Stereochemistry of the most active racemate of norbormide. A selective rat toxicant.
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Animals↗
Biomedical subjects
B Nilsson
Publications and source records attributed to B Nilsson.
Variables predicting oral mucosal lesions in allogenic bone marrow recipients.
One hundred and forty-eight (72%) of 205 allogenic bone marrow transplant recipients developed mucosal lesions in the oral cavity during the aplastic period after transplantation. Lesions were most frequent 8 to 9 days after transplantation. Factors that correlated with the development of mucosal lesions after univariate and multivariate analysis were a marrow cell dose of less than 3 x 10(8) cells/kg body weight, (p less than 0.0001), prolonged aplastic period (white blood cell count less than 0.2 x 10(9) cell/l during more than 14 days (p less than 0.005), herpes simplex virus-1 seropositivity of the recipient (p less than 0.01), and conditioning with total body irradiation (p less than 0.02).
Adolescent↗
Blood lymphocyte characteristics as predictors of prognosis in chronic lymphocytic leukemia of B-cell type.
The prognostic information of blood lymphocyte characteristics and clinical findings was assessed in 62 patients with chronic lymphocytic leukemia of B cell type. Bivariate and multivariate survival analyses were performed using age, Rai stage, surface membrane immunoglobulin (smIg) isotype pattern of the leukemic clone, total lymphocyte counts, numbers of proliferating lymphocytes and T cell subpopulations. Rai stages III and IV, high numbers of blood lymphocytes in S-phase (S+) and sm mu isotype were found to be partly independent factors predicting short therapy-free survival. Patients with a sm mu+ leukemic cell clone had a shorter therapy-free and total survival compared to those with sm mu+/delta+ and sm delta+ leukemic cells. Moreover, patients with high numbers of blood S+ lymphocytes had a shorter therapy-free and total survival compared to those with few S+ cells. These prognostic variables were valid also in patients with a low tumour burden (Rai stages 0, I and II) and may thus be of clinical importance as a guideline for therapeutic intervention.
Actuarial Analysis↗
Kinetic analysis of the interaction between protein A domain variants and human Fc using plasmon resonance detection.
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.
Amino Acid Sequence↗
Sunbed use in Swedish urban adolescents related to behavioral characteristics.
BACKGROUND: Sunbed use among Swedish adolescents has not been extensively studied, nor has the social learning process associated with it. The purpose of this study was to explore Swedish adolescents' sunbed use in relation to sex, age, smoking, perceived physical attractiveness, attitudes to artificial and natural UV exposure, psychosomatic symptoms, and risk knowledge. METHODS: In the spring of 1993, 60 school classes comprising 1,502 students ages 14-19 were randomly selected to answer a questionnaire concerning sunbed use and sunbathing habits, smoking, perceived physical attractiveness, psychosomatic symptoms, and need for information about and knowledge of the risks of UV exposure. RESULTS: Of 1,252 respondents, 57% had used sunbeds (females 70%, males 44%) > or = four times during the previous year. A marked increase (P < 0.001) in both sunbed use and smoking was detected between the 8th and the 9th grade (at ages 14-15). Sunbed use was also significantly correlated with sex, age, excessive tanning in natural sunlight, and low perceived physical attractiveness. The need for information on risks of high UV exposure was greatest among the best informed students and among students with high UV exposure (sunbed use, excessive tanning in natural sunlight). CONCLUSIONS: It seems doubtful whether further information on UV risks would result in altered behavior among highly exposed students, who seem receptive to information and have good knowledge. For a better understanding of the mechanisms underlying the association between sunbed use, smoking, and self-esteem, more in-depth, qualitative studies are required.
Adolescent↗
Elevated serum beta-2-microglobulin--a prognostic marker for development of AIDS among patients with persistent generalized lymphadenopathy.
For evaluation of its prognostic value, the level of serum beta-2-microglobulin was determined in early serum samples from 88 patients with persistent generalized lymphadenopathy in a prospective longitudinal study. Patients with serum beta-2-microglobulin greater than 2.6 mg/l were found to have a significantly higher risk of developing AIDS earlier when compared to patients with a lower level (p less than 0.001).
AIDS-Related Complex↗
Endometrial stromal sarcoma of the uterus. A clinical and histopathological study. The Radiumhemmet series 1936-1981.
Twenty-eight cases of endometrial stromal sarcoma treated from 1936 to 1981 at Radiumhemmet were reviewed. Histopathologically, 16 were classified as high-grade stromal sarcomas and 12 were of a low grade. A significant relation between mitotic count and relative survival within 10 years of the diagnosis was found (p less than 0.05) showing a more favorable outcome for patients with low counts compared with patients with higher counts. Primary treatment included surgery and radiotherapy in 21 cases. Two advanced cases were only irradiated and five cases were treated with surgery alone. Adjuvant radiotherapy seems to be of benefit in high-grade tumors, demonstrated in a 5-year survival rate of 73%, which exceeds most reported results. Five out of seven women dying of low-grade tumors were diagnosed in an advanced stage.
Adult↗
Enzyme-linked immunosorbent assays.
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Enzyme-Linked Immunosorbent Assay↗
Soluble complement receptor 1 (TP10) preserves adult porcine islet morphology after intraportal transplantation into cynomolgus monkeys.
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Animals↗
Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation.
BACKGROUND: Intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus, but intraportal thrombosis remains a possible complication. The thrombotic reaction may explain why graft loss occurs and islets from more than one donor are needed, since contact between human islets and ABO-compatible blood in vitro triggers a thrombotic reaction that damages the islets. We investigated the possible mechanism and treatment of such thrombotic reactions. METHODS: Coagulation activation and islet damage were monitored in four patients undergoing clinical islet transplantation according to a modified Edmonton protocol. Expression of tissue factor (TF) in the islet preparations was investigated by immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To assess TF activity in purified islets, human islets were mixed with non-anticoagulated ABO-compatible blood in tubing loops coated with heparin. FINDINGS: Coagulation activation and subsequent release of insulin were found consistently after clinical islet transplantation, even in the absence of signs of intraportal thrombosis. The endocrine, but not the exocrine, cells of the pancreas were found to synthesise and secrete active TF. The clotting reaction triggered by pancreatic islets in vitro could be abrogated by blocking the active site of TF with specific antibodies or site-inactivated factor VIIa, a candidate drug for inhibition of TF activity in vivo. INTERPRETATION: Blockade of TF represents a new therapeutic approach that might increase the success of islet transplantation in patients with type 1 diabetes, in terms of both the risk of intraportal thrombosis and the need for islets from more than one donor.
Adult↗
Phosphorylation of plasma proteins with emphasis on complement component C3.
Phosphorylation of complement component C3 by different protein kinases in vitro has been demonstrated to alter the functional properties of the protein. Extracellular phosphorylation mediated by activated platelets is a newly described mechanism by which the function of plasma proteins can be regulated. Upon activation of platelets a casein kinase is released concomitant with large amounts of ATP and Ca2+. These components are sufficient to phosphorylate proteins e.g., C3 extracellularly. In vivo, in patients with SLE, the phosphate content in plasma proteins, including C3 has been demonstrated to increase during exacerbation. The changes were linked to platelet activation by a covariation with the levels of beta-thromboglobulin. The purpose of this review is to summarise the findings in this field.
Animals↗
Preconditioning protects against ischemia/reperfusion injury of the liver.
Ischemic preconditioning (IPC) of an organ may induce protection against the injury caused by longer duration of ischemia and subsequent reperfusion. In a standardized model of such injury in the rat liver, we used the following protocol to investigate whether adenosine played a role in IPC by preventing its enzymatic degradation by dipyridamole pretreatment according to the following protocol: group 1, nonischemic control rats; group 2, ischemic control rats subjected to 60 minutes of ischemia by clamping of the common hepatic artery followed by 60 minutes of reperfusion; group 3, IPC with 10 minutes of ischemia followed by 15 minutes of reperfusion, prior to the ischemia/reperfusion period as in group 2; group 4, pharmacologic preconditioning with administration of dipyridamole prior to the ischemia/reperfusion period as in group 2. Peripheral liver blood flow was significantly reduced during clamping (groups 2 to 4). After unclamping, blood flow was still reduced in the ischemic rats (group 2) but had returned to preclamp values in the animals that had been subjected to ischemic (group 3) or pharmacologic (group 4) preconditioning. Liver cell injury was significantly increased in the ischemia group (group 2) only. In our experimental model of ischemia/reperfusion injury in the rat liver, we found an equally beneficial effect with ischemic and pharmacologic preconditioning. Adenosine appears to be a crucial factor in IPC.
Adenosine↗
Role of cyclooxygenase-2 for fluid secretion by the inflamed gallbladder mucosa.
Inflammatory fluid secretion by the gallbladder mucosa in experimental cholecystitis is induced by activation of cyclooxygenase, which leads to an increase in prostaglandin formation. Cyclooxygenase exists as a constitutive (cyclooxygenase-l) and an inducible (cyclooxygenase-2) isoform. The aim of this study was to demonstrate the role of cyclooxygenase-2 in inflammatory fluid secretion of the feline gallbladder. Experiments were performed 10 weeks after a surgical procedure in which chronic cholecystitis was induced in cats by ligation of the cystic duct and implantation of a gallstone in the gallbladder. Gallbladder fluid transport was continuously monitored via a perfusion system. In inflammed gallbladders the continuous fluid secretion was reversed to absorption by intravenous injection of the selective cyclooxygenase-2 blocker, NS 398 (P <0.001). Increased levels of the inducible cyclooxygenase-2 were shown by immunoblotting in inflamed gallbladders. Selective pharmacologic blockage of cyclooxygenase-2 reduced the prostaglandin E2 release to the inflamed gallbladder lumen (P <0.01). These data suggest that cyclooxygenase-2 is involved in the inflammatory response during chronic cholecystitis. Selective cyclooxygenase-2 blockers may offer an alternative to traditional nonsterodial anti-inflammatory drugs with fewer side effects in patients with cholecystitis who are awaiting operation.
Animals↗
Nuclear DNA content, proliferative activity, and p53 expression related to clinical and histopathologic features in endometrial carcinoma.
The purpose of this study was to evaluate the prognostic impact of image cytometry DNA ploidy, MIB-1, and p53 in relation to clinicopathologic variables in 376 consecutive patients with endometrial carcinoma stages I-IV. Following primary treatment 358 patients were considered tumor-free. Relapses and tumor-specific deaths of these patients were noted. Image cytometry DNA ploidy (n = 340) and expression of MIB-1 (n = 318) and p53 (n = 323) were studied. In univariate analysis, stage (P < 0.001), histopathologic subtype (P < 0.001), degree of differentiation (P < 0.001), HRT (P = 0.034), DNA ploidy (P < 0.001), and p53 (P < 0.001) were significant predictors of relapse. Patient age showed that the estimated mean risk of relapse increases with nearly 64% per decade in life (P 0.003), and the MIB-1 expression with 21% per 10-unit increment (P 0.004). In multivariate analysis, degree of differentiation, MIB-1, and p53 lost their prognostic capability. However, after stage and histopathologic subtype, image cytometry DNA ploidy was the strongest predictor of outcome and was of value in predicting the risk for relapse. The combination of DNA ploidy, MIB-1, and p53 expression was an even stronger predictor of relapse-free survival than the individual prognostic factors.
Adenocarcinoma↗
Wine--an important source of lead exposure.
Blood lead levels in 32 male chronic alcoholic patients were measured and related to drinking habits. An external reference group and a group with previous high alcohol consumption served as controls. Blood lead concentrations were significantly higher (P less than 0.05) in the group with current high alcohol consumption (mean +/- S.D.) (90 +/- 48 micrograms/l, n = 17) than in the external reference group (57 +/- 27 micrograms Pb/l, n = 35). The blood lead concentrations in the latter group were similar to those in the group with previous high alcohol consumption (55 +/- 20 micrograms Pb/l, n = 15). Patients with excessive consumption of wine only (average intake 2.61 wine/day, range 1.3-4.5 l/day) had particularly elevated blood lead concentrations (149 +/- 31 micrograms Pb/l, n = 5), whereas blood lead levels were close to the control value in patients with excessive consumption of spirits only (68 +/- 28 micrograms Pb/l, n = 7). Furthermore, within the external reference group blood lead levels were higher in those who regularly drank more than 0.51 of wine on several occasions each week (96 +/- 22 micrograms Pb/l, n = 6) than in those who consumed less wine (48 +/- 20 micrograms Pb/l, n = 29). In a recent study of table wines sold in Sweden the average lead concentration in 84 samples was found to be 73 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A synthetic IgG-binding domain based on staphylococcal protein A.
A synthetic IgG-binding domain based on staphylococcal protein A was designed with the aid of sequence comparisons and computer graphic analysis. A strategy, utilizing non-palindromic restriction sites, was used to overcome the difficulties of introducing site-specific changes into the repetitive gene. A single mutagenized gene fragment was polymerized to different multiplicities, and the different gene products were expressed in Escherichia coli. Using this scheme, protein A-like proteins composed of different numbers of IgG-binding domains were produced. These domains were changed to lack asparagine--glycine dipeptide sequences as well as methionine residues and are thus, in contrast to native protein A, resistant to treatment with hydroxylamine and cyanogen bromide.
Amino Acid Sequence↗
Primary carcinoma of the vagina: factors influencing the age at diagnosis. The Radiumhemmet series 1956-96.
The objective to this retrospective study of 341 cases of primary carcinoma of vagina (PCV) diagnosed between 1956 and 1996 was to find whether epidemiological, clinical, and histopathological variables were related to the age at diagnosis of patients with PCV. The univariate statistical analysis showed that younger age at diagnosis significantly correlated with a history of cervical dysplasia, hysterectomy, gynecological infections, and tumors located in the upper part of the vagina, whereas older age at diagnosis significantly correlated with late menarche and exophytically growing tumors. In the multivariate regression analysis, the remaining independent predictors were a history of cervical dysplasia and age at menarche. Further, parity >/=4 as well as nulliparity, smoking, and unstable marital status were more common among patients with PCV than among those in the general Swedish female population. This study indicates that the etiology of vaginal carcinoma may be age related. In young patients, the disease seems to be etiologically related to cervical neoplasia and thus human papillomavirus (HPV) dependent. However, in the most common age group, the older patients, there might be another (probably non-HPV-related) etiology associated with hormonal factors and trauma to the vagina.
Adenocarcinoma↗
Clinical and histopathologic factors related to prognosis in primary squamous cell carcinoma of the vagina.
The goal of this retrospective study concerning primary carcinoma of the vagina (PCV) was to analyze clinical and histopathologic prognostic factors in one of the largest known material, which comprised 314 patients. PCV is a rare disease, and the majority of published studies are based on small materials; therefore, the established knowledge concerning prognostic factors is insufficient. Routine treatment is based on irradiation with risk for undertreatment or overtreatment, which leads to unnecessary complications in the absence of prognostic factors. The overall 5-year disease-specific survival rate in this study was 45% and in stage I 75%. In the univariate statistical analysis, several factors correlated significantly with disease-specific survival. However, in the multivariate analysis, there were only three factors that independently could predict poor survival-high age at diagnosis, large tumors (> or =4 cm), and advanced stage. Common background factors with no prognostic significance were prior hysterectomy, other gynecological malignancies, and pelvic irradiation. In conclusion, this study has elucidated three strong prognostic factors that might be considered in the choice of therapy and also for modification of the FIGO guidelines. Increased knowledge concerning complementary biologic markers to discriminate between low- and high malignant tumors is however of great importance.
Adult↗