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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 217 records · Page 12Linked to original sources
PubMed1995

Novel agonists for metabotropic glutamate receptors: trans- and cis-2-(2-carboxy-3-methoxymethylcyclopropyl)glycine (trans- and cis-MCG-I).

New derivatives of 2-(carboxycyclopropyl)glycine (CCG), (2S,1'S,2'R,3'S)- and (2S,1'S,2'R,3'R)-2-(2-carboxy-3-methoxymethylcyclopropyl) glycine (trans- and cis-MCG-I), effectively inhibited forskolin-stimulated cyclic AMP formation in a concentration dependent manner in cultured spinal neurones of rats. They effectively depressed monosynaptic excitation in the spinal reflex of newborn rats with IC50 values of 0.3 and 3 microM, respectively, which was sensitive to (+)-MCPG. They did not cause any depolarization even when the concentration was increased up to 0.3 mM. However, after treatment with quisqualate, cis-MCG-I caused a depolarization of motoneurones in the newborn rat spinal cord in a concentration dependent manner with a threshold concentration of 1 microM (quisqualate effect). The depolarizing activity developed after quisqualate treatment gradually decreased but lasted for more than 2 hr. The depolarization induced by cis-MCG-I seemed pharmacologically similar to that of phosphonate-containing analogues of glutamate such as L-AP4 or L-AP6 under the "quisqualate effect". These novel CCG derivatives would be expected to provide useful probes for elucidating the physiological function of mGluRs.

Animals↗
PubMed1995

The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system.

Non-A beta component of Alzheimer's disease amyloid (NAC) is the second component in the amyloid from brain tissue of patients affected with Alzheimer's disease. Its precursor protein (NACP) was shown to be a brain-specific protein. In rat brain, NACP was more abundant in the neocortex, hippocampus, olfactory bulb, striatum, thalamus, and cerebellum and less abundant in the brain stem. Confocal laser microscopy analysis revealed that anti-NACP immunostaining was colocalized with synaptophysin-immunoreactive presynaptic terminals. Ultrastructural analysis showed that NACP immunoreactivity was associated with synaptic vesicles. NACP sequence showed 95% identity with that of rat synuclein 1, a synaptic/nuclear protein previously identified in rat brain, and good homology with Torpedo synuclein from the electric organ synapse and bovine phosphoneuroprotein 14 (PNP-14), a brain-specific protein present in synapses. Therefore, NACP is a synaptic protein, suggesting that synaptic aberration observed in senile plaques might be involved in amyloidogenesis in Alzheimer's disease.

Alzheimer Disease↗
PubMed1995

High-energy underwater shock wave treatment for internal iliac muscle metastasis of prostatic cancer: a first clinical trial.

The first clinical trial of high-energy shock wave (SW) combined with chemotherapy to treat metastasis of prostate cancer in the internal iliac muscle was conducted. The patient, a 57-year-old man, diagnosed as having mucin-producing, poorly differentiated adenocarcinoma of the prostate invading the bladder wall, had been treated by total cystoprostatectomy. Five months later, metastatic tumors were found in the left axillar subcutaneous tissue and the right internal iliac muscles. For the axillar metastasis we performed radiation and left subclavicular arterial infusion of cisplatin 70 mg, THP-adriamycin (THP) 50 mg and methotrexate 50 mg. For the right internal muscular metastasis, 10,000 to 20,000 shots of SW and simultaneous intravenous injection of carboplatin 100 mg and THP 10 mg were carried out. Neither of the tumors decreased in size, but on magnetic resonance images, the SW-treated tumor exhibited a central low-intensity area. The SW-treated tumor was resected and central necrosis and a collection of mucin in the central area were observed. Hormone-resistant prostate cancer is well-known to be a multidrug-resistant tumor. It is noteworthy that SW and chemotherapy induced necrosis in such a refractory cancer without any significant side effects.

Adenocarcinoma↗
PubMed1995

[Haemophilus aphrophilus isolated from the blood of a patient with infective endocarditis].

On July 1994, a 62-year-old female, having a history of mitral regurgitation, was admitted because of high fever, hematuria and conjunctival petechiae. She was diagnosed as having infective endocarditis with mitral valve vegetation proved by ultrasonic cardiography. The gram negative rods were isolated from blood cultures performed five times, performed prior to the administration of antibiotics. The isolates were identified as strains of H. aphrophilus. After two days of treatment with PCG (12 million units/day), the organism became undetectable from the blood. Since the minimal inhibitory concentrations (MICs) of PCG and ABPC were ranged between 0.06-2.0 micrograms/ml and 0.06-0.5 microgram/ml, respectively, ABPC was selected as a first choice antibiotic instead of PCG. ABPC was given 12 g/day for the first 3 days, then 6 g/day for 28 days, followed by 3 g/day for 7 days. The patient recovered and was discharged after the 55 hospital days. H. aphrophilus grew on BTB lactose agar, chocolate agar and sheep blood agar, but failed to grow on MacConkey agar. H. aphrophilus produced smooth transparent nonhaemolytic micro colonies after 48 hours on sheep blood agar and chocolate agar plates. Atmosphere with 5% CO2 failed to enhance their growth. All the five strains of H. aphrophilus isolated, required neither factors V nor X. Positive synthesis of porphyrin from delta-aminolevlinic acid confirmed their ability to grow without X factor. For the correct identification of H. aphrophilus strains, fermentation test of glucose, lactose, maltose and sucrose in either phenol red broth or CTA medium are necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗
PubMed1995

Hemodynamic effects and pharmacokinetics of oral milrinone for short-term support in acute heart failure.

The present study evaluated the acute hemodynamic response, effects on subjective symptoms and physical findings, and the pharmacokinetics of a single oral dose (2.5, 5, or 10 mg) of milrinone in 31 patients with acute or decompensated heart failure. We found a significant increase in cardiac index (29, 31, and 29%, respectively, p < 0.01) and a significant decrease in pulmonary capillary wedge pressure (39, 43, and 47%, respectively, p < 0.01) accompanied with improvement in subjective symptoms and physical findings. These hemodynamic effects persisted for 4-8 h after each dosage of milrinone. Dose-dependent hemodynamic response was observed between the drug concentration and percent maximum changes in pulmonary capillary wedge pressure (peak milrinone concentration, 2.5 mg: 99.99 +/- 57.49, 5 mg: 187.11 +/- 71.37, and 10 mg: 300.94 +/- 158.5 ng/ml). The finding, together with results of the Prospective Randomized Milrinone Survival Evaluation (PROMISE) study, suggests lower dose of milrinone will be useful for the short-term inodilator support in patients with acute or decompensated heart failure.

Acute Disease↗
PubMed1995

Episodic memory changes are associated with the APOE-epsilon 4 allele in nondemented older adults.

OBJECTIVE: To compare the memory performances of nondemented older adults with and without the epsilon 4 allele of the apolipoprotein E (APOE-epsilon 4). BACKGROUND: Few studies have examined the cognitive status of subjects at high risk for the development of dementia of the Alzheimer type (DAT). A newly reported risk factor for DAT allows for an examination of the cognitive performances of nondemented subjects who are at risk by virtue of being either heterozygous or homozygous for the APOE-epsilon 4 allele. METHODS: The California Verbal Learning Test (CVLT) was administered to 52 nondemented older adults. Subjects were divided into two groups on the basis of the presence (n = 17) or absence (n = 35) of one or two APOE-epsilon 4 alleles. RESULTS: APOE- epsilon 4 and non-epsilon 4 groups did not significantly differ in demographic, mental status, and functional characteristics. APOE-epsilon 4 subjects demonstrated significantly poorer mean performances than non-epsilon 4 subjects on nine CVLT variables. Seven group differences remained significant, and three approached significance (0.05 < p < 0.10), after the effects of age and gender were taken into account. Six of the 14 APOE-epsilon 4 subjects who completed annual follow-up evaluations developed either DAT or questionable DAT, whereas none of the 26 non-epsilon 4 subjects who received follow-up demonstrated any cognitive decline. CONCLUSIONS: Results suggest that episodic memory changes in older adults are associated with APOE-epsilon 4 allele; sensitive cognitive markers such as those of the CVLT may precede the subsequent development of DAT.

Aged↗
PubMed1995

Apolipoprotein E epsilon 4 allele frequency is not increased in progressive supranuclear palsy.

We examined apolipoprotein E (ApoE) immunoreactivity and allele frequency in 12 autopsied cases of progressive supranuclear palsy (PSP), a neurodegenerative disease characterized by diffuse neurofibrillary tangle (NFT) formation without beta-amyloid deposits. In spite of the ApoE immunoreactivity associated with NFTs, in PSP the ApoE allele frequency was comparable with that of age-matched normal controls. This suggests that in Alzheimer's disease the increased frequency of ApoE epsilon 4 does not influence neurofibrillary degeneration, but is probably linked to beta-amyloid deposition.

Alleles↗
PubMed1995

Changes in protein kinases in brain aging and Alzheimer's disease. Implications for drug therapy.

There is ample evidence for the involvement of aberrant protein phosphorylation reactions in aging and age-associated neurological disorders. Alzheimer's disease (AD) in particular. The exact nature of this involvement, however, is not yet elucidated. In the brain tissue of AD patients, there are numerous examples of altered protein phosphorylation pathways. Individual protein kinases and phosphorylation by these kinases in AD brain tissues have been found to be altered. Protein kinases studied include protein kinase C (PKC), protein tyrosine kinase (PTK), casein kinase II (CKII), Ca++/calmodulin-dependent kinase II and mitogen-activated protein (MAP) kinases, all of which are thought to be necessary for cell survival. Interestingly, different protein kinases are involved in different aspects of AD pathology. It is postulated that the perturbation of amyloid beta/A4-protein precursor (APP) metabolism triggers abnormal protein phosphorylation reactions responsible for dysfunction and eventual death of neurons in the brain. The association of APP mutation with certain familial types of AD strongly suggests that there might be a link between aberrant APP metabolism, protein phosphorylation cascades and the eventual expression of AD pathology (plaques and tangles) and neurodegeneration. In summary, recent studies emphasise the prime importance of protein phosphorylation in aging and AD. This raises the possibility that future pharmacological interventions might be devised to interfere with this kinase cascade for the prevention or treatment of age-associated neurological disorders.

Aging↗
PubMed1995

Fulminant Mycoplasma pneumoniae pneumonia with marked elevation of serum soluble interleukin-2 receptor.

We treated a married couple who developed Mycoplasma pneumonia at the same time, and whose clinical courses and serum soluble interleukin-2 receptor (sIL-2R) levels were markedly different. The 30-year-old wife developed acute respiratory failure and her sIL-2R levels were extremely increased. After pulse therapy, her clinical state was improved, with a marked decrease in sIL-2R. In contrast, the 36-year-old husband, also suffered from the pneumonia with a moderate increase of sIL-2R, and recovered without any complications. The difference in their clinical states may be reflected in their serum sIL-2R levels, a marker of T cell activation in vivo.

Acute Disease↗
PubMed1995

[A case of Guillain-Barré syndrome with ophthalmoplegia showing high titers of anti-GQ1b and -GD1b antibodies in the serum].

A 24-year-old housewife developed double vision, tingling sensation, and weakness in the legs following a flu-like illness. She then developed dysphagia and difficulty in standing. On admission her eyes were fixed in midline due to ophthalmoplegia. Doll's eye sign was negative. She had severe generalized muscle weakness and no sensory deficits. All tendon reflexes were lost. CSF protein was 58 mg/dl with cell count of 2/mm3. Antibodies to campylobacter jejuni, mycoplasma, EBV, and other microbes were negative. We treated her with plasmapheresis after which she showed rapid clinical recovery, although the ophthalmoplegia improved slightly later. Increased titer of IgG class antibodies to GD1b and to GQ1b, and of IgM antibody to GQ1b, were detected in the serum taken during the acute phase of the illness. In parallel with clinical amelioration, both the anti-GD1b and -GQ1b antibodies decreased in titer, or became negative. Since there is no common epitope to GD1b and GQ1b gangliosides, we speculated that the anti-GD1b and -GQ1b antibodies were induced independently by different antigens in this patient. Moreover, the presence of high titer IgM antibody to GQ1b possible indicates that this patient was at the relatively early stage of infection of unknown microbe, which then induced the IgG antibodies to GD1b and GQ1b by cross sensitization, which might correlate with the tetraplegia and the ophthalmoplegia, respectively.

Adult↗
PubMed1995

[Increased production of nitric oxide in the immediate and late asthmatic responses in models of guinea pig experimental asthma].

Nitric oxide is produced in mammalian airways by constitutive and inducible nitric oxide synthase, and endogenous nitric oxide can be detected as exhaled gas. Patients with asthma have large numbers of airway epithelial cells and inflammatory cells that contain nitric oxide synthase, and nitric oxide levels in exhaled air are high during immediate asthmatic responses. To examine the dynamics of nitric oxide synthase in the tracheas of guinea pigs, cumulative dose-response studies of 5-HT were done on tracheal strips, in the presence or absence of arginine and its analogues. This assay indicated that relative the activity of nitric oxide synthase was greater 6 hr after the challenge than immediately after, which suggests that nitric oxide is involved in the pathogenesis of bronchial asthma attacks.

Animals↗
PubMed1994

Tissue-dependent alternative splicing of mRNA for NACP, the precursor of non-A beta component of Alzheimer's disease amyloid.

A cDNA clone encoding an alternatively spliced form of the precursor of the non-A beta component of Alzheimer's disease amyloid (NACP) was isolated from a human fetal brain cDNA library. This cDNA contains the entire NAC coding sequence but lacks an 84-base-pair nucleotide stretch 3' to the NAC sequence, resulting in a 112-amino-acid protein, NACP112, in contrast with the originally cloned molecule, NACP140. RT-PCR analysis demonstrated that the mRNA for two types of NACP mRNA are expressed in both fetal and adult brain. Northern blot analysis revealed that NACP140 mRNA was expressed mostly in brain and in minor amount in all the tissues examined. However, the expression levels of NACP140 mRNA apart from brain were higher in heart, skeletal muscle, and pancreas, contrasting with the predominant expression of total NACP mRNA in brain with a slight expression in placenta. These results suggest differential regulation of NACP RNA splicing among tissues.

Alternative Splicing↗
PubMed1994

Apolipoprotein-E epsilon-4 is associated with increased neurofibrillary pathology in the Lewy body variant of Alzheimer's disease.

Brains from demented patients with both Alzheimer's disease (AD) pathology and brainstem and neocortical Lewy bodies have fewer neurofibrillary tangles than pure AD, but share with AD an increased apolipoprotein-E epsilon-4 (APOE4) allelic frequency. We applied the Braak and Braak AD neuropathology staging protocol, based on entorhinal and neocortical neurofibrillary pathology, to 40 such Lewy body variants of AD (LBV) and 97 cases of pure AD and compared the results in APOE4 positive and APOE4 negative subgroups. APOE4 was associated with more severe neurofibrillary pathology in LBV but not in pure AD, where a ceiling effect appears to be operative.

Aged↗
PubMed1994

Increase of synaptic density and memory retention by a peptide representing the trophic domain of the amyloid beta/A4 protein precursor.

The secreted form (sAPP) of the Alzheimer amyloid beta/A4 protein precursor (APP) has been shown to be involved in the in vitro regulation of fibroblast growth and neurite extension from neuronal cells. The active site of sAPP responsible for these functions is within a small domain just C-terminal to the Kunitz-type protease inhibitor (KPI) insertion site. We report here that a 17-mer peptide, containing this active domain of sAPP, can induce cellular and behavioral changes when infused into rat brains. After 2 weeks of APP 17-mer peptide infusion, the animals were tested for reversal learning and memory retention and were sacrificed for morphological examination of brains. We found that administration of the APP 17-mer peptide resulted in an 18% increase in the number of presynaptic terminals in the frontoparietal cortex. At the behavioral level, 17-mer-infused animals with nonimpaired learning capability showed an increased memory retention that seemed to interfere with reversal learning performance. This APP 17-mer effect on memory retention was not observed in animals with impaired initial learning capacity. These results suggest that APP is involved in memory retention through its effect on synaptic structure.

Amino Acid Sequence↗
PubMed1994

A novel metabotropic glutamate receptor agonist: (2S,1'S,2'R,3'R)-2-(2-carboxy-3-methoxymethylcyclopropyl)glycine (cis-MCG-I).

A novel agonist for metabotropic glutamate receptors, (2S,1'S,2'R,3'R)-2-(2-carboxy-3-methoxymethylcyclopropyl)glycine (cis-MCG-I), effectively inhibited monosynaptic excitation in newborn rat spinal cords with EC50 of 3 microM without causing any depolarization. Furthermore, cis-MCG-I inhibited the forskolin-stimulated cyclic AMP formation in rat cultured cortical cells with IC50 of 1.5 microM. cis-MCG-I neither stimulated the phosphoinositide hydrolysis nor activated ionotropic glutamate receptors even in high concentrations. However, after a brief exposure of spinal cords to quisqualate, it caused depolarization in a dose-dependent manner. This compound would provide useful information for elucidating physiological functions of metabotropic glutamate receptors.

Animals↗