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Biomedical subjects

M Ishida

Publications and source records attributed to M Ishida.

At least 433 records · Page 24Linked to original sources

[Anti-tumor and adverse effect of etoposide and cisplatin on human choriocarcinoma transplanted to nude mice--a correlation between effect and tissue distribution of the drugs].

The study dealt with anti-tumor and adverse effects of etoposide and cisplatin on human choriocarcinoma cell line (GCH-1) transplantable in nude mice in relation to the rate of their uptake into tumor tissue. Nude mice were divided into 3 groups (etoposide, cisplatin and MTX-group), 7 to 9 per group and received drug treatment which started when their tumor grew to 100 approximately 300 mm3 in volume. All drugs were intraperitoneally administrated to nude mice (each drug: 1/4 mouse LD50 dose X3, weekly). The inhibiting action on the tumor was observed to be etoposide greater than cisplatin greater than MTX. The body weight loss of nude mice was observed to at its maximum in the cisplatin-treated group. The serum beta-HCG level did not rise in the drug-treated groups but rose in the non-treated control group. No histopathological changes characteristic of each drug were found. A concentration of etoposide and cisplatin in various tissues was serially measured after one shot intraperitoneal injection of etoposide 25 mg/kg or cisplatin 5 mg/kg. Etoposide reached its peak concentration after 30 minutes in tumor, liver and kidney and, after 4 hours, was left with 37.1%, 10.4% and 2.3% concentrations after 30 minutes in tumor, liver and kidney, respectively. Cisplatin showed similar kinetics, but was found to remain at a comparatively high concentration in both liver and kidney. Thus, it was demonstrated that etoposide and cisplatin were active against the human choriocarcinoma cell line. Furthermore, the less adverse effect of etoposide was felt to be partially due to its lower residue in liver and kidney.

Animals↗

Immunological study of tissue polypeptide antigen (TPA)--demonstration of keratin-like sites and blood group antigen-like sites on TPA molecules.

We examined the immunological cross-reactivity between tissue polypeptide antigen (TPA) and keratin protein because of the reported sequence homology between these two proteins. TPA showed positive immuno-reactivity against both polyclonal and monoclonal antibodies for keratin. The binding of [125I]TPA with anti-keratin could be displaced dose-dependently by unlabeled keratin. However, no cross-reaction between keratin and anti-TPA was found. TPA also showed the positive immuno-reactivity with antibodies for blood group antigens (A, B and Lewis substances), but keratin did not. A standard solution of Lewis substance reacted with neither anti-TPA nor with anti-keratin. These data strongly suggest that TPA has an immunological similarity with both keratin protein and blood group antigens. When [125I]TPA and [125I]keratin were gel-filtered on a Sephadex G-200 column, the radioactivities of TPA and keratin were found mainly in the void volume fraction (MW greater than 200 000) and the MW of approximately 60 000, respectively. Chromatography on Sepharose 6B suggested that the MW of [125I]TPA was 320 000. When sera of cancer patients were gel-filtered on a Sephadex G-200 column, TPA activity was distributed mainly in the void volume fraction in all tested cases. This experiment suggests that TPA may be a glycoprotein (MW is 320 000) with both keratin-like and blood group antigen-like determinants.

Antibody Specificity↗

Inhibitory actions of tuberostemonine on the excitatory transmission at the crayfish neuromuscular junction.

At the crayfish neuromuscular junction, tuberostemonine, an alkaloid from Stemona japonica, reduced the amplitude of both the excitatory junctional potential (e.j.p.) and the glutamate response in a dose-dependent manner at concentrations above 0.1 mM. Tuberostemonine acted presynaptically on the crayfish neuromuscular junction to reduce a quantal content of extracellularly recorded e.j.p.s, and postsynaptically to reduce their unit size. The decay of the excitatory synaptic current was accelerated by tuberostemonine. The gradual decline of the successive glutamate currents induced by a train was facilitated by the presence of tuberostemonine even in the muscle fibre pre-treated with concanavalin A. The rate of recovery from the refractory form of the glutamate receptor to the free reactive one was slightly affected by tuberostemonine when it was determined by using a paired pulse method. The inhibitory action of tuberostemonine on glutamate responses was voltage-dependent and hyperpolarization increased the drug action. These results indicate that tuberostemonine acts in part as an open-channel blocker at the crayfish neuromuscular junction.

Alkaloids↗

Importance of coronary collaterals for restoration of left ventricular function after intracoronary thrombolysis.

In an evaluation of the role of coronary collaterals in the early period of acute myocardial infarction (AMI), 30 patients with acute total coronary occlusion treated with intracoronary thrombolysis 2 to 8 hours after the onset of symptoms were studied. Only 13 patients with well-developed collaterals in the early period of AMI and successful thrombolysis showed improvement of global and regional ejection fraction (EF) from the acute phase to the chronic phase (global EF from 50% to 71%, p less than 0.001; regional EF from 25.4% to 49.2%, p less than 0.001). In patients with no or less well-developed collaterals and successful thrombolysis, global and regional EF were similar to those in patients in whom thrombolysis was unsuccessful. Among the 19 patients with successful thrombolysis, there was no significant correlation between the duration of ischemia and the improvement of regional EF (r = -0.03, difference not significant). These data suggest that the extent of coronary collateral vessels in the early period of AMI is an important determinant of restoration of left ventricular function after intracoronary thrombolysis.

Acute Disease↗

Cross-reactivities of neuropeptide Y and peptide YY with pancreatic polypeptide antisera: evidence for the existence of pancreatic polypeptide in the brain.

Highly purified neuropeptide Y (NPY) and peptide YY (PYY) did not cross-react in our human pancreatic polypeptide (hPP) radioimmunoassay, nor did 125I-labelled NPY and PYY, even with anti-hPP serum at low dilution (1:1000). However, both [125I]NPY and [125I]PYY significantly cross-reacted with anti-bovine PP (bPP) serum at low dilution (1:1000, similar to that used in immunohistochemistry). These results suggest that radioassayable hPP-like peptide in the porcine or canine brain is probably pancreatic polypeptide itself, otherwise immunohistochemically detected bPP-like peptide may represent both NPY and PP.

Amino Acid Sequence↗

Antigenic characterization of hemagglutinin-neuraminidase (HN) protein of avian paramyxoviruses by specific antisera to isolated HN subunits.

Specific antisera for the isolated HN proteins of eight reference strains of avian paramyxoviruses could be prepared in guinea pigs by intraperitoneal injection of guinea pig red blood cells (GRBC) coated with purified HN proteins. In the hemagglutination inhibition (HI) tests, all reference strains reacted strongly with each homologous antiserum to the isolated HN showing that a low level of cross-reactivity among the reference strains was greatly diminished by using specific antisera. Immuno-double-diffusion (IDD) tests showed that all antisera except those to turkey/Wisconsin/68 and duck/Hong Kong/D3/75 gave single well-defined lines only with the homologous viruses. The remaining two antisera developed a single definite precipitin line together with weak lines with homologous virus. Two isolates in Japan were clearly identified in HI and IDD tests with specific antisera to the HN subunits of the reference strains suggesting that the antisera were useful for identification of avian paramyxovirus isolates. Two isolates in Japan, H-70 from a munia-bird and Y-7 from a duck were found to have HN proteins related closely to those of finch/N. Ireland/Bangor/73 and duck/Hong Kong/199/77, respectively.

Animals↗

Characterization of reference strains of Newcastle disease virus (NDV) and NDV-like isolates by monoclonal antibodies to HN subunits.

The hemagglutinin-neuraminidase (HN) subunits of NDV and NDV-like isolates were analyzed antigenically by monoclonal antibodies to the HN of Miyadera and Taka viruses. In immuno-double-diffusion (IDD) tests, all NDVs examined gave clear lines of precipitation with some of the potent monoclonal antibodies, but it was difficult to determine with certainty the immunological properties of HN subunits due to a rare disagreement with the results obtained in other immunological tests. Monoclonal antibodies used in the tests were found to show different immunological reactivities with the viruses. Monoclonal antibodies belonging to the 1st group (1/29) inhibited the hemagglutinating (HA) activity of all strains but not the neuraminidase (NA) activity. The second monoclonal antibody (5/205) inhibited both the HA and NA activities of the restrictive NDV strains, indicating antigenic changes in HN molecules. However, the inhibitory activity of this monoclone to neuraminidase appeared to be greatly diminished when neuraminyl lactose was used as substrate. Although the 3rd type of monoclonal antibody (5/220) showed HI activity against several strains, this antibody did not inhibit NA activity of any viruses. The remaining monoclone to the HN of Taka virus inhibited the HA activity of all reference strains of NDV and many NDV-like isolates but did not affect NA activity. Two inhibitory activities of four monoclonal antibodies against different viruses, HI and hemolysis-inhibition, were not always consistent with inhibition of virus growth. HI and NI tests with the above four monoclonal antibodies showed that the strains tested fell into five antigenic groups according to their reaction patterns with mouse hybridoma antibodies.

Animals↗

Further studies on quantification of drug-induced tremor in mice: effects of antitremorgenic agents on tremor frequency.

The effects of diazepam, dantrolene and atropine on drug-induced tremors were investigated in mice from the point of view of the tremor frequency. The study involved a power spectral analysis of the random current induced by movement of a magnet (attached to the mouse) on a wire coil. To induce tremor, tremorine and harmaline were subcutaneously injected. The power spectral density function defined the frequency composition of the tremor and its severity was determined quantitatively in terms of the mean square value of the data in any frequency range of concern. Diazepam markedly depressed the power spectral density of the tremorine- and harmaline-induced tremor and reduced the tremor frequency. With higher doses of diazepam, the peak frequency of the tremorine-induced tremor shifted to the lower frequency side as if the tremor components were taken into the component of the spontaneous motor activity. Dantrolene and atropine suppressed the power spectral density without affecting tremor frequency. The relationship between the change of tremor frequency and the site of action of antitremorgenic agents are discussed.

Animals↗

Construction of novel shuttle vectors and a cosmid vector for the glutamic acid-producing bacteria Brevibacterium lactofermentum and Corynebacterium glutamicum.

Novel cloning vectors for glutamic acid-producing bacteria have been constructed. Two cryptic plasmids, pAM330 from Brevibacterium lactofermentum and pHM1519 from Corynebacterium glutamicum, were used as precursors, and recombined with pBR325 or pUB110. Resultant composite plasmids were able to propagate and to express the CmR or KmR phenotype in B. lactofermentum and C. glutamicum. A smaller, high-copy-number plasmid, pAJ43, was also isolated following deletion of a part of the pAM330-pBR325 composite plasmid. Furthermore, a cosmid vector, which can be packaged and transduced through phage infection, has been developed using a cohesive-end fragment of the f1A phage and plasmid pAJ43. These plasmids are suitable for use as cloning vectors in the glutamic acid-producing bacteria.

Brevibacterium↗

Studies on circulating antibody against carcinoembryonic antigen (CEA) and CEA-like antigen in cancer patients.

Characteristics of auto-antibodies for carcinoembryonic antigen (CEA) detected in sera from 3 cancer patients (2 colorectal and 1 breast cancer) were examined. The antibodies belonged to polyclonal immunoglobulin G (IgG). The binding of auto-antibodies with the labeled CEA was inhibited by not only the unlabeled CEA but also NCA-2 (feces and meconium). However, no binding with NCA was observed. Among these auto-antibodies the antibody directed against blood group Lewis determinants which are known to be present in many purified CEA preparations was not found. Previously we had suggested that CEA, NCA-2 and NCA may contain immune determinant in common with alpha 1-acid glycoprotein (AG). These auto-antibodies showed significantly enhanced reactivity for the labeled CEA preparation after purification by anti-AG affinity chromatography in spite of no immunological reaction with AG. These results suggest that auto-antibodies are raised against the common antigenic determinants of both CEA and NCA-2 which do not exist in NCA. These antibodies might be directed to common amino acid sequence shared by CEA and NCA-2, though not excluding the carbohydrate moiety. We surveyed about 500,000 cancer patients but could find only 3 patients who showed a difference in the values of CEA by the indirect and direct method. Thus, the existence of this type auto-antibody to CEA in cancer patients is a rare phenomenon.

Aged↗

Aqueductal stenosis--results of vestibular function tests.

A case of aqueductal stenosis is reported. The patient was a 14-year-old Japanese girl who was suffering from bilateral tinnitus and unsteadiness of gait. A series of neuro-otological tests revealed prolonged acoustically evoked brain stem response (ABR) latency, disturbed standing reflex, inhibited optokinetic nystagmus (OKN) and ataxic eye tracking test (ETT). Marked distension of the lateral and third ventricles was noticed on CT examination of the brain. A positive contrast ventriculogram using iotalamic acid showed occlusion of the cerebral (Sylvian) aqueduct. All of these results are suggestive of benign, non-neoplastic aqueductal stenosis with associated hydrocephalus. The patient underwent ventriculo-peritoneal shunt and, following the surgery, the results of neuro-otological, including radiological, re-examination indicated a remarkable recovery.

Adolescent↗

TI-233 as a glutamate channel blocker at the crayfish neuromuscular junction.

Effects of TI-233 (4-isopropyl-1-[N2-(5,6-dimethyl-aminonaphthalene-1-sulphonyl)-L-arginyl ]- piperidine) on glutamate-induced responses and nerve-evoked synaptic responses were compared at the crayfish neuromuscular junction. Intracellularly recorded excitatory junctional potentials (e.j.ps) were markedly augmented by TI-233 when they were evoked at long intervals, whereas the unit size of extracellular e.j.ps was hardly affected by TI-233 and, at that stage, the glutamate-induced current was markedly reduced by TI-233. The decay rate of extracellular e.j.ps was slightly increased 3 min after the addition of TI-233 at concentrations higher than 0.05 mM. Repetitive stimulation of the excitatory axon at a high frequency caused a gradual decrease in the amplitudes of extracellular e.j.ps in the presence of TI-233. After prolonged application of TI-233 with repetitive nerve stimulation, the glutamate-induced response became significantly smaller than the control. TI-233 increased the input resistance of the crayfish muscle fibre and facilitated transmitter release at the excitatory neuromuscular junction. These two effects would entirely explain the augmentation of intracellular e.j.ps by TI-233. TI-233 (greater than 3 microM) reduced the amplitude of current responses to trains of glutamate pulses in a dose-dependent manner, but this reduction by TI-233 was time- and activity-dependent. The effect of TI-233 on glutamate-induced responses was voltage-dependent and hyperpolarization increased this effect. Pretreatment of the muscle fibre with concanavalin A did not affect the gradual decline, caused by TI-233, of the successive currents evoked by a train of glutamate pulses. The apparent differences between the glutamate-induced current and nerve-evoked synaptic response revealed by TI-233 can be explained by open-channel block of the glutamate-activated ion-channel, and do not confute the hypothesis that glutamate is the natural transmitter substance at this junction.

Animals↗

Purification and some properties of a low molecular weight trypsin inhibitor from acute pancreatitis urine.

Urinary trypsin inhibitors (UTIs) from the urine of a patient with acute pancreatitis consisted of three forms with different molecular weights. These were highly purified by ammonium sulfate precipitation, Sephadex G-75, SP-Sephadex C-25 and trypsin-Sepharose 4B column chromatography. The lowest molecular weight of UTIs was estimated to be 6,200 daltons. Moreover, five residues of N-terminal amino acids and a C-terminal amino acid were the same as those of pancreatic secretory trypsin inhibitor.

Acute Disease↗

Increased ferritin levels in the fluid of thyroid cyst.

High ferritin levels in the aspirate of thyroid cyst (Six yellow clear, 4 yellow turbid and 10 chocolate colored turbid) without apparent sings of malignancy were found. The mean concentration in the 3,000 X g supernatant of the fluid was 40,116 ng/ml, and the 3,000 X g precipitate was 11,147 ng/ml. All cases showed normal levels of serum ferritin. Con A binding with ferritin was distributed from low to high. These ferritins showed a molecular weight of approximately 450,000 which was the same as found in human spleen and liver. The continuous increase in ferritin levels in thyroid cyst fluid was found by a chronological study in some cases. When tumor markers such as CEA, NCA, CA 19-9 and alpha 1-acid glycoprotein (alpha 1-AG, acute phase reactant) were examined simultaneously, an increase in some of the cyst fluid was observed. However, the incidence and the rate of increase of these tumor markers and acute phase reactant were low compared to ferritin. Neither a correlation between ferritin and CEA, nor between ferritin and CA 19-9 was found. The increase in ferritin in thyroid cyst fluids may be due to the increased synthesis, release and storage by the inflammatory cells.

Antigens, Neoplasm↗