Biomedical subjects
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BACKGROUND: Obliteration of a giant fusiform aneurysm without significant therapeutic morbidity is extremely difficult. Ischemic complications have been often reported. METHODS: Two patients with giant fusiform aneurysms of the circle of Willis are presented. Both patients underwent proximal parent artery clipping after a bypass procedure. Balloon occlusion tests confirmed both patients' ability to tolerate flow reduction after proximal clipping. RESULTS: Although both patients awoke from anesthesia without neurologic deficit, they developed contralateral hemiparesis several hours after the operation as a result of a small infarct in the basal ganglia. These ischemic events might be attributed to the delayed thrombosis involving the orifice of the distal perforating arteries. CONCLUSIONS: In the treatment for giant fusiform aneurysms of the circle of Willis, special attention should be paid not only to flow reduction, but also to delayed thrombus propagation that may not be predicted by preoperative balloon occlusion testing.
BACKGROUND: One of the most important goals in the surgical treatment of spinal dural arteriovenous fistulae is complete interruption of the flow in the fistula. To confirm complete interruption, we use intraoperative microdoppler monitoring. METHODS: Three patients with spinal dural arteriovenous fistulae with perimedullary venous drainage underwent surgical treatment using microdoppler monitoring. All of them suffered from congestive myelopathy before treatment. Microdoppler monitoring was performed on the perimedullary draining vein to detect the arterial spectrum before and after the interruption of the arteriovenous shunt. RESULTS: In all patients, an arterial spectrum was detected on the dorsal perimedullary vein. Sequential monitoring demonstrated the effects of each surgical procedure, which included epidural coagulation of the fistulae or intradural ligation of the retrogradely draining radiculomedullary veins. After complete interruption of the fistula, the arterial spectrum disappeared completely. In a patient with duplicated dural arteriovenous fistulae, the direction of the flow of the second arteriovenous shunt could be demonstrated by microdoppler monitoring combined with temporary clipping. This is especially useful in a complex case with duplicated fistulae. In all patients, postoperative angiography demonstrated complete disappearance of the arteriovenous fistulae. The patients all showed remarkable improvement with no therapeutic morbidity. CONCLUSION: Intraoperative microdoppler monitoring is an easily available and useful technique to safely confirm complete obliteration of spinal dural arteriovenous fistulae.
OBJECTIVES: We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction. BACKGROUND: Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor. METHODS: In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses. RESULTS: There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group. CONCLUSIONS: This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.
The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing alpha-hydroxy-beta-amino acids is discussed. We demonstrated that substituent groups on the P1 aromatic rings of the inhibitors exert significant influence on their biological activity. Inhibitors bearing an alkyl or a fluorine atom at the meta and para position on their P1 benzene ring were found to be good inhibitors. We also discovered that the substitution positions of the P2 benzamides were crucial for good antiviral potency. In this study, inhibitor 48 was the most potent [IC90 (CEM/HIV-1 IIIB) 27 nM] and showed good pharmacokinetics in rats.
The synthesis and the SAR study of novel pseudo symmetric inhibitors of HIV-1 protease are described. Michael addition of amino acid derivatives to vinyl ketones was utilized to derive a potent (nM) series of HIV-1 protease inhibitors.
Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmonary bronchial smooth muscle of the rat induced force when the Ca2+ concentration was clamped at 1 microM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway smooth muscle contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments.
We constructed a hirudin cDNA cassette, HV-1.1, that encodes mature hirudin variant-1 fused to the signal peptide of human tissue-type plasminogen activator (t-PA). The cassette was subcloned into retroviral vectors and used to transduce human vascular endothelial cells in vitro. Hirudin antigen and activity were measured by ELISA and thrombin inhibition assays, respectively. Transduced cells secreted up to 35 +/- 2 ng/10(6) cells/24 h of biologically active hirudin; expression was stable for at least 7 weeks. Recombinant hirudin, expressed from the HV-1.1 cassette, had a specific activity of 7.1 +/- 0.2 antithrombin units per microgram (ATU/microgram), compared with specific activities of approximately 12 ATU/microgram for both native leech hirudin and recombinant hirudin produced in yeast. Protein sequencing and mass spectroscopic analysis revealed the presence of an extra N-terminal serine residue, indicating aberrant cleavage of the t-PA signal peptide and likely accounting for the diminished activity. We therefore constructed a second cDNA cassette, HV-1.2, in which hirudin secretion was directed by the signal peptide of human growth hormone. Hirudin expressed from the HV-1.2 cassette had a specific activity of 13.5 +/- 0.2 ATU/microgram. Protein sequencing and mass spectroscopic analysis demonstrated proper cleavage of the growth hormone signal peptide. Thus, we achieved high level retrovirus-mediated secretion of biologically active hirudin from endothelial cells in vitro. Use of these vectors may permit sustained local antagonism of thrombin activity in vivo.
The case of a 5-month-old boy with tuberous sclerosis and West syndrome is reported. Tonic spasms were noted from the age of 4 months. High-dose pyridoxal phosphate could not control the seizures completely. Very short and low-dose adrenocorticotropic hormone (ACTH) therapy (i.e. 0.011 mg/kg per dose, 12 times in 20 days) controlled the seizures, while pyridoxal phosphate was on. Early tapering of ACTH was successfully done while abnormal electroencephalogram (EEG) findings remained. Although side effects such as hypertension and brain shrinkage were transiently observed, both the cognitive and seizure prognoses were excellent at the age of 3 years and 2 months. The good response to a small dosage of ACTH might be due to some responsiveness of the high-dose pyridoxal phosphate and the underlying cause of tuberous sclerosis with normal development before onset. The present case illustrates that the duration and dosage of ACTH therapy in West syndrome should be modified according to the individual's requirements.
In this paper, we evaluated experimentally the feasibility of transferring a pedicled venous flap with perivenous areolar tissue into an ectopic site and investigated the role of each vein, the perivenous areolar tissue and nerve in the viability of pedicled venous flaps. Three groups of flaps were created using a rabbit-ear model: Group 1 (n = 11), containing perivenous areolar tissue and a draining vein; Group 2 (n = 10), perivenous areolar tissue, a draining vein and nerve; Group 3 (n = 10), only perivenous areolar tissue. Macroscopic, angiographic and histological assessments were performed 14 days after transfer. The total survival areas including superficial necrosis of Groups 1, 2 and 3 were 52.7%, 82.5% and 0%, respectively. There were significant differences in mean survival area and mean total survival area including superficial necrosis between Group 1 and Group 2 (P < 0.05). In contrast, all flaps in Group 3 became necrotic. These data suggest that a preserved vein is the necessary condition, and additional arterial flow through the preserved nerve and a small vascular network within the areolar tissue may play an important role in flap survival.
Elevation in serum human growth hormone (GH) level is known to be a factor that causes goiter development. The present study was designed to analyze sonographic and scintigraphic appearances of the thyroid in patients with acromegaly. The records of 48 consecutive patients with acromegaly were examined. Two patients had a history of operation for thyroid cancer. One had an atrophic thyroid gland after 131I treatment for Graves' disease. Goiter was palpable in 39 of the remaining 45 patients. Neither ultrasonography (US) nor scintigraphy was performed in 17 patients, including 6 with no palpable goiter and 11 with small diffuse goiter (group 1). Of the remaining 28 patients who underwent US, 14 had a moderately or markedly enlarged diffuse goiter (group 2), 13 were diagnosed as having adenomatous goiter (group 3), and 1 had a solitary cystic nodule. Among 11 patients in group 3 who underwent 123I or 99mTc thyroid scintigraphy, 6 showed uneven uptake, and 2 with undetectably reduced levels of thyrotropin (TSH) showed localized functioning areas. The mean serum TSH concentration in group 3 was significantly lower than that in group 1 or 2 (p<0.01). The duration of illness as acromegaly was significantly longer in group 2 and 3 as compared with group 1 (p<0.05). These results suggest that long-term stimulation by GH and insulin-like growth factor-I of thyroid follicular cells might be responsible for thyroid enlargement, presence of functioning lesions, slight overactivity of the thyroid, and the subsequent formation of multiple nodules in acromegalic patients. In conclusion, excluding two patients with thyroid cancer and one with Graves' disease, goiter was palpable in 39 of the 45 patients with acromegaly, among whom 14 (13 adenomatous goiters and 1 solitary cystic nodule) showed nodular enlargement.
Monoterpenes display chemopreventive and therapeutic activity in rat mammary tumor models. Monoterpenes can also inhibit cell growth and induce apoptosis of cultured cells. In this study, the monoterpene perillyl alcohol (POH) was found to induce transient expression of the c-jun and c-fos genes transcriptionally. POH also transiently induced phosphorylation of c-Jun protein. These events were associated with transcriptional activation of an AP-1-dependent reporter gene. These results suggest that POH might affect c-Jun activity via the Jun N-terminal kinase/stress-activated protein kinase pathway and modulate expression of AP-1 target genes.
DNA endonuclease derived from the yeast VMA1-gene product recognizes and cleaves 31 base-pairs of double-stranded DNA (dsDNA). Mixtures of the endonuclease (VDE) with a full DNA substrate consisting of 34 base-pairs, with nicked substrates each having a nick in either DNA chain, and with cleaved substrates each having a cleaved-off chain are prepared. Molecular weights (MWs) of eluted peaks from gel filtration columns were estimated from elution profiles in the presence of Mg2+ ions. Each mixture exhibited an elute peak at about 63k MW, larger than the MW of VDE unbound to dsDNA. This indicates that VDE and dsDNA substrates form stable complexes. The mixture of VDE either with the full substrate or with the nicked substrate having a nick in the anti-sense chain eluted an additional 25k-MW peak, which presumably corresponds to a cleaved product. The complex of VDE with the full substrate was eluted at 62k-MW location in the absence of Mg2+ ions and yielded a single crystal. Stable complexes of VDE either with the dsDNA substrates or with the cleaved products are obtainable.
OBJECTIVE: Pentosidine, an advanced glycation end product (AGE), has recently been observed to be elevated in rheumatoid arthritis (RA). The aim was to elucidate which pentosidine levels, i.e. in serum, synovial fluid or urine, are more related to the disease status of RA. METHODS: We measured levels of pentosidine in serum, synovial fluid or urine in RA compared with osteoarthritis (OA), and examined the relationship between pentosidine and RA disease activity. Subjects were 20 patients with RA and 22 patients with OA. RESULTS: In total RA and OA patients combined, there was a significant correlation between pentosidine in serum, synovial fluid and urine. Pentosidine in serum and synovial fluid was significantly higher in RA than in OA. In RA, there were significant correlations between pentosidine in serum and synovial fluid and C-reactive protein, Lansbury index (LI) and erythrocyte sedimentation rate. CONCLUSIONS: These results demonstrate that pentosidine levels in body fluids correlated with each other, and pentosidine in serum and in synovial fluid is associated with the systemic inflammatory activity of RA. Higher or similar concentrations of pentosidine in serum compared with synovial fluids indicate that the elevated pentosidine levels in serum in RA are not derived from the synovial fluid, but from an increase in the formation of pentosidine in the whole body in RA. Among body fluids, serum pentosidine was the superior indicator for RA disease status.
OBJECTIVE: To investigate urinary fractions of free and peptide forms of pyridinoline cross-links in arthritis. PATIENTS AND METHODS: The free and total forms of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured by high-performance liquid chromatography (HPLC) in 30 pre-menopausal and 22 post-menopausal normal women, 38 women with rheumatoid arthritis (RA) and 62 women with osteoarthritis (OA). Peptide forms were calculated as total minus free. Free Dpyr and peptide form were also measured by deoxypyridinoline and carboxy-terminal telopeptide of type I collagen (CTx) immunoassays. RESULTS: In normal women, all fractions of Pyr and Dpyr and immunoassays were elevated in post-menopause compared to pre-menopause. In post-menopausal normal women, the free form increased more than the peptide form. In RA, an increase in the fractions of Pyr was greater than Dpyr. Peptide and total cross-links correlated with the disease activity of RA and they were elevated in RA patients with high disease activity. Free Dpyr and CTx were significantly lower in OA than in normal women. Peptide and total Pyr and Dpyr, and immunoassayed Dpyr were significantly higher in the radiographic later stage of OA than in the early stage of OA. CONCLUSIONS: The menopause, RA and OA may have different effects on the urinary excretion of free and peptide-bound pyridinoline cross-links.
Ossification takes place in the posterior longitudinal ligament and ligamentum flavum of the spine under certain conditions of unknown nature. Ossification of these ligaments has the following characteristics: (1) ectopic bone formation occurring within the spinal ligaments; (2) ossification accompanies ligamentous tissue hyperplasia and cell proliferation; (3) before ossification, fibrocartilaginous cell proliferation, calcification and tissue resorption with vascular ingrowth take place sequentially; (4) ossification of the ligament has a specific site of predilection and often occurs in combination with senile ankylosing vertebral hyperostosis (Forestier's disease) or diffuse idiopathic skeletal hyperostosis; and (5) ossification and symptom development are remarkably more frequent in the Japanese population. Recent studies revealed that bone morphogenetic proteins and transforming growth factor-beta played an important role in the matrix hyperplasia and ossification of the spinal ligament, and metabolic and genetic aberration often characterized patients suffering from this disorder.
OBJECTIVE: The pathogenesis of moyamoya disease is unknown. The purpose of this study was to detect proteins associated with the pathogenesis of moyamoya disease. CLINICAL PRESENTATION: Cerebrospinal fluid (CSF) samples from three patients with moyamoya disease and four control patients who had cervical lesions but no intracranial lesion were studied. INTERVENTION: CSF proteins separated by two-dimensional polyacrylamide gel electrophoresis were analyzed with the SWISS-2DPAGE and SWISS-PROT databases. In the CSF samples from all three patients with moyamoya disease, a polypeptide spot (Mr = 12,000, pI = 5.35) was observed. This spot was not evident in samples from the four control patients and has not been reported in the SWISS-2DPAGE and SWISS-PROT databases. CONCLUSION: A CSF protein, which is possibly novel and associated with moyamoya disease, has been detected. The analysis of CSF by two-dimensional polyacrylamide gel electrophoresis may reveal a clue by which the molecular mechanism of moyamoya disease may be elucidated.
We took culture of throat swab from 77 subjects who were negative for infection of HBV, HCV, HIV and syphilis infection before and after endoscopy. Moreover, the existence of bacterium including Helicobacter pylori at overcoat of endoscopic instrument was investigated right after examination and after disinfection of endoscope. Povidoneiodine, 70% alcohol and 1% benzalkonium chloride was used as a disinfectant for endoscope, and it took less than 10 minutes to wash by hand to disinfection. alpha-haemolytic streptococci, Staphylococcus epidermids, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Candida, Pseudomonas aeruginosa and MRSA were cultured in throat swab. The rate of adhesion of bacterium especially such as Candida, K. pneumoniae and S. epidermids to endoscope was considerably high. 23 of 77 subjects had H. pylori infection, and the adhesion of H. pylori to endoscope was found to be 65.2% of the subjects. On the contrast, no bacterium was detected from the endoscopic instrument after careful disinfection. These findings stress the importance of postoperative disinfection of the endoscope to prevent the chance to acquire bacterial infection.