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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 307 records · Page 17Linked to original sources

Changes in factor VIII binding capacity of von Willebrand factor and factor VIII coagulant activity in two patients with type 2N von Willebrand disease after hemostatic treatment and during pregnancy.

The changes of the FVIII binding capacity of vWF after the infusion of FVIII/vWF concentrate was studied in two patients with type 2N vWD, and also during pregnancy in one of them. After infusion of FVIII or DDAVP to the patients, FVIII:C in plasma increased as expected, but it then decreased, with a markedly short half-life, of about 2 h, due to the defect in the FVIII binding capacity of vWF in plasma. However, after infusion of FVIII/vWF concentrate (40 U of FVIII:C/kg), FVIII:C increased, from 4-6 to 100-160 U/dl, more than the expected values, and decreased with the half-life expected. The FVIII binding capacity of vWF in plasma changed in parallel with the concentration of exogenous normal vWF, with a half-life of more than 24 h. During pregnancy, no increase of FVIII:C was observed, although vWF:Ag increased from 40 (before pregnancy) to 90 U/dl in plasma at 35th week of gestation. The FVIII binding capacity of vWF in plasma showed no increase during pregnancy. Accordingly, the administration of FVIII/vWF concentrate to the patient at delivery resulted in adequate hemostasis.

Deamino Arginine Vasopressin↗

Nerve coaptation studies with and without a gap in rabbits.

Appropriate matching of proximal and distal fibers is a major objective when suturing a lacerated nerve. Recent studies suggest that neurotropic factors may influence motor/sensory specificity and affect the functional outcome. This was studied in animal models by direct coaptation of cut nerve ends inside a 5-mm collagen tube with and without appropriate sensory/motor alignment, as well as in models where the cut nerve ends were placed in a 10-mm collagen tube with a 5-mm gap, with and without appropriate sensory/motor alignment. The radial nerve of 49 New Zealand white rabbits was chosen because it has distinct motor and sensory divisions. The animals were killed at 24 weeks and electrophysiologic, histologic, and muscle contraction studies were performed. Axon counts and diameters were measured from the distal motor and sensory stumps. Nerve conduction velocity, dry muscle weight, and motor axon counts were not statistically different between the groups. The malaligned group without a gap had better regeneration in sensory nerves than other groups. The muscle contraction force of the malaligned group without a gap was significantly less than the other groups. The malaligned group with a 5-mm gap had the same muscle contraction force as the aligned group without a gap. In this study, a short nerve gap lessened the misdirection of motor fibers after nerve-end coaptation.

Anastomosis, Surgical↗

Modeling DNA hydration: comparison of calculated and experimental hydration properties of nuclic acid bases.

Hydration properties of individual nucleic acid bases were calculated and compared with the available experimental data. Three sets of classical potential functions (PF) used in simulations of nucleic acid hydration were juxtaposed: (i) the PF developed by Poltev and Malenkov (PM), (ii) the PF of Weiner and Kollman (WK), which together with Jorgensen's TIP3P water model are widely used in the AMBER program, and (iii) OPLS (optimized potentials for liquid simulations) developed by Jorgensen (J). The global minima of interaction energy of single water molecules with all the natural nucleic acid bases correspond to the formation of two water-base hydrogen bonds (water bridging of two hydrophilic atoms of the base). The energy values of these minima calculated via PM potentials are in somewhat better conformity with mass-spectrometric data than the values calculated via WK PF. OPLS gave much weaker water-base interactions for all compounds considered, thus these PF were not used in further computations. Monte Carlo simulations of the hydration of 9-methyladenine, 1-methyluracil and 1-methylthymine were performed in systems with 400 water molecules and periodic boundary conditions. Results of simulations with PM potentials give better agreement with experimental data on hydration energies than WK PF. Computations with PM PF of the hydration energy of keto and enol tautomers of 9-methylguanine can account for the shift in the tautomeric equilibrium of guanine in aqueous media to a dominance of the keto form in spite of nearly equal intrinsic stability of keto and enol tautomers. The results of guanine hydration computations are discussed in relation to mechanisms of base mispairing errors in nucleic acid biosynthesis. The data presented in this paper along with previous results on simulation of hydration shell structures in DNA duplex grooves provide ample evidence for the advantages of PM PF in studies of nucleic-acid hydration.

Base Composition↗

Sevoflurane, enflurane and isoflurane have no persistent postanaesthetic effects on the central nervous system in cats.

Several reports have appeared on postanaesthetic convulsive disorders in humans after enflurane and isoflurane anaesthesia. However, it is controversial if enflurane induces epileptiform electroencephalogram (EEG), abnormal behaviour, or both, lasting for several days after anaesthesia in laboratory animals. We chronically implanted electrodes for EEG recording in the cortex, medial amygdala and dorsal hippocampus, and for reticular multi-unit activity (R-MUA) in the midbrain reticular formation in five cats. Two weeks later they were anaesthetized with 5.0% sevoflurane, 3.5% enflurane or 4.8% isoflurane for 3-4 h. EEG recordings, R-MUA and behaviour were observed for 1-3 h, during both wakefulness and sleep, every day for 5-7 days after anaesthesia. None of the cats showed abnormal behaviour, or EEG or R-MUA abnormalities after any of the anaesthetics, not only during wakefulness but during slow-wave and paradoxical phases of sleep. These results suggest that if seizures occur after anaesthesia, volatile anaesthesia itself may not be the cause.

Amygdala↗

Halothane and diazepam inhibit ketamine-induced c-fos expression in the rat cingulate cortex.

BACKGROUND: Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has psychotomimetic side effects. Recent studies have shown that noncompetitive N-methyl-D-aspartate antagonists cause morphologic damage to the cingulate and retrosplenial cortices and induce c-fos protein (c-Fos) in the same regions. Although benzodiazepines are effective in preventing these side effects, the neural basis of the drug interactions has not been established. METHODS: The effects of diazepam and halothane on c-Fos expression induced by ketamine were studied. Diazepam (1 and 5 mg/kg) or vehicle were administered subcutaneously, followed 7 min later by 100 mg/kg ketamine given intraperitoneally. Halothane (1.0 and 1.8%), was administered continuously from 10 min before ketamine administration until brain fixation. Two hours after ketamine injection, rats were perfused and their brains fixed and extracted. Brain sections were prepared in a cryostat and c-Fos expression was detected using immunohistochemical methods. RESULTS: Ketamine induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices, thalamus, and neocortex. Diazepam suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices in a dose-dependent manner, leaving the thalamus and neocortex less affected. Halothane suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices and the neocortex in a dose-dependent manner, leaving the thalamus relatively unaffected. CONCLUSION: Halothane and diazepam inhibited ketamine-induced c-Fos expression in the cingulate and retrosplenial cortices, leaving the thalamus relatively unaffected.

Anesthetics, Inhalation↗

Free flaps based on the anterior interosseous artery.

Free flaps based upon the anterior interosseous artery were defined anatomically by 15 dissections. The anterior interosseous artery runs distally for the entire length of the anterior interosseous nerve on the palmar surface of the interosseous membrane. A dorsal branch of the anterior interosseous artery penetrates the interosseous membrane about 5 cm proximal to the distal radioulnar joint and gives off a tributary radially. This tributary ascends the ulnar aspect of the radius to provide blood to the radius and the dorsal wrist skin. Based on these anatomical findings, four types of free flaps were possible: fasciocutaneous, osteocutaneous, neurovascular flaps, and one muscle flap. All seven dorsal wrist flaps successfully covered the defects. Three of four nerve flaps demonstrated patency of the arterial pedicle with digital Allen's test and good sensory recovery of the reconstructed area. One reconstruction of Blauth type II hypoplastic thumb using an ipsilateral pronator quadratus free-muscle flap provided a functionally and cosmetically satisfactory result.

Adolescent↗

Two cases of protothecosis in Nagoya, Japan.

Two cases of protothecosis caused by Prototheca wickerhamii have been reported from Nagoya in a 12 year period in both cases the infection presented on the cheeks of otherwise healthy women. Biopsies showed numerous PAS positive staining organisms with the distinctive mulberry like endosporulation in the dermis. Prototheca wickerhamii was identified on sugar assimilation tests of colonies isolated from tissue on Sabouraud agar. Case 1 responded to 11 months of oral ketoconazole therapy. Case 2 might not respond to itraconazole. The source of the infections has not been identified.

Adult↗

Long-term administration of natural interferon-alpha in patients with chronic hepatitis C: relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus.

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-alpha (IFN alpha) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFN alpha and normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P < 0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type 1b. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10(5) copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10(5) copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P = 0.0061) and genotype (P = 0.0015). These results suggest that the pre-administration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.

Aged↗

The inhibitory effects of iberiotoxin and 4-aminopyridine on the relaxation induced by beta 1- and beta 2-adrenoceptor activation in rat aortic rings.

1. In rat aortic rings contracted by phenylephrine, the relaxation induced by isoprenaline was partly inhibited by iberiotoxin, (ibTX), tetraethylammonium, 4-aminopyridine (4-AP) and 1,9-dideoxyforskolin, but not by glibenclamide. 2. In the presence of 4-AP, 1,9-dideoxyforskolin failed to inhibit further the relaxant response to isoprenaline. Cromakalim-induced relaxation was inhibited by glibenclamide. 3. In the absence of endothelium, ibTX and 4-AP still inhibited the relaxant response to isoprenaline. 4. The inhibitory effect of ibTX on the relaxant response to isoprenaline was eliminated by pretreatment with ICI-118,551, a beta 2-adrenoceptor antagonist, but not by atenolol, a beta 1-adrenoceptor antagonist. 5. The inhibitory effect of 4-AP on the relaxation induced by isoprenaline was abolished by atenolol, but not by ICI-118,551. 6. The inhibitory effect of ibTX on the isoprenaline-induced relaxation in the presence of atenolol was completely abolished by MDL 12,330A, an adenylate cyclase inhibitor. Further, the inhibitory effect of 4-AP on the isoprenaline-induced relaxation in the presence of ICI-118,551 was markedly reduced by MDL 12,330A. 7. The relaxation induced by dibutyryl cyclic AMP was partly inhibited by 4-AP but not by ibTX. However, in the presence of KT5720, an inhibitor of cyclic AMP-dependent protein kinase, ibTX failed to inhibit further the relaxation induced by isoprenaline. 8. These results suggest that, in rat aortic rings, KCa channels are involved in the relaxation induced by isoprenaline. In addition, KCa channels are mainly activated by beta 2-adrenoceptors through cyclic AMP-dependent pathways. Further, the inhibition of isoprenaline-relaxation by 4-AP may be related to the activation of beta 1-adrenoceptors and cyclic AMP formation.

4-Aminopyridine↗

[Rapid detection of the hemolysin genes in Aeromonas sobria by the polymerase chain reaction].

The hemolysin of Aeromonas sobria is one of the important virulence factors in this organism. Rapid detection and identification test for A. sobria is important for early and specific diagnosis of this infectious disease. We evaluated the polymerase chain reaction (PCR) for the rapid detection of A. sobria. Two pairs of synthetic oligonucleotide primers (ASA1-s and a; AerAAS-s and a) were used in PCR technique to detect the different hemolysin genes (ASA1 and aerAAS) in A. sobria. The PCR identified 91% of ASA1-positive and 23.4% of aerAAS-positive strains in beta-hemolytic A. sobria. Other species of Aeromonas, Plesiomonas shigelloides, Vibrio cholerae O1 and V. parahaemolyticus tested were negative in the PCR with two pairs of primers. The PCR technique for detection of two hemolysin genes suggested the possibility of application of this method for detection of A. sobria in A. sobria-associated infections.

Aeromonas↗

Age dependence of cerebrovascular response mechanisms in domestic pigs.

Hypercapnia-induced cerebral vasodilation in the newborn pig is a prostanoid-associated response. In some adult models, hypercapnic cerebral vasodilation is associated with the generation of nitric oxide (NO). Acetylcholine (ACh) produces a NO-dependent cerebral vasodilation in many adult models, but topical ACh is a prostanoid-associated cerebral vasoconstrictor in the newborn pig. We hypothesized that mediators influencing cerebral response can be age dependent. Juvenile domestic pigs were compared with newborn pigs, and pial arteriolar diameters were measured by use of a closed cranial window during hypercapnia and topical ACh (10(-5) M). Four different conditions were explored: control, topical N omega-nitro-L-arginine (L-NNA, 10(-3) M), indomethacin (5 mg/kg i.v.), and both L-NNA and indomethacin. All animals were anesthetized with alpha-chloralose. As opposed to the complete block in the newborn, indomethacin only partially attenuated the hypercapnic cerebral vasodilation in the juvenile pig.L-NNA, which had no effect on the response of the newborn, produced a partial attenuation of the hypercapnic response of the juvenile. The combination of indomethacin and L-NNA blocked the response in both age groups. Topical ACh in both age groups initially produced cerebral vasoconstriction, but, in the juvenile, this was followed by a sustained cerebral vasodilation. Indomethacin blocked the early vasoconstriction in both age groups. L-NNA, which had no effect in the response of the newborn to ACh, blocked the vasodilation seen in the juvenile. The combination of both inhibitors blocked all response to ACh in the juvenile. These data indicate that although the cerebral vascular responses to ACh and hypercapnia are prostanoid associated and NO independent in the newborn pig, NO assumes an increasing role in dilatory responses with development.

Acetylcholine↗

Interleukin-1 beta peptides induce cerebral pial arteriolar dilation in anesthetized newborn pigs.

Inflammatory cytokines may affect cerebral circulation under pathological conditions. Responses of cerebral pial arterioles to one such cytokine, interleukin (IL)-1 beta and its inhibitor [soluble IL-1 receptor (sIL-1R)] were examined in anesthetized newborn pigs using closed cranial windows. Levels of prostanoids and cyclic nucleotides in periarachnoid cerebral spinal fluid (CSF) were measured. To examine the structure-activity relationship of the parent IL-1 beta molecule, two IL-1 beta fragments with amino acid sequences of 187-204 [IL-1 beta-(187-204)] and 208-240 [IL-1 beta-(208-240)] were tested for their effects on pial arterioles. Diameter changes of pial arterioles were sequentially recorded every 5 min for 30 min after topical application of IL-1 peptides. CSF was sampled at the end of the 30 min. IL-1 beta dose dependently induced arteriolar dilation and increased prostaglandin E2 (PGE2), 6-keto-PGF1 alpha adenosine 3',5'-cyclic monophosphate (cAMP), and guanosine 3',5'-cyclic monophosphate (cGMP). Intravenous indomethacin blocked the IL-1 beta-induced vasodilation, the increased prostanoids, and the increased cAMP, but not the increased cGMP. Neither heat-inactivated IL-1 beta nor IL-1 beta vehicle affected arteriolar diameter or CSF levels of prostanoids. The sIL-1R blocked the IL-1 beta-induced vasodilation and the increased CSF prostanoids. IL-1 beta-(208-240) also induced pial arteriolar dilation; however, its vasodilatory potency was 1,000 times less than that of the whole IL-1 beta molecule. IL-1 beta-(187-204) did not induce pial arteriolar dilation even when its dose was increased to the level of IL-1 beta-(208-240). These results suggest that IL-1 beta, through the activation of membrane-bound IL-1 beta receptors, induces pial arteriolar dilation via mechanisms that involve prostanoids and cyclic nucleotides. The results also indicate that the 208-240 amino acid sequence of IL-1 beta has a sequence-specific physiological function.

6-Ketoprostaglandin F1 alpha↗

Gastrointestinal physiology-regulated dogs for bioavailability evaluation of an oral controlled-release dosage form composed of pulsatile release granules.

Gastrointestinal (GI) physiology-regulated beagle dogs (regulated dogs) were regulated by a combined treatment using intramuscular pentagastrin and intravenous atropine sulfate. In the regulated dogs, the gastric pH was shifted to around 2, and the GI transit time was prolonged to approximate that in humans. Pranoprofen, an acidic anti-inflammatory agent, was granulated around sucrose seeds, and then coated with low substituted hydroxypropyl cellulose used as a swelling agent to afford plain granules (A-granule). Then, A-granule was coated stepwise with ethyl cellulose used as an outer shell material to afford two kinds of pulsatile release granules (B- and C-granules). In the dissolution study using pH 1.2 and 6.8 media, A-, B- and C-granules exhibited lag times of 0, 1 and 2h, respectively. Even in intact beagle dogs, the absorption profiles for A- and B-granules corresponded with those expected from the dissolution profiles. In contrast, the bioavailability of C-granule was only 35% in the intact dogs, but was 55% in the regulated dogs. Thus, the absorption of pranoprofen from pulsatile release granules after a longer lag time should be influenced by the location in the GI tract. Next, a controlled-release (CR) dosage form of pranoprofen was tentatively prepared by combining A-, B- and C-granules at the ratio of 3:4:3 (w/w in contents of pranoprofen). The bioavailability of the CR dosage form was significantly diminished in the intact dogs, being about 70% as much as that in the regulated dogs. Therefore, the regulated dogs would be superior to the intact dogs in avoiding the underestimation of the bioavailability of a CR dosage form with a pulsatile release property.

Animals↗

[Pharmacological profiles of a novel tachykinin NK-2 receptor antagonist, TAC-363].

We examined the pharmacological profiles of a novel tachykinin NK-2 receptor antagonist, Na-(tert-butylcarbamoyl)-L-glutaminyl-L-tryptophyl-alpha-azap++ + henylalanine 2-benzyloxyethylamide (TAC-363). In vitro studies showed that TAC-363 caused a rightward shift of the contraction response curve with a slight inhibition of maximal response for the neurokinin A (NKA)-induced contraction of the hamster trachea and parallel rightward shift of the curve for the substance P (SP)-induced contraction of the guinea-pig ileum. The pA2 values were 9.82 and 8.42 on the contraction by NKA and SP, respectively. The selectivity of TAC-363 to NK-2 receptor was 25 times higher than that to NK-1 receptor. The compound did not affect the histamine and acetylcholine-induced bronchoconstriction in guinea-pig ileum. Intravenous administration (0.1-1 mg/kg) of the compound inhibited dose-dependently both NKA- and capsaicin-induced bronchoconstriction in guinea-pigs. The inhibitory effect of the compound lasted up to 60 min on NKA-induced bronchoconstriction in guinea-pigs. These results suggest that TAC-363 is a potent and selective NK-2 receptor antagonist, which is effective in vitro and in vivo. It may be useful in the treatment of NKA-dependent pathology, especially bronchial asthma.

Animals↗

Capsaicin-induced calcitonin gene-related peptide release from isolated rat stomach measured with a new chemiluminescent enzyme immunoassay.

The peripheral capsaicin-sensitive afferent nerve has been reported to play an important role in gastroprotection and to release a calcitonin gene-related peptide (CGRP). We developed a new chemiluminescent enzyme immunoassay (CLEIA) for CGRP and measured capsaicin-induced CGRP release from the isolated and inverted rat stomach. The basal CGRP release from the stomach was 0.40 +/- 0.02 pg/mg wet weight in a 30-min incubation. Capsaicin (1 x 10(-8)-1 x 10(-5) M) stimulated CGRP release in a concentration-dependent manner. In the stomach from rats with defunctionalization of afferent neurons, the levels of the basal and capsaicin-induced CGRP release were below the limit of detection. On the other hand, the capsaicin-induced CGRP release was not blocked by tetrodotoxin treatment. The gangliosym-pathectomy abolished the increase in the CGRP levels. However, the capsaicin-induced CGRP release was not affected by pretreatment with 6-hydroxydopamine, a neurotoxin that causes a complete degeneration of adrenergic nerve terminals. In conclusion, the CLEIA system may be useful for detecting the released CGRP and studying the activity of capsaicin-sensitive nerves, particularly the CGRP-containing nerves. Our results also confirmed that although the CGRP-containing nerve runs in the sympathetic nerve trunk, the activity of the nerve is not affected by adrenergic nerves, and the capsaicin-induced CGRP release may be attributable to the tetrodotoxin-resistant component.

Adrenergic Agents↗

Pathogenicity of Haemophilus parasuis serovars 4 and 5 in contact-exposed pigs.

The pathogenicities of Haemophilus parasuis strains SW124 (serovar 4) and Nagasaki (serovar 5) were examined by contact-exposure of specific pathogen-free (SPF) pigs. Ten pigs were divided into three groups. Two of four pigs in the first group were inoculated intranasally (IN) with 2 x 10(8) CFU of strain SW124, and the other two pigs were mingled with these IN-exposed ones. All the four pigs were subclinically infected in this group. The four pigs of the second group were likewise exposed to strain Nagasaki (two IN-inoculated pigs with 3 x 10(8) CFU of strain Nagasaki). All four pigs in this group died of Glässer's disease. Two pigs kept as controls showed neither abnormality nor positive H. parasuis isolation.

Animals↗

[Development of quality of life questionnaire for patients with colorectal cancer in surgical area--a study of reliability and validity of Tokyo Yamabuki Forum Version].

We developed a new questionnaire in the surgical area based on a core quality of life (QOL) questionnaire for patients with gastrointestinal cancer. In this study, we investigated the validity and reliability of a QOL questionnaire (Tokyo Yamabuki Forum Version) for patients with colorectal cancer. The questionnaire was composed of 17 items including 5 scales (basic sensory scale, psychological scale, physiological scale, defection-related scale and active scale) and a face scale as an global scale. The time needed to answer questionnaires was expected to be around 7 minutes and the questionnaires should basically be answered by the patients themselves everyday in the hospital. The study was performed in 10 hospitals in the Tokyo area, and 394 samples collected from 21 patients with rectal and colonic cancers were analyzed. A number of respondents failed to answer the question "Do you feel your foods tasty?", so we judged this item inappropriate and deleted it from the analysis. Fifteen items, including 5 scales showed satisfactory internal consistency and construct validity in correlation and factor analyses. Performance status showed a low correlation between each item, each scale and the global scale, while SDS and STAI showed an inordinately negative correlation with the fundamental and physical scales. Especially, SDS revealed an extremely close correlation with the active scale, and STAI showed an excessive correlation with the psychological scale. In the time course of QOL under chemotherapy, reductions (aggravations) were observed in both the total score of 15 items and global scale within one week postoperatively, but after that recovered to preoperative levels at 2 weeks postoperatively. A tendency to QOL improvement was observed 2 weeks after starting chemotherapy or chemoimmunotherapy. QOL of 13 patients was measured over 3 months, and the longest term was 8 months. The results suggested that this QOL questionnaire has sufficient reliability and validity to be usable for patients with colorectal cancer in the surgical area and that this model is applicable for long-term QOL surveys and frequent measurement.

Adult↗