Sequencing of two alternatively spliced mRNAs corresponding to the extracellular domain of the rat receptor for advanced glycosylation end products (RAGE)

The phosphorylation of glucose to glucose-6-phosphate, catalyzed by hexokinase, is the first committed step in glucose uptake into skeletal muscle. Two isoforms of hexokinase, HKI and HKII, are expressed in human skeletal muscle, but only HKII expression is regulated by insulin. HKII messenger RNA, protein, and activity are increased after 4 h of insulin infusion; however, glucose uptake is stimulated much more rapidly, occurring within minutes. Studies in rat muscle suggest that changes in the subcellular distribution of HKII may be an important regulatory factor for glucose uptake. The present studies were undertaken to determine if insulin causes an acute redistribution of HKII activity in human skeletal muscle in vivo. Muscle biopsies (vastus lateralis muscle) were performed before and at the end of 30 min insulin infusion, performed using the euglycemic clamp technique. Muscle biopsies were subfractionated into soluble and particulate fractions to determine if insulin acutely changes the subcellular distribution of HKII. Insulin decreased HKII activity in the soluble fraction from 2.20 +/- 0.31 to 1.40 +/- 0.18 pmoles/(min[chempt]micrograms) and increased HKII activity in the particulate fraction from 3.02 +/- 0.46 to 3.45 +/- 0.46 pmoles/(min[chempt]micrograms) (P < 0.01 for both). These changes in HKII activity were correlated with changes in HKII protein, as determined by immunoblot analysis (r = 0.53, P = 0.05). Insulin had no effect on the subcellular distribution of HKII activity, which was primarily restricted to the soluble fraction. These studies are consistent with the conclusion that, in vivo in human skeletal muscle, insulin changes the subcellular distribution of HKII within 30 min.     

Breast abscess with lethal septicemia due to Pseudomonas aeruginosa in a patient with AIDS

OBJECTIVE: The incidence of Pseudomonas aeruginosa in HIV-infected patients has increased over the last years. We describe a case of pseudomonal breast abscess complicated with fatal septicemia in an AIDS patient. CASE REPORT: A 21-year-old woman was admitted for fever, chills, nausea, vomiting and pain in the breast. She had a swelling in the right breast of 3 days duration. HIV infection had been confirmed 6 years earlier. CD4 count was 2/mm3. Surgical drainage produced a blue-green purulent discharge which grew Pseudomonas aeruginosa on culture. Despite cloxacilin, then ceftazidime and amikacin, initial improvement was followed 2 weeks later by nodular pulmonary infiltration with cavitation. P. aeruginosa was recovered from sputum and blood cultures, but stepwise resistance developed and the patient died 3 months after admission. DISCUSSION: Breast abscesses are infrequent in nonlactating women. P. aeruginosa is rarely involved, even in HIV patients. Due to the risk of resistance, prompt administration of appropriate antibiotics is required.     

An analysis of the results of histological and histochemical research on the integumental tissues and the digestive system of nematodes of the suborder Strongylata after the use of anthelmintics

The analysis of the action of various anthelmintics on the integuments and digestive system of Strongylate nematodes indicated that all the used agents caused varying structural disorders. The swelling of the cuticle and its detachment from the subcuticle occurred with the overwhelming majority of the anthelminths on the integuments of the Strongylate nematodes. The digestive system showed an ample epithelial vacuolation in the intestinal wall, as well as swelling and destruction in the mitochondria and endoplasmic reticulum. Almost all the used agent lowered the levels of glycogen and RNA in the tissue of Strongylate nematodes.     

A questionnaire study among 171 medical candidates enrolled in a PhD program. Three elements in the PhD education: supervision, research courses and international relations

One hundred and seventy-one medical doctors (median age 34 years) registered as Ph.D.-students at the Medical Faculty, University of Aarhus, were given a questionnaire concerning the Ph.D-program (91% reply rate). The Ph.D.-students had typically graduated four years before enrollment and had gained basic clinical experience. Eighty-four percent had been involved in research projects prior to their formal research education. In general, the Ph.D.-students found the supervision offered by senior researchers adequate, although, more Ph.D.-students in clinical than in preclinical departments would have liked their main supervisor to be more enthusiastic and have more specific expertise. By tradition, the Medical Faculty in Aarhus offers a broad introductory course on research methodology, this was appreciated by the Ph.D.-students. However, they found that too much time was allocated for this purpose. The Ministry of Education recommends that Ph.D.-students gain experience from international collaboration, preferably from a stay abroad. However, only 24% of Ph.D.-students had stayed at an international collaborating institution. Although the overall evaluation of the medical Ph.d.-program was positive, the Ph.D.-students pointed out weaknesses and conflicts requiring adjustment.     

WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation

The casp9 protein plays a critical role in apoptosis induced by a variety of death stimuli. A regulator of apoptosis, Apaf-1, binds to and activates pro-casp9 in the presence of cytochrome c and dATP, a requirement that is bypassed by deletion of the WD-40 repeats located in the C-terminal half of Apaf-1. In this report, we used constitutively active Apaf-1 mutant lacking the WD-40 repeat region to study the mechanism and regulation of pro-casp9 activation. Mutational analysis revealed that only a small portion of the CED-4 homologous region (residues 456-559) could be deleted without destroying the ability of Apaf-1-(1-559) to activate pro-casp9. Apaf-1 can self-associate to form oligomers. Disruption of Apaf-1 self-association by deletion (Delta109-559) or mutation of the P-loop region (K149R) abrogated Apaf-1-mediated pro-casp9 activation. Forced oligomerization of the caspase recruitment domain of Apaf-1 was sufficient for pro-casp9 activation. Dimerization of chimeric Fpk-pro-casp9 protein with the dimerizer drug FK1012 induced pro-casp9 processing and apoptosis in cells. Significantly, the C-terminal region containing WD-40 repeats interacted with its N-terminal CED-4 homologous region, as determined by immunoprecipitation experiments. Importantly, expression of the WD-40 repeat region inhibited Apaf-1 self-association and proteolytic activation of pro-casp9. These studies provide a mechanism by which Apaf-1 promotes autoactivation of pro-casp9 through Apaf-1 self-association, a process that is negatively regulated by the WD-40 repeats.     

Lumbar disc degeneration in relation to occupation

Angiogenic growth factors are essential for cancer metastasis, and the growth of metastatic foci also depends on these angiogenic growth factors as well as autocrine or paracrine growth factors. We therefore investigated whether vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase) are localized more often in primary tumors with hepatic metastasis than in those without such metastasis and whether transforming growth factor (TGF-alpha) and epidermal growth factor receptor (EGF-R) are coexisted more often in hepatic metastases than in primary tumors of gastric cancer. Resected specimens from 82 patients with gastric cancer were examined immunohistochemically. The primary antibodies used were anti-VEGF, anti-dThdPase, anti-TGF-alpha and anti-EGF-R. VEGF expression was found to be higher in primary cancers with than in those without hepatic metastasis (p < 0.001), while VEGF was frequently observed in both hepatic metastases and in the primary tumors. Localization of dThdPase was also higher in advanced than in early gastric cancers (p = 0.021). High co-presence of TGF-alpha and EGF-R was detected more frequently in cancers with deep gastric wall invasion than in those without such invasion (p = 0.050), and also more often in cancers with venous invasion (p = 0.007) and those in the advanced stage (p = 0.020). Co-presence of TGF-alpha and EGF-R was found to be higher, though not significantly, in hepatic metastases (58.8%) than in primary tumors (29.4%). These findings suggest that localization of VEGF may play an important role in hepatic metastasis, and that the expression of VEGF, dThdPase and the TGF-alpha/EGF-R pathway may be responsible for the growth of hepatic metastasis.     

Allotype-associated differences in concentrations of human IgA2

A prospective clinical trial comparing adverse postmyelographic effects and myelographic quality of metrizamide and iohexol was conducted. Using a predetermined, randomized assignment, 24 horses exhibiting neurologic signs were administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via cerebellomedullary puncture. Each horse was evaluated postmyelographically for adverse effects. Myelographic quality was assessed by a numerical scoring method. Adverse effects were observed more frequently with metrizamide (21) compared with iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting neurologic signs and prolonged anesthetic recovery were the most common complications after myelography. There was no difference in myelographic quality (p > 0.05). We conclude that iohexol is safer than metrizamide for equine myelography and that quality myelograms can be obtained with either contrast medium.     

Mumps orchitis; review of 8 cases]

The occurrence of secondary hypogonadism is a common finding in males who seek help with erectile dysfunction, although the relationship to diminished testosterone is unclear. Two possibilities exist regarding both the genesis and maintenance of the hypogonadotropic hypogonadal state. First, a defect in hypothalamic function, resulting in downregulation as well as in alterations of anterior pituitary function; second, estradiol inhibition of gonadotropin release, both of which result in decreased testosterone production. As testosterone levels decrease and estradiol levels increase, the ratio of free testosterone to estradiol reaches a critical point and the estrogenic gonadotropin suppressive effects predominate. This ratio may signal the biological point of no return and could become one of the criteria for defining the separation of the transitional hypogonadal state from the final 'end stage' hypogonadotropic hypogonadal state. As the aging process continues, there is a relative accumulation of fatty tissue, and aromatization accelerates the conversion of testosterone to estradiol. This additional secondary estradiol inhibition results in the maintenance of the testosterone deficient state, and the aging process continues uncontested.