PubMed HealthSearch

Biomedical subjects

H Kinoshita

Publications and source records attributed to H Kinoshita.

At least 19 recordsLinked to original sources

An attempt to generate an antitumor effect in the regional lymph nodes against endometrial cancer cells by inducing antitumor cytokines.

Phytohemagglutinin-stimulated regional lymph node cells obtained from gynecological cancer patients exerted a significant antiproliferative activity against an endometrial cancer cell line, RL95-2 on a human tumor clonogenic assay, and released a high amount of tumor necrosis factor alpha (TNF alpha), and interferons. The activity was thought to be partly due to released TNF alpha, because RL95-2 was highly sensitive to recombinant TNF alpha. However, anti-TNF alpha failed to inhibit the activity, which indicated the probability of some as yet unclarified participation of cytokines. Therefore, the regional lymph nodes might be used as sites of endogenous cytokine therapy in endometrial cancer patients.

Antibodies

Activation of GABAergic function necessary for afterdischarge generation in rat hippocampal slices.

Involvement of gamma-aminobutyric acid (GABA)-mediated function in epileptogenesis was studied in rat hippocampal slices, in which repetition of high-frequency electrical stimulation induced afterdischarges (ADs) to create an in vitro model for ictal activity. A GABAA receptor antagonist, bicuculline, fully blocked the ADs. On the other hand, the presence of bicuculline caused single stimuli to evoke short-duration epileptiform bursts, a well-known model for interictal activity. Therefore, we conclude that activation of GABAergic function appears to be necessary for ictal activity, while its dysfunction induces interictal activity, and propose a modification to the simple disinhibition hypothesis for epileptogenesis.

4-Aminopyridine

Identification of biologically active and inactive human uroguanylins in plasma and urine and their increases in renal insufficiency.

Uroguanylin, a 16-amino acid peptide, is an endogenous activator of intestinal and possibly renal guanylate cyclase C (GC-C). Using two synthetic topological isoforms of human uroguanylin, one bioactive, the other inactive, we prepared two antisera specific for the individual isoforms and developed sensitive radioimmunoassay (RIAs). The respective plasma concentrations of the bioactive and inactive uroguanylins in the normal individuals tested were 5.0 +/- 0.3 fmol/ml (mean +/- SE) and 1.6 +/- 0.1 fmol/ml. These concentrations increased in chronic renal failure (CRF). The major endogenous uroguanylin molecule in normal human urine was 16 amino acids long, whereas in the plasma and urine of CRF patients the major molecule was 10-kDa prouroguanylin. The RlAs established are promising tools for clarifying the physiological functions and pathophysiological implications of uroguanylin in water and electrolyte homeostasis.

Biomarkers

Characteristic histologic features of human hepatocellular carcinoma with mutant p53 protein.

To characterize hepatocellular carcinoma (HCC) cells with mutant (m) p53 protein histologically, we examined 68 main nodules and 20 accessory lesions of 72 patients with HCC who underwent hepatic resection between October 1990 and September 1993. Some sections were fixed in periodate-lysine-paraformaldehyde, embedded in OCT compound, and stained with the mouse monoclonal antibody PAb1801 to m-p53 protein by the immunoperoxidase technique with avidin-biotin complexes. Other sections were fixed in 20% buffered formalin, embedded in paraffin, and stained with the mouse monoclonal antibody DO-1 to m-p53 protein in the same way. Lesions in which cells had nuclei stained for m-p53 protein were defined as being positive for the protein; 25 of the 68 main nodules and 14 of the 20 accessory lesions were positive. Large main nodules were more likely to be positive than small ones. Microscopic examination showed that a larger proportion of poorly differentiated main nodules than well differentiated nodules were positive. Larger proportions of main nodules with extracapsular invasion, septa, portal thrombi, or intrahepatic metastases were positive than main nodules without these features. Accessory lesions that seemed to be metastatic were almost all positive, but few accessory lesions that seemed to be of multicentric occurrence were positive. Our results suggest that lesions with m-p53 protein had a high grade of malignancy and metastasized readily.

Adult

Echocardiography-guided pericardiocentesis with a needle attached to a probe.

Pericardiocentesis with a needle attached to a probe was performed under two-dimensional echocardiographic guidance in 9 patients with pericardial effusion after cardiac operations. The first 5 mm of the tip of a puncture needle for percutaneous transhepatic cholangiodrainage is scratched with a scalpel to give the tip high echo intensity. When the probe is placed on the skin, the direction of puncture at that probe angle appears automatically on the monitor.

Drainage

Grip posture and forces during holding cylindrical objects with circular grips.

Individual finger position and external grip forces were investigated while subjects held cylindrical objects from above using circular precision grips. Healthy females (n = 11) and males (n = 15) lifted cylindrical objects of various weights (0.5, 1.0 and 2.0 kg), and varied diameters (5.0, 7.5 and 10.0 cm) using the 5-finger grip mode. The effects of 4-, 3- and 2-finger grip modes in the circular grip were also investigated. Individual finger position was nearly constant for all weights and for diameters of 5.0 and 7.5 cm. The mean angular positions for the index, middle, ring and little fingers relative to the thumb were 98 degrees, 145 degrees, 181 degrees, and 236 degrees, respectively. At the 10-cm diameter, the index and middle finger positions increased, while the ring and little finger positions decreased. There were no differences in individual finger position with regard to gender, hand dimension, or hand strength. Total grip force increased with weight, and at diameters greater or lesser than 7.5 cm. Total grip force also increased as the number of fingers used for grasping decreased. Although the contribution of the individual fingers to the total grip force changed with weight and diameter, the thumb contribution always exceeded 38% followed by the ring and little fingers, which contributed approximately 18-23% for all weights and diameters. The contribution of the index finger was always smallest (> or = 11%). There was no gender difference for any of the grip force variables. The effects of hand dimension and hand strength on the individual finger grip forces were subtle.

Adult

Expression patterns of multidrug-resistance (MDR1), multidrug resistance-associated protein (MRP),glutathione-S-transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) genes in renal cell carcinomas and normal kidney.

PURPOSE: Expression levels of the multidrug-resistance (mdr1), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) genes in normal kidney and renal cell carcinomas were analyzed to study the complexity of the roles of these genes. MATERIALS AND METHODS: The reverse transcription-polymerase chain reaction (RT-PCR) assay was used with beta 2 microglobulin (beta 2 m) as the internal control. RESULTS: In normal kidneys, the expression levels of the 4 genes in individual normal kidney samples correlated significantly with one another. Comparisons of the expression levels between normal kidneys and renal cell carcinomas showed that only the mean MRP gene expression level was higher in renal cell carcinomas than in normal kidneys (p = 0.018). The expression patterns of the 4 genes in renal cell carcinomas differed markedly for nonpapillary and papillary tumors. The mean MRP/beta 2 m ratio for the papillary type was significantly lower than that for the nonpapillary alveolar type carcinoma (p = 0.004). The 4 genes showed moderate positive correlations with one another in alveolar type renal carcinoma similar to the correlations observed in normal kidneys. In contrast, in papillary type, MRP expression was inversely correlated with mdr1 and Topo II expression. CONCLUSION: Differences in cytogenetic changes, origins and natural histories between papillary and nonpapillary carcinoma may be associated with these distinct expression patterns of the resistance-related genes. Further study is required to clarify whether the differences in the expression patterns between these 2 structural types of carcinoma affect their chemosensitivities and clinical outcomes.

ATP-Binding Cassette Transporters

Sinusoidal capillarization and arterial blood supply continuously proceed with the advance of the stages of hepatocarcinogenesis in the rat.

Hepatocellular carcinoma (HCC) is supplied only with arterial blood and has capillaries instead of sinusoids, unlike the normal hepatic tissue. In order to reveal the sequential changes of sinusoidal structure and blood supply during hepatocarcinogenesis, we examined hyperplastic nodules (HPN), atypical hyperplastic nodules (AHPN) and HCC in F344 rats fed with 2-acetylaminofluorene for 25-35 weeks. The extent of arterial blood supply and the degree of sinusoidal capillarization were assessed by the staining of hepatic nodules with arterially infused ink and by immunohistochemical and ultrastructural analyses of the sinusoids, respectively. The proportion of arterialized nodules was 47% in HPN, 57% in AHPN and 85% in HCC, which indicates that arterialization begins at the stage of HPN and a few HCC still receive portal venous blood. The proportion of Factor-VIII-related antigen (F-VIII)-positive nodules was 25% in HPN, 40% in AHPN and 100% in HCC. Non-arterialized nodules did not express F-VIII, while some F-VIII-negative nodules were already arterialized. Electron microscopically, non-arterialized HPN exhibited normal features of sinusoids, while arterialized HPN showed disappearance of Kupffer cells and partial defenestration of sinusoidal endothelial cells. In non-arterialized and arterialized AHPN, basement membrane became continuous and lipid droplet-containing stellate cells were no longer seen. In HCC, endothelial fenestrae were diminished and basement membrane became thick. The present study has demonstrated that sinusoids are altered in the following order as hepatocarcinogenesis advances from HPN to HCC; onset of arterialization and decrease of endothelial fenestrae, expression of F-VIII by endothelial cells, disappearance of Kupffer cells, diminution of lipid droplets in stellate cells and thickening of basement membrane.

Animals

A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma.

To clarify whether pre-operative transcatheter arterial embolization (TAE) improves survival after hepatectomy, a prospective randomized comparative study was done. Of a total of 115 registered patients having solitary hepatocellular carcinoma (HCC) 2 to 5 cm in diameter, 18 (15.7%) were excluded after randomization. As a result, 97 patients were chosen as subjects and divided into two groups: hepatectomy with (group A: n=50) and without (group B: n=47) pre-operative TAE. The period of observation of the patients who survived the surgery was between 4.0 and 6.6 years. The randomization appeared to have provided well-balanced groups of patients and the clinico-pathological characteristics of the two groups were quite similar. The necrotic part of the cancerous lesions, as confirmed by operative specimens, amounted to 74.8+/-33.4% (mean +/-SD) in group A and 6.8+/-7.2% in group B (P<0.01). However, the cancer-free survival rates after hepatectomy in both groups showed little difference (39.1+/-7.0 (%+/-SE) and 31.1+/-0.1, respectively). We speculate that TAE is not effective against such HCC accessory lesions as minute intrahepatic metastasis and tumor thrombus and that pre-operative TAE does not improve post-operative survival.

Adult

Inhibitory mechanism of intestinal ethanol absorption induced by high acetaldehyde concentrations: effect of intestinal blood flow and substance specificity.

This study describes the effects of high blood acetaldehyde concentrations on the intestinal absorption of ethanol and 2-butanone using an in situ single-pass perfusion technique on the rat intestine and the colored microsphere method to measure intestinal blood flow. We found that high blood acetaldehyde concentrations inhibit intestinal ethanol absorption in an inverse proportion to peak acetaldehyde concentrations, decrease intestinal blood flow, and inhibit intestinal absorption of 2-butanone. The decrease of the intestinal blood flow, induced by high blood acetaldehyde concentrations, is a major mechanism inhibiting intestinal ethanol absorption, but other mechanisms are also thought to inhibit absorption. Therefore, inhibition by high acetaldehyde concentrations is not the only factor affecting ethanol absorption.

Acetaldehyde

[Properties of a hemolysin produced by group B streptococci].

The hemolysin produced by group B streptococci (GBH) has an isoelectric point (pI) of 5.8 and it shows a hemolytic activity in the absence of 2-mercaptoethanol (2-ME). The hemolytic activities of GBH were compared to that of streptolysin O (SLO) and streptolysin S (SLS). These hemolysins differed with respect to the binding and release of hemoglobin (Hb). GBH was bound to phospholipids on the membranes of target erythrocytes, followed by the gentle release of K+ and slow Hb release without lag time. Incontrast SLO released Hb as rapidly as K+. GBH induced hemolysis was inhibited by the addition of 30 mM raffinose. These results indicate that the effective diameter of the pores formed by GBH was about 1.1 nm. GBH showed a lower hemolytic efficiency than SLO, reflecting the fact that these hemolysins destroy erythrocytes by a different mechanism. Intracellular K+ and Hb were released at a different rate in GBH treated cells, indicating that a colloid-osmotic process is involved in the lytic mechanism.

Bacterial Proteins

Exogenous tetrahydrobiopterin causes endothelium-dependent contractions in isolated canine basilar artery.

Tetrahydrobiopterin is an essential cofactor in the biosynthesis of nitric oxide, but in the presence of O2, autooxidation of tetrahydrobiopterin leads to the production of superoxide anions and the subsequent chemical inactivation of nitric oxide. As a result, the present experiments were designed to determine the effect of exogenous tetrahydrobiopterin on isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric force recording in modified Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37 degrees C; pH 7.4). A radioimmunoassay technique was used to measure guanosine 3',5' cyclic monophosphate production (cGMP). Tetrahydrobiopterin (10(-7) to 10(-4) M), but not dihydrobiopterin or biopterin, caused endothelium-dependent contractions. Superoxide dismutase (150 U/ml) abolished tetrahydrobiopterin-induced contractions, but a H2O2 scavenger, catalase (1,200 U/ml), and hydroxyl radical scavengers deferoxamine (10(-4) M) and dimethylsulfoxide (10(-4) to 10(-3) M) did not significantly affect the contractions. A cyclooxygenase inhibitor, indomethacin (10(-5) M), significantly reduced the contractile effect of tetrahydrobiopterin. With the prostaglandin H2/ thromboxane A2 receptor antagonist, SQ-29548 (10(-6) M) present, contractions reversed to relaxations. In rings with endothelium, tetrahydrobiopterin (10(-4) M) significantly decreased the levels of cGMP. These studies suggest that autooxidation of exogenous tetrahydrobiopterin induces endothelium-dependent contractions by 1) chemical inactivation of nitric oxide by superoxide anions and 2) activation of arachidonic acid metabolism via the cyclooxygenase pathway with subsequent release of endoperoxide and/or thromboxane A2 from endothelial cells.

Animals

Blink reflex in cerebral palsy: evaluation of late components in patients with normal auditory brainstem responses.

The electrically elicited blink reflex was examined and evaluated quantitatively in 60 controls and seven patients with cerebral palsy due to perinatal asphyxia who exhibited normal auditory brainstem responses. In the controls, the early component (R1) latency changed slightly from infancy to adulthood, and the late component (R2 and R2') latencies decreased to adult values by 4 to 6 years of age. The electromyographic activity of R2 and R2' increased later and became mature in the young adolescent period. Prolonged R2 latency and decreased R2 amplitude were observed more frequently than R1 abnormalities in the patients. The electromyographic activity of R2 in the patients was lower than that in control subjects more than 13 years old. Almost all patients showed bilateral cerebral atrophy and dilated lateral ventricles, but only one patient exhibited distinct pontine atrophy on cranial computed tomographic scan. These electrophysiologic abnormalities suggest that decreased excitability of interneurons of the reflex arc was present in the patients, particularly in older ones. The blink reflex test seems to be more sensitive than the auditory brainstem response for detecting brainstem dysfunction in patients with cerebral palsy due to neonatal asphyxia.

Adolescent

Discrimination of grip force for preschool children aged 5 to 6 years.

The ability to discriminate grip force was investigated in 30 preschool children aged 5 to 6 years in an experiment controlling for motivation and muscle fatigue. The subjects were required to maintain a relatively high force during the discrimination with forces of the standard stimulus being 1.0, 2.0, and 3.0 kgf. Comparison stimuli changed at an interval of 0.1 kgf. Discrimination was measured in terms of the lower threshold, upper threshold, and interval of uncertainty. Since the statistical analyses indicated that there were no significant gender differences, data for boys and girls were combined. Although the upper and lower thresholds and the interval of uncertainty increased with the force required by the standard stimuli, Weber fractions did not remain constant when the stimulus intensity changed, unlike the findings in previous studies for adults.

Adult

A case of obstructive icterus caused by incarceration of a pancreatic stone in the common channel of the pancreatobiliary ducts.

A 51-year-old man had repeated admissions and discharges from the hospital for alcohol dependence and alcoholic hepatitis. Thereafter, with a diagnosis of chronic pancreatitis, he was examined on an outpatient basis. He presented with right hypochondriac pain as the chief complaint, and was admitted to the hospital because of a suspected acute exacerbation of chronic pancreatitis. Pyrexia and jaundice were present from about the 5th hospital day, and he was admitted to Kurume University Hospital with a diagnosis of obstructive icterus. Percutaneous transhepatic biliary tract drainage (PTBD) was immediately performed. A roentgenogram revealed moderate dilatation of the extrahepatic bile ducts and stricture of the intrapancreatic common bile duct. No calculi were observed in the gallbladder or bile ducts by ultrasonography of the abdominal region. The main pancreatic duct was dilated to 10 mm, and a strong echo, probably a calculus, was observed in the main pancreatic duct. Pancreatoduodenectomy was performed with a diagnosis of stricture of the common bile duct due to chronic pancreatitis with a pancreatic stone. Examination of the excised specimens revealed a rigid pancreatic head; and when the common bile duct was incised, no stricture was observed. A milk-white calculus about 10 mm in diameter was observed in the common channel of the lower portion of the common bile duct. The orifice of the pancreatic duct was also observed at the same site. The common channel was about 20 mm long, and malfusion of the pancreatobiliary ducts was observed. The obstructive icterus was due to an impaction of the pancreatic stone at the confluence of the pancreatobiliary ducts. The calculus was composed of calcium carbonate, and the histopathological findings in the pancreas showed chronic pancreatitis.

Gallstones

[Prospective randomized trial comparing 1/2 FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus palliative therapy for the treatment of unresectable pancreatic and biliary tract carcinomas (the 2nd trial in non-resectable patients). Japanese Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract].

The efficacy of 1/2 FAM, which consists of 5-fluorouracil (5-FU), adriamycin (ADM) and mitomycin C (MMC), was compared with that of palliative treatment in patients with unresectable pancreatic and biliary tract carcinomas in a multicenter randomized trial. The patients assigned to 1/2 FAM group were treated with 5-FU 200 mg/m2/day IV, ADM 15 mg/m2/day IV and MMC 5 mg/m2/day IV. These 3 drugs were given concurrently as the initial dose within a week after palliative operation, and this regimen was repeated for at least 2 whole courses, at 4-week intervals before the next course of therapy. Those randomized to the control group were subjected to palliative treatment alone. Completely eligible for analysis were 42 cases of the 1/2 FAM group and 41 of the control group. There was no significant difference between the groups with respect to the overall and differentiated survival times according to the tumor sites and the clinical efficacy. As for the duration of 50% inhibition of tumor progression, a significantly better outcome was obtained in 1/2 FAM group. Tumor progression was most significantly inhibited in patients with gallbladder carcinoma. In 1/2 FAM group, tumor reduction was achieved in 1 CR and 2 PR patients. The most frequent adverse reaction was gastrointestinal manifestations, along with diarrhea and alopecia. 1/2 FAM did not contribute to the life prolongation, but inhibited the tumor progression for a significantly longer duration and, to a lesser extent, reduced the tumor size in unresectable pancreatic and biliary tract carcinomas. This regimen is suggested to be useful particularly in the treatment of the latter carcinoma.

Adult

[Surgical treatment of esophageal cancer in four patients after gastrectomy for gastric cancer].

The incidence of another cancer in subjects with esophageal cancer is high. Gastric cancer is the most common. We report surgical treatment for esophageal cancer in four patients who underwent gastrectomy for gastric cancer earlier. Extended lymphadenectomy of the neck, mediastinum, and abdomen was performed together with subtotal esophagectomy for three patients with thoracic esophageal cancer. In the two patients who had undergone subtotal gastrectomy and Billroth II reconstruction, the esophagus was reconstructed with part of the colon from the left side, perifused by the left colic artery. In a third patient, who had undergone total gastrectomy and jejunal interposition, reconstruction was done with part of the colon from the right side. In the remaining patient, who had cervical esophageal cancer and who had undergone total gastrectomy, cervical esophagectomy and total laryngectomy were done, followed by free jejunal interposition. One patient with thoracic esophageal cancer died of pulmonary metastasis of the esophageal cancer 24 months after surgery. The three other patients were not found to have recurrence in the most recent follow-up. Esophagectomy and reconstruction are more risky and complicated in patients who have already undergone gastrectomy for malignancy. However, in patients who have undergone curative surgery for gastric cancer, curative treatment for esophageal cancer such as esophagectomy together with extended lymphadenectomy is indicated.

Aged

[Late pericardial effusion after open-heart surgery: usefulness of pericardiocentesis under echocardiographic guidance].

Late pericardial effusion (PE) after open heart surgery has a potential for serious complications, including tamponade necessitating urgent drainage. From October 1990 to March 1995 moderate to massive PE developed following 9 of 359 (2.5%) cardiac procedures between 11 and 55 days postoperatively (mean, 18.6 days). Only one of these nine patients had evidence of cardiac tamponade; the other 8 patients had moderate symptoms including malaise, weight gain, and dyspnea on exertion. All patients except one were being treated with warfarin and anti-platelet agents. Echocardiography detected posterior PE of variable magnitude in all 9 patients; anterior PE was present in only one of these patients. Pericardiocentesis under echocardiographic guidance using an echo transducer with a built in puncture needle was performed in all patients. A flexible catheter was left in place for 24 to 72 hours for suction. In each case, 300 to 712 ml of old bloody fluid (mean, 475 ml) was evacuated, with relief of symptoms. Despite continuing anticoagulant therapy, there was no recurrence of pericardial effusion. The technique we have described simplifies pericardiocentesis and helps to avoid complications in this procedure.

Adult