N-2-nitrophenylthio amino acid N-carboxyanhydrides. The solid-phase synthesis of two decapeptides, and their cyclization to [Gly5, Gly10]gramicidin S and antamanid.
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Biomedical subjects
Publications and source records attributed to T Christensen.
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Testicular androgen binding protein (ABP) was purified from the epididymis of 1500 adult rabbits by the sequential use of ammonium sulphate precipitation, ion exchange chromatography on DEAE cellulose, gel filtration on Sephadex G-200, hydroxyl-apatite chromatography and preparative polyacrylamide gel electrophoresis. This procedure yielded a 1000-fold increase in specific activity compared to that of the 1500,000 x g supernatant, and the recovery of active ABP was about 3-5%. ABP is acid glycoprotein with a molecular weight of 65-68,000 daltons. Antisera to rabbit ABP raised in quinea pigs inhibit 3H-DHT binding to ABP as measured by SS-PAGE. When diluted rabbit serum containing TeBG is treated with the same dilutions of these antisera, identical binding inhibition curves are found. Thus, ABP and TeBG in rabbits appear to possess identical immunological determinants.
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Uncomplicated major surgery is followed by a pronounced increased feeling of fatigue extending throughout the first month in about one-third of patients. Postoperative fatigue correlates with the degree of surgical trauma but is not related to duration of general anesthesia and surgery or to preoperative nutritional status, age, or sex. Fatigue also correlates with postoperative deterioration in nutritional parameters and impaired adaptability of heart rate during exercise. Furthermore, a postoperative decrease in muscle force and endurance is related to postoperative fatigue, whereas psychological factors are of minor importance. These findings suggest postoperative fatigue to be mediated by the endocrine-metabolic response to surgery, impaired nutritional intake, or immobilization, but the relative role of these factors remains to be established. Until then, therapeutic measures against the development of postoperative fatigue should aim at reducing the surgical stress response, effective treatment of pain to facilitate mobilization, and exercise to increase postoperative nutritional intake.
Glomerular hyperfiltration is a characteristic feature of insulin-dependent diabetes. We examined the relative roles of renal size, as well as glycemic parameters (HbA1c, glycosylated albumin, plasma glucose) in addition to growth hormone, somatomedin C, beta-hydroxybutyrate, alanine, and glycerol in determining the glomerular filtration rate (GFR). Sixty-two insulin-dependent patients with normal urinary albumin excretion rates (AER less than 15 micrograms/min), who were less than 50 years of age, were included in the study. Data were subjected to multiple regression analysis with GFR as a dependent variable. Renal volume was the primary statistical determinant of hyperfiltration, but HbA1c also significantly correlated with GFR. No correlation was found with glycosylated albumin or blood glucose, but RPF correlated strongly with GFR, and borderline correlation was found between renal volume and HbA1c. Renal hyperfiltration, defined as a GFR greater than 150 ml/min, was found in approximately 50% of patients with HbA1c values greater than 9.5%. Other studies suggest that such patients have a much higher risk of developing clinically evident diabetic nephropathy over the ensuing years. Renal volume appears to be the major determinant of GFR, but long-term metabolic control, as evidenced by the level of HbA1c, also contributes, partly independent of renal volume. Short-term metabolic control, as evaluated by blood glucose and serum-fructosamine, did not correlate with GFR. We suggest that exact determination of GFR and renal volume should be included in long-term prospective controlled intervention trials in patients with insulin-dependent diabetes mellitus (IDDM).
Changes in cellular uptake of glutamate following transient cerebral ischemia is of possible importance to ischemia induced cell death. In the present study, we employed in situ hybridization and immunohistochemistry to investigate the influence of cerebral ischemia on expression of mRNA and protein of the astrocyte glutamate transporter GLT1, and of glial fibrillary acidic protein. Different subfields of CA1 and CA3 of the rat hippocampus were studied at various time-points after ischemia (days 1, 2, 4, and 21). In CA1, GLT1-mRNA was decreased at all time-points after ischemia except from day 2, whereas in CA3, decreases were seen only on day 1. Expression of GLT1-protein in CA1 was unchanged during the initial days after ischemia, but decreased markedly from day 2 to 4. In CA3, GLT1-protein increased progressively throughout the observation period after ischemia. Following the degeneration of CA1 pyramidal cells, a positive correlation between the number of CA1 pyramidal cells and expression of either GLT1-mRNA or -protein was evident selectively in CA1. Increases in expression of mRNA and protein of glial fibrillary acidic protein were present from day 2, most notable in CA1. The present data provide evidence that expression of GLT1 in CA1 of the hippocampus is not decreased persistently before the degeneration of CA1 pyramidal cells, but is downregulated in response to loss of these neurons. Since the reduction in GLT1 expression evolved concomitantly with the degeneration of CA1 pyramidal cells, it may contribute to the severity of CA1 pyramidal cell loss. A progressive postischemic increase in GLT1 expression in CA3 may be linked to the resistance of CA3 neurons to ischemic cell damage.
Glomerular filtration rate (GFR), renal plasma flow (RPF), kidney volume, and urinary albumin excretion rate were measured in 24 insulin-dependent diabetics, aged 29 +/- 7 years (mean +/- SD) with diabetes duration of 8 +/- 4 years who were randomly allocated to either continuous subcutaneous insulin infusion (CSII) (n = 12) or unchanged conventional insulin treatment (CIT) (n = 12). GFR, RPF, and kidney volume were identical but significantly increased above normal values in the two groups at the start of the study. After 24 months of CSII treatment, significant reduction in GFR was seen compared to pretreatment values (145 +/- 21 ml/min vs 139 +/- 21 ml/min, 2p less than 5.0%). However, RPF was not reduced after 24 months of CSII treatment (608 +/- 104 ml/min vs 601 +/- 106 ml/min). In the CIT group no changes in GFR or RPF was seen, and kidney volume remained unchanged in both groups; urinary albumin excretion was normal or near normal in both groups and remained unchanged. Thus, improved glycemic control in long-term IDDM patients is associated with normalization (reduction) of renal "hyperfunction," but despite this, no reduction was seen in the associated nephromegaly.
We constructed a synthetic Escherichia coli expression system in which various promoter elements can be changed easily. In this study we investigated the effect of a number of portable Shine-Dalgarno regions (SD regions) on the synthesis of two modified recombinant human growth hormones (hGH). The production of these modified hGH was measured during exponential growth and after the bacteria had reached stationary phase. The results show that the optimal distance between the SD region (AGGAGG) and the ATG start codon is approximately 11 nucleotides. However, the nucleotide sequence in this region also influences expression: 6-10 adenines result in comparable expression levels despite the varying lengths. Two overlapping SD regions reduce expression of the growth hormones considerably, whereas two potential ATG start codons do not affect expression. Having a SD-ATG region partly or totally complementary to the 5' end of the 16S ribosomal RNA does not alter translation efficiency. Estimation of the delta G values for the association between the 16S rRNA and the ribosome-binding region suggests that these are not indicators of expression efficiency.
We investigated whether the known neuroprotective effects of two selective glutamate receptor antagonists, the NMDA antagonist MK-801 and the AMPA antagonist NBQX, are reflected in the regional cerebral protein synthesis rates (CPSR) in rats with middle cerebral artery occlusion (MCAO). Rats treated with either saline, MK-801 (5 mg/kg i.p.) or NBQX (30 mg/kg i.p. x 3) were subjected to permanent MCAO. Regional CPSR and volumes of gray matter structures displaying normal CPSR were measured in coronal cryosections of the brain by quantitative autoradiography following an i.v. bolus injection of 35S-labelled L-methionine 2 h after occlusion. MCAO completely inhibited protein synthesis in the lateral part of striatum and part of the adjacent frontoparietal cortex corresponding to the ischemic focus. Surrounding this, a metabolic penumbra with approximately 50% reductions in CPSR was present. Treatment with MK-801 significantly increased the volume of tissue with normal CPSR in the ischemic hemisphere compared to controls, whereas this was not seen with NBQX treatment. The results suggest that MK-801 and NBQX have different effects on peri-infarct protein synthesis after MCAO. Since both compounds reduce infarct size, it is questionable that acute inhibition of protein synthesis in focal ischemia is of significant importance to the final outcome of a stroke lesion.
The diameter and the elastic properties of the femoral artery were investigated by means of ultrasound M-mode. The nature of individual variations was determined in 27 medical students at the age of 21-23 years. A significant positive correlation was found between height and increasing arterial cross sectional area. The influence of age upon arterial luminal size and elasticity was estimated in a group of 43 persons with a wide range of age. There was a significant rise in stiffness proportional to age, but none in luminal size.
During a 20 year period, 33 patients with traumatic rupture of the descending thoracic aorta were operated upon. In the absence of an indication for acute surgery our policy was to defer operation at least 4 weeks after the trauma. Six patients were operated upon within 24 hours (Group I), 5 after 4-13 days due to suspected expansion of mediastinal widening (Group IIa), 10 were operated upon electively after 4-12 weeks (Group IIb), and 12 were operated upon for chronic traumatic aneurysms (Group III). The number of operative deaths/reoperations due to bleeding were: Group I, 2/1; Group IIa, 1/2; Group IIb, 0/0; and Group III, 1/0. There were no late deaths related to the operation or the inserted prosthesis. Of 26 survivors, 21 underwent a follow-up study 1.5-20 years (mean 8.2 years) postoperatively. Except for 6 patients with paralysis of the left recurrent laryngeal nerve none of the patients had sequelae which could be related to the operation or the inserted prosthesis. CT-scanning of the chest revealed neither pseudoaneurysms nor significant stenosis in the suture lines or prosthetic areas. The results indicate that delayed operation of traumatic thoracic aortic ruptures on selected patients may be performed with acceptable results.
The arterial wall stiffness in the common femoral artery was determined by means of an ultrasound technique in 47 insulin-dependent diabetics and 24 controls aged 20 to 39 years. They were all without vascular symptoms and signs, and were selected in such a way that they were thought to be free of age correlated changes. Furthermore, patients in potential risk groups, as for arterial disease of non-diabetic type, were excluded. The arterial wall stiffness was significantly increased in the diabetic group as compared with a control group. Furthermore, there was a significant correlation to the diabetic duration. Possible pathogenetic reasons are discussed.
By means of ultrasonography, arterial wall stiffness, arterial wall thickness, and the elastic modulus of the common femoral artery were estimated in a group of 19 young insulin-dependent diabetics. The ultrasound technique for determination of these parameters is described as well as the echo-anatomy of the arterial wall. In accordance with a previous investigation a significant rise in arterial wall stiffness was found. Furthermore, there was a highly significant correlation between the stiffness and the thickness of the arterial wall. The elastic modulus also correlated to the stiffness. It is concluded that the diabetic macroangiopathy is characterized by an increased stiffness of the arterial wall caused by increased thickness as well as by progressive alterations of the elastic characteristics of the wall tissue. Possible pathogenetic reasons are discussed.
By means of an ultrasonographic technique the systolic and diastolic diameters of the common femoral artery were investigated in a group of 50 young insulin-dependent diabetics selected as being free from late diabetic complications and atherosclerotic involvement. After correction for normal physiologic variations there was no correlation of arterial diameters to duration of diabetes and no statistical difference in relation to a control group. It is known that there is a progressive increase of the arterial wall thickness in medium-sized arteries in diabetes. Therefore, it is concluded that there is a corresponding dilatation of the arteries. The reasons for this dilatation are discussed from a biophysical point of view. Furthermore, it is concluded that the increased arterial wall stiffness caused by an increasing elastic modulus and thickness reflects the earliest changes in the diabetic macroangiopathy. Occlusions and narrowing seem only to exist in patients with severe late diabetic complications.