Direct one-pot synthesis of alpha-siloxy-Weinreb amides from aldehydes.

A one-pot method for synthesizing alpha-siloxy-Weinreb amides from aldehydes was developed with use of N,O-dimethylhydroxylamine and a masked acyl cyanide reagent bearing a tert-butyldimethylsilyl group avoiding the competitive reaction toward N-methoxy-N-methyl-2-amino-1-siloxymalononitrile.

Flexible synthetic routes to poison-frog alkaloids of the 5,8-disubstituted indolizidine-class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F.

Background: The 5,8-disubstituted indolizidines are the largest class of poison-frog alkaloids found in anuran skin, and are of considerable interest because of their inhibitory effects on the neuronal nicotinic acetylcholine receptors. Many synthetic strategies for the construction of this nucleus have been reported: however, a flexible route has not been reported to date.

Results: Synthesis of lactam chiral building blocks for the flexible synthesis of the title alkaloids has been achieved using a Michael-type conjugate addition reaction to a chiral cyclic enamine ester as the key step in constructing the trisubstituted piperidine ring system.

Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors.

We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of alpha7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked alpha7 and alpha4beta2 currents with similar potencies.

Rapid and transient intracellular oxidative stress due to novel macrosphelides trigger apoptosis via Fas/caspase-8-dependent pathway in human lymphoma U937 cells.

The ability of the derivatives of macrosphelides (MS) core (simplified 16-membered core structure of natural MS) to induce apoptosis in human lymphoma U937 cells was investigated. Of the five compounds examined, MS core with ketones at 8 and 14 positions (MS5) showed the highest potency to induce apoptosis, while another, MS3 with one ketone, was minimal potent. MS5 was found to induce apoptosis in the U937 cells in a time- and dose-dependent fashion, as confirmed by DNA fragmentation analysis.

OSW-1 analogues: modification of the carbohydrate moiety.

4 OSW-1 analogues featuring modified carbohydrate moieties were prepared. The purpose of these modifications was to assess the importance of certain chemical functions with respect to biological activity. The synthesis and biological activity of the target molecules are shown.

Synthetic organic chemistry based on small ring compounds.

Small ring systems are important topics in both organic and inorganic chemistry, and draw considerable attention from both theoretical and preparative perspectives. This review intends to summarize the studies, focusing on the preparative aspects, that have been carried out in our laboratory. Namely, synthesis of (+)- and (-)-alpha-cuparenone, (+)-ipomeamarone, (+)-epiipomeamarone, (-)-ngaione, (-)-alpha-bisabolol, (-)-aplysin, (-)-debromoaplysin, (-)-mesembrine, (-)-filiformin, (-)-debromofiliformin, and (-)-4-deoxyverrucarol via successive asymmetric epoxidation and enantiospecific ring expansion of cyclopropylidenes, (+)-equilenin via successive ring expansion-insertion reaction, estrone, estradiol, chenodeoxycholic acid, 19-norspironolactone, 19-nordeoxycorticosterone, cortisone, adrenosterone, 11-oxoprogesterone, and 1alpha,25-dihydroxyvitamin D3 via intramolecular cycloaddition reaction of o-quinodimethanes.

Repeated bacteraemia caused by Streptococcus mutans in a patient with Sjogren's syndrome.

Streptococcus mutans, considered to be a pathogen for dental caries, is known to cause bacteraemia and infective endocarditis. Herein, an unusual case of repeated bacteraemia caused by S. mutans identified in a 71-year-old male is described.

Streptococcus mutans clonal variation revealed by multilocus sequence typing.

Streptococcus mutans is the major pathogen of dental caries, a biofilm-dependent infectious disease, and occasionally causes infective endocarditis. S. mutans strains have been classified into four serotypes (c, e, f, and k).

[A case of advanced colon cancer invading the rectum effectively treated with chemoradiation therapy before surgery].

A 56-year-old man was hospitalized for anemia with appetite loss and body weight loss. He was diagnosed as advanced sigmoid colon cancer which invaded the rectal colon (Ra) and prostate (SI, N 0, P 0, H 0, M (-), cStage IIIa). We administered neoadjuvant chemoradiotherapy for fear of non-curative resection of the sigmoid colon and rectum after colostomy was performed.

Enhancement of macrosphelide-induced apoptosis by mild hyperthermia.

Hyperthermia is a useful adjunct in cancer therapy as it can increase the effectiveness and decrease the toxicity of currently available cancer treatments such as chemotherapy and radiation. In the present study, we investigated whether 41 degrees C hyperthermia (mild HT) for 20 min can enhance macrosphelide (MS5)-induced apoptosis in human lymphoma U937 cells. Our results revealed that, compared with MS5 (5 microM) and mild HT alone, the combined treatment exhibited significant enhancement in apoptosis at 6 h, which was evaluated by observing morphological changes and DNA fragmentation.

Myasthenia gravis with concomitant severe paraspinal muscle degeneration and mitochondrial DNA4977 deletion.

Recent reports have discussed the many causes of dropped head syndrome and bent spine syndrome. We described a case of myasthenia gravis with concomitant severe degeneration of spinal muscle, mitochondrial DNA4977 deletion and sensorineural deafness. These associations were thought to be independent, however this is an important case to consider the etiology of bent spine syndrome.

Myasthenia gravis and diabetes mellitus: a 35-year retrospective study.

Background: The most common treatment of myasthenia gravis is high-dose prednisolone administration and thymectomy. A well-known adverse effect of prednisolone is hyperglycemia, however, to date there is no such detailed report.

Patients And Methods: We treated 325 myasthenia gravis patients in a recent 35 years period, and found 11 patients with diabetes mellitus.

Enhancement of hyperthermia-induced apoptosis by a new synthesized class of furan-fused tetracyclic compounds.

The combined effects of hyperthermia (44 degrees C, 20 min) or X-rays (10 Gy) and a new class of furan-fused tetracyclic synthesized compounds (DFs), on apoptosis in human lymphoma U937 cells were investigated. Among the tested compounds (DF1 approximately 6), the combined treatment of 10 microM DF with TIPS (triisopropylsilyloxy) (Designated #3 DF3) and hyperthermia showed the largest potency to induce DNA fragmentation at 6 h after hyperthermia but no enhancement was observed if it was combined with X-rays. Enhancement of hyperthermia-induced apoptosis by DF3 in a dose-dependent manner was observed.

Serotype distribution of Streptococcus mutans a pathogen of dental caries in cardiovascular specimens from Japanese patients.

The involvement of oral bacteria in the pathogenesis of cardiovascular disease has been studied, with Streptococcus mutans, a pathogen of dental caries, detected in cardiovascular lesions at a high frequency. However, no information is available regarding the properties of S. mutans detected in those lesions.

Detection and serotype distribution of Actinobacillus actinomycetemcomitans in cardiovascular specimens from Japanese patients.

Actinobacillus actinomycetemcomitans, an important pathogen in periodontitis, has also been detected in cardiovascular tissues. Sixty heart valves were collected during valve replacement surgery from 60 patients (one from each), 10 were from patients with infective endocarditis (IE group) and 50 were from patients with other valvular diseases (non-IE group). In addition, 46 samples of aneurysmal tissue were taken from 46 patients with a thoracic or abdominal aneurysm (Aneurysm group, one from each).

Placebo analgesia: a PET study.

Placebo analgesia involves complex mechanisms and sometimes has a marked effect on patients in pain. In this study we examined changes in regional cerebral blood flow (rCBF) under three different conditions (resting, hot, painful) before and after placebo administration using H(2)(15)O and positron emission tomography in ten healthy subjects. In five subjects, placebo administration significantly decreased pain-intensity score (placebo responders), and rCBF in the medial prefrontal cortex (MPFC), posterior parietal cortex (PPC), and inferior parietal lobe (IPL) increased after placebo administration compared with before placebo administration under the painful condition.

To reduce catheter-related bloodstream infections: is the subclavian route better than the jugular route for central venous catheterization?

The most important targets of hospital-acquired infection control are to reduce the incidence of surgical-site, catheter-related, and ventilator-associated infections. In this report, we address previously presented infection-control strategies for central venous (CV) line catheterization, using a CV catheter-related infection surveillance system. Data concerning CV catheter insertion were collected from all facilities in our 650-bed hospital, excluding the operating and hemodialysis wards.

Flexible synthesis of poison-frog alkaloids of the 5,8-disubstituted indolizidine-class. II: Synthesis of (-)-209B, (-)-231C, (-)-233D, (-)-235B", (-)-221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors.

Background: The 5,8-disubstituted indolizidines constitute the largest class of poison-frog alkaloids. Some alkaloids have been shown to act as noncompetitive blockers at nicotinic acetylcholine receptors but the proposed structures and the biological activities of most of the 5,8-disubstituted indolizidines have not been determined because of limited supplies of the natural products. We have therefore conducted experiments to confirm proposed structures and determine biological activities using synthetic compounds.

[A case of primary HIV infection presenting as mononeuritis multiplex].

A 34-year-old man presented with gait disturbance. He had a low grade fever and diarrhea for a few days prior to admission. Two weeks after he started to have diarrhea, he developed gait disturbance with a left foot drop.

Histological and immunohistological changes of the skeletal muscles in older SJL/J mice.

SJL/J mice have been studied as the model animals for autoimmunological diseases. Recently it was clarified that SJL/J mice have a defect of dysferlin. Human limb girdle muscular dystrophy 2B and Miyoshi myopathy also have a defect of dysferlin.

Synthesis and anti-tumor activity of a fluorinated analog of medroxyprogesterone acetate (MPA), 9alpha-fluoromedroxyprogesterone acetate (FMPA).

We synthesized 9alpha-fluoromedroxyprogesterone acetate (FMPA) in order to test whether it is a more potent anti-angiogenic agent than medroxyprogesterone acetate (MPA), which has been widely used as a therapeutic agent for breast and endometrium cancers. FMPA was previously synthesized in 10 steps (total yield: 1%). An efficient synthesis of FMPA has been achieved in 6 steps (total yield: 12%).