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T Chiba

Publications and source records attributed to T Chiba.

At least 19 recordsLinked to original sources

Functionally essential cytoplasmic domain of the erythropoietin receptor.

The cytoplasmic domains of the erythropoietin receptor essential for signal transduction were identified by assessing a series of truncated and deletional mutant receptors. A 91-amino acid region proximal to the transmembrane domain was required for growth signaling. In this region, residues between 353Pro and 362His and between 278Gln and 308Leu appeared to constitute the essential cytoplasmic domains. These two domains contain the conserved amino acids common in the cytokine receptor superfamily, which indicates that these domains in the cytoplasmic regions of the erythropoietin receptor may be important for interaction with common signal transducers or protein tyrosine kinases.

Amino Acid Sequence

Determination of flavin contents in neutrophils by a sensitive chemiluminescence assay: evidence for no translocation of flavoproteins from the cytosol to the membrane upon cell stimulation.

A sensitive and specific chemiluminescence (CL) method with bacterial luciferase was adapted for accurate measurement of the flavins FAD and FMN in the membrane and cytosolic fractions of neutrophils prepared from pig and human blood. The FAD and FMN contents (FAD/FMN = 100:2) in the membranes were essentially the same in resting (R) and myristate-stimulated (S) cells, although O2(-)-generation was markedly enhanced exclusively in S membranes. The O2(-)-forming activity of S samples remained unchanged or even increased after washing the membranes with buffer, although one-third of the FAD was lost during washing (a decrease from 140 to 95 pmol/10(8) cell-equivalent (CE) during washing). The cytosol is known to contain at least three components that are essential for O2- production (p47-phox, p67-phox, and a G-protein), and that are translocated to membranes upon activation, but its flavin content was one tenth of that of the membranes. The cytosol was treated with fatty acids in the absence of membranes to induce substantial precipitation of p47-phox, p67-phox and a protein of 32 kDa. No difference relative to a solvent-control was noted in the low flavin content of the precipitate indicating that these cytosolic components are not flavoproteins. These results do not support the possibility of translocation of a cytosolic flavoprotein to the membrane upon activation of the respiratory burst.

Animals

Tryptophan residue of Trp-Ser-X-Trp-Ser motif in extracellular domains of erythropoietin receptor is essential for signal transduction.

The Trp-Ser-X-Trp-Ser motif commonly exists just outside the transmembrane domains of all cytokine receptors so far isolated. The role of this conserved motif in erythropoietin receptor was examined by assessing a series of mutant receptors on erythropoietin-induced signal transduction. Replacement of one of the two conserved Trp residues in the motif to Gly was found to completely abolish the binding of erythropoietin to the receptor and also to lose the ability to transduce the factor-dependent growth signal. While the mutants with one Ser residue converted to Gly or Ala retained full biological activities, the replacement of both conserved Ser residues diminished the functions of the receptor. Furthermore, the receptors lacking a part or all of the Trp-Ser-X-Trp-Ser motif did not respond to erythropoietin. The Trp-Ser-X-Trp-Ser motif, especially Trp residue, located in extracellular domains of the erythropoietin receptor thus appears to play a critical role in receptor-mediated signal transduction.

Amino Acid Sequence

Calcitonin inhibits the growth of human gastric carcinoma cell line KATO III.

Calcitonin has a wide variety of actions on gastrointestinal function. In this study, we investigated the effects of calcitonin on the growth of human gastric carcinoma cell line KATO III in comparison with those of calcitonin gene-related peptide (CGRP). Calcitonin, but not CGRP, significantly and dose-dependently inhibited the growth of KATO III cells. This inhibition of cell growth was accompanied by an increase in cyclic AMP production. The proliferation of KATO III cells was also inhibited by forskolin and dibutyryl cyclic AMP, although agents which do not stimulate cyclic AMP production had no effect. Furthermore, in the presence of GTP, calcitonin stimulated adenylate cyclase activity in KATO III cell membranes, and this increase was reduced in the absence of GTP. On the other had, neither calcitonin nor CGRP enhanced the turnover of inositolphospholipid or the intracellular Ca2+ level. In addition, 125I-labeled human calcitonin was specifically bound to KATO III cell membranes, and this binding was dose-dependently displaced by unlabeled calcitonin but not CGRP. Furthermore, the specific binding of 125I-labeled human calcitonin to KATO III cell membranes was significantly reduced by addition of GTP but not ATP. These results suggest that calcitonin inhibits the growth of human gastric carcinoma cell line KATO III by stimulating cyclic AMP production via a GTP-dependent process coupled to specific calcitonin receptors.

Adenylyl Cyclases

Effects of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide (CGRP) on glucose metabolism in the rat.

In this study, we compared the effects of islet amyloid polypeptide (IAPP) and calcitonin gene-related peptide (CGRP) on glucose metabolism both in vivo and in vitro in the rat. Intravenous injection of rat CGRP caused a significant increase in plasma glucose concentration with a simultaneous increase in plasma insulin levels, whereas neither IAPP-NH2 nor IAPP-COOH had any effect. Moreover, intravenous infusion of CGRP decreased tolerance to intragastric administration of glucose (O-GTT) without altering plasma insulin levels, but again IAPPs had no effect. On the other hand, 125I-[Tyr0]rat CGRP specifically bound to the liver plasma membrane, and not only CGRP but also IAPP-NH2 dose-dependently displaced the specific binding of 125I-[Tyr0] CGRP, whereas IAPP-COOH had no effect. Conversely, CGRP as well as IAPP-NH2 but not IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by a CGRP receptor antagonist, human CGRP-I(8-37). However, neither CGRP nor IAPP-NH2 had any effect on glucose production in rat isolated hepatocytes. These results suggest that (1) IAPP-NH2 but not IAPP-COOH induces adenylate cyclase activation via CGRP receptors on rat liver plasma membranes, and (2) CGRP might not involve its action on the liver in the changes of glucose metabolism.

Amyloid

Cell proliferation kinetics of human gastric carcinoma: an immunohistochemical study with a monoclonal antibody against DNA polymerase-alpha.

Cell proliferation kinetics of human gastric carcinoma were studied immunohistochemically using a monoclonal antibody against DNA polymerase-alpha (Pol-alpha). The distribution patterns and percentages of proliferative cells were examined in cases with various histological types of gastric carcinoma and compared with those of normal epithelium of the gastric foveolae. Pol-alpha-positive epithelial cells were localised at the isthmus of the normal foveola, while Pol-alpha-positive cancer cells were distributed irregularly in the cancer nests. The percentage of Pol-alpha-positive cells (%PPC) was significantly higher in the carcinoma [mean (S.D.) 41.6 (12.9)%] than in the normal foveola [24.8 (6.4)%] (P < 0.01). Also, the intestinal-type carcinoma showed a relatively higher %PPC [44.9 (12.0)%] than the diffuse type [36.2 (15.1)%] (P<0.05), and the %PPC of signet ring cell carcinoma was extremely low [7.3 (2.2)%] (P< 0.01). Pol-alpha-positive cancer cells were observed most abundantly in the lamina propria of the mucosa. They decreased in number with the depth of cancer infiltration down to the subserosa.

Adult

Bannayan-Zonana syndrome associated with lipomas, hemangiomas, and lymphangiomas.

Bannayan-Zonana syndrome is a rare disorder characterized by macrocephaly and multiple soft tissue and visceral hamartomas. This report presents a sporadic patient with macrocephaly, lipomas, hemangiomas, and lymphangiomas who died of cardiac and respiratory failure due to progressive cervicomediastinal arteriovenous fistulous hemangiomas at the age of 9 years.

Abnormalities, Multiple

Late complications in long-term survivors of biliary atresia.

Ninety patients with biliary atresia surviving more than 5 years were analysed with respect to late complications occurring after the age of 4 years. Thirty-five had complications including cholangitis, portal hypertension, hypersplenism, gastrointestinal bleeding, and esophageal varices. These complications occurred at various times. The background factors of late complications were past history of cholangitis soon after the operation, advanced age at operation, re-operation, high portal pressure at initial operation, and a long interval before disappearance of jaundice after surgery. These factors are mostly related to the first operation and its postoperative course. Therefore, we stress that late complications can be prevented by intensive treatment of the patient at the time of the first operation.

Adolescent

Cutaneous leiomyosarcoma.

A child's head-sized tumor on the upper back developed in a 43-year-old man. In spite of an extensive operation for the tumor, he died of multiple metastasis 15 months after the operation. Histologically, tumor cells proliferated throughout the dermal and subcutaneous regions, and a boxed-in appearance was noted with silver staining. Because electron microscopic observations strongly suggested a smooth muscle origin, we diagnosed this case as cutaneous and subcutaneous leiomyosarcoma.

Adult

The microvasculature of the human bone marrow correlated with the distribution of hematopoietic cells. A computer-assisted three-dimensional reconstruction study.

Surgical specimens of ordinary bone marrow from eight patients were submitted to computer-assisted three-dimensional reconstruction from resin-embedded, semi-thin serial sections. This was undertaken with the aim of contributing to a better understanding of hematopoietic microenvironment by establishing the basic architecture of the bone marrow, particularly the microvasculature and its relation to the hematopoietic cell series. The basic vascular structure was found to consist of mutually intertwining sinuses and hematopoietic cords (or compartments), the latter with an arteriole running along the axis. This allowed to define the unitary structure of the bone marrow as a hematopoietic cord with a central arteriole and surrounded by sinuses. Here granulopoietic cells were distributed mostly along the wall of the central arteriole. Erythropoietic cells, located mainly around the sinus wall, proved to be forming a continuous network of cord instead of separate "islands" as usually assumed, justifying a designation of "erythroblastic cords". Megakaryocytes were positioned in close vicinity to the sinus wall. These findings appear not only to be helpful in analyzing factors involved in the in vivo hematopoiesis of man, but also to visualize the importance of structural studies of bone marrow.

Adult

Distribution of neuropeptides in rat pterygopalatine ganglion: light and electron microscopic immunohistochemical studies.

The distribution and quantity of neuropeptides in the rat pterygopalatine ganglion were studied by using complete serial paraffin sections of the ganglion immunostained with antiserum against several neuropeptides. The pterygopalatine ganglion, composed of 4932 +/- 291 (mean +/- SD) neurons, was triangular in shape with a tapering caudal tail. The most commonly found peptide in neurons was vasoactive intestinal polypeptide (VIP) (99.0%), followed by neuropeptide Y (NPY) (54.1%) and enkephalin (10.5%). The rostro-ventromedial and caudal parts of the ganglion where intensely VIP-immunoreactive neurons predominate project to the nasal mucosa, while the rostro-dorsolateral part of the ganglion where NPY-immunoreactive neurons predominate projects to the Harderian gland. The coexistence of VIP/NPY (47.4%), VIP/NPY/enkephalin (6.6%) or VIP/enkephalin (3.9%) in the ganglionic neurons was recognized. Calcitonin gene-related peptide (CGRP)- and substance P-immunoreactive varicosities formed synaptic contacts with the somatic spine or soma, which confirmed that the reflex arch, composed of axon collaterals of trigeminal ganglionic neurons and parasympathetic ganglionic neurons, operates through direct synapses. Enkephalin-immunoreactive varicosities, which were probably derived from parasympathetic preganglionic neurons, also made synaptic contact with the somatic spine.

Animals

[Age-related effects of gastroduodenoscopy on arterial oxygen saturation].

Although endoscopy is widely used for safe and accurate examinations of gastroduodenal disease cases, several investigators reported arterial oxygen desaturation occurring during endoscopy. Endoscopy-induced oxygen desaturation is hazardous because it increases the risk of cardiac arrhythmia. This study is designed to investigate whether gastroduodenal endoscopy causes remarkable oxygen desaturation in elderly patients in comparison with younger ones and to study whether nasal oxygen administration can prevent it. Forty-four patients over 61 years old and 37 patients younger than 60 were divided into two groups, to one of which 100% oxygen (2 l/min) was administered through nasal prongs. During endoscopy, blood pressure, pulse rate, and arterial oxygen saturation (SaO2) were recorded at one-minute intervals by a pulse oximeter. Intubation of the endoscope caused a transient drop in oxygen saturation both younger and older patients with greater drops in older subjects (1.7 +/- 0.4% in the young and 3.3 +/- 0.8% in the old groups). In the older groups, two out of 20 patients who had no oxygen administration showed a saturation decrease of over 7%. On the other hand, no younger subject showed such a large degree of oxygen desaturation. Oxygen administration effectively prevented the endoscopy-induced desaturation both in younger and in older patients. In summary, the results of this study suggested that older subjects had a greater decrease of oxygen saturation during gastroduodenofiberscopy and that oxygen administration is useful to prevent the endoscopy-induced desaturation.

Aging

Vitamin A: differentiating action on gastric cancer cells and gastric mucosal cells in elderly people.

Since RA is effective only in gastric mucosal cells but not in isolated parietal cells, it is strongly suggested that RA acts on multi-potential stem cells in the gastric mucosa, facilitating their differentiation into mature parietal cells. Moreover, although RA was very effective in newborn rats as well as in young people, responsiveness to RA is decreased in the elderly people especially with atrophic gastritis. This unresponsiveness in the elderly people might be involved in the development of gastric cancer.

Aged

[Effects of MPTP on the mouse retina].

MPTP is known as a selective neurotoxin which destroys dopamine-containing neurons, and induces a model of Parkinson's disease. In the retina, MPTP acts on the amacrine cells which contain dopamine. In the present study, C57BL/6J mice were treated i.p. with MPTP (cumulative dose, 150 mg/kg), and the role of dopamine in the mouse retina was investigated electrophysiologically and immunohistochemically. ERGs were recorded before and 10, 30 and 50 days after MPTP injection. The amplitude of the oscillatory potentials was greatly reduced, and that of the b-wave to a lesser degree, while the a-wave was slightly reduced 10 days after injection. These ERG changes tended to return to the control level 50 days after injection. Immunohistochemical analysis showed that 10 days after MPTP injection the number of tyrosine hydroxylase positive amacrine cells was reduced by approximately 50%, and that these changes had lasted at least until 50 days after MPTP injection.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

[The clinicopathological evaluation of automated cytochemical hematology system (Technicon H1) in patients with leukemia and myelodysplastic syndrome].

To determine the usefulness of the H1 system, we applied it to 14 patients with acute leukemia and 19 patients with myelodysplastic syndrome (MDS). We revealed interesting cytogram patterns in several patients with acute leukemia, ALL (L2), ALL (L3), and AML (M7). In the basophil and lobularity cytogram, their blast cells were clustered mainly in the blast box. However, a small cluster appeared in the basophil area and was expressed as pseudo-basophilia of 4.4%, 9.6%, and 21%, respectively. We speculated that not only normal basophils but also some type of leukemic blasts could be resistant to rupture of the cell membrane induced by a surfuctant at a low pH. Characteristics of H1 cytogram and histogram pattern have hardly been reported in patients with MDS. From the analysis of H1 pattern of 19 cases, we found that the (1) the values of RDW and HDW were high in comparison to those for aplastic anemia and normal controls and (2) the MPXI (mean peroxidase activity index) was significantly low at the time of diagnosis. MPXI had declined at the terminal stage in cases of death with bone marrow failure. These characteristics were concluded to be useful in clinicopathological diagnosis using the H1 automatic hematological system.

Adolescent

Gastroesophageal reflux after endoscopic injection sclerotherapy.

The effect of sclerotherapy of esophageal varices on the gastroesophageal reflux was studied. Gastroesophageal reflux was monitored by a 24-h pH-monitoring catheter introduced into the distal esophagus. The results of pH monitoring of 16 patients who underwent sclerotherapy were compared with those of 21 patients with untreated varices. Seven of the 16 treated patients showed high occurrence rates of gastroesophageal reflux comparable to those observed in cases with severe reflux esophagitis. In the untreated group, only one patient showed pathological reflux (there was a significant difference between treated and untreated groups; p less than 0.01). When the level of reflux was compared with factors that might influence sclerotherapy-induced gastroesophageal reflux, there was a positive correlation between the magnitude of reflux and amount of sclerosant injected paravariceally in the submucosal tissue (p less than 0.05). The results indicate that the paravariceal injection of sclerosant for the treatment of esophageal varix may cause pathological gastroesophageal reflux after sclerotherapy is completed.

Analysis of Variance

Growth signal erythropoietin activates the same tyrosine kinases as interleukin 3, but activates only one tyrosine kinase as differentiation signal.

By Western blotting with anti-phosphotyrosine-specific antibody, we demonstrated that both erythropoietin (Epo) and interleukin 3 (IL3) induce rapid and transient tyrosine phosphorylation of a common set of proteins of 45, 55, 69, 87, 90, 95 and 160 KDa as a growth signal in Epo- and IL3-dependent FD-M6 cells. In contrast, only two proteins of 87 and 90 KDa were transiently phosphorylated in Epo-induced erythroid differentiation of SKT6 cells. Furthermore, no tyrosine phosphorylation was observed in dimethyl sulfoxide-induced differentiation of SKT6 cells. Taken together with other observations, these results indicate that Epo, IL3 and GM-CSF activate the same tyrosine protein kinases as growth signal and that Epo-induced differentiation signal uses only a part of the tyrosine kinase pathway.

Animals

Efferent projections of the infralimbic (area 25) region of the medial prefrontal cortex in the rat: an anterograde tracer PHA-L study.

The efferent projections of the infralimbic region (IL) of the medial prefrontal cortex of the rat were examined by using the anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). Major targets of the IL were found to include the agranular insular cortex, olfactory tubercle, perirhinal cortex, the whole amygdaloid complex, caudate putamen, accumbens nucleus, bed nucleus of the stria terminalis, midline thalamic nuclei, the lateral preoptic nucleus, paraventricular nucleus, supramammillary nucleus, medial mammillary nucleus, dorsal and posterior areas of the hypothalamus, ventral tegmental area, central gray, interpeduncular nucleus, dorsal raphe, lateral parabrachial nucleus and locus coeruleus. Previously unreported projections of the IL to the anterior olfactory nucleus, piriform cortex, anterior hypothalamic area and lateroanterior hypothalamic nucleus were observed. The density of labeled terminals was especially high in the agranular insular cortex, olfactory tubercle, medial division of the mediodorsal nucleus of the thalamus, dorsal hypothalamic area and the lateral division of the central amygdaloid nucleus. Several physiological and pharmacological studies have suggested that the IL functions as the 'visceral motor' cortex, involved in autonomic integration with behavioral and emotional events. The present investigation is the first comprehensive study of the IL efferent projections to support this concept.

Amygdala