaboration of AMPS.
The effects of sufficient milk intake as well as of 32 hours of fasting after birth, administration of actinomycin D (intraperitoneal application of 1 mg/kg five weight), and fasting in combination with actinomycin D on the development of body and liver weights, crude protein levels in homogenate and supernatant of liver, kidneys, and M. semitendinosus as well as on the activities of certain tissue enzymes were analysed with four groups of piglets (n = 4). Fasting, administration of actinomycin, and fasting in combination with actinomycin D resulted in rapid reduction in body and liver weights, while the crude protein levels in those tissues were not affected with significance. GOT and fructose-1,6-diphosphatase activities in supernatant from liver tended to decline under fasting conditions. The ATPase activity in the homogenate of the above tissues did not change in response to differentiated treatment.
Twenty-eight piglets from three litters were analysed for postnatal development (0 to 6 days of age) of the crude protein levels and activities of various enzymes (GOT, GPT, serine dehydratase, xanthinoxidase, fructose-1,6-diphosphatase) in the supernatant of liver, kidneys, and muscles. Both the weight and crude protein levels of the liver increased after birth, which improved the capability of metabolic regulation. GOT and fructose 1,6-diphosphatase activities in the liver tissue increased over the first days after birth. Serine dehydratase activity was not detectable with regularity. GPT activity in the tissues concerned was low by comparison to GOT and underwent little postnatal change. The activity of xanthinoxidase in the liver tissue tended to go up after birth. ACTH (3 IU/kg live weight) was administered to piglets aged five days and did not increase the activity of GOT and fructose-1,6-diphosphatase in the liver after five hours.