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Biomedical subjects

J Shimada

Publications and source records attributed to J Shimada.

At least 19 recordsLinked to original sources
PubMed1996

Controlling substrate preference and transglycosylation activity of neopullulanase by manipulating steric constraint and hydrophobicity in active center.

The substrate specificity and the transglycosylation activity of neopullulanase was altered by site-directed mutagenesis on the basis of information from a three-dimensional structure predicted by computer-aided molecular modeling. According to the predicted three-dimensional structure of the enzyme-substrate complex, it was most likely that Ile-358 affected the substrate preference of the enzyme. Replacing Ile-358 with Trp, which has a bulky side chain, reduced the acceptability of alpha-(1-->6)-branched oligo- and polysaccharides as substrates. The characteristics of the I358W-mutated enzyme were quite different from those of wild-type neopullulanase and rather similar to those of typical starch-saccharifying alpha-amylase. In contrast, replacing Ile-358 with Val, which has a smaller side chain, increased the preference for alpha-(1-->6)-branched oligosaccharides and pullulan as substrates. The transglycosylation activity of neopullulanase appeared to be controlled by manipulating the hydrophobicity around the attacking water molecule, which is most likely used to cleave the glucosidic linkage in the hydrolysis reaction. We predicted three residues, Tyr-377, Met-375, and Ser-422, which were located on the entrance path of the water molecule might be involved. The transglycosylation activity of neopullulanase was increased by replacing one of the three residues with more hydrophobic amino acid residues; Y377F, M375L, and S422V. In contrast, the transglycosylation activity of the enzyme was decreased by replacing Tyr-377 with hydrophilic amino acid residues, Asp or Ser.

Amino Acid Sequence↗
PubMed1996

[A 32-year-old man who developed a posterior fossa mass 12 years after the radiation therapy for cerebellar arteriovenous malformation].

We report a 32-year-old man who developed cerebellar ataxia and a posterior fossa mass 12 years after the radiation therapy for a cerebellar arteriovenous malformation (AVM). The patient was well until 19 years of the age when he had an acute onset of vertigo and vomiting. A spinal tap was performed and the CSF was bloody. He was admitted to another hospital where an arteriovenous malformation was found in the cerebellum by angiography. Four years after the onset, he developed tingling sensation in the distribution of the second division of the right trigeminal nerve. He was admitted to the neurosurgery service of our hospital where the cerebellar AVM was confirmed. He was transferred to University of California where Bragg peak stereotaxic radiotherapy was successfully performed; this utilizes high energy alpha-ray produced by a cyclotron. Three years after the radiotherapy, marked reduction in the size of the AVM was confirmed by angiography. Twelve years after the onset of his initial symptom, he noted unsteadiness of gait. He was readmitted to our neurosurgery service where obstructive hydrocephalus was found. He was treated by ventriculoperitoneal shunting and placement of a Ommaya reservoir. After these therapy, he noted marked improvement in his gait and ataxia. However, in 1993, his unsteadiness of gait recurred, and he was again admitted to our neurosurgery service on June 20, 1993. On admission, T1-weighted MRI revealed a slightly low signal intensity mass lesion in the right cerebellar hemisphere compressing the brain stem; a spotty high signal intensity lesion and another small low intensity lesion were seen within the mass. Vertebro-basilar angiograms revealed upward displacement of the superior cerebellar arteries. No arteriovenous nidus was visualized. On July, 3rd, the cyst was surgically drained and the Ommaya reservoir was removed. Post-operative course was uneventful, however, he developed head tremor after the surgery. Neurologic examination on July 20, 1993 revealed an alert and well oriented man in no acute distress. General physical examination was unremarkable. Neurologic examination revealed no dementia; higher cerebral functions appeared intact. The optic discs were flat, and visual fields were intact. Ocular movements were full but convergence was restricted. Horizontal gaze nystagmus was noted more in the right lateral gaze. Pupils were intact. Facial sensation and facial muscles were intact. Hearing was normal. His voice was of nasal quality. Pharyngeal reflex was diminished. The tongue showed deviation to the left without atrophy. Head tremor at 5 c/s was noted. He was able to stand with support but was unable to walk. No muscle atrophy or weakness was noted. The finger-to-nose and the heel-to-knee tests showed dysmetria and decomposition more on the right. Rapid alternating movements were ataxic on the right. Muscle tone was diminished on the right. Muscle stretch reflexes were normally elicited and were symmetric. The plantar response was flexor bilaterally. Sensation was intact. On July 21, a posterior fossa exploration was performed. After the surgery, he was treated with 30 mg/day of alotinolol which showed no effect on his head tremor. He was then treated with gradually increasing doses of clonazepam; when he received 8 mg/day of clonazepam, his tremor showed marked improvement. He was discussed in a neurologic CPC on the nature of the posterior fossa lesion and his tremor. Opinions were divided between delayed radiation necrosis and a radiation-induced brain tumor. The chief discussant arrived at the conclusion that the patient had delayed radiation necrosis compressing the brain stem and cerebellar hemispheres. Regarding the nature of his tremor, he thought that his head tremor was of cerebellar type of postural tremor. Histologic examination of the biopsied specimen revealed accumulation of relatively fresh blood constituents in the deep area of the cerebellum forming a mass. Most of the

Adult↗
PubMed1995

"Strong medicine": Cambodian views of medicine and medical compliance.

OBJECTIVE: To identify important determinants of noncompliance among Cambodian refugees. DESIGN: Open-ended interviews. SETTING: University-affiliated ambulatory care clinic in an inner-city hospital. PARTICIPANTS: Thirty adult Cambodian refugees (15 men and 15 women) who were regular utilizers of a refugee clinic. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of the participants described being noncompliant with at least one of their medications. Four common causes of noncompliance were identified: 1) misunderstanding the intent of the medication; 2) side effects; 3) concern about the effect of medication on "internal strength"; and 4) Cambodian ideas about pharmacokinetics. CONCLUSIONS: Noncompliance was commonly reported by the Cambodian respondents. Noncompliance was both intentional and unintentional; the unintended noncompliance derived from patients' attempting to comply with therapy according to Cambodian ideas about the body and Western medication. This article suggests clinical approaches to enhance compliance with prescribed regimens among recent Cambodian immigrants and refugees.

Adult↗
PubMed1995

Synthesis and preliminary evaluation of [11C]KF15372, a selective adenosine A1 antagonist.

As a radioligand for mapping the presynaptic adenosine A1 receptors in the central nervous system by PET, [1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine ([11C]KF15372), a selective adenosine A1 antagonist, was prepared by the reaction of 8-dicyclopropylmethyl-3-propylxanthine and [11C]propyl iodide with decay-corrected radiochemical yield of 5% based on the [11C]propyl iodide, radiochemical purity of > 99%, sp. at. of 10-56 GBq/mumol and preparation time of 45-55 min. Another 11C-labeled A1 antagonist with much lower affinity for the A1 receptors, 7-[11C]methyl-KF15372 ([11C]KF17109), was also prepared using [11C]methyl iodide with a decay-corrected radiochemical yield of > 50%. In mice, the brain uptake of [11C]KF15372 (1.91% ID/g at 5 min) decreased gradually with time. Carrier KF15372 competitively reduced the brain uptake to a level (43% of the control) comparable to the brain uptake of [11C]KF17109. On the other hand, an A2 antagonist 3,7-dimethyl-1-propargylxanthine showed no effect on the brain uptake of [11C]KF15372. The results show that [11C]KF15372 has potential as a PET radioligand for mapping the adenosine A1 receptors and that [11C]KF17109 may be a reference compound reflecting the non-specific uptake of the [11C]KF15372.

Animals↗
PubMed1995

[Clinical and bacteriological effects of cefetamet pivoxil against community-acquired respiratory tract infections].

We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT-PI) in community-acquired respiratory tract infections and obtained the following findings. 1. Of the 420 respiratory tract infection cases that were treated with CEMT-PI according to a same protocol at a total of 42 institutions in Tokyo, Kanagawa-ken, Saitama-ken and Chiba-ken from February to the beginning of April 1994, 359 cases in which clinical evaluations were considered possible were selected as the subjects of the clinical study. Regarding genders of patients, slightly more females (56.3%) than males were included. Diagnoses given to these patients included laryngopharygealitis (60.7%), tonsillitis (14.2%) and acute bronchitis (13.6). Outpatients accounted for 94.4% of the subjects. 2. For the bacteriological study, a written material describing the method of collecting specimens, storage and transport in detail was distributed to the above mentioned institutions. The isolation and identification of suspected causative bacteria, determination of minimum inhibitory concentrations (MIC) and investigation of beta-lactamase production were conducted all together. Suspected causative bacteria were detected from 238 (66.3%) out of the 359 cases. They included 85 strains of Haemophilus influenzae, 76 strains of Streptococcus pneumoniae, 20 strains of Streptococcus pyogenes and 17 strains of Moraxella subgenus Branhamella catarrhalis. 3. Clinical efficacy rates (the ratio of those excellent+good) among those who were treated with 1 CEMT-PI tablet (194 mg, titer) twice a day was 76.5% and among those who were given 2 tablets twice a day was 87.4%. The improvement rate of the latter was higher at a significant level of P < 0.05. 4. The clinical efficacies classified by suspected causative bacteria (single bacterium) were 93.3% against M.(B.) catarrhalis, 91.7% against beta-streptococci, 87.1% against H. influenzae and 78.4% against S. pneumoniae, etc. Though 7 (9.2%) of the 76 strains of S. pneumoniae were benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), the bacteriological efficacy was assessed either excellent or good in all of the 7 patients from whom PISP were detected. The clinical efficacy was assessed 100.0% in those from which a plural number of bacteria were detected. The 13 cases from which small numbers of Staphylococcus aureus was detected with other bacterium were also included in these cases.

Administration, Oral↗
PubMed1995

[A successful usage of latissimus dorsi muscle flap in the surgery of synchronous gastric and pulmonary double cancer in an elderly patient--a case report].

A 77-year-old man, with both an advanced gastric cancer Borrman IV type (CME) S2N1P0 M0 stage II and lung cancer of left upper lobe pT3N1M0 stage IIIA, simultaneously received total gastrectomy with R2 lymph node dissection, and Roux-Y reconstruction, and left upper lobectomy with R2 lymph node dissection combined with partial pericardiectomy. A latissimus dorsi muscle flap with thoracodorsal artery and vein was used for covering the intrathoracic esophagojejunostomy, repairing of the pericardial defect and separating the thoracic cavity from the abdominal cavity. Postoperative esophagograms showed a leakage, which was localized by the muscle flap coverage without extensive spread. The leakage healed spontaneously after a left sub-diaphragmatic drainage. Our experience described here indicates that a latissimus dorsi muscle flap coverage is a useful operative method for double cancers of the lung and stomach requiring intrathoracic procedures.

Aged↗
PubMed1995

Closure of leaks by fibrin gluing. Effects of various application techniques and temperatures.

This study was performed to determine the differences in covering power obtained with fibrin gluing using three different methods, layered, mixing, and spraying. The experimental system consisted of a 2 x 2 cm plastic plate with a hole 1 mm in diameter, a plastic syringe, and a digital manometer. The internal pressure of the syringe barrel was measured with the digital manometer. Five minutes after fibrin glue membranes (1 mm in thickness) had been prepared on the plastic plate with the layered, mixing, or spray method, the plunger of the syringe was pushed slowly, and the maximum internal pressure in the syringe barrel was measured, just before the breakage of the membrane. Experiments were performed five times at each four temperatures, 12 degrees C, 17 degrees C, 22 degrees C and 37 degrees C. Covering power of fibrin glue membranes (units: mmHg; atmospheric pressure 760 mmHg) were as follows: 1) Layered method (12 degrees C: 810.0 +/- 68.6, 17 degrees C: 769.0 +/- 10.2, 22 degrees C: 812.0 +/- 112.4, 37 degrees C: 773.6 +/- 24.4). 2) Mixing method (12 degrees C: 956.6 +/- 219.3, 17 degrees C: 972.4 +/- 243.5, 22 degrees C: 1045.2 +/- 233.0, 37 degrees C: 1059.0 +/- 220.2). 3) Spray method (12 degrees C: 1010.0 +/- 231.1, 17 degrees C: 1144.4 +/- 170.6, 22 degrees C: 1148.0 +/- 234.7, 37 degrees C: 1250.0 +/- 111.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1995

Everninomicin, a new oligosaccharide antibiotic: its antimicrobial activity, post-antibiotic effect and synergistic bactericidal activity.

Antimicrobial activity of everninomicin (SCH) 27899) in comparison with two glycopeptides (vancomycin, teicoplanin) and six beta-lactam agents was evaluated against recent clinical isolates of Gram-positive bacteria. Everninomicin showed the highest activity against the species tested and MICs90% of everninomicin against Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium and Clostridium difficile were 0.1, 0.1, 0.2, 0.39, 0.1 microgram/ml, respectively. MICs90% of everninomicin against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) were 0.78 microgram/ml. Laboratory induced resistance to everninomicin in strains of S. aureus and E. faecalis occurred in a stepwise manner and at a very slow rate. Post-antibiotic effect against strains of S. aureus and E. faecalis were 1.8 and 2.6 h, respectively, and a little longer than that of vancomycin. Adherence to glass surface of an MRSA strain was strongly repressed by the addition of sub MIC of everninomicin in combination with fosfomycin.

Aminoglycosides↗
PubMed1994

Anti-human immunodeficiency virus type 1 activity of phosphorothioate analogs of oligodeoxynucleotides: penetration and localization of oligodeoxynucleotides in HIV-1-infected MOLT-4 cells.

Phosphorothioate antisense oligodeoxynucleotide against HIV-1 rev (S-ODN-rev) inhibits virus-induced cytopathic effects (CPE) in acute infection and inhibits the expression of HIV-1 core protein, p24, in chronically infected cells in vitro. HIV-1 reverse transcriptase activity was not affected by S-ODN-rev at the high concentrations of 5-25 microM, which were 250-1250 times higher than the concentration required to achieve 100% HIV-1-induced CPE inhibition. [32P]-labeled S-ODN-rev was rapidly uptaken by MOLT-4 cells, whereas [32P]-SO-ODN-rev and [32P]-O-ODN-rev were not. In the observation of FITC-S-ODN-rev-treated MOLT-4 cells by a confocal laser scanning microscope, diffuse fluorescence was apparently observed in the cytoplasm. Interestingly, fluorescence signals were accumulated in the nuclear region of chronically infected MOLT-4/HIV-1 cells 60 min after incubation. FITC-labeled homooligomer, FITC-S-dC20 and FIT-C-S-dT20, also accumulated in the nucleus of MOLT-4/HIV-1 cells, but weak fluorescence was observed on the cell membrane and in the cytoplasm of the FITC-S-random treated MOLT-4/HIV-1 and MOLT-4 cells.

Cell Line, Transformed↗
PubMed1994

Possible physiological role of endogenous adenosine in defecation in rats.

Evacuated feces after intraperitoneal administration of selective adenosine receptor antagonists were evaluated in rats. The selective adenosine A1 receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (100-300 micrograms/kg i.p.) and (R)-7,8-dihydro-8-ethyl-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1 -i]purin- 5(4H)-one (KF20274) (30-300 micrograms/kg i.p.), significantly increased defecation, whereas the selective adenosine A2 receptor antagonist 4-amino-8-chloro-1-phenyl[1,2,4]triazolo[4,3-a]quinoxaline (CP-66,713) failed to cause a significant increase at up to 10 mg/kg i.p. The defecation caused by DPCPX (100 micrograms/kg) was markedly alleviated by (2S)-N6-(2-endo-norbornyl)adenosine ((S)-ENBA) (30-300 micrograms/kg s.c.), a selective adenosine A1 receptor agonist, but not influenced by 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosin e (CGS 21680) (30-1000 micrograms/kg s.c.), a selective adenosine A2 receptor agonist. These results suggest that endogenous adenosine plays a physiological role in sustained inhibition of defecation via adenosine A1 receptors.

Adenosine↗
PubMed1994

KF17837 ((E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine), a potent and selective adenosine A2 receptor antagonist.

8-(3,4-Dimethoxystryryl)-1,3-dipropyl-7-methylxanthine exhibited high affinity and selectivity for adenosine A2A receptors in binding assay using rat striatal A2A receptors labeled with [3H]2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosin e (CGS21680). The affinity was stereo selective: the E isomer, KF17837, showed a Ki value of 1.0 +/- 0.057 nM for the A2A receptors, whereas the Z isomer showed much lower affinity. KF17837 had 62-fold selectivity for the A2A receptors versus rat forebrain A1 receptors labeled with [3H]N6-cyclohexyladenosine (CHA). KF17837 was rapidly photoisomerized to form a stable equilibrium mixture (18% E - 82% Z), KF17837S, which showed Ki values of 7.9 +/- 0.055 nM and 390 +/- 68 nM for the A2A and A1 receptors, respectively. The inhibition type was competitive for [3H]CGS21680 binding. In rat pheochromocytoma PC12 cells KF17837S antagonized cAMP accumulation induced by 1 microM CGS21680 via the A2A receptors, with an IC50 value of 53 +/- 10 nM. cAMP accumulation induced by 10 microM 5'-N-ethylcarboxamidoadenosine via the A2B receptors in Jurkat cells (human T-cell line) was inhibited by KF17837S with an IC50 value of 1500 +/- 290 nM. These results indicate that KF17837S (and hence KF17837) is a highly potent and selective adenosine A2A receptor antagonist.

Adenosine↗
PubMed1994

KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity.

KF17837 is a novel selective adenosine A2A receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A2A receptor agonist, CGS 21680 (10 micrograms), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg/kg i.p.) and by reserpine (5 mg/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg/kg p.o., respectively. Moreover, KF17837 (0.625 mg/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg/kg i.p.) plus benserazide (6.25 mg/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A2A receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine A2A receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism.

Adenosine↗
PubMed1994

Inhibition of the renal excretion of tazobactam by piperacillin.

A 1:4 by weight of combination of tazobactam, a new beta-lactamase inhibitor, and piperacillin, is now under development in Japan. After bolus iv administration of the combination to beagle dogs, piperacillin both significantly raised the area under plasma concentration time curve (AUC0 approximately infinity) and significantly decreased the total body clearance (Cltot) of tazobactam. The percentage binding of tazobactam and piperacillin to dog and human serum protein was the same for the combination as for the individual compounds. Piperacillin significantly decreased the renal clearance (Clr) and the clearance ratio (Cr) of tazobactam in dogs. Further, probenecid significantly decreased Clr of both tazobactam and piperacillin, and the Cr of tazobactam and piperacillin approximately reached unity. These results indicate that piperacillin inhibits the renal excretion of tazobactam. Both tazobactam and piperacillin are secreted by a tubular anion transport system which is identical to the probenecid secretion system.

Animals↗
PubMed1994

Effect of topical preparation of mycophenolic acid on experimental allergic contact dermatitis of guinea-pigs induced by dinitrofluorobenzene.

The effects of a topical preparation of mycophenolic acid on the experimental allergic contact dermatitis induced by dinitrofluorobenzene was investigated. Visual assessment of skin reactions showed significant efficacy of a topical preparation of mycophenolic acid. This efficacy appeared from the early stage and endured up to 3 days. Morphological changes in the epidermis and dermis layers of animals treated with a mycophenolic acid cream were moderate compared with that in animals treated with vehicle only. In particular, hyperkeratosis was strongly suppressed. Since suppression of inflammatory cell infiltration was also observed, this efficacy might reach to the epidermis and dermis layer.

Administration, Topical↗