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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 469 records · Page 26Linked to original sources

Polyethylene glycol superoxide dismutase and catalase attenuate increased blood-brain barrier permeability after ischemia in piglets.

BACKGROUND AND PURPOSE: Transport of urea across the blood-brain barrier is increased during postischemic cerebral reperfusion in the piglet. Ischemia/reperfusion also has been observed to increase apparent superoxide anion generation on the surface of the brain. The present study was designed to address the hypothesis that the increased transfer of urea into the brain after ischemia/reperfusion could be due to superoxide anion-induced alterations in blood-brain barrier permeability. METHODS: Blood-to-brain transfer of carbon-14-labeled urea was measured in four groups (n = 7 each) of newborn pigs: 1) control (no ischemia, no pretreatment), 2) pretreatment with polyethylene glycol superoxide dismutase (1,000 IU/kg) and polyethylene glycol catalase (10,000 IU/kg i.v.) but no ischemia, 3) no pretreatment and 20 minutes of ischemia followed by 2 hours of reperfusion, and 4) pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase in addition to ischemia/reperfusion. The following brain regions were investigated: cerebrum, caudate, midbrain, pons, medulla, and cerebellum. RESULTS: Polyethylene glycol superoxide dismutase inhibited generation of superoxide anion by the brain during reperfusion after ischemia. Regional transfer of [14C]urea from blood to brain increased at 2 hours' reperfusion. This ischemia-induced increase in blood-to-brain transfer of [14C]urea was attenuated by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase: e.g., cerebrum Kin was 28 +/- 2 in the control group, 26 +/- 3 in the pretreated/no ischemia group, 67 +/- 5 in the untreated/ischemia group, and 40 +/- 2 ml.g-1.s-1.10(6) in the pretreated/ischemia group. After ischemia/reperfusion, cerebral blood flow was unchanged by pretreatment with polyethylene glycol superoxide dismutase and polyethylene glycol catalase. CONCLUSIONS: These data suggest that production of a partially reduced species of oxygen contributes to the increased urea transfer across the blood-brain barrier after ischemia in the newborn pig.

Animals↗

Alterations in cerebrovascular reactivity after positive pressure ventilation.

Pressure ventilation of the newborn can adversely affect the cardiovascular system. Increasing airway pressure increases cerebral venous pressure, thus stressing brain vasculature. To test the hypothesis that cerebral venous distension caused by mechanical ventilation alters cerebral microvascular responses, we studied cerebrovascular responses before, during, and after positive pressure ventilation. Anesthetized newborn pigs were ventilated with a standard time-cycled, pressure-limited infant respirator. Pial arterioles were measured in response to hypercapnia, topical isoproterenol, and topical norepinephrine during control [mean airway pressure (Paw) = 0.9 +/- 0.05 kPa (4.8 +/- 0.3 cm H2O)] conditions, during 40-60 min of increased Paw [2.5 +/- 0.2 kPa (13.9 +/- 1.3 cm H2O)], and when the Paw was lowered again. Pial arteriolar dilation in response to hypercapnia was not changed by increasing Paw. Similarly, responses to isoproterenol and norepinephrine were unaltered during raised Paw. However, a significant decrease in responses to topical isoproterenol and norepinephrine was observed after increased Paw. These experiments show that specific prostanoid-independent cerebrovascular responses are altered subsequent to pressure ventilation, whereas prostanoid-dependent dilation to hypercapnia was not affected. These changes suggest that the newborn cerebral vasculature is affected by positive pressure ventilation, further raising the possibility that ventilation-induced alterations in microvascular responses could make the brain more vulnerable to added stresses after pressure ventilation.

Animals↗

[Effects of FRG-8813, a new type histamine H2-receptor antagonist, on various experimental gastric and duodenal lesions in rats].

We examined the anti-ulcer effects of FRG-8813, a new type histamine H2-receptor antagonist, on various experimental gastric and duodenal lesions in rats. FRG-8813, administered orally, inhibited the formation of lesions dose-dependently in experimental models with the exception of the Shay ulcer model. The anti-ulcer potency of FRG-8813 was 4 approximately 10 times greater than that of cimetidine when the ED50 values of both compounds were compared. Famotidine and cimetidine inhibited lesion formation at higher doses than the anti-secretory doses. The anti-ulcer action of FRG-8813, however, appeared at even lower doses than those of anti-secretory action. These results suggest that FRG-8813 is able to prevent lesion formation with anti-secretory action plus other mechanisms unlike typical histamine H2-receptor antagonists.

Acetamides↗

[Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing of gastric and duodenal ulcer in rats and spontaneously ulcerative mice].

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.

Acetamides↗

Cytological mapping of Om mutants of Drosophila ananassae.

Semidominant, optic morphology (Om) mutants in Drosophila ananassae have been genetically mapped to at least 25 loci throughout the genome (Hinton, 1984; 1988). Among them, four X-linked Om mutants were proved to be associated with the insertion of a transposable element, tom (Shrimpton et al., 1986; Tanda et al., 1988). In the present study, cytological mapping of autosomal Om mutants was carried out by in situ hybridization to polytene chromosomes using a cloned tom element as a probe. The cytological site for each autosomal Om mutant has been determined to a single band of the salivary gland chromosomes.

Animals↗

Blood flow dependence of local capillary permeability of Cr-EDTA in the rabbit skeletal muscle.

To examine direct influences of capillary blood flow on its permeability of water-soluble substances, we measured the local capillary permeability in the rabbit tenuissimus muscle at various capillary blood flow levels by the use of microscopic tissue clearance method. After staining the muscle with Cr-EDTA (M.W.: 341) as the test tracer by suffusing its solution around the tissue, subsequent concentration change in the tissue due to the tracer washout by capillary blood flow was measured from the intensity change on the TV monitor through the vital-microscope. The decay constant of obtained tissue clearance curve has been theoretically predicted to be equal to the local capillary permeability surface area product (PS) per unit tissue volume (Vt). The local capillary permeability (P) could be quantified by calculating the capillary surface area (S) from the perfused capillary density in the visualized microscopic field. The calculated values of P and PS/Vt in the high flow state were 6.00 +/- 0.70 (X 10(-6) cm/s) and 5.85 +/- 0.77 (X 10(-4)/s), respectively, which were significantly larger than those in the low flow state (p < 0.01). It was suggested that there was a mechanism in the red cell passage through the capillary which facilitated the substance exchange across the capillary wall.

Animals↗

[Masticatory training with chewing gum on young children].

Mastication is a developmental function. It matures through learning experiences. The biting force is one of the components of masticatory function. The biting force increases with age. During the developmental stage, it is believed feasible to enhance the maturation of the masticatory function by increasing the biting force. The previous results of masticatory training for adults and school children had revealed 20% to 30% increase of the biting force. In this study, masticatory training with specially fabricated chewing gum for young (preschool) children was performed. The subjects were 5 males and 5 females from 3 years old to 5 years old. These children were instructed to bite on the chewing gum for 5 minutes, 2 times a day, for 3 months. The results show that there was a 94% average increase of biting force after 3 months of training. It was also noted that the rate of the increase of the biting force was remarkable during the first month of training.

Age Factors↗

Prophylactic oral acyclovir in outbreaks of primary herpes simplex virus type 1 infection in a closed community.

Oral acyclovir was given prophylactically to 37 children in the early stages of three outbreaks of herpes simplex virus type 1 (HSV-1) infection and the results were compared with those in untreated control subjects in two other outbreaks. The rates of seroconversion to HSV were significantly reduced in children treated with acyclovir compared with control subjects (91% vs 27%, P less than .001). The incidence of symptomatic disease was also significantly reduced (82% vs 0%, P less than .001). In some children receiving prophylactic acyclovir, anti-HSV antibody titers did not rise despite the presence of replicative HSV on throat swabs just before the start of treatment. Restriction endonuclease analysis of isolated HSV-DNA confirmed that one strain was responsible for the five outbreaks. No resistance to acyclovir was detected during the study, and no adverse effects of treatment were noted. In conclusion, short-term prophylactic acyclovir may limit the spread and reduce clinical manifestations of HSV infections in closed communities, although this use should be restricted to communities where severe symptoms are observed.

Acyclovir↗

Relapse of herpes simplex encephalitis in children.

The polymerase chain reaction method was used to diagnose herpes simplex encephalitis in children. Initial samples of cerebrospinal fluid from 15 patients with herpes simplex encephalitis were all positive for the herpes simplex virus DNA by polymerase chain reaction assay. In terms of early diagnosis, polymerase chain reaction assay became positive significantly earlier than the detection of intrathecally produced anti-herpes simplex virus antibody using the enzyme-linked immunosorbent assay (4.4 vs 8.9 days after onset; P less than .01). Serial examinations showed that the presence of virus DNA in cerebrospinal fluid continued for 3 to 18 days after the neurologic onset (mean 10.1 days). Four of the 15 patients had a relapse of encephalitis after completing acyclovir therapy. The mean duration of initial acyclovir therapy in the recurrent group was significantly shorter than that in the nonrecurrent group. In recurring cases, herpes simplex virus DNA reappeared temporarily in the cerebrospinal fluid of two patients. These results show that polymerase chain reaction assay is a useful diagnostic tool for the early and noninvasive diagnosis of herpes simplex encephalitis in children. Results also suggest that a comparatively short duration of acyclovir therapy may be related to a relapse of herpes simplex encephalitis in some children.

Acyclovir↗

[A case of bilateral panophthalmoplegia caused by paranasal malignant lymphoma extending into the skull base].

A case of bilateral panophthalmoplegia developed after paranasal malignant lymphoma is described, and previously reported cases are reviewed. A 74-year-old female was hospitalized with the chief complaints of bilateral ptosis and bilateral deep orbital pain that had developed over a 10-day period. Neurological examination revealed bilateral dilated pupils, panophthalmoplegia, and hypalgesia in the area of the ophthalmic nerve on both sides. Laboratory studies and endocrinological examination were free from abnormal findings. Skull X-ray films showed a soft tissue lesion in the sphenoidal and ethmoidal sinus and this was associated with bony structure destruction in the surrounding area. Computed tomography demonstrated a heterogeneously enhanced mass lesion in the paranasal sinus extending into the intrasellar region and bilateral cavernous sinus. Meticulous investigation has so far revealed no distant lesions either in the thoracic or abdominal lesions. Subtotal tumor resection was undergone via the transsphenoidal route at which time tumor extension into the nasal cavity and sellar floor destruction were confirmed. Diffuse and mixed B-cell type malignant lymphoma was the pathological diagnosis. Postoperatively, improvement of abnormalities of pupils, panophthalmoplegia, and ptosis was achieved but this was only transient. Despite focal radiation therapy and repeated chemotherapy, the patient died 14-months after the diagnosis was made. On reviewing the literature, it is shown that the incidence of bilateral panophthalmoplegia among patients who develop disturbance of ocular movement is extremely low (0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A case report of multiple bone metastases of breast carcinoma effectively treated with mild chemo-endocrine therapy].

A woman with multiple bone metastases three years after radical mastectomy for right breast carcinoma was admitted to the Department of Radiology, National Hakodate Hospital. She underwent radiotherapy for the metastasis of the seventh cervical vertebra, and her back pain decreased. Six courses of combination chemotherapy were undertaken using MTX, CPM, 5-FU, VCR and predonine, but her multiple bone metastases progressed. Then, she was treated with chemo-endocrine therapy which consisted of tamoxifen 30 mg daily and CPM 100 mg daily given orally. Two months later, UFT 400 mg daily was administered instead of CPM. This therapy has been effective for 8 years, and she has remained alive and well. On bone scintigram, the abnormal radioisotope uptake almost disappeared. Also, X-ray film showed no osteolytic change and no destruction of bone. These results suggest that it is important to select a suitable combination of drugs for each patient with advanced breast carcinoma.

Administration, Oral↗

Human recombinant tumor necrosis factor and interferon affect the activity of neurons in the organum vasculosum laminae terminalis.

It is generally thought that fever is induced by blood-borne cytokines via an action on hypothalamic thermosensitive neurons. Recent studies suggest that the organum vasculosum laminae terminalis (OVLT), which lacks the blood-brain barrier, may be necessary for fever induction by systemic pyrogens. We have examined the responses of neurons in the OVLT to the pyrogenic cytokines, human recombinant tumor necrosis factor alpha (TNF) and interferon alpha 2 (IFN), by recording extracellular single-units in brain slice preparations from guinea pigs. Of all the OVLT neurons tested with TNF (900-5000 ng/ml perfusate/min) and IFN (1200-8500 units/ml perfusate/min), administered for 2.5 min, 44% increased their firing rates (FR) for 30.6-57.5 min (average, 47.4 min) with onset latencies of 6.1-9.8 min (average, 7.9 min). The remaining 56% of the neurons did not change their FR after TNF or IFN. Carrier vehicles for these cytokines produced no FR change. The results suggest the possibility that the OVLT may be a site where chemical signals of blood-borne cytokines are transduced into neuronal signals.

Animals↗

Phosphorylation of keratin intermediate filaments by protein kinase C, by calmodulin-dependent protein kinase and by cAMP-dependent protein kinase.

Keratins, constituent proteins of intermediate filaments of epithelial cells, are phosphoproteins containing phosphoserine and phosphothreonine. We examined the in vitro phosphorylation of keratin filaments by cAMP-dependent protein kinase, protein kinase C and Ca2+/calmodulin-dependent protein kinase II. When rat liver keratin filaments reconstituted by type I keratin 18 (molecular mass 47 kDa; acidic type) and type II keratin 8 (molecular mass 55 kDa; basic type) in a 1:1 ratio were used as substrates, all the protein kinases phosphorylated both of the constituent proteins to a significant rate and extent, and disassembly of the keratin filament structure occurred. Kinetic analysis suggested that all these protein kinases preferentially phosphorylate keratin 8, compared to keratin 18. The amino acid residues of keratins 8 and 18 phosphorylated by cAMP-dependent protein kinase or protein kinase C were almost exclusively serine, while those phosphorylated by Ca2+/calmodulin-dependent protein kinase II were serine and threonine. Peptide mapping analysis indicated that these protein kinases phosphorylate keratins 8 and 18 in a different manner. These observations gave the way for in vivo studies of the role of phosphorylation in the reorganization of keratin filaments.

Amino Acids↗