XH-14 analogues as adenosine antagonists

To investigate the utilization of dietary amino acids for hepatic protein synthesis, seven female pigs ( 28 d old, 7.5 kg) were implanted with catheters in a carotid artery, the jugular and portal veins, and the stomach. A portal flow probe was also implanted. The pigs were fed a high protein diet once hourly and infused intragastrically with [U-13C]algal protein for 6 h. Amino acid labeling was measured in arterial and portal blood, in the hepatic free and protein-bound pools and in apolipoprotein B-100 (apoB-100), albumin and fibrinogen. The isotopic enrichments of apoB-100-bound [U-13C]threonine, leucine, lysine and phenylalanine were 33, 100, 194 and 230% higher than those of their respective hepatic free amino acid pools (P < 0.01). Using the labeling of apoB-100 to estimate that of the protein synthetic precursor, the fractional rate of hepatic protein synthesis was 42 +/- 2%/d. Between 5 and 8% of the dietary tracer amino acids was used for hepatic protein synthesis. In contrast to the small intestinal mucosa, in which the majority of the metabolized amino acids were apparently catabolized, protein synthesis utilized from 48% (threonine) to 90% (lysine) of the hepatic uptake of tracer amino acids. It appears that hepatic protein synthesis consumes nutritionally significant quantities of dietary essential amino acids in first pass and that extracellular, especially portal, essential amino acids are channeled to hepatic protein synthesis in the fed state.     

Defective repair of oxidative damage in mitochondrial DNA in Down''s syndrome

BACKGROUND: Synthetic homopyrimidine peptide nucleic acids (PNAs) can bind complementary targets in double-stranded DNA, generating strand-displacement complexes, and so offering an opportunity to modulate specific gene expression. Several issues remain to be addressed before these attributes can be exploited in vivo, however. RESULTS: The kinetics of the interaction between a homopyrimidine PNA and a complementary homopurine target on double-stranded DNA were analyzed in the presence or absence of a preformed strand-displacement complex proximal to the target. The complex was established under low salt conditions by the binding of a different homopyrimidine PNA to a target situated adjacent to the first PNA target. These two targets were placed next to each other on opposite strands at distances of 0, 2, 4 and 8 base pairs apart. The presence of a preformed strand-displacement complex near the target accelerates the binding of PNA to double-stranded DNA in a salt-dependent manner. The influence of salt on the binding rates was also examined. The binding rate is increased by a factor of 1 x exp(70[NaCl]), that is, 16-fold at 40 mM NaCl and more than 10(4)-fold if extrapolated to 140 mM NaCl. This effect is significantly reduced if the two targets are 2 base pairs apart and completely absent if the distance is 4 base pairs or more. CONCLUSIONS: The perturbation of the DNA helix imposed by a PNA strand-displacement complex only propagates a few base pairs. It is therefore possible to target sites in the immediate vicinity of strand invasion complexes specifically. The results presented have implications for the mechanism of strand displacement and for the application of PNA in a genomic context.     

Parity as a risk factor for cancer cervix

PURPOSE: To analyze the likelihood of perioperative transfusion using the data of the abstracted patient discharge records. MATERIAL AND METHODS: It was studied the data of the records of the pediatric patients in whom were done surgical procedures for 1996. The abstracted patient discharge records are codified according the ICD-9-CM codes. RESULTS: 1,166 pediatric patients were operated, of whom were transfused 25 (2.1%). The transfusion rate was higher in patients less than 3 years old, who were operated with three o more surgical procedures simultaneously, who were admitted newly after the admittance here studied, and patients operated of spine, dorsolumbar spine, pharynx, thorax and mediastinum, central nervous system, colon, vessels and hip. CONCLUSIONS: Given the variability of the transfusion rate, to know it will allow a better planning of the surgical transfusions, the policy of the hospital blood bank and to increase the information to patient about the risk of the elective surgery.     

Widespread arterial thrombosis in association with metastatic carcinoma--a case report

Inferential studies suggest that circulating insulin concentrations positively regulate leptin secretion by adipocytes. In humans, however, insulin requires prolonged periods of time, and relatively artificial set-ups before a relationship with leptin can be observed. In the present work, serum leptin concentrations were measured in five patients with insulinoma before and one month after surgery and in five control subjects matched by sex and body mass index (BMI). The control subjects presented a mean serum leptin concentration of 6.7+/-1.5 microg/l and a BMI of 24.9+/-1.1. The mean serum leptin concentration in patients with insulinoma was 11.8+/-3.1 microg/l (P < 0.05 vs controls), with a BMI of 26.3+/-1.9. After surgery, there was a non-significant reduction in BMI (25.8+/-1.7), and a clear reduction in serum leptin concentration (5.6+/-2.4 microg/l, P < 0.05 vs pre surgical values and no difference vs control subjects). The fasting area under the curve (AUC) of insulin concentration (in mU/l per 120 min) before surgery was 14421+/-4981 and after surgery was 1306-/+171 (P < 0.05). Before surgery, serum leptin concentrations significantly correlated with BMI (r = 0.71) and AUC of insulin (r = 0.82), a correlation that was lost after surgery. In conclusion, serum leptin concentrations are significantly elevated in patients with chronically high insulin levels due to insulinoma. After surgical treatment and normalization of insulin values, leptin levels return to normal.     

Effect of various lipid-bile salt mixed micelles on the intestinal absorption of amphotericin-B in rat

We investigated the effect of the somatosensory functions to the outcomes of motor functions in 28 patients with thalamic hemorrhage. The disturbance of the pyramidal tracts was assessed by the destruction of the internal capsule found in computed tomography (CT). The disturbance of the somatosensory function was analyzed by the N20 component of short-latency somatosensory evoked potentials (SSEP). The outcomes of motor function was evaluated after 3 months of ictus. Correlations between the outcomes of motor function, disturbance of the pyramidal tract, and disturbance of the somatosensory function were discussed. The result indicated that functional outcomes statistically correlated with neither disturbance of the internal capsule alone nor disturbance of N20 alone. But, there was statistically significant between functional outcomes and the combination of disturbance of the internal capsule with disturbance of N20 (p < 0.05, Wilcoxon signed-rank). There was not statistical difference in hematoma volume or consciousness. The implications of these results suggest that somatosensory function may affect the recovery of motor functions.     

Renal lesion growth in children with tuberous sclerosis complex

Clostridium difficile-associated diarrhea (CDAD) is regarded as an emerging nosocomial infection. All patients positive for C. difficile in Sweden were recorded during 1995, including primary care patients. Those positive for toxin in feces were defined as CDAD cases. A total of 5,133 CDAD cases were recorded (58 per 100,000 inhabitants per year), as compared with 86 cases diagnosed in 1978 and 553 in 1983. CDAD was almost twice as prevalent as all (combined) diagnosed domestic cases of reportable bacterial and protozoal diarrhea. The age-specific incidence was little affected by gender but increased > 10-fold over the age range of 60-98 years. The differences in overall CDAD incidence were sixfold between counties and threefold between major hospitals. Among hospitalized patients the incidences were highest in geriatric/rehabilitation wards, followed by infectious diseases and internal medicine wards; 28% of all cases involved no recent hospitalization and were defined as community-acquired CDAD.     

Developmental aspects of dendritic cells in vitro and in vivo

Our knowledge in immunology has been dramatically increased by several excellent investigations elucidating the role of the Fas (Apo-1/CD95) receptor/ligand (FasL) system in complex immunological processes such as the acquisition of self tolerance in T cells, progression of autoimmunity, clonal deletion of activated T cells, B-cell regulation and the establishment of "immune privileged" sites such as testis or retina. In addition to these regulatory immunological activities, Fas/FasL interaction was also shown to participate in active defense mechanisms of the host against infected or transformed cells thereby inducing apoptosis in target cells. However, the same mechanism seems also to be part of an escape strategy utilized by tumor cells in various neoplastic malignancies of both hematopoetic as also non-hematopoetic origin. We ourselves were able to demonstrate that neoplastic plasma cell lines, as well as native malignant myeloma cells constitutively express FasL mRNA and protein. The FasL molecule is functionally active and able to induce programmed cell death in Fas sensitive target T cells in vitro. These target T cells were protected from programmed cell death by preincubation of T cells with a Fas-blocking monoclonal antibody (mAb) or of myeloma cells with a FasL-neutralizing mAb. respectively. Furthermore, overexpression of the caspase inhibitor, cowpoxvirus protein CrmA, also protected target T cells from being killed by myeloma cells, identifying Fas/FasL mediated signaling as the effector pathway utilized by malignant plasma cells. Our observations strongly suggest the engagement of Fas/FasL interaction in the escape strategy of this malignancy. The molecular basis of this evasive mechanism differs in essential respects from those described in melanoma, lung cancer, hepatocellular carcinoma, or astrocytoma, since downregulation of Fas or instrinsic insensitivity towards Fas-mediated signaling were not prerequisites for the occurrence of this phenomenon in Fas-sensitive multiple myeloma cell lines. However, myeloma cell lines resisted cocultivation with FasL-expressing target T cells in vitro. The aim of this review is to discuss the role of Fas/FasL interaction in the establishment of malignant disease, in the light of our findings on myeloma cells and also by drawing upon similar observations of other investigators on different kinds of tumor cells and cell lines and further to consider its possible relevance in formulating novel approaches to cancer therapy.