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Biomedical subjects

A Tokunaga

Publications and source records attributed to A Tokunaga.

At least 109 records · Page 6Linked to original sources

[Clinical evaluation of granisetron injection against nausea and vomiting induced by anticancer drugs including cisplatin].

The antiemetic effect and safety of granisetron injection on nausea and vomiting induced by anticancer drugs were studied in the patients treated with anticancer drugs including 50 mg/m2 or more of cisplatin (CDDP). Granisetron is already on the market, and drip infusion of granisetron at 40 micrograms/kg has been used widely in clinical practice. In this clinical investigation, a simpler administration method of its slow (30 to 60 seconds) intravenous injection at 40 micrograms/kg just before CDDP administration was used. The clinical efficacy, safety and usefulness against nausea and vomiting were investigated in 22 patients, and the study medication was assessed as "remarkably effective" or "effective" in 16 patients (72.7%). Neither adverse experience nor abnormal laboratory test value was reported. In the usefulness rating, the study medication was assessed as "extremely useful" or "useful" in 16 out of 22 patients (72.7%). The above results have shown that the slow intravenous injection of granisetron has an excellent antiemetic effect on nausea and vomiting induced by anticancer drugs including CDDP and a high degree of safety.

Adult↗

Relationship of C-erbB-2 protein expression and gene amplification to invasion and metastasis in human gastric cancer.

BACKGROUND: Amplification and/or overexpression of the C-erbB-2 gene has been demonstrated in breast and gastric cancer and is thought to be involved in the process of gastric cancer metastasis. METHODS: The expression of C-erbB-2 protein in human gastric cancer was examined by immunohistochemistry and amplification of the C-erbB-2 gene by Southern blot hybridization. RESULTS: C-erbB-2 protein was located on the cell membrane of cancer cells in formalin-fixed, paraffin-embedded sections. Fourteen percent of specimens were positive for C-erbB-2, and no positive reaction was evident in noncancerous tissue. The presence of C-erbB-2 in gastric cancer was correlated with the depth of invasion, histologic type, growth pattern, and presence of liver metastasis. C-erbB-2 was found more often in advanced cancers (P < 0.05), papillary adenocarcinoma (P < 0.01), nonscirrhous cancer (P < 0.05), and cancers with liver metastasis (P < 0.01). The incidence of C-erbB-2 positivity in lymph nodes with metastasis was higher than in primary sites (P < 0.01) and was significantly higher in differentiated adenocarcinoma (P < 0.01). Patients with C-erbB-2-positive tumors had poorer survival rates those with C-erbB-2-negative tumors in the early stages (P < 0.001), but not in the advanced stages. Amplification of the C-erbB-2 gene was detected at the primary site and in metastatic nodes in the same case, and expression of the protein was also evident. CONCLUSIONS: The expression and/or gene amplification of C-erbB-2 is related to invasion and nodal involvement in differentiated adenocarcinoma of the human stomach.

Adenocarcinoma↗

Sequential changes in the cell mediators of peritoneal and wound fluids after surgery.

The concentrations of cell mediators in the peritoneal and wound fluids of patients who underwent abdominal surgery or mastectomy were determined sequentially and compared with the concomitant changes in blood components. The level of interleukin-6 (IL-6) in the peritoneal and wound fluids was significantly higher than the plasma level after gastrectomy (P < 0.001), cholecystectomy (P < 0.05), and mastectomy (P < 0.05), although the level of plasma IL-6 was also higher postoperatively than before surgery (P < 0.001, P < 0.05). Significantly higher levels of tumor necrosis factor-alpha were detected in the peritoneal and wound fluids (P < 0.01, P < 0.05, respectively) after surgery despite its absence in plasma. A platelet-specific protein and a protein specific for fibroblasts were also measured. Thus, mediators derived from various cells were shown to be present in human peritoneal and wound fluids, indicating that the local production of these mediators plays an important role in the process of tissue repair.

Adult↗

Intussusception caused by a carcinoma of the cecum during pregnancy: report of a case and review of the literature.

A case of intussusception due to a carcinoma of the cecum during pregnancy is reported. A 27-year-old pregnant female was admitted to Shimodate Municipal Hospital because of abdominal pain, nausea and vomiting. Her abdomen was distended, and a relatively hard mass was palpable in the right hypochondrium. Following a diagnosis of intussusception by ultrasonography, a laparotomy was performed. The lesion causing the intussusception was found to be a carcinoma of the cecum, and thus a right hemicolectomy with lymph node dissection was carried out. Histological examination revealed that the tumor was a well-differentiated adenocarcinoma which had invaded the muscularis propria but was superficial to the subserosa. None of the lymph nodes were cancerous. The incidence of colonic cancer above the peritoneal reflection during pregnancy is very low. Only 24 cases have been previously reported; our patient is only the 25th case, as well as being the first case demonstrating Dukes' A. Due to the intussusception, ultrasonography was effective for diagnosis and the patient was able to undergo a curative operation at an earlier stage than other patients.

Adenocarcinoma↗

Expression of muscarinic and nicotinic receptor mRNA in the salivary gland of rats: a study by in situ hybridization histochemistry.

Expression of muscarinic receptor mRNA subtypes (m1-5) and nicotinic receptor subunits (alpha 2-4, and beta 2) was examined in the rat submandibular gland by in situ hybridization histochemistry, using oligonucleotide probes for the muscarinic receptor and RNA probes for the nicotinic receptors. m2, alpha 3, and beta 2 mRNA were strongly expressed in the submandibular ganglion, and m3, alpha 2, alpha 3, alpha 4, and beta 2 were expressed in the striated and interlobular duct cells. Both muscarinic and nicotinic receptors were coexpressed in the same ganglion neurons, while none of these mRNA were detected in the terminal secretory units.

Animals↗

Neurite outgrowth from N18TG2 neuroblastoma induced by H-7, a protein kinase inhibitor, in the presence of colchicine.

Our previous studies have demonstrated that the protein kinase inhibitor H-7 promotes neurite outgrowth from mouse neuroblastoma N18TG2 cells as well as from primary cerebellar cells, and also that the neurites induced by H-7 were more tolerant of colchicine (COL) than those induced by dibutyryl cAMP (dB-cAMP). In the present study, we tested the effects of H-7 and dB-cAMP on neurite growth from N18TG2 cells in the presence of COL. We found that only H-7 promoted neurite formation in the presence of COL. The percentage of cells with neurites induced by H-7 in the presence of COL (H-7 + COL) was similar to that induced by H-7 alone. The neurites induced by H-7 + COL grew straight. They were very thin (less than 1 micron in diameter) and had round varicosities, as did the neurites induced by H-7 alone. By transmission electron microscopy, the neurites induced by H-7 + COL were found to contain longitudinally arranged intermediate filaments (IF). Microtubules (MT) were not observed within the neurites. We also examined the effect of cytochalasin B (CB) on the neurites induced by H-7 + COL and by H-7 alone. The neurites induced by H-7 + COL were tolerant to CB, but those induced by H-7 were resorbed completely within 24 h after CB was applied. Neurites tolerant to CB contained longitudinally IF. Simultaneous application of CB with H-7 + COL or with H-7 alone did not induce neurite formation.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Significance of serum markers pepsinogen I and II for chronic atrophic gastritis, peptic ulcer, and gastric cancer.

Chronic atrophic gastritis (CAG) is closely correlated with gastric cancer and is predominant in Japan. Epidemiologically, food habits are the primary factor in both CAG and gastric cancer. Two potential serum markers for CAG have recently been investigated, i.e., the concentration of serum pepsinogen (PG) and the presence of serum antibodies against Helicobacter pylori. Serum PG I and II and the PG I:PG II ratio have been reported to be useful as indicators of recurrent peptic ulcer and for screening of patients at risk from gastric cancer. In this study, we examined PG I and II in serum from 483 patients by RIA (DAINABOT), and endoscopic examination performed in the same patients before serological assay revealed CAG in 68, peptic ulcer in 91, and gastric cancer in 48. Analysis of the mean values according to patients age showed that CAG patients in their forties to eighties had low (< 40 ng/ml) levels of PG I, peptic ulcer patients in their teens to eighties had high (> or = 70 ng/ml) levels, except for those in their seventies, and gastric cancer patients in their twenties to sixties had low (< 3.0) PG I:PG II ratios, except for those in their sixties. Thus serum PG assay has potential utility for detection of CAG, peptic ulcer, and gastric cancer.

Adolescent↗

Insulin-like growth factor binding protein-3 is present in the alpha-granules of platelets.

The lysis of the alpha-granules of platelets has been shown to release insulin-like growth factors (IGFs). One of the major regulators of the activity of IGFs is the IGF binding proteins (IGFBPs), but IGFBPs were thought to be absent from platelet alpha-granules. Human platelets were isolated, and the contents of the alpha-granules were released by thrombin digestion. IGFBP-3 was identified in the lysate by RIA and a ligand-binding Western blot; no other IGFBPs were observed. Platelet IGFBP-3 was present as the characteristic glycosylated doublet at 45 and 43 kilodaltons on ligand-binding Western blot, but was not associated with the acid-labile subunit in the alpha-granule. Thus, the IGFs in platelet alpha-granules coexist with IGFBP-3, which can play a major role in regulating and targeting the actions of IGFs when released by lysis.

Blood Platelets↗

Effect of famotidine on gastric mucosal lesions induced by gold thioglucose in rats.

Rats that were given an intraperitoneal injection of gold thioglucose (GTG, 0.3 mg/g) developed hemorrhagic lesions in the gastric mucosa 24 hours after the injection. The gastric juice volume and the generation of acid and pepsin were significantly increased 24 hours after the GTG injection (p < 0.01). Simultaneous administration of famotidine (3 mg/kg) with GTG significantly reduced gastric juice secretion and the generation of acid and pepsin (all p < 0.01), as well as suppressing the development of hemorrhagic lesions. These results indicate that there is a relationship between the hemorrhagic lesions induced by GTG and increased acid and pepsin generation. Rats treated with GTG seem to be a useful new animal model for the investigation of pepsin secretion.

Animals↗

[The relationship between flow velocity waveforms of umbilical and fetal middle cerebral arteries and cord blood gas values].

Umbilical artery (UA) and fetal middle cerebral artery (MCA) flow velocity waveforms were obtained from 55 fetuses just prior to elective cesarean section at 36-39 weeks of gestation and the resistance index (RI) was calculated for each waveform. Cord blood samples were obtained from both the umbilical artery and the vein at cesarean section and the blood gas values were measured immediately. The coefficients of correlation between the cord blood gas values and the resistance indices were obtained. 1. UA-RI had a significant negative correlation with pH and Po2, and a positive correlation with Pco2. 2. MCA-RI had a significant positive correlation with pH and Po2, and a negative correlation with Pco2. 3. The UA-RI/MCA-RI ratio had a significant negative correlation with pH and Po2, and a positive correlation with Pco2. 4. The best correlation was found in the UA-RI/MCA-RI ratio, and the UA-RI, MCA-RI and UA-RI/MCA-RI ratios had a closer correlation with umbilical arterial blood gas values than with umbilical venous blood gas values. A Doppler study of fetal blood distribution would be a useful method in the noninvasive assessment of the fetal blood gas state at 36-39 weeks of gestation.

Blood Flow Velocity↗

Histochemical study of the lumbar colonic nerve supply to the internal anal sphincter and its physiological role in dogs.

The sympathetic innervation of the internal and sphincter (IAS) and its physiological role in maintaining sphincter tone were histochemically and mechanically studied in dogs anesthetized with pentobarbital sodium. Numerous catecholamine-fluorescent nerve fibers with varicosities were identified in the IAS of normal dogs. Such fibers were markedly reduced at one week and one month after resection of the hypogastric nerves (HGNs) or the lumbar colonic nerve (LCN), and disappeared after combined HGN and LCN resection. IAS tone decreased to 37.2% of baseline at 1 h after LCN resection and to 69.9% after HGN resection. It returned to the preoperative level at one week and one month after resection. The restored IAS tone was decreased again by acute transection of the previously intact HGNs or LCN. Combined LCN and HGN resection also caused a marked reduction of IAS tone (36.9%) at 1 h after the procedure, and was then restored to the preoperative level with time. The restored tone was not decreased by phentolamine administration. These findings confirmed that both the LCN and the HGN innervate the IAS and play a physiological role in the development of resting tone. The restoration of IAS tone after denervation may be due to intrinsic myogenic properties of the sphincter.

Acetylcholine↗

Magnocellular neurosecretory neurons with ferritin-like immunoreactivity in the hypothalamic supraoptic and paraventricular nuclei of the rat.

Immunohistochemistry for rat liver ferritin (FRT) revealed an intensive labeling in some structures of the rat brain. In the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei, almost all neurosecretory neurons with vasopressin (AVP)-like immunoreactivity were immunostained with FRT. After water deprivation, a marked enlargement of cell body and an immunoreactivity to transferrin receptors were found in AVP-, FRT- and double (AVP+FRT)-labeled neurons in the SON and PVN.

Animals↗

Abnormal expression of embryonic neural cell adhesion molecule (N-CAM) in the developing mouse cerebellum after neonatal administration of cytosine arabinoside.

We have previously found that neonatal administration of cytosine arabinoside (Ara-C) induces cerebellar malformation, including arrest of granule cell migration and destruction of glial palisade. In the present study, the expression of neural cell adhesion molecule (N-CAM) and its distribution were examined in the mouse malformed cerebellum induced by neonatal Ara-C administration. Western blot analysis demonstrated that, in the control group, the embryonic form of N-CAM (E-N-CAM) was expressed in the 7-day-old mouse (P7) cerebellum, but not in the P14 cerebellum which exhibited only the adult form of N-CAM (A-N-CAM). On the other hand, E-N-CAM was expressed in the Ara-C treated cerebellum not only at P7 but also at P14. Immunohistochemical studies revealed that E-N-CAM was observed in the area below the external granular layer (EGL) of the P7 cerebellum in both the control and Ara-C treated mice. In contrast, E-N-CAM immunoreactivity was found in the arrested EGL cells in the Ara-C treated cerebellum of P14 mice but not in the age-matched controls. Therefore, E-N-CAM was aberrantly expressed in the arrested EGL at P14. From the present and previous findings, it was speculated that the aberrant expression of E-N-CAM in the arrested EGL cells is attributed to abnormal cellular interactions, probably arrested EGL cell-to-Bergmann glia.

Animals↗

Correlation between epidermal growth factor receptor concentration and the growth of human gastric cancer xenografts in nude mice.

Seven human gastric cancer xenografts with different concentrations of EGF receptor were established in nude mice. The expression of EGF receptor in the tumors was demonstrated by Western blotting with anti-EGF receptor antibody, binding assay with 125I-EGF and immunohistochemistry with anti-EGF receptor antibody. Western blotting revealed EGF receptor doublet bands at molecular masses of 150 KDa and 170 KDa in all of the samples. The concentration of 125I-EGF binding activity in the tumors ranged from 36.0 to 11,000 fmol/mg protein, with a mean of 345 fmol/mg protein. EGF receptor was also demonstrated immunohistochemically on the apical border of the glands and the cell membrane of the tumor cells. There seemed to be a close correlation between the concentration of 125I-EGF binding activity and the doubling time of these tumors in nude mice (gamma = -0.68). However, no definite correlation was observed between EGF ligand binding and histological features of intestinal type or diffuse type. The expression of EGF receptor appears to facilitate the growth of human gastric cancer xenografts in nude mice.

Animals↗

Gradient expression of neural cell adhesion molecule (NCAM) in the pontine migratory stream of fetal rats.

Immunohistochemical localization of a neural cell adhesion molecule (NCAM) was examined in the subpial pontine migratory stream of the fetal rat with a monoclonal antibody specific for the rat NCAM, MAb-AF11. Although the pontine cell strand showed weaker expression of NCAM than the parenchymal areas of the brainstem, within the cell strand, NCAM-immunoreactivity was somewhat greater in the anterior part of the stream near the neurons' destination than the caudal part. The weak NCAM gradient in the pontine migratory stream may contribute to formation of the pontine cell strand and the basal pontine gray.

Animals↗

Retinal projections in the house musk shrew, Suncus murinus, as determined by anterograde transport of WGA-HRP.

Retinal projections in the house musk shrew (Suncus murinus) were determined by the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Unilateral injection of WGA-HRP into the vitreous body resulted in the terminal labeling of the optic projections in the suprachiasmatic nucleus (SCH), the ventral (CGLv) and dorsal (CGLd) lateral geniculate nuclei, the intergeniculate leaflet (IGL), the pretectum, the superficial layers of the superior colliculus (CS), and the dorsal terminal nucleus (DTN) of the accessory optic system (AOS). Labeling of the SCH was bilateral, with ipsilateral predominance, and covered the whole dorsoventral extent of the nucleus. Immunohistochemical studies revealed that VIP-like immunoreactive neurons and fibers were present in almost all parts of the SCH. No hypothalamic regions other than the SCH received the optic fibers. The ipsilateral projections to the CGLv, CGLd, and IGL were sparse, and a considerable number of uncrossed retinal fibers were found in the pretectal olivary nucleus. No retinal projections to the lateral posterior thalamic nucleus (LP) were found. Ipsilateral optic fibers projected sparsely to the medial part of the CS. The AOS consisted of a small DTN with a very few crossed retinal projections but no lateral and medial terminal nuclei. In addition, the AOS had no inferior fascicle.

Animals↗

Distribution of efferent neurons projecting to the tectum and cerebellum in the rat prepositus hypoglossi nucleus.

Distributions of efferent neurons projecting to the superior colliculus (SC), the pretectum, and the cerebellar cortex were studied in the rat prepositus hypoglossi nucleus (PRH) by retrograde labeling with wheat germ agglutinin-horseradish peroxidase (WGA-HRP). After injection of the tracer into the unilateral SC, small- and medium-sized neurons were labeled throughout the entire rostrocaudal extent of the PRH, with the highest proportion in the middle part of the nucleus. After application of WGA-HRP to the unilateral pretectal region, including the nucleus of the optic tract, numerous labeled neurons appeared in the bilateral PRH. The highest distribution was found in the most rostral part of this nucleus. Furthermore, small neurons of the supragenual nucleus of the facial nerve also were labeled. Injection of WGA-HRP into lobules VI-VII of the cerebellar vermis resulted in the labeling of mainly medium-sized neurons in the bilateral PRH, primarily in the caudal third. WGA-HRP-labeled neurons were less frequently observed in the PRH after unilateral injection into the flocculus and paraflocculus. Retrograde double labeling by fluorescent dyes showed that a few neurons in the middle part of the PRH sent divergent axons to vermal lobules VI-VII and the SC.

Amidines↗