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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 793 records · Page 44Linked to original sources

Antitumor effect of normal intestinal microflora on Ehrlich ascites tumor.

In order to investigate the antitumor activity of intestinal microflora, the constitution of normal flora was examined in humans, guinea pigs and mice. It was clarified that Eubacterium, Bifidobacterium and Bacteroides were the predominant bacterial genera in humans. In addition, neither Clostridium nor Enterobacteriaceae was detected in guinea pigs and neither Clostridium nor Bifidobacterium was present in mice. Total bacterial counts in tumor-bearing mice were reduced in comparison with those in normal mice. Especially, in the ileum of tumor-bearing mice, the incidence of anaerobic bacterial genera was strikingly decreased. From the bacteria found, 59 living and killed strains isolated from intestinal microflora were examined for antitumor activity against Ehrlich ascites tumor. It was observed that 11 of the tested strains had antitumor activity. Four of these were toxic to the host, and in particular, all mice injected with Pseudomonas aeruginosa (TYM-8) died within several days. Eubacterium lentum (TYH-11), Propionibacterium acnes (TYM-28), Proteus mirabilis (TYM-7) and Serratia marcescens (TY-142), in which antitumor activity was recognized with living and formalin-killed bacteria, cured the tumor-bearing mice, and the culture supernatant of S. marcescens contained apparent antitumor activity.

Adolescent↗

Antitumor activity and its properties of Eubacterium lentum.

In the present study, some basic effects of Eubacterium lentum (TYH-11), isolated from normal intestinal flora, upon the immune system and various experimental tumor cell lines were investigated. E. lentum showed no direct cytotoxicity against Ehrlich ascites tumor, while Serratia marcescens (TY-142) did show direct cytotoxicity. E. lentum presented striking antitumor activity which differed according to the injection route and time. This strain showed antitumor activity against 11 experimental tumor cell lines including Ehrlich ascites tumor, Meth-A, etc., but not against EL4 or Lewis lung carcinoma. The antitumor activity in this strain was recognized to lie in the cell wall and granular fractions. The effect of this strain on the immune system was studied by using plaque formation and the footpad reaction. When mice received 5 injections of E. lentum, the plaque number increased to treble the control level. Spleen weight was also increased following administration of E. lentum. In normal and tumor-bearing mice immunized with SRBC alone, the footpad reaction was increased significantly to the control level by administration of E. lentum.

Animals↗

Immunohistochemistry of human gastrointestinal cancer-associated antigen detected by monoclonal antibody PA 8-15.

A murine monoclonal antibody (MAb), PA 8-15, was produced against a newly established human pancreatic adenocarcinoma cell line, SUIT-2. With the avidin-biotin immunoperoxidase technique, PA 8-15 MAb reacted strongly with 27 of 28 formalin-fixed paraffin-embedded pancreatic adenocarcinoma tissues. All six gall bladder carcinomas and all nine biliary tract carcinomas also showed positive reactions. In addition, PA 8-15 MAb reacted with gastric carcinomas (6/10), colorectal carcinomas (7/11), and some other primary adenocarcinomas. The distribution of PA 8-15 antigen on the same tissues of pancreatic cancer was different from those of CA 19-9 and DU-PAN-2 antigens and CEA. PA 8-15 MAb stained only the epithelium of the pancreatic duct, gall bladder and bile duct in normal adult tissues, and some normal fetal glandular epithelial cells. However, PA 8-15 MAb was not reactive with inflammatory or benign tumors of the digestive system except for the epithelium, as was seen in normal adults. Reactivity of PA 8-15 MAb with tissue specimens largely disappeared after treatment with neuraminidase, while oxidation with periodate or trypsin digestion did not alter the staining intensity, indicating that antigenic determinants may be at least partly of sialylated carbohydrate nature. These results suggest that PA 8-15 MAb detects a new oncofetal antigen in gastrointestinal cancers, especially of the pancreatico-biliary tract.

Animals↗

Oxic and hypoxic cells in a murine squamous cell carcinoma.

[125I]Iododeoxyuridine labeling of a squamous cell carcinoma and follow-up of 125I activity at the tumor in situ revealed that the 125I activity remained at a constant level from the 24th to the 100th hour post-labeling and then decreased with a half time of about 200 hr. Autoradiographic studies with [3H]thymidine showed that the tumor cells were labeled around capillaries, spread through the corded structure (the cord) and finally reached the necrotic regions. One could speculate that the constant 125I period represents the transit time of the labeled cells through the cord and that the decline occurs mostly in the necrotic regions. X-Irradiation shortened the constant period of 125I activity by about 24 hr and accelerated the declining rate in a dose-dependent manner. When tumors were made hypoxic by clamping the legs, the declining rate decreased significantly. When misonidazole (a hypoxic radiosensitizer) was administered before X-rays, the declining rate increased to a level higher than that of the oxic tumors. From the time course studies, it was suggested that the tumor cells immediately after 125I-labeling were oxic, that they became gradually hypoxic during their transit through the cord and that they became anoxic when they reached the necrotic regions.

Animals↗

Psychopathology of K. Schneider's mania.

An investigation of 107 patients diagnosed as having mania, according to the criteria of K. Schneider, showed that this mania is a syndrome of affective, psychomotor, behavioral and formal thought disturbances, while productive psychotic symptoms are rare. Four psychopathological subgroups were defined: (1) mixed mania, (2) irritable mania, (3) megalomania, and (4) flight-of-ideas mania.

Bipolar Disorder↗

Nonpsychopathological features of K. Schneider's mania.

The nonpsychopathological features of 107 patients diagnosed as having mania were compared to those of 1,208 patients with the diagnosis of schizophrenia. Both diagnoses were made according to K. Schneider's criteria. Significant differences were found between the two groups in regard to the age of onset, marital status and educational and occupational levels. Manic patients tended to become ill more as age advances than schizophrenics, and exhibited better educational and occupational levels. The premorbid adjustment level of manic patients was found to be higher than that of schizophrenics.

Adult↗

Villous tumor of the colon: correlation of histologic, macroscopic, and radiographic features.

Forty-six patients with villous or tubulovillous tumors of the colon were examined to study the correlation between histologic and macroscopic or radiographic features and to define more accurately villous tumors of the colon. There was good correlation between the histologic and macroscopic or radiographic features. As villous elements became more prominent on histologic studies, the macroscopic appearance was more villous and granular but less nodular on the surface. Reticular and/or granular patterns with a feathery margin were more frequently seen on radiographs in cases of dominant villous elements. The macroscopic and radiographic characteristics of villous tumor frequently appeared when villous elements composed over 75% of the whole tumor on histologic studies. The authors propose that villous tumor of the colon can be accurately diagnosed when villous elements compose over 75% of the tumor.

Adenoma↗

Intrahepatic ramification of the portal vein in the right and caudate lobes of the liver.

We defined the subsegmental divisions and the ramification patterns of the portal vein in the right and caudate lobes using 25 human liver casts. The ramifications of the portal vein and the subdivisions of the liver were classified based on the major portal veins with the largest diameter and those having a diameter of not less than two thirds of the largest vein in each subsegment. The following results were obtained. (1) The portal trunk showed three ramification patterns and the basic pattern was bifurcation (80%). (2) The anterior portal vein first ramified into several anterior-inferior portal veins (P5) and ran toward the superior direction to bifurcate into 2 major portal veins in the anterior-superior subsegment (S8). (3) There were three types of ramification patterns of the portal veins in S8: bifurcation (84%), trifurcation and one-pedicle type. (4) There were also three branching types of the largest vein (P5-max) in P5: ramification from the anterior portal vein, P8-anterior vein supplying the anterior region of S8 and P8-posterior vein supplying the posterior region of S8. (5) The posterior portal vein showed two ramification patterns of the bifurcation (36%) and nonbifurcation type. (6) The major portal veins in the caudate subsegment ramified at various sites such as the portal trunk, left, right and/or other portal veins.

Humans↗

Pemphigus foliaceus with anti-intercellular and anti-basement membrane zone antibodies. Blocking immunofluorescence and Western immunoblotting studies.

In a patient with clinical, histologic, and routine direct immunofluorescence (IF) findings compatible with pemphigus foliaceus (PF), anti-intercellular and anti-basement membrane zone (BMZ) antibodies were found on indirect IF. Blocking IF studies using the biotin-avidin method revealed that intercellular staining of this patient's serum was significantly decreased by sera of PF patients, however, reaction of this patient's serum was not blocked by sera of PV and BP patients. Western immunoblot analysis using the SDS extracts of normal human epidermis demonstrated that this patient's serum reacted with 370-, 220-, 170-, 130- and 21-kD proteins. Another PF serum reacted with 170- and 21-kD proteins. BP sera reacted with 220-, 68-, 46 and 21-kD proteins. Considering the results of the previous reports and this study, 220- and 170-kD protein bands are specific for BP and PF, respectively, and this is the first case of PF with both anti-intercellular and anti-BMZ circulating antibodies including immunoblotting analysis.

Aged↗

The measurement of platelet aggregation and ATP-release in mice with liver damage induced by carbon tetrachloride (CCl4) using a whole blood aggregometer.

Time course change in platelet function on liver damaged mice was studied by a whole blood aggregometer. The liver damaged animals were produced by single and multiple injections (p.o.) of 20% CCl4 in olive oil to ddY mice (6 weeks). Platelet aggregation and ATP-release were induced with collagen (final conc. of 2 micrograms/ml), ADP (final conc. of 20 microM) and arachidonic acid (AA: final conc. of 100 microM). After a single injection of CCl4, platelet counts increased at 5 and 12 hr, and then they decreased from 24 to 120 hr. Multiple injections of CCl4 resulted in a significant increase in platelet counts. A single injection of CCl4 suppressed aggregation by collagen at 24 and 48 hr and diminished the rate of ATP-release from 12 to 48 hr. AA-induced platelet aggregation was depressed at 48 hr, and ATP-release was also diminished from 24 to 72 hr after a single injection. ADP-induced platelet aggregation was decreased 24 and 48 hr after a single injection and at 48 hr after multiple injections, while, the rate of ATP-release by ADP was significantly increased after single and multiple injections. These changes in platelet functions might be consistent with our original report on the alterations in coagulative and fibrinolytic activities with CCl4-induced liver injury.

Adenosine Diphosphate↗

Inhibitory effect of glycyrrhetinic acid on testosterone production in rat gonads.

We studied the effects of shakuyaku-kanzo-toh (a Chinese herbal medicine) and its components on testosterone production by rat gonads. We used paeoniflorin as a main component of shakuyaku (paeoniae radix), glycyrrhizin as a main component of kanzo (glycyrrhizae radix) and glycyrrhetinic acid as a main metabolite of glycyrrhizin. Oral administration of shakuyaku-kanzo-toh, glycyrrhizin, and glycyrrhetinic acid decreased in vitro basal testosterone production in Leydig cells by LH stimulation. Glycyrrhizin and glycyrrhetinic acid caused a significant decrease in testosterone production with an accumulation of 17 alpha-hydroxyprogesterone when incubated with isolated Leydig cells, while paeoniflorin showed no such effect. The inhibitory effect of glycyrrhetinic acid was far more potent than that of glycyrrhizin, causing about 90% inhibition at 10 micrograms/ml. Glycyrrhizin and glycyrrhetinic acid did not change the cyclic AMP or progesterone level in the Leydig cells. When 14C-labeled androstenedione was incubated with microsomal fraction of testicular or ovarian tissue, glycyrrhizin and glycyrrhetinic acid inhibited the conversion of androstenedione to testosterone, indicating that these compounds inhibit the activity of 17 beta-hydroxysteroid dehydrogenase (EC. 1.1.1.64). The ED50 of glycyrrhetinic acid was about 4 microM.

17-alpha-Hydroxyprogesterone↗

Effect of maternal hyperglycaemia on insulin secretion by monolayer cultures of pancreatic cells from neonatal rats: a perifusion study.

The effect of maternal hyperglycaemia on the function of neonatal B cells was examined using a perifusion technique in pancreatic monolayer cultures of neonatal rats from normoglycaemic mothers (C), and those made slightly hyperglycaemic (SH) and highly hyperglycaemic (HH) by injection of streptozotocin. Monolayer cultures were kept for 7 days in medium containing 5.5 mmol glucose/1 plus 1 mmol 2-deoxy-glucose/1. On day 0, B cells in the C group responded to 16.7 mmol glucose/1, 10 mmol leucine/1 and 10 mmol 2-ketoisocaproate/1 in a monophasic fashion with no significant rise in the second phase. However, compared with the C group, a significant increase in the second-phase secretion in response to glucose and 2-ketoisocaproate was observed in the SH group, although there was no difference in the first-phase secretion. In the HH group the insulin secretion was lower in the first phase but not in the second phase. After culture for 7 days, B cells in the C group showed a biphasic response to the secretagogues, with a great increase in the second-phase secretion. In the SH group, the second phase of insulin secretion was increased but the increment was far less than that in the C group. The secretory response was remarkably low in the HH group compared with other groups. From these results, we conclude that at an early stage of culture slight maternal hyperglycaemia causes a hypersensitivity of neonatal B cells but impairs the normal development of the function of B cells during culture, and that high hyperglycaemia results in impaired insulin secretion throughout the whole period of culture studied.

Animals↗

Effects of p-tert-butylphenyl trans-4-guanidinomethylcyclohexane carboxylate hydrochloride (NCO-650) and its metabolite, p-tert-butylphenol(BP) on drug-metabolizing enzymes and fine structure in rat liver.

The effects of p-tert-butylphenyl trans-4-guanidinomethylcyclohexane carboxylate hydrochloride (NCO-650) and its metabolite, p-tert-butylphenol(BP), on the drug-metabolizing enzymes and fine structure in the rat liver were examined. Aminopyrine demethylase activity was inhibited by the administration of NCO-650 and BP at a dose of 2 and 10 mg/kg, p.o. The increases of microsomal cytochrome b5 and cytochrome P-450 contents were noticed at 1, 12 and 24 hr after NCO-650 and BP administration. Ascorbate-dependent lipid peroxidation of mitochondria and microsome increased by the administration of NCO-650 and BP, but NADPH-dependent lipid peroxidation decreased by these drugs. In the morphological observations of fine structure in the liver, NCO-650 and BP caused the swelling and decrease of rough endoplasmic reticulum and the increase of smooth endoplasmic reticulum. The morphological changes of liver fine structure were related to the changes of drug-metabolizing enzymes in the liver by the administration of NCO-650 and BP, which may be suggest the transitory and functional responses of these drugs in the liver. The effect of BP on the drug-metabolizing enzymes and fine structure in the liver was similar to that of NCO-650.

Aminopyrine N-Demethylase↗

Face EMG Topographic analysis of mimetic movements in patients with Bell's palsy.

A face EMG topography system was newly designed and manufactured by the authors. During mimetic actions, such as wrinkling the forehead, closing the eyes, blinking, grinning and blowing out the cheeks, EMG from 16 disk electrodes were concurrently recorded from the frontalis, orbicularis oculi, and orbicularis oris muscles on both sides. The EMG spike potentials fed to on-line computer processing were integrated and calculated with an interpolation formula in the computer, and the colour topographic figures derived from these calculations were displayed on CRT and printed out. These topograms were related to the amount of muscular activity. This technique was applied to 33 patients with Bell's palsy to document the degree and the time course of their mimetic dysfunction. The results obtained were reliable and reproducible. This technique will be useful as one of the proposed methods on grading of facial movement loss in clinical practice.

Adult↗

Biphasic ventricular dilatation following posterior fossa subdural hematoma in the full-term neonate.

Five full-term neonates with a posterior fossa subdural hematoma caused by birth injury are reported. All of the patients were successfully treated with surgery. They all presented with biphasic ventricular dilatation as demonstrated by serial computerized tomography (CT) scanning. The initial dilatation due to obstructive hydrocephalus disappeared after removal of the hematoma; however, a second dilatation without obstruction of the ventricular system developed between 2 and 4 weeks after surgery. A ventriculoperitoneal shunt was required in one case because of progressive enlargement of the head size in the chronic stage. The other four patients showed transient dilatation of the ventricles without symptoms of increased intracranial pressure. Subarachnoid hemorrhage associated with posterior fossa subdural hematoma is considered to be the most likely causative factor for the delayed ventricular dilatation. The degree of dilatation roughly depended on the volume of the subarachnoid clot that was demonstrated on the initial CT scan.

Birth Injuries↗

Physical properties of flowing blood.

The changes of viscosity, optical reflection and electrical resistivity of blood due to flow are dependent on the orientation and deformation of red cells. From electrical point of view, it can be assumed that blood is suspension of small insulating particles (red cells) in conductive fluid (plasma) when the frequency of supplied voltage is lower than several hundreds KHz. When blood flows, red cells deform and orient in flow direction. Therefore, flowing blood shows anisotropic electrical and optical properties. In steady flow, blood resistivity longitudinal to flow decrease with flow rate, and transverse one increases. Blood flow in living body is not steady but pulsatile. We measured both longitudinal and transverse resistivity changes, optical reflection change and viscosity change of sinusoidally flowing blood in a rectangular conduit. The results are 1) during one period of sinusoidal flow the longitudinal resistivity change is opposite to that of transverse one, 2) the waveform of reflection light change is similar to that of resistance change, and 3) minimum points of both longitudinal resistivity and viscosity changes do not appear at the moment when flow is zero but are delayed. When the amplitude of sinusoidal flow is small and oscillation frequency is high, the phase difference between the zero crossing period of flow and the period of minimum change in resistivity, increases up to 90 degrees. Viscosity of blood decreases with increase of amplitude and frequency of sinusoidal flow.

Animals↗