Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma.

Inoperable adenocarcinoma in colon or lung shows resistance to conventional anti-cancer therapy. For these cancers, the feasibility of transcriptionally targeted killing of carcinoembryonic antigen (CEA)-producing adenocarcinoma cells was investigated. Adenovirus vectors carrying a CEA promoter to express E.

Effect of donepezil hydrochloride (E2020) on extracellular acetylcholine concentration in the cerebral cortex of rats.

Donepezil hydrochloride (donepezil), a potent and selective acetylcholinesterase inhibitor, has been developed for the treatment of Alzheimer's disease. We studied the effect of oral administration of this drug on the extracellular acetylcholine (ACh) concentration in the cerebral cortex of rats using microdialysis. We also observed fasciculation, a peripheral cholinergic sign induced by activation of neuromuscular transmission, after oral administration of the drug as an index of peripheral cholinergic activation.

Telomerase activity in the synovial tissues of chronic inflammatory and non-inflammatory rheumatic diseases.

Telomerase is a ribonucleoprotein complex which can compensate for telomeric loss originating from each cell division, and its activation plays a critical role in cellular immortality. We previously found that telomerase is activated not only in immortal cancer cells but also in activated lymphocytes. To assess the diagnostic significance of telomerase activity in RA synovial tissues, we quantitatively examined telomerase activity in synovial tissue samples obtained from 47 patients with RA, 31 with osteoarthritis (OA), and 23 with other joint diseases.

Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats.

The effects of oral administration of the centrally acting acetylcholinesterase (AChE) inhibitors, donepezil hydrochloride (donepezil: E2020: (+/-)-2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-indan-1-one monohydrochloride), tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) and ENA-713 (rivastigmine: (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate), which have been developed for the treatment of Alzheimer's disease, on the extracellular acetylcholine concentration in the hippocampus of rats were evaluated by using a microdialysis technique without adding cholinesterase inhibitor to the perfusion solution. We also compared the inhibition of brain AChE and the brain concentrations of these drugs. Donepezil at 2.

Alteration of perceived fragrance of essential oils in relation to type of work: a simple screening test for efficacy of aroma.

The perceptional change of fragrance of essential oils is described in relation to type of work, i.e. mental work, physical work and hearing environmental (natural) sounds.

Dermatomyositis associated with rapidly progressive fatal interstitial pneumonitis and pneumomediastinum.

We describe two cases of dermatomyositis (DM), which subsequently developed into rapidly progressive fatal interstitial pneumonitis and pneumomediastinum during steroid therapy. Both cases showed the classical cutaneous manifestations of DM, but the muscular symptoms were absent or mild. Both rapidly progressive interstitial pneumonitis and pneumomediastinum can occur in DM showing less inflammatory changes in the muscles.

[Discovery and development of donepezil hydrochloride for the treatment of Alzheimer's disease].

The most consistent change of neurotransmitter in the brain of Alzheimer's patients is the dramatic decrease of cholinergic innervation due to the loss of neurons in the basal forebrain. The most widely studied acetylcholinesterase inhibitors (AChEIs) have been physostigmine and tacrine. Physostigmine has very short duration, and tacrine has liability to hepatotoxicity.

Peptide N- and P/Q-type Ca2+ blockers inhibit stimulant-induced hyperactivity in mice.

omega-Conotoxin GVIA and omega-agatoxin IVA are specific peptide blockers of N- and P/Q-type calcium channel, respectively. Effects of their intracerebroventricular injection (1-3 pmol/mouse) on psychostimulant-induced hyperactivity were investigated in mice. omega-Conotoxin GVIA antagonized methylphenidate-, methamphetamine- and phencyclidine-induced hyperactivity in a dose-dependent manner.

Rheumatoid arthritis associated with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a distinct clinicopathologic entity, which is characterized by chronic recurrent sinopulmonary infection and inflammation. We describe 3 patients with rheumatoid arthritis (RA) associated with DPB and consider that DPB is one of the bronchopulmonary manifestations associated with RA.

Effects of rabeprazole, a gastric proton pump inhibitor, on biliary and hepatic lysosomal enzymes in rats.

The effects of rabeprazole (E3810), omeprazole and chloroquine on hepatic lysosomal function were studied. After chloroquine (50 mg/kg), rabeprazole (5 mg/kg) or omeprazole (5 mg/kg) was given intraperitoneally to rats for 6 days, the bile was collected via a bile duct cannula for 5 hr, and hepatic and biliary lysosomal enzyme (N-acetyl-beta-glucosaminidase and beta-galactosidase) activities were measured. The latency (an index for the hepatic lysosomal membrane integrity) was calculated from the N-acetyl-beta-glucosaminidase activity.

Telomerase activity in rheumatoid synovium correlates with the mononuclear cell infiltration level and disease aggressiveness of rheumatoid arthritis.

Objective: To determine whether the presence of telomerase activity in synovial tissues could provide insights into the pathogenesis of rheumatoid arthritis (RA).

Methods: Synovial tissue samples obtained from patients with RA or osteoarthritis (OA) were examined for telomerase activity using the telomeric repeat amplification protocol (TRAP).

Results: Telomerase activity was detected in over half the RA synovial tissues (14/25, 56%) but in no OA synovial tissue samples (0/15).

Quantitative reverse transcription-PCR-HPLC for nerve growth factor mRNA using a deletion RNA as an internal standard.

We have developed a convenient method for the routine measurement of the absolute amount of nerve growth factor (NGF) mRNA in tissue samples. The method consists of RNA extraction, amplification by reverse transcription-PCR and detection by high-performance liquid chromatography. The addition of a deletion mutant RNA to tissue samples as an internal standard enabled correction for RNA recovery during extraction, and the target mRNA and the internal standard were both amplified with the same PCR primers.

Genetic Variation in the VP7 Gene of Human Rotavirus Serotype 3 (G3 Type) Isolated in China and Japan.

Sequence analysis of the VP7 gene was performed on twenty-one human isolates of serotype 3 related-rotavirus in China and Japan. The five Chinese isolates were found to be not similar to the 16 Japanese isolates and to SAff11 (simian rotavirus). The Chinese isolates, especially CHW2 and CH-32, were different from the major serotype 3 human isolates.

Long-lasting muscle relaxant activity of eperisone hydrochloride after percutaneous administration in rats.

Potency and duration of muscle relaxant activity of eperisone hydrochloride were examined after percutaneous administration in the intercollicular decerebrated rat rigidity model and compared to those of eperisone after intravenous injection. A continuous movement was loaded on the hindlimb of the rat model to maintain stable rigidity. The tonus of the hindlimb was recorded by EMG from the triceps surae and was quantified by using the public domain NIH Image program.

Genetic variation in the VP7 gene of human rotavirus serotype 3 (G3 type) isolated in China and Japan.

Sequence analysis of the VP7 gene was performed on twenty-one human isolates of serotype 3 related-rotavirus in China and Japan. The five Chinese isolates were found to be not similar to the 16 Japanese isolates and to SA11 (simian rotavirus). The Chinese isolates, especially CHW2 and CH-32, were different from the major serotype 3 human isolates.

Scleroderma-polymyositis overlap syndrome associated with anti-Ku antibody and rimmed vacuole formation.

Scleroderma-polymyositis overlap syndrome is strongly associated with certain autoantibodies, such as anti-PM-Scl antibody and anti-Ku antibody. We describe a case of scleroderma-polymyositis overlap syndrome associated with anti-Ku antibody, which revealed rimmed vacuole formation in addition to intranuclear and intracytoplasmic filamentous inclusions in muscle biopsy specimens.

Development of ischemic colitis and scleroderma renal crisis following methylprednisolone pulse therapy for progressive systemic sclerosis.

We describe a patient with progressive systemic sclerosis who developed ischemic colitis and scleroderma renal crisis following steroid pulse therapy. The possible pathogenic mechanisms of ischemic colitis and scleroderma renal crisis development are discussed. We conclude that the administration of steroids in high doses, especially via steroid pulse therapy, should be undertaken with caution for progressive systemic sclerosis patients.

Specific growth inhibition of small-cell lung cancer cells by adenovirus vector expressing antisense c-kit transcripts.

Antisense methods to control aberrant gene expression have been investigated as therapeutic strategies. A proto-oncogene c-kit, which encodes a transmembrane tyrosine kinase, is overexpressed in some malignancies, including small-cell lung cancer (SCLC), and is thought to be involved in their pathogenesis. To test the feasibility of using adenovirus vectors for antisense strategies and to target c-kit in SCLC therapy, we constructed replication-deficient recombinant adenovirus vectors which express fragments of c-kit transcripts in antisense (Ad.

Synthesis and structure-activity relationships of acetylcholinesterase inhibitors: 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine hydrochloride and related compounds.

Following the discovery of a new series of anti-acetylcholinesterase (anti-AChE) inhibitors such as 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine (1), we reported that its rigid analogue, 1-benzyl-4-(2-isoindolin-2-ylethyl)piperidine (5), had more potent activity. We have extended the structure-activity relationship (SAR) study for the rigid analogue and found that the 2-isoindoline moiety in compound 5 can be replaced with a indanone moiety (8) without a major loss in potency. Among the indanone derivatives, 1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidine (13e) (E2020) (IC50 = 5.

Involvement of P-type calcium channels in high potassium-elicited release of neurotransmitters from rat brain slices.

Several types of voltage-dependent calcium channels appear to occur in neurons, although coupling of the particular subtype of calcium channels to the release of neurotransmitter has not been clearly understood. We have examined the effects of subtype-specific inhibitors of the calcium channels on depolarization-induced release of endogenous neurotransmitters from brain slices. High potassium-induced release of glutamate and aspartate from hippocampal and striatal slices was almost completely inhibited by a P-type channel blocker, omega-agatoxin IVA.

[Cyclophosphamide-responsive subclinical Sjögren's syndrome in a patient with initial peripheral and central nervous system involvement].

A 36-year old woman was admitted because of painful dysesthesia of her extremities, suggesting the presence of mononeuritis multiplex. Laboratory data was almost within normal limits, with the exception of lupus anticoagulant positivity and increase of IgM level. We considered the possibility of connective tissue diseases and examined the patient accordingly.

[Protein-losing enteropathy and cerebral infarction associated with systemic lupus erythematosus].

A 26-year old woman, who was diagnosed as having systemic lupus erythematosus at the age of 23 year old, presented diarrhea and headache. She showed severe hypoproteinemia (serum total protein 3.7 g/dl, serum albumin 1.

Endotoxin clearance through whole body rinse out in relation to histologic integrity in the rat.

The effects of normothermic whole body rinse out (NWBRO) with FC-43 perfluorocarbon emulsion on the course of endotoxic shock were examined in male Wistar rats. These animals, conscious and unrestrained, were infused over 10 min with 60 mg/kg of E. coli endotoxin (LD100) and observed for 6 hr.