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Biomedical subjects

T Kubo

Publications and source records attributed to T Kubo.

At least 703 records · Page 39Linked to original sources

Clinicopathological and histochemical studies of linitis plastica type gastric cancer with special reference to early gastric cancer in the region of the fundic gland.

In this study, early gastric cancer in the region of the fundic gland was found to occur predominantly in women. Many lesions of this type were identified in the posterior wall of the middle portion of the stomach. Histologically, the lesions were classified as poorly differentiated carcinomas in all cases of early cancer. On the other hand, in 9 patients with cancer of linitis plastica type having IIc lesions (less than 2.0 cm in diameter) located in the region of the fundic gland, the tumor focus was also in the posterior wall of the middle portion of the stomach. Giant folds were present diffusely in all other portions of the gastric mucosa in these latter cases. These cases also had diffuse infiltration of cancer cells into the submucosa, muscle layer and extraserosal regions. Histologically, the lesions were classified, in all cases of linitis plastica type, as poorly differentiated carcinomas including signet ring cells. Acid mucopolysaccharides (AMPS) and sialic acid were histochemically detected in the interstitial tissues of early gastric carcinomas and linitis plastica type gastric cancers. The AMPS digestion rates were higher for early cancer tissue. The present results support the hypothesis that early gastric cancer in the region of the fundic gland may occur in conditions favorable to tumor growth and may develop into cancer of linitis plastica type.

Adult↗

[Marked bone marrow necrosis preceding acute myeloblastic leukemia in childhood].

A 3-year-old boy was transferred to our hospital because of fever, abdominal pain and severe systemic bone pain on October 16, 1989. Hematological examination showed hemoglobin 8.7 g/dl, white blood cell count 5300/microliters with 9% neutrophils and platelet count 5.5 x 10(4)/microliters. Bone marrow aspiration and biopsy revealed markedly necrotic cells. Blood chemistry showed transient elevation of CRP, serum LDH, FDP, FDP-Ddimer and fibrinogen. Tc99m pyrophosphate bone scanning showed multiple uptake spots in various bone. Although the sign of fever, abdominal pain and bone pain disappeared spontaneously after three weeks, anemia persisted. About two months later from bone marrow necrosis, abnormal cells appeared in the bone marrow. A diagnosis of AML (M3) was made and a combination chemotherapy started. This case is remarkable for elevation of acute phase protein in association with bone marrow necrosis.

Bone Marrow↗

[Establishment and characterization of a new gastric cancer cell line (OCUM-1), derived from Borrmann type IV tumor].

A new human gastric cancer cell line (OCUM-1), which was derived from Borrmann type IV tumor of the stomach, was established. The cell line grew sometimes singly and sometimes in clusters, and continued to grow for more than 3 years. It's doubling time was 33.2 hours, chromosomal mode was 50, and nuclear DNA ploidy pattern was diploid. The cells could grow in nude mice. It produced carcinoembryonic antigen, carbohydrate antigen 19-9, and cancer-associated antigen SPan-1 and expressed epidermal growth factor receptor. Supplementation of epidermal growth factor to culture medium increased the cell number statistically significantly. It was decreased by supplementation of chondroitin sulphate. So the cell line OCUM-1 might be useful for the study of gastric cancer, especially Borrmann type IV gastric cancer.

Adult↗

Evidence that endogenous catecholamines are involved in alpha 2-adrenoceptor-mediated modulation of the aortic baroreceptor reflex in the nucleus tractus solitarii of the rat.

Microinjections of alpha-methylnoradrenaline and tyramine into the rat nucleus tractus solitarii (NTS) potentiated the depressor and bradycardiac responses to aortic nerve stimulation whereas yohimbine injected similarly inhibited them. NTS pretreatment with yohimbine inhibited the baroreflex potentiation effects of alpha-methylnoradrenaline and tyramine whereas intraventricular pretreatment with 6-hydroxydopamine inhibited only that of tyramine. These results provide evidence that endogenous catecholamines in the rat NTS are involved in alpha 2 adrenoceptor-mediated modulation of the aortic baroreceptor reflex.

Animals↗

Nicotine releases stereoselectively and Ca2(+)-dependently endogenous 3,4-dihydroxyphenylalanine from rat striatal slices.

In superfused slices of rat striatum, nicotine-evoked release of endogenous 3,4-dihydroxyphenylalanine (DOPA) was studied in comparison with that of dopamine (DA). (+/-)-Nicotine (0.1-10 microM) constantly and repetitively released DOPA and DA over a similar time course in a concentration-dependent manner. The ratio of DOPA and DA evoked was approximately 1:2-3. The turnover rate of DOPA was about 300 times higher compared to DA. (+/-)-Nicotine (10 microM)-induced DOPA release was mecamylamine (20 microM)-sensitive, Ca2(+)-dependent and tetrodotoxin (0.3 microM)-insensitive. The (+)-isomer induced no DOPA release. These characteristics of DOPA release were almost the same as those of DA. Nicotine evokes endogenous DOPA via nicotinic cholinergic receptors in a manner similar to the transmitter DA. These findings further support a probable role of DOPA as a neuroactive substance in the rat central nervous system.

Animals↗

Interleukin-6 enhances murine megakaryocytopoiesis in serum-free culture.

We investigated the effect of interleukin-6 (IL-6) on murine megakaryocytopoiesis in a serum-free culture system. The addition of IL-6 to a culture containing interleukin-3 (IL-3) resulted in a significant increase in the number of megakaryocyte colonies by bone marrow cells of normal mice. The megakaryocytic progenitors that survive exposure to 5-fluorouracil (5-FU) exhibited a more significant response to IL-6 and IL-3. Polyclonal anti-IL-6 antibody neutralized the stimulatory effect of IL-6 on megakaryocyte colony growth supported by IL-3. Delayed addition experiments and replating experiments of blast cell colonies showed that megakaryocytic progenitors are supported by IL-3 in the early stage of the development but require IL-6 for their subsequent proliferation and differentiation. In addition, IL-6 increased the size of megakaryocytes in granulocyte-macrophage-megakaryocyte colonies. The combination of granulocyte colony-stimulating factor or granulocyte-macrophage colony stimulating factor with IL-3 resulted in an increase in the granulocyte-macrophage colony growth of bone marrow cells of 5-FU-treated mice or normal mice, respectively, but had little effect on the enhancement of pure and mixed megakaryocyte colony growth. These results suggest that IL-6 plays an important role in murine megakaryocytopoiesis.

Animals↗

Purification and characterization of lipopolysaccharide-binding protein from hemolymph of American cockroach Periplaneta americana.

A protein having affinity to lipopolysaccharide of Escherichia coli K12 was purified to homogeneity from the hemolymph of Periplaneta americana. This protein, with an average molecular mass of 450 kDa. was a homooligomer of a 28-kDa subunit protein. Comparative studies using lipopolysaccharide molecules of E. coli and Salmonella minnesota suggested that this protein recognizes and binds to a specific carbohydrate structure of E. coli lipopolysaccharide. Ca2+ was required for this protein to bind to lipopolysaccharide, but other divalent cations could not replace Ca2+.

Acute-Phase Proteins↗

Role of central serotonergic systems in the development of hypertension in spontaneously hypertensive rats.

The spontaneously hypertensive rat (SHR) maintained a higher blood pressure level at and after 8 weeks old than the genetical control Wistar-Kyoto strain (WKY). At 10 weeks old, the turnover rate of 5-hydroxytryptamine (5-HT) was lower in the hypothalamus of SHR than of WKY. Following portacaval anastomosis (PCA) in SHR, the blood pressure was significantly decreased in comparison with that of sham-operated control SHR. In WKY, no significant change in the blood pressure response was observed. PCA treatment increased the 5-HT turnover including that in SHR. If the SHR with PCA was bred with food pellets containing higher concentrations of leucine and isoleucine, the blood pressure increased and the 5-HT turnover decreased. These findings suggest that the central serotonergic system is involved in the development of hypertension.

Anastomosis, Surgical↗

Modulation of the aortic baroreceptor reflex by neuropeptide Y, neurotensin and vasopressin microinjected into the nucleus tractus solitarii of the rat.

Neuropeptide Y (NPY), neurotensin, arginine vasopressin (AVP), angiotensin II (ANG II), atrial natriuretic peptide (ANP) and calcitonin gene-related peptide (CGRP) have been suggested as putative neurotransmitters in the nucleus tractus solitarii (NTS) where baro- and chemoreceptor afferents terminate. To investigate modulation of the aortic baroreceptor reflex by neuropeptides, we microinjected these neuropeptides into the medial area of the rat NTS and examined their effects on the depressor and bradycardic responses to electrical stimulation of the aortic nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. NPY (3 ng) and neurotensin (0.3 ng) injected into the NTS caused a decrease in blood pressure and/or heart rate, and facilitated the depressor and bradycardic responses to aortic nerve stimulation. AVP (3 ng) produced an increase in blood pressure and heart rate, and inhibited the responses to aortic nerve stimulation, whereas d(CH2)5Tyr(Me)AVP(100 ng), a V1 vasopressin receptor antagonist, did not affect the basal cardiovascular parameters and the baroreflex responses. ANG II (0.3 and 3 ng) caused a decrease in blood pressure and heart rate whereas at 0.3 ng it did not affect the baroreflex responses. ANP (3 ng) and CGRP (3 ng) did not affect the basal blood pressure and heart rate, and the responses to aortic nerve stimulation. These findings indicate that NPY, neurotensin and AVP microinjected into the rats NTS can modify the aortic baroreceptor reflex. Some of these neuropeptides may play a role in modulation of the aortic baroreceptor reflex within the NTS.

Angiotensin II↗

Electrical stimulation-evoked release of endogenous aspartate from rat medulla oblongata slices. Effects of inhibitors of aspartate aminotransferase and GABA transaminase.

The effects of aminooxyacetic acid (AOAA), an aspartate aminotransferase (AAT) inhibitor, L-canaline, an ornithine aminotransferase inhibitor, and gamma-acetylenic GABA and gabaculine, both gamma-aminobutyric acid transaminase (GABA-T) inhibitors, on the release of aspartate from slices of rat medulla oblongata and hippocampus were studied. The slices were superfused and electrically stimulated. There was a Ca2(+)-dependent stimulus-evoked release of endogenous aspartate. AOAA (10(-4) and 10(-3) M) decreased the evoked release of aspartate in the medulla oblongata but not in the hippocampus. In addition, AOAA produced a decrease in the spontaneous efflux and tissue content of aspartate in the medulla oblongata. L-Canaline (5 x 10(-5) M), gamma-acetylenic GABA (10(-4) M) and gabaculine (10(-5) M) did not affect the evoked release of aspartate in the medulla oblongata, while these agents produced a decrease in spontaneous efflux and tissue content of aspartate. These findings suggest that AAT participates in the synthesis of transmitter aspartate in the medulla oblongata of the rat. It appears that there are the pools of transmitter aspartate and non-transmitter aspartate in the rat medulla oblongata.

4-Aminobutyrate Transaminase↗

An immunohistological study of breast cancer--with special reference to the expression of carbohydrate antigens and estrogen receptor status.

An investigation carried out on 100 cases of primary breast cancer, both clinicopathologically and immunohistologically, revealed estrogen receptor (ER)-positive cases to be found significantly more often in early stage cancer than advanced stage cancer. On the other hand, ER negative cases were found to have a greater incidence of high-grade lymph node metastasis and were seen significantly more frequently in large tumors. Span-1, CA19-9, and SLEX antigens were detected in 33 per cent, 38 per cent, and 64 per cent of the total cases, respectively and the ratio of ER negative cases was significantly higher in each antigen positive group. Irrespective of the presence or absence of lymph node metastasis, ER negative cases were found significantly more often in antigen-positive groups than in their counterparts and tumor size tended to be greater in the antigen-positive cases. The results of this study thus indicated that the disease progression in breast cancer appears to be correlated with ER status and carbohydrate antigen expression.

Antigens, Neoplasm↗

Combined effects of intraperitoneal administration of recombinant interleukin-2 and streptococcal preparation OK-432 in murine tumors.

The combined effects of rIL-2 and OK-432 were investigated against a Meth-A tumor, a syngeneic tumor of inbred BALB/c mice. An analysis of the effector cells was also performed. The treatment resulted in an inhibition in vivo of tumor growth and increased survival of the Meth-A tumor-bearing mice. Splenic cells obtained from Meth-A inoculated mice which received combination therapy were not only NK-sensitive YAC-1 and LAK-sensitive EL-4 cells, but also NK-resistant Meth-A cells, as shown in a 4-h 51Cr-release assay. Syngeneic killer cell activity against Meth-A cells was abolished almost completely with anti-Thy 1.2 treatment and about 70% of the activity was abolished with anti-asialo GM1 treatment in a complement-dependent cytotoxic assay. It was not changed by the removal of macrophages and B cells from the splenic cells. Mice which survived for 60 days after the start of therapy rejected Meth-A inoculation when rechallenged, suggesting the establishment of a specific immunity. Combination therapy appeared to be beneficial against Meth-A cells and T-cells appeared to play a determining role in the treated Meth-A bearing mice. It was suggested that more than two populations of killer cells exist in the spleen treated with the combined therapy and they may have the same characteristics as activated T and NK cells with or without specific killer T-cells.

Animals↗

Measurement of 239Pu in soil and plants in the Nishiyama District of Nagasaki.

Nishiyama district in Nagasaki is located approximately 3000 m east of the hypocenter of the atomic bomb that was dropped on 9 August 1945. This district is also known as an area where there was a concentrated radioactive fallout with the black rain that was carried by a westerly wind. The Nagasaki atomic bomb was a Pu bomb, and the fallout must have included 239Pu without fission in addition to fission products. The presence of 239Pu in Nishiyama district has been confirmed previously. In this study, the distribution of 239 + 240Pu concentration in the uncultivated soil and the transfer factor of 239 + 240Pu to agricultural products in Nishiyama district were examined. The concentration of 239 + 240Pu in the uncultivated soil was 20 Bq kg-1, which was approximately eight times as high as that in the control districts. The transfer factor of 239 + 240Pu to agricultural products was 10(-4) - 10(-3), which was 1/100-1/200 of that of 137Cs.

Agriculture↗

Recombinant interleukin-2-induced regression of pulmonary metastasis of renal cell carcinoma.

A patient having renal cell carcinoma with multiple pulmonary metastasis was treated with recombinant interleukin-2. Pulmonary metastatic nodes were markedly diminished. The response was maintained for 4 months. At Autopsy, many fibrotic areas in which metastatic carcinoma was thought to have previously existed and then healed were observed in the bilateral pulmonary lobes, although a few microscopically tiny metastatic lesions still remained.

Carcinoma, Renal Cell↗

Ureteral action potential and histological changes in the upper urinary tract receiving the formalin.

The present study investigates the ureteral action potential and histological changes of pelvi-ureteral system after injection of the formalin into the obstracted ureters or the renal pelvis. In the first experiment, formalin was injected into the obstructed ureters of 18 dogs for 30 minutes. In the second, formalin was injected into the obstracted renal pelvis of 13 dogs for 30 minutes using ureteral balloon catheters, and then renal pelvis were released from obstraction and catheters were removed. In these experiments, ureteral electromyogram were recorded and histological changes of pelvi-ureteral system were also observed microscopically. Results 1. After injection of formalin into the ureters, ureteral action potential disappeared and had not restored. Histologically, damage was observed in the ureteral smooth muscle as well as in the mucosa. 2. After injection of formalin into the renal pelvis, ureteral action potential disappeared in 46% of the ureters. In 54% of the ureters, action potential had not disappeared, however discharge interval became irregular. Histological changes of the renal pelvis was not related to the presence or absence of ureteral action potential. The results of the present study show that ureteral smooth muscle play part in the conduction of the ureteral excitation, and have an irregular autonomic discharge.

Action Potentials↗

[Studies on function of the upper urinary tract. XXIX. Canine ureteral electromyogram isolated from "so-called Pacemaker"].

Many workers have reported that ureteral peristaltic movement is controlled by the "so-called Pacemaker". But, in our recent studies, it was revealed that the existence of pacemaker is not always necessary for the peristaltic movement. In this study, we made isolated and non-isolated prototype models, using 18 mongrel dogs, to explore the influential factors on ureteral peristaltic discharge. Bilateral kidney and ureter were exposed transperitoneally. Unilateral upper urinary tract was prepared to preserve the pacemaker without renal blood supply, and contralateral one was prepared not to preserve the pacemaker by cutting at the proximal portion of the ureter. Vesico-ureteral reflux (VUR) was caused on these two models. A luminal pressure and ureteral electromyogram was recorded. In the result, there is spontaneous peristaltic discharges of the ureter which had the tendency to increase peristaltic frequency according to the increase of the luminal pressure. It was suggested that adequate expanding stimulation is the factor of peristaltic discharge to increase, and the peristaltic discharge under this condition propagates from upper to lower portion of the ureter.

Action Potentials↗

Beta-alanine, like glycine, microinjected into the rat nucleus tractus solitarii increases blood pressure.

Microinjections of beta-alanine and glycine into the nucleus tractus solitarii (NTS) of the rat, led to an increase in blood pressure and heart rate. The responses to glycine but not to beta-alanine could be blocked by strychnine. Both amino acids reduced the responses to aortic nerve stimulation. High K+ stimulation caused a calcium-dependent release of beta-alanine from tissues in the area of the NTS. These results suggest that beta-alanine and glycine may modulate the cardiovascular control within the NTS.

Animals↗