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Biomedical subjects

M Itoh

Publications and source records attributed to M Itoh.

At least 613 records · Page 34Linked to original sources

Hypoglossal afferents to lamina I neurons of the cervical spinal cord projecting to the parabrachial nucleus in the cat.

Attempts were made to determine the hypoglossal sensory inputs to the parabrachial nucleus (PBN) through the spinal cord. Wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) was injected into the cat hypoglossal nerve. HRP-labeled fibers, predominantly derived from the glossopharyngeal and vagal nerves, were observed to terminate in lamina I of the upper cervical spinal cord. A few fibers were also distributed to laminae IV-V and VII-VIII ipsilaterally. WGA:HRP injection into the lateral portion of the PBN also resulted in retrograde labeling in lamina I with ipsilateral predominance. Light-microscopic data raised the possibility of a relay of hypoglossal sensory information to the PBN in lamina I of the cervical spinal cord. In order to confirm the spinal relay, electron-microscopic observations were carried out on lamina I of C1 spinal cord after sectioning of the hypoglossal nerve and WGA:HRP injection into the lateral portion of the PBN on the same side in each animal. It was of particular interest that degenerated hypoglossal afferent fibers made synaptic contacts with lamina I neurons, which were retrogradely labeled with HRP.

Afferent Pathways↗

[The efficacy of endopyeloureterotomy via a transpelvic extraureteral approach].

To evaluate the efficacy of endopyeloureterotomy via a transpelvic extraureteral approach for the treatment of ureteropelvic junction obstruction or upper ureteric stenosis, we analysed the results of 85 patients treated with this procedure between Aug. 1988 and June 1993. Eighty-five patients underwent 87 procedures. Each patient has been followed-up more than 6 months postoperatively. Of 87 procedures, 71 were performed in patients with ureteropelvic junction obstruction and 16 were in patients with stenosis of the upper third ureter. Primary disease was 59 and secondary disease was 28. Twenty-one procedures were performed in patients with the stenotic segment over 2 cm. The operative procedure was performed by first incising with a 22 Fr. urethrotome (ACMI Co.); the dilated renal pelvic or ureteral wall posterolaterally as long as 1-1.5 cm junction from the stenotic segment toward ureteropelvic junction, then bringing the urethrotome out retroperitoneally through the incision and finally incising the stenotic segment with the cold knife under direct vision. A 12-16 Fr. PTCS tube (Sumitomo Behkuraito Co.) was left in place for 3 weeks as a stent. Mean operative time was 101 min and average length of incised segment was 3.7 cm. Complication included pneumothorax (1 case), pseudo ureter (1 case) and renal arterial anexryma (1 case). Followed-up period ranged from 6 to 64 months with the average being 26 months. Of 87 procedures, 80 (92%) achieved a disappearance or improvement of the obstructive change and 7 failed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Treatment with triiodothyronine (T3) against multinodular goiter fails to prevent the onset of Graves' disease.

We report two cases who developed hyperthyroidism and positive thyroid stimulating antibody (TSAb) while they were treated with T[3] under the diagnosis of follicular adenoma of thyroid for four or eleven years, respectively. In both cases thyroid scintigraphy revealed an increased radioiodine uptake with multinodular defects. The uptake of 131I was not suppressed by the administration of T[3]. Histological examination showed encapsulated nodule surrounded by diffuse hyperplasia. TBII or TSAb appeared in accordance with increased plasma levels of T[3] and T[4]. In spite of suppressed TSH the appearance of TSAb and subsequent manifestations of Graves' disease suggested that T[3] failed to prevent the immune mechanism which was involved in the production of TSAb.

Journal Article↗

[Severe hyperbilirubinemia after cisplatin-based chemotherapy].

Cisplatin is the most effective and widely used anti-cancer drug for ovarian cancer. We report 2 cases with severe hyperbilirubinemia after cisplatin-based chemotherapy. Case 1 was a 67-year-old woman with stage IV ovarian cancer. After operation, she had 2 courses of chemotherapy consisting of cisplatin (90 mg) and cyclophosphamide (550 mg). The regimen was changed to low-dose consecutive cisplatin (10 mg/day, day 1-day 5) because of her ileus and poor performance status. After 2 courses of cisplatin alone, her total bilirubin was elevated to 19.1 mg/dl. She died of respiratory distress. At autopsy, chronic cholangiolitis with intrahepatic bile stasis were noted. Case 2 was a 60-year-old woman with stage IIIc ovarian cancer. After operation she was treated with carboplatin (383 mg/day, day 1) and cisplatin (102 mg/day, day 3). One month after completing the first chemotherapy, her bilirubin elevated to 20.5 mg/dl. It took 3 months to normalize the serum bilirubin with steroid administration. During the second course using the same regimen as in the first course, the bilirubin elevated again. Cisplatin was suspected to be the drug inducing her hyperbilirubinemia. She was consecutively treated with carboplatin alone and the bilirubin did not elevate. Both cases had blood transfusion and intravenous hyperalimentation. It is difficult to disregard the effect of other drugs and therapy. In case 2, her bilirubin elevated repeatedly after cisplatin administration. Cisplatin may thus be the drug which induces the liver dysfunction.

Aged↗

Role of mucus in gastric mucosal injury induced by local ischemia/reperfusion.

The role of gastric mucus was evaluated in a rat model of gastric epithelial damage induced by local ischemia/reperfusion (I/R) stress. In this model, blood-to-lumen chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) clearance served as an index of injury. Tetraprenyl acetone (TPA; 100 mg, 200 mg/kg IP) was used to stimulate mucus production. Administration of TPA increased both the hexosamine content in gastric tissue and the amount of alcian blue-periodic acid Schiff (AB-PAS) stained mucus in the mucosa in a dose-dependent manner. Increases in 51Cr-EDTA clearance induced by I/R were significantly attenuated by TPA in a dose-dependent manner. N-acetyl-L-cysteine (NAC; 0.6%, 0.8%) was perfused into the gastric lumen to assess the effect of reduction in mucus on the injury induced by I/R. Although mean values of hexosamine content were increased by perfusion with NAC, AB-PAS-stained mucus in the mucosa was significantly decreased in a dose-dependent manner. Perfusion of NAC did not change basal 51Cr-EDTA clearance but significantly exacerbated the increase in clearance induced by I/R in a dose-dependent manner. These results indicate that gastric mucus protects the gastric mucosa against I/R stress in vivo.

Acetylcysteine↗

[Studies on SY5555 in the field of pediatrics].

SY5555, a new oral penem, in the form of dry syrup (powder which is dissolved before use) was evaluated for its pharmacokinetics and clinical efficacy in pediatric patients. Oral administration of 5 mg/kg and 10 mg/kg of SY5555 in dry syrup resulted in respective maximum plasma concentrations of 1.08 +/- 0.38 micrograms/ml (n = 4) and 2.50 +/- 1.81 micrograms/ml (n = 4), half-lives (T 1/2) of 2.72 +/- 1.86 hours (n = 3) and 1.14 +/- 0.88 hours (n = 4), and urinary excretion until 6 hours of 4.7% (n = 1) and 3.86 +/- 2.01% (n = 4). Clinical efficacy was evaluable in 22 patients, and the overall efficacy rate was 100%. As for bacteriological efficacy, all 5 strains of pathogenic organisms identified were eradicated (eradication rate, 100%). No remarkable adverse reactions or abnormal laboratory values were observed.

Administration, Oral↗

[In vivo visualization of neurotransmitter function in the human brain by PET].

Measurement of cerebral blood flow and energy metabolism using PET with 15O and 18F labeled tracers allows quantitative evaluation of cerebral metabolism that can be perturbed in pathological states. Neurotransmission is a new target that is visualized by labeling of substrates of enzymes that are involved in neurotransmitter synthesis or degradation. Neuronal receptors are mapped by introducing the labeled ligands that are specifically bound to the receptors in question. We developed unique tracers that label dopamine D2 or histamine H1 receptors. With other available ligands for the muscarinic cholinergic receptors and [18F] fluorodopa, we started clinical investigations to document the state of neurotransmission in patients with epilepsy, Parkinson's disease and dementia. Using [11C] doxepin we observed an increase of H1 receptors in the epileptic foci that showed decreased glucose metabolic rate at the interictal phase. This phenomenon is compatible with reported increase of mu opiate receptors in the brains of epileptic patients. Brain uptake of FDOPA (Ki), calculated by the graphical plot was found relatively stable with age both in the normal population and dementia patients. However, the striatal Ki of FDOPA of severely demented patients significantly reduced, compared with the normal aged subjects. The correlation analysis between FDOPA Ki and severity of dementia as assessed by mini-mental state examination revealed a significant reduction of Ki associated with the disease progression. Increase in D2 receptor density as assessed by the uptake of YM 09151-2 was observed in cases with reduced FDOPA uptake, which may correspond to the state of supersensitivity of the D2 receptors.

Brain↗

Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates.

Twenty-four edible plants were investigated for the presence of melatonin, heretofore considered to be a molecule found only in the animal kingdom. The amount of melatonin in different plants varied greatly with highest melatonin being present in plants of the rice family. Melatonin was identified by radioimmunoassay and verified by high performance liquid chromatography with fluorescence detection. Feeding a diet containing plant products rich in melatonin to chicks increased radioimmunoassayable levels of melatonin in their blood. Likewise, melatonin extracted from plants inhibited binding of [125I]iodomelatonin to rabbit brain. Thus, melatonin ingested in foodstuffs enters the blood and is capable of binding to melatonin binding sites in the brain of mammals.

Animals↗

Effect of kanji and kana reading on cerebral blood flow patterns measured by PET.

To investigate the respective functions of pathways in processing visual information from different types of symbols, by positron emission tomography (PET) we examined the effect on cerebral blood flow (CBF) of reading the Japanese morphogram (kanji) versus the syllabogram (kana). Nine Japanese men were presented with three visual conditions in random order 2 minutes before the scan: eyes open controls, kanji morphogram reading, and kana syllabogram reading. Three words written in kanji or kana were shown, and subjects were instructed to read them silently and to identify the word unrelated logically to the other two. The reading and analyzing tasks activated wide areas of vision-related cortices. The comparison of the kanji and kana readings showed higher metabolism, with the former only in the posterior part of the primary visual cortex. Most of the CBF increases were common for both stimuli, although the patterns of these increases differed slightly. The correlation matrix of CBF change in the left hemisphere showed a ventral connection in kanji reading and a dorsal connection in kana reading. Our results suggest there is a functional differentiation in the brain between patterned and sequential perception when reading Japanese morphograms and syllabograms.

Adult↗

Surgery for complications of chronic obstructive lung disease.

Chronic obstructive lung disease (COLD) is a clinical entity characterized by chronic airway obstruction that includes pulmonary emphysema and chronic bronchitis with airway obstruction. Although most complications are treated medically, there are a few cases in which medical treatment is not effective and surgical treatment is necessary. Most complications of COLD requiring surgical treatment are those associated with bullous emphysema, such as pneumothorax, lung carcinoma associated with bulla, and infection of bulla. In this article, the indications, practical aspects, and problems and risks of surgical treatment for complications of COLD are discussed.

Humans↗

Mode of inflammatory cell infiltration in testes of mice injected with syngeneic testicular germ cells without adjuvant.

We previously established an experimental model for autoimmune inflammation of the testis in mice by active immunisation with viable syngeneic testicular germ cells without the use of adjuvants. In the present study, the mode of spread of the inflammation was investigated histologically to determine vulnerable sites for the inflammatory cell infiltration. The results showed that lymphocytic infiltration first appeared in the tunica albuginea adjacent to the tubuli recti and the rete testis. In the next stage, infiltration with lymphocytes, macrophages, polymorphonuclear leucocytes and plasma cells occurred around the tubuli recti and subsequently a mixture of these cells spread centrifugally to the peripheral interstitium of the testis with persistent involvement of the region of the tubuli recti and the tunica albuginea. In the final stage, the inflammatory cells invaded the tubules. However, even in cases with the most severe testicular inflammation, the interstitium in the rete testis region showed only slight inflammatory changes, and no inflammation was seen in the ductuli efferentes, the epididymis or the vas deferens.

Animals↗

Positron emission tomographic study of central histamine H1-receptor occupancy in human subjects treated with epinastine, a second-generation antihistamine.

Histamine H1-receptor occupancy in the human brain was measured in healthy young volunteers by positron emission tomography (PET) using [11C]doxepin. d-Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 +/- 4.2% of the averaged values of available histamine H1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Epinastine, a non-sedative antihistamine, occupied 13.2 +/- 18.5% of the available H1 receptors in the human frontal cortex after its administration in a single oral dose of 20 mg. There was significant correlation between H1 receptor occupancy by epinastine and its plasma concentration in each subject. PET data on the human brain were essentially compatible with those on H1-receptor occupancy in the guinea pig brain as determined by an in vivo binding technique, although for the same H1-receptor occupancy, the dose was less in humans than in guinea pigs. Our PET studies demonstrated that receptor occupancy by a second-generation H1 antagonist, epinastine, was less than 20% of the total H1 receptors, and that the low receptor occupancy was closely related to the low incidence of central side effects.

Adult↗

Role of endogenous acid in gastric mucosal injury induced by local ischemia-reperfusion in the rat.

The role of endogenous acid was evaluated in a rat model of gastric epithelial damage induced by local ischemia-reperfusion (IR). Because no gross lesion was induced in this model, the damage was quantified by measuring the blood-to-lumen [51Cr]EDTA clearance. A proton pump inhibitor (omeprazole) or an H2-receptor antagonist (T-593) was used to suppress luminal acidity from pH 5 to pH 6.3-7.0. Both drugs significantly attenuated the increase in clearance induced by IR, indicating an important role for endogenous acid. A second series of experiments was performed to confirm whether the change in pH from around 5 to 7 was sufficient to reduce IR-induced gastric mucosal damage. Phosphate-buffered saline was perfused into the gastric lumen to neutralize the endogenous luminal acid. Although the luminal acid was completely neutralized, no reduction in clearance was observed. These data indicate that endogenous luminal acid does not play an important role in gastric injury induced by local IR stress and that a proton pump inhibitor or H2-receptor antagonist may suppress IR injury by a mechanism other than reducing luminal acidity, i.e., reducing consumption of ATP needed for acid secretion, thereby improving gastric mucosal energy metabolism.

Animals↗

Specific interaction of the CD45 protein-tyrosine phosphatase with tyrosine-phosphorylated CD3 zeta chain.

The CD45 transmembrane protein-tyrosine phosphatase (PTPase, EC 3.1.3.48) plays an essential role in T-cell activation by activating the Lck and/or Fyn protein-tyrosine kinases. However, numerous experiments have indicated that CD45 may have both stimulatory and inhibitory roles in T-cell activation. Thus, it is unlikely that the two kinases are the sole substrates of the CD45 PTPase. Furthermore, the complex regulation of the alternative splicing of the extracellular domain in various leukocyte lineages also suggests additional roles for the CD45 PTPase. To identify such functions, it is necessary to identify physiologically relevant substrates of the CD45 PTPase other than the two protein-tyrosine kinases. To this end, we searched for high-affinity substrates of the CD45 PTPase among the tyrosine-phosphorylated T-cell proteins by using purified glutathione S-transferase-CD45 fusion molecules. The enzymatically inactive CD45 C828S mutant protein, in which the cysteine residue at the catalytic center was changed to a serine residue, bound tightly to the phosphorylated CD3 zeta chain. This binding was specific to CD45 PTPase, as neither the leukocyte common antigen-related molecule (LAR) PTPase nor the CD45-LAR hybrid PTPases bound the phosphorylated CD3 zeta chain. Furthermore, phosphorylated CD3 zeta chain was preferentially dephosphorylated by the wild-type CD45 PTPase under conditions that did not significantly dephosphorylate other cellular proteins. Thus, the phosphorylated CD3 zeta chain is a specific and high-affinity substrate of the CD45 PTPase. These results suggest that CD45 is involved in the termination of the T-cell response via dephosphorylation of CD3 zeta chain.

CD3 Complex↗

Functional anatomy of taste perception in the human brain studied with positron emission tomography.

Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) in 10 normal volunteers with the purpose of measuring rCBF changes related to taste physiology. Discrimination of 0.18% saline from pure water was associated with significantly increased rCBF values in the thalamus, the insular cortex, the anterior cingulate gyrus, the parahippocampal gyrus, the lingual gyrus, the caudate nucleus, and the temporal gyri. The results indicate that rCBF changes in these structures may reflect oral exposure to salt.

Adolescent↗

Molecular cloning of murine BST-1 having homology with CD38 and Aplysia ADP-ribosyl cyclase.

Human BST-1, a bone marrow stromal cell surface antigen, is a glycosyl-phosphatidylinositol-anchored protein that facilitates the growth of pre-B cells. We report here the molecular cloning of murine BST-1 cDNA. The deduced amino acid sequence of murine BST-1 had 71% similarity with human BST-1 and 30 and 25% similarity with CD38 and Aplysia adenosine diphosphate-ribosyl cyclase, respectively. Murine BST-1 mRNA was expressed in the bone marrow, spleen and thymus in lymphoid organs, and the lung, kidney and heart in non-lymphoid organs. Restriction fragment length polymorphism (RFLP) was shown in BALB/c, DBA/2 and NZB vs C57BL/6, A/J, CBA/N, NZW, BXSB and MRL/lpr. RFLP was mapped to the 5' portion of the murine BST-1 gene.

3T3 Cells↗

Multi-focal metabolic disturbances in human brain after cerebral infarction studied with 18FDG and positron emission tomography.

We measured cerebral metabolic rates for glucose (CMRGlc) in the remote brain areas of 7 patients, who were affected by unilateral cortical infarction, at a chronic stage using 2[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography. There were significant decreases of CMRGlc compared with each control value (p < 0.01), not only in the cerebral cortex directly damaged by the ischaemic insult, but also in the ipsilateral thalamus and in the contralateral cerebellum, areas in which no lesions had been detected by MRI or CT scan. The present study indicates that different mechanisms may be responsible for multi-focal metabolic disturbances in the remote areas after stroke. We suggest that these multi-focal brain dysfunctions may exacerbate clinical symptoms at a chronic stage of stroke.

Adult↗