Electrocatalytic intermolecular olefin cross-coupling by anodically induced formal [2+2] cycloaddition between enol ethers and alkenes.
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STUDY DESIGN: A retrospective case study of patients with intraspinal cyst having a distinct connection with the corresponding intervertebral disc. OBJECTIVES: To propose a new clinical entity, "discal cyst," by clarifying the clinical, radiographic, and histologic aspects of the disease. SUMMARY OF BACKGROUND DATA: Several types of intraspinal cysts with different pathogenesis, causing symptoms indistinguishable from those of lumbar disc herniation, have been reported, such as perineural cysts, synovial cysts, and ganglion cysts. However, to the authors' knowledge, no detailed analysis has been made of cysts that have a distinct connection with the corresponding intervertebral disc. METHODS: Clinical pictures, radiographic findings, and surgical and histologic findings in eight surgically treated patients with intraspinal cyst having a distinct connection with the intervertebral disc were reviewed. Possible pathogenesis and a proposal for nomenclature were also discussed. RESULTS: This disease can be characterized by (1) clinical symptoms indistinguishable from those of typical disc herniation, manifesting as a unilateral single nerve root lesion; (2) incidence at slightly younger age and at upper intervertebral levels than with typical disc herniation; (3) T1 low signal and T2 high signal intensity, round to oval mass lesion on magnetic resonance imaging, compatible with a liquid-containing cyst; (4) minimal degeneration of the involved disc, either on discography/computed tomographic discography or magnetic resonance imaging; (5) a connection between the cyst and the corresponding intervertebral discs on discograms with severe radiating pain in the affected leg at the time of injection; (6) immediate relief of symptoms after simple removal of the cyst; (7) cyst wall consisting of dense fibrous connective tissue containing bloody to clear serous discharge; and (8) absence of disc materials and a specific lining cell layer on histologic examination. Although the exact cause is unknown, underlying minor disc injury may serve as a basis for cyst formation. CONCLUSION: Eight cases of intraspinal cysts communicating with the intervertebral disc presenting symptoms identical to those of disc herniation are presented. Because all cysts were connected to the corresponding disc and the development of the cyst was assumed to be related to underlying disc injury, it is proposed to name this clinical entity discal cyst.
The point of maximum activity is specific to a particular substrate-enzyme system but may vary with different substrates and the same enzyme. The specificity of enzymes has, however, been generally reported only at their "optimal" pH. In this article, we introduce the Michaelis-Menten equation taking pH into account, and apply it to the pH-activity profile of the thermolysin-catalyzed dipeptide synthesis. It has been reported to date that the pH-activity profile of thermolysin follows a bell-shaped curve with a maximal activity at or near pH 7.0. The profiles obtained in this study, however, indicated that the optimal pH varied from 5.8 (for F-AspPheOMe) to 7.3 (for Z-ArgPheOMe), and the order of thermolysin activity was greatly dependent on the pH of reaction media. We have succeeded in evaluating the substrates-induced change of the dissociation states of the active site of thermolysin using the hydrophobicity of substrates. We have obtained apparent kinetic parameters which are independent of the pH of reaction media. The apparent specificity of thermolysin which were independent of pH of the reaction media was in order L-Leu > L-Asp > L-Arg > L-Ala > L-Gly > L-Val and Z > Boc = F at P1 and P2 positions, respectively.
Fully grown starfish oocytes are arrested at prophase of meiosis I. The hormonal stimulation of 1-methyladenine (1-MA) induces meiosis reinitiation and germinal vesicle breakdown (GVBD). Optimal development occurs when maturing oocytes are fertilized between GVBD and first polar body emission. In the absence of sperm, oocytes complete both meiotic divisions to yield haploid interphase-arrested eggs. We now report that spontaneous and synchronous activation of caspase-3 in starfish eggs occurs 9-12 h after 1-MA stimulation. Then, caspase-dependent membrane blebbing and egg fragmentation occur, indicating that mature eggs undergo apoptosis if not fertilized. Activation of caspase-3 and induction of apoptosis are blocked both by a MEK inhibitor and by emetine treatment which inhibits MEK kinase (Mos) synthesis. Conversely, when recombinant GST-Mos is injected into the emetine-treated eggs, apoptosis is induced. These results indicate that persistent activation of the Mos/MEK/MAP kinase cascade gives the death-activating signal in starfish eggs. Fertilization inactivates the MAP kinase pathway and suppresses apoptosis, followed by normal development.
STUDY DESIGN: A retrospective follow-up study of conservatively treated patients with mild cervical myelopathy caused by cervical soft disc herniation. OBJECTIVE: To investigate the outcome of conservative treatment for patients with mild myelopathy caused by cervical soft disc herniation and to evaluate usefulness of magnetic resonance findings in the prediction of the outcomes. SUMMARY OF BACKGROUND DATA: Recent studies on conservative treatment for cervical soft disc herniation have focused mainly on radiculopathy, and not on myelopathy. METHODS: Twenty-seven patients with mild cervical myelopathy secondary to cervical soft disc herniation were treated conservatively for more than 6 months by cervical bracing and restriction of daily activities. Of the 27 patients, 17 patients (Group A) underwent conservative treatment only and it was associated with improvement in their neurologic deficits, while the other 10 patients (Group B) ultimately underwent decompression surgery because of neurologic deterioration. Comparisons between the two groups were made in regard to JOA scores, patient satisfaction, and magnetic resonance findings, including location of the disc herniation (focal or diffuse in the sagittal plane, median or paramedian in the axial plane). RESULTS: The JOA scores were 13.6 +/- 1.6 in Group A and 14.1 +/- 1.6 in Group B before treatment, 14.9 +/- 1.0 and 12.9 +/- 2.1, respectively, at 3 months, and 16.2 +/- 0.8 and 16.0 +/- 1.2, respectively, at the final follow-up. The JOA scores at 3 months were significantly lower in Group B than in Group A. Satisfaction with the results of treatment at the final follow-up was reported by 77% of the patients in Group A and 90% in Group B. Focal-type herniation was present in 47% of the patients in Group A and 70% in Group B, while median-type herniation was diagnosed in 77% in Group A and 30% in Group B. Follow-up magnetic resonance imaging of the patients in Group A showed spontaneous regression of a herniated mass in 10 patients (59%). Diffuse-type herniations were more likely to regress spontaneously than focal-type herniations (78% vs. 37%). CONCLUSIONS: Conservative treatment is an effective treatment option for mild cervical myelopathy caused by cervical soft disc herniation. A good outcome can be expected in patients with a median-type and/or diffuse-type herniation on magnetic resonance imaging.
To clarify the reason for the high acyl-CoA hydrolase (ACH) activity found in dog liver microsomes, the ACH was purified to homogeneity using column chromatography. The purified enzyme, named ACH D1, exhibited a subunit molecular weight of 60 KDa. The amino terminal amino acid sequence showed a striking homology with rat liver carboxylesterase (CES) isozymes. ACH D1 possessed hydrolytic activities toward esters containing xenobiotics in addition to acyl-CoA thioesters, and these activities were inhibited by a specific inhibitor of CES or by CES RH1 antibodies. These findings suggest that this protein is a member of the CES multigene family. Since ACH D1 appears to be a protein belonging to the CES family, we cloned the cDNA from a dog liver lambdagt10 library with a CES-specific probe. The clone obtained, designated CES D1, possessed several motifs characterizing CES isozymes, and the deduced amino acid sequences were 100% identical with those of ACH D1 in the first 18 amino acid residues. When it was expressed in V79 cells, it showed high catalytic activities toward acyl-CoA thioesters. In addition, the characteristics of the expressed protein were identical with those of ACH D1 in many cases, suggesting that CES D1 encodes liver microsomal ACH D1.
N-Methyl-4-phenylpyridinium (MPP(+)) and 2,9-di-methyl-norharmanium (2,9-Me2NH(+)), which is a beta-carbolinium proposed as an endogenous MPP(+)-like toxin underlying Parkinson's disease, are strong mitochondrial toxins. We have measured the extracellular lactate levels as a marker for the in vivo cell hypoxia in the striatum of freely moving rats. The perfusions with MPP(+) and 2,9-Me2NH(+) increased extracellular lactate levels in a dose-dependent manner. These increases in lactate levels were significantly prevented by the co-perfusion with 10 microM L-deprenyl, a selective monoamine oxidase (MAO)-B inhibitor, but not by pargyline, a non-specific MAO inhibitor. The increase in extracellular lactate levels was considered to be the reflection of the cell damage resulted from the impairment of mitochondrial function. The present results suggested that L-deprenyl would rescue nerve cells from these toxins through the direct influence on the mitochondrial electron transport.
[reaction: see text]. Novel anodic intermolecular carbon-carbon bond formation has been accomplished by the oxidative carbon-sulfur bond fission of benzylic dithioacetals to give a wide variety of aromatic compounds. The substitution reaction successfully took place by the selective anodic oxidation of a sulfur atom of a dithioacetal. Stepwise double-substitution reactions were also achieved by the regulation of oxidation potential.
STUDY DESIGN: A retrospective analysis of the long-term outcomes of standard discectomy for lumbar disc herniation. OBJECTIVES: To investigate the long-term outcomes of standard discectomy to address postoperative problems, including residual low back pain and recurrent herniation. SUMMARY OF BACKGROUND DATA: Most previous investigators found that favorable outcomes of standard discectomy were maintained for the long-term postoperative period. Although they observed postoperative complications such as residual low back pain and recurrent herniation, detailed analyses of these results have not been conducted. METHODS: The long-term follow-up results in patients who were observed for a minimum of 10 years after standard discectomy were evaluated by using the Japanese Orthopedic Association scoring system through direct examinations and questionnaires. Radiography also was used in patients who agreed to visit the hospital, and findings were compared with those on preoperative radiographs. RESULTS: The average recovery rate calculated by using Japanese Orthopedic Association scores was 73.5 +/- 21.7%. Even though residual low back pain was found in 74.6% of the patients, only 12.7% had severe low back pain. The majority of the patients with severe low back pain were under 35 years of age at the time of operation, with preoperative advanced disc degeneration. The final Japanese Orthopedic Association scores in the patients with decreased disc height were significantly lower than those in patients with no decrease. However, the disc height of patients with a recurrent herniation was preserved. CONCLUSION: The long-term outcome of standard discectomy in this series was favorable. Although patients with preserved disc height generally had favorable results, the risk of recurrent disc herniation was high in this population.
Squalene monohydroperoxide (Sq-OOH), the initial product of ultraviolet-peroxidated squalene, was used to investigate the effect of peroxidative challenge upon the glutathione contents in rabbit ear skin and primary-cultured fibroblasts derived from rabbit ear skin. The cellular reduced glutathione (GSH) contents decreased during 30-minute incubations in vitro with Sq-OOH, and oxidized glutathione (GSSG) was formed concomitantly, indicating that Sq-OOH had a potential for GSH-depleting activity in vitro. When Sq-OOH was applied topically to the skin in vivo, only GSSG contents increased significantly within 30 minutes. Moreover, pretreatment with the GSH depletors, DL-buthionine sulfoximine (BSO) and diethyl maleate (DEM), could potentiate the cytotoxicity and comedogenicity induced by Sq-OOH. These findings suggest that the endogenous antioxidant, glutathione, is quite sensitive to Sq-OOH and may be an important material for protecting cells and/or tissues against the oxidative stress induced by Sq-OOH treatment.
Two patients with non-Hodgkin's lymphoma (NHL) suffered from hematemesis due to exfoliative esophagitis early after autologous peripheral blood stem cell transplantation (PBSCT). The chemotherapy regimens used for these 2 patients were the same and consisted of high-dose ranimustine, carboplatin, etoposide, and cyclophosphamide (MCVC regimen), which have been widely used in autologous PBSCT for NHL in Japan. Esophageal bleeding in both patients was stopped by conservative treatment without any special endoscopic manipulations. Gastrointestinal bleeding after hematopoietic stem cell transplantation is usually caused by viral infections, graft-versus-host disease, or conditioning chemo-radiotherapy. Although severe esophagitis is common in patients receiving stem cell transplantation, the exfoliative form detected by endoscopic examination has not been reported. We conclude that high-dose chemotherapy and frequent vomiting during treatment are risk factors for lower-esophageal bleeding in these cases.
OBJECTIVE: The urinary ratio of 6beta-hydroxycortisol to cortisol is known as a possible marker of CYP3A4 activity. We investigated the correlation between this ratio and the disposition of alprazolam, which is a substrate of CYP3A4. METHODS: Twelve healthy volunteers took a single dose (0.8 mg) of alprazolam at 0800 hours. Blood samplings were conducted up to 48 h after the dosing. Urine was collected during the 24 h prior to dosing. Quantification of alprazolam in plasma and that of cortisol and 6beta-hydroxycortisol in urine was performed using high-performance liquid chromatography. RESULTS: Mean (+/-SD) values of peak plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve [AUC(0-48)] and elimination half-life (tl/2) of alprazolam were 12.0+/-3.0 ng/ml, 1.5+/-0.9 h, 200+/-41 ng/ml h and 16.0+/-4.3 h, respectively. Mean (+/-SD) urinary ratio of 6beta-hydroxycortisol to cortisol was 3.28+/-0.67. No significant correlations were found between urinary ratio of 6beta-hydroxycortisol to cortisol and any pharmacokinetic parameters of alprazolam (Cmax: rs= -0.06; tmax: r(s)= 0.34; AUC(0-48): rs=0.08; t1/2: r(s)= -0.36). CONCLUSION: This study suggests that the urinary ratio of 6beta-hydroxycortisol to cortisol is unlikely to predict pharmacokinetics of alprazolam.
Osteopetrosis is a rare genetic disorder in which the function of osteoclasts is defective, resulting in impaired bone resorption. This disease is usually accompanied by myelosuppression due to decreased marrow space and by osteomyelitis, especially in the submandibular bone. We report the case of a 72-year-old woman with an autosomal dominant form of osteopetrosis who suffered from peripheral T-cell lymphoma. Accurate clinical and pathological diagnoses and staging were difficult due to nonspecific reactive hyperplasia of the lymph nodes, even though we used several scintigraphic techniques and [18F]fluorodeoxyglucose positron emission tomography. We also paid special attention to myelosuppression and exacerbation of osteomyelitis after combination chemotherapy. Severe infectious complications were avoided by early administration of G-CSF for leukocytopenia and by continuous oral administration of antibiotics. The patient achieved complete remission after four courses of chemotherapy and this status has been maintained for 6 months.
We report a rare case of chronic eosinophilic leukemia (CEL) with a chromosomal abnormality of t(6;11)(q27;q23). The patient was diagnosed as having thyroid cancer with metastases to the lung and cervical lymph nodes in 1993. Percutaneous ethanol injection therapy (PEIT), total thyroidectomy, and radiotherapy were performed. The patient was also diagnosed as having prostatic cancer with bone metastasis in July 1999, and hormonal therapy was performed. At the time of the diagnosis of prostatic cancer, leukocytosis with eosinophilia was also revealed. Thereafter, cytogenetical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of bone marrow showed t(6;11)(q27;q23) translocation and MLL/AF6 fusion products, respectively. No transcripts of the BCR/ABL chimeric gene were found by RT-PCR in bone marrow. Analysis of serum cytokines revealed a slight elevation of GM-CSF but no elevation of IL-3 or IL-5. Tissue damage due to infiltration of eosinophils was not observed throughout the clinical course. On the basis of the cytogenetic and molecular abnormality, the patient was diagnosed as having CEL, rather than reactive eosinophilia due to thyroid or prostatic cancer or other reactive inflammation. This is the first case report of CEL with t(6;11)(q27;q23) translocation.
PURPOSE: To determine the optimal incision to eliminate astigmatism after cataract extraction. SETTING: Hara Eye Hospital, Utsunomiya, Japan. METHODS: Patients having cataract extraction through a 3.2 mm corneal limbal incision without limbal sutures were divided into 2 groups. Group 1 comprised 98 eyes of 80 patients without preoperative astigmatism and Group 2, 72 eyes of 62 patients with no astigmatism postoperatively. In Group 1, the incisions that caused postoperative corneal changes were retrospectively evaluated. In Group 2, the types of incisions that induced an astigmatism-free cornea postoperatively were retrospectively studied. Patients were examined preoperatively and 6 months postoperatively. RESULTS: In Group 1, 23 of 40 eyes (57.5%) with an incision between 9 and 12 o'clock (BENT incision) and 10 of 58 eyes (17.2%) with an incision at 12 o'clock remained astigmatism free postoperatively (P <.0001). One eye (2.5%) with a BENT incision and 17 (29.3%) with a 12 o'clock incision had astigmatism greater than 1.0 diopter (D) postoperatively (P <.001). In Group 2, 72 eyes had less than 1.2 D of preoperative astigmatism. No eye with more than 1.2 D of astigmatism was astigmatism free postoperatively, even when the incision was made at the steepest meridian. CONCLUSIONS: The results indicate that to reduce astigmatism in eyes with preoperative astigmatism of 0.5 D or more, a limbal 3.2 mm BENT incision should be placed at 10:30 o'clock. To prevent astigmatism postoperatively, the incision should be placed at the steepest meridian in eyes with preoperative astigmatism greater than 0.5 D; for preoperative astigmatism greater than 1.2 D, a 3.2 mm incision at the corneal limbus is insufficient and a wider incision or an additional incision is required.
Variously oxidized 12 natural abietanes, 6,7-dehydroferruginol methyl ether (3), ferruginol (5), 11-hydroxy-12-oxo-7,9(11),13-abietatriene (7), royleanone (9), demethyl cryptojaponol (12), salvinolone (14), sugiol methyl ether (16), sugiol (17), 5,6-dehydrosugiol methyl ether (19), 5,6-dehydrosugiol (20), 6beta-hydroxyferruginol (23), and taxodione (25) were synthesized. Antimicrobial activities of synthesized phenolic diterpenes and their related compounds against MRSA and VRE were evaluated. Phenols (12-hydroxyabieta-8,11,13-trien-6-one 22 and 23), catechols (12 and 14) and taxodione 25 showed potent activity with 4-10 microg/mL of MIC against MRSA and 4-16 microg/mL of MIC against VRE. (-)-Ferruginol showed more potent activity than natural type (+)-ferruginol. Quinone methide 7 showed the most potent activity with 0.5-1 microg/mL of MIC against both MRSA and VRE.
1. The effects of carbamazepine (CBZ) and its possible mechanisms on the first ovulation were investigated in immature female rats. The first ovulation was induced by administration of equine chorionic gonadotropin (eCG) at 0800 h at 26 days of age. 2. A single s.c. injection of 360 mg x kg(-1) CBZ at 1300 h on the first pro-oestrus (day 28) completely inhibited the first ovulation on the morning of day 29. A marked elevation in 13, 14-dihydro-prostaglandin F2alpha (13, 14H2-PGF2alpha) forming capacity, a sensitive indicator of luteinizing hormone (LH) surge, was not detected in the CBZ-treated group at 0800 h on day 29 (72 h after eCG treatment). The elevation in serum LH levels at 57 h after eCG treatment was not observed in the CBZ-treated group, either. The blocking of the first ovulation and 13, 14H2-PGF2alpha forming capacity were recovered by an i.p. injection of human CG on day 28 in all animals. 3. However, the first ovulation was not blocked by repeated injections of 360 mg x kg(-1) CBZ at 1300 h once daily for 3 days (days 26 - 28). The repeated injections of CBZ caused a great fall (64% decrease) in the serum levels of CBZ at 4 h after the final CBZ injection as compared with the case of a single injection of CBZ and resulted in a delay for 5 h the occurrence of LH surge, which is normally observed around 57 h after eCG injection. 4. A significant increase in the activity of microsomal CBZ catabolism by the repeated injections of CBZ was quantitatively verified by the HPLC analysis. But, the activity of CBZ metabolism in the single injected-animals showed almost similar levels to that in the control. 5. The present results demonstrated that a single injection of CBZ blocks the ovulation by inhibiting LH surge but that the failure of the inhibition of ovulation by repeated injections of CBZ is due to a decrease in serum CBZ levels mediated through CBZ-induced hepatic enzyme induction.
A 21-year-old woman with severe aplastic anemia received an allogeneic bone marrow transplant (allo-BMT) from an HLA-matched and ABO-matched sibling donor after conditioning with cyclophosphamide, rabbit ATG (Lymphoglobuline; Aventis-Pharma), and total lymphoid irradiation. She had a long history of cyclosporin A (CsA) therapy before conditioning. She complained of severe headache and convulsions on day 0, and findings on magnetic resonance images suggested CsA-induced encephalopathy. CsA was immediately stopped, and tacrolimus for prevention of graft-versus-host disease (GVHD) was started on day 2. Hematological engraftment was observed on day 14 without serious GVHD. Prompt diagnosis, replacement of immunosuppressive agents, and careful monitoring of serum drug concentrations are thought to have contributed to the patient's good clinical course, since CsA-induced encephalopathy tends to be recurrent but to improve completely without any sequelae.