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Biomedical subjects

M Kataoka

Publications and source records attributed to M Kataoka.

At least 325 records · Page 18Linked to original sources

Search for immunobiological parameters predictive of clinical effects of OK-432 in patients with malignant ascites.

Although OK-432, a potent BRM, has been known to induce the remarkable improvement of clinical conditions in cancer patients through its strong effects on their immune capabilities, no specific immune parameters have been identified to best predict the clinical outcome after the OK-432 treatment. In an attempt to identify early parameters indicative of the clinical effects, we have administered 0.1 mg of OK-432 intraperitoneally to a total of 12 patients with malignant ascites and examined peritoneal fluid and peripheral blood obtained on 4 days before, 1, 3, and 7 days after the OK-432 injection using various immunobiological assays. Four weeks later, clinical improvements were evaluated by the disappearance of malignant cells from and/or substantial decrease in ascites. Four patients (responders) showed the improvements while 8 patients (nonresponders) showed no clinical evidence for improvement. In a few parameters among the many examined, significantly different patterns of changes were noted between responders and nonresponders. Thus, in nonresponder patients MO and T cell population returned to an initial low level after early increases (on days 1 and/or 3), while they remained increased day 1 through 7 in responders. In responder patients, the cytotoxicity of peritoneal mononuclear cells against K562 and Daudi cells were augmented on day 7, but not in nonresponder patients. The in vitro stimulation of the mononuclear cells with OK-432 enhanced the cytotoxic activity and induced the interferon (IFN) production in the responders but not in nonresponders. These parameters will be useful for the early prediction of the expected clinical effects of OK-432.

Adult↗

Analysis of antitumor effects of OK-432 against syngeneic mouse fibrosarcoma: combination effect of OK-432 and recombinant lymphokines.

OK-432, a streptococcal preparation with potent biological response modifying activities, had the ability to cure mice bearing BAMC-1 (fibrosarcoma) ascites when it was injected intraperitoneally five times, 2, 4, 6, 8, and 10 days after the tumor inoculation. Previously, it was shown that the OK-432 injection on day 2 was indispensable since only a minimal antitumor effect was obtained when an inflammation-inducing agent such as thioglycolate instead of OK-432 was injected on day 2, followed by four OK-432 injections on days 4, 6, 8 and 10. In the present study, the injection of OK-432 on day 2 and a subsequent injection of either IL-2 or IFN-gamma on day 4 or 6 showed a significant antitumor effect, achieving a complete cure in approximately 50% of mice treated, although none of the mice could be cured by a single injection of either OK-432, IL-2, or IFN-gamma on day 2. Interestingly, however, the mice treated with an injection of a lymphokine (IL-2 or IFN-gamma) on day 2 followed by OK-432 on day 4 were not cured either. Peritoneal cells on day 12 in mice treated with OK-432 and either of the lymphokines contained pantropic killer cells, which were Thy-1+ and asialo GM1+ (AsGM1+). Moreover, the antitumor effect of the combined treatment was abolished when mice were pre-treated with anti-AsGM1. No significant antitumor effect was observed in athymic nu/nu mice. Together with our previous findings, these results indicate that lymphokines induced by OK-432 administration may account for some of its therapeutic effects and that these lymphokines may also facilitate the subsequent induction of specific killer cells. These results warrant further investigation on possible effective therapeutic protocols with the combined use of OK-432 and lymphokines.

Animals↗

Early and delayed I-123 IMP SPECT in epileptic patients with partial seizures and normal CT.

Forty-six epileptic patients with partial seizures and normal CT underwent 48 examinations of early and delayed SPECT using I-123 IMP in the interictal phase. One of them underwent a follow-up SPECT in a more stable state compared to the first SPECT. Another patient, with informed consent, underwent a follow-up SPECT in combination with pharmacologic activation with bemegride. Early SPECT was performed 30 minutes after an IMP injection and delayed SPECT 4 to 4 1/2 hours later. Temporal changes in uptake pattern were visually classified into six types and compared with known patterns of SPECT uptake in relation to ischemic, hyperemic, and other changes. These were also correlated with the amount of epileptic activity seen on the EEG.

Adolescent↗

Aberrant elevation of tyrosine-specific phosphorylation in human gastric cancer cells.

Phosphotyrosine-containing proteins in various human cancer cell lines were studied by immunoblotting with anti-phosphotyrosine antibody. Of 29 cell lines derived from oral epidermoid cancer, esophageal cancer, gastric cancer, colon cancer, pancreatic cancer, hepatocellular carcinoma and malignant melanoma, 3 of the 6 gastric cancer cells showed aberrant elevation of tyrosine-specific phosphorylation. On the other hand, both esophageal cancer cells and colon cancer cells, which were reported to have amplified epidermal growth factor receptor and activated p60v-src kinase, respectively, showed no apparent elevation of tyrosine-specific phosphorylation, and their profiles of phosphorylation were similar to that of normal human fibroblasts. Two gastric cancer cells, NUGC-4 and MKN-45, showed similar profiles of phosphorylation but their responses to growth factors differed from each other. Tyrosine phosphorylation in NUGC-4 was strongly activated by treatment with epidermal growth factor and quickly reduced by the acid treatment which is effective in removing growth factors from cellular surface receptors. On the contrary, phosphorylation in MKN-45 did not respond to either growth factor or acid treatment. These results suggest that NUGC-4 and MKN-45 have tyrosine kinases which are activated by different mechanisms but share similar substrates.

ErbB Receptors↗

Five genes involved in self-transmission of pSN22, a Streptomyces plasmid.

An 11-kbp multicopy plasmid, pSN22, was isolated from Streptomyces nigrifaciens SN22. pSN22 is self-transmissible (conjugative), is maintained stably in S. lividans, and forms pocks in a wide range of Streptomyces strains. Mutational analyses showed that a fragment of pSN22 contained five genes involved in plasmid transfer and pock formation. traB was essential for plasmid transfer. traA was required for pock formation, but not for plasmid transfer. spdA or spdB were concerned with pock size; mutations in these genes decreased pock size. The fifth gene, traR, could be deleted together with other genes to give nontransmissible plasmids, but plasmids with insertions or deletions only within traR became nonviable. traR is probably needed to counterbalance the lethal effects of another plasmid gene. Transfer of pSN22 promoted the cotransfer of nontransmissible plasmids and enhanced chromosome recombination between the host and recipient strains, suggesting that plasmid transfer accompanies cytoplasmic mixing.

Conjugation, Genetic↗

Regulation and function of the Streptomyces plasmid pSN22 genes involved in pock formation and inviability.

pSN22 is an 11-kb multicopy plasmid from Streptomyces nigrifaciens which is being studied in Streptomyces lividans. A segment of about 7 kb of pSN22 contains five genes involved in conjugation. Three of them, traA, traB, and traR, are essential for plasmid transfer and for the mobilization of chromosomal markers (fertility), while the remaining two genes, spdA and spdB, merely enhance the efficiency of plasmid transfer, resulting in the formation of larger pocks. In vitro promoter-probing experiments identified a 550-bp BglII-SmaI DNA fragment with promoter activity in both orientations; Northern (RNA blot) hybridization identified corresponding divergent transcripts of 1 and 5.2 kb for traR and the traA-traB-spdB operon, respectively. The traR gene product repressed its own transcription and also the transcription of the traA-traB-spdB operon. Plasmids containing a functional traB gene could not "survive" without traR being present in the same cell either in cis or in trans, presumably because unregulated expression of traB is lethal to the host. Plasmids with a functional traA gene but without traR had a low transformation efficiency and inhibited the growth of host cells.

Blotting, Northern↗

Quantitative lymphoscintigraphy using 99Tcm human serum albumin in patients with previously treated uterine cancer.

To evaluate the clinical usefulness of lymphoscintigraphy using 99Tcm human serum albumin (99Tc-HSA) in assessing lymphoedema in the lower extremities, lymphoscintigraphy was performed by subcutaneous injection of 7.4 MBq of 99Tcm-HSA in 26 patients with uterine cancer, previously treated by operation (OP) and/or radiation therapy (RT), and in five controls. Radioactivity at the injection site in the lower extremities was counted for 3 min at 10 min (A) and at 3 h (B) after injection, and clearance of 99Tcm-HSA was defined as (1-(B)/(A)) x 100(%). Clearance in controls was 46.8 +/- 3.9%, which was significantly more than those in the other treatment groups. Clearances in patients treated with both OP and RT were less than those in patients treated with either OP or RT alone (30.1 +/- 11.4 vs. 41.9 +/- 8.9, 43.7 +/- 9.6%, respectively; p less than 0.01). The clearance in legs with lymphoedema was less than those without lymphoedema in patients treated with both OP and RT (16.6 +/- 7.7 vs. 34.9 +/- 9.3%; p less than 0.01) and in patients treated with RT (33.1 +/- 7.4 vs. 48.0 +/- 5.6%; p less than 0.01). There was a significant difference between clearance in controls and clearance in non-oedematous patients' legs treated with OP and RT (p less than 0.01). In patients treated with RT alone, radiation dose was closely correlated with 99Tcm-HSA clearance and with the development of lymphoedema. These data suggest that lymphoscintigraphy using 99Tcm-HSA is useful in evaluating lymphoedema and that radiation dose is one of the factors in the development of lymphoedema.

Adult↗

Ultrastructural characteristics of lymphokine-activated killer cells of the rat in comparison with natural killer cells.

Lymphokine-activated killer (LAK) cells with a broad spectrum of tumor cell killing have been reported to be related to natural killer (NK) cells morphologically and phenotypically. We here examine the ultrastructural characteristics of LAK cells of the rat, comparing them to those of normal and OK-432-activated NK cells. Results show that, five days after the culturing of spleen lymphocytes with human recombinant interleukin-2, there were induced LAK cells, which were large granular lymphocytes and had a cytotoxic capacity against NK-resistant P-815 tumor cells. They were larger in size than NK cells and richer in cell organelles such as ribosomes, rough endoplasmic reticulum, a Golgi apparatus, granules and vesicles. The granules of LAK cells were shown to be related to multivesicular bodies as those of NK cells; they included multivesicular bodies, fully dense granules and intermediate forms between them. The average numbers and sizes of the granules and the proportion of multivesicular bodies and intermediate forms among the total granules were greater in LAK cells than in NK cells. The density of the small vesicles packed in multivesicular bodies and intermediate forms was much higher in LAK cells. At the contacting surface of the LAK cells bound to the target cells, exocytosis of multivesicular bodies was shown to occur. We recognized here two populations of LAK cells with different types of vesicles, one containing rod-cored vesicles and the other a new type of vesicles termed "demilune-cored vesicles". The latter vesicles were the same in size as the rod-cored ones and contained a dense core located eccentrically. Between these two populations of LAK cells, there was no difference concerning the profile of the dense granules. The present study indicates that, although LAK and NK cells share several ultrastructural features, the former show markedly enriched cell organelles, which indicate an accelerated metabolism of the cell for continuous proliferation.

Animals↗

The intracellular distribution of cell organelles in natural killer cells during the cytolysis of bound tumor cells, with special reference to the rod-cored vesicles.

The secretory function of the natural killer (NK) cells has been considered to be essential for cytolytic activity against their target cells. In this study, the distribution and spatial relationship of various cell organelles which participate in the secretory process, i.e., Golgi apparatus, vesicles, granules and microtubules, were examined ultrastructurally in non-treated and OK-432-activated rat NK cells bound to the tumor cells, with special reference to the rod-cored vesicles which are the most characteristic structure of the NK cells. Rod-cored vesicles and their closely related structures, "empty" vesicles, were derived from the end portion of the Golgi trans cisternae and became accumulated in the central area which was surrounded by the Golgi apparatus, nucleus and contact surface. Some of the vesicles appeared to be further transported to the contact area along the microtubules extending from the centrioles toward the bound targets. The access of the vesicles to the contact surface occurred at that portion where subplasmalemmal actin lattice was thin. The distribution of the dense granules and multivesicular bodies was similar to that of the vesicles, but the area of their occurrence was a little wider. At the outer aspect of the Golgi apparatus was situated the endoplasmic reticulum from which transitional vesicles came to the inner or cis cisternae of the apparatus. The present observations indicate that the cell organelles of the conjugated NK cells are purposefully arranged in the cytoplasm in such order that the generated rod-cored vesicles and "empty" ones are efficiently directed toward the bound tumor cells.

Animals↗

Synthesis of [carbonyl-14C]sparfloxacin.

A new antimicrobial quinolone, sparfloxacin (5-amino-1-cyclopropyl-7- (cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline -3- carboxylic acid, AT-4140; CAS 110871-86-8), was labeled by 14C for studies of disposition and metabolism. Ethyl pentafluoro[carbonyl-14C]benzoylacetate (I) was reacted with ethyl orthoformate, cyclopropylamine and then potassium tert-butoxide to give a quinolone intermediate (IV). A benzylamino derivative (V) obtained by condensation of IV and benzylamine was subject to catalytic hydrogenolysis and hydrolyzed to give the carboxyl derivative (VII), which was condensed with cis-2,6-dimethylpiperazine to form [carbonyl-14C]sparfloxacin. The average yield of 3 preparations was 41.5% and specific activities were 310.8-366.3 MBq (8.4-9.9 mCi)/mmol. Both chemical and radiochemical purities were greater than 99%.

Chromatography, Thin Layer↗

[Hyper-thermo chemotherapy of esophageal cancer with thermosensitive liposome, TAC-1043].

Antitumor activity of the thermosensitive liposome, TAC-1043, was examined. The TAC-1043, produced by Takeda Chemical Industries, Ltd., contained entrapped cisplatin in a large unilamellar vesicle (LUV). LUV is composed of dipalmitoylphosphatidyl choline (DPPC) and distearoylphosphatidyl choline (DSPC) in the ratio of 9:1. The in vitro sensitivity of TAC-1043 was examined by SDI assay with MTT, using human esophageal cancer cell lines (TE-2, KY). TAC-1043 was effective at the concentration of 10 micrograms/ml, 41 degrees C and 43 degrees C. The in vivo effect of TAC-1043 together with hyperthermia was examined using mouse tumor MM 48. TAC-1043 combined with hyperthermia significantly suppressed the tumor proliferation.

1,2-Dipalmitoylphosphatidylcholine↗

[The early changes in bone mineral metabolism due to radiation--measurement of bone mineral density in lumbar vertebra by quantitative computed tomography].

Osteosclerosis, osteonecrosis and compression fracture are commonly observed several years after radiation. Since lumbago usually occurs several months after radiation, the possibility that bone mineral metabolism is disturbed during and immediately after radiation cannot be ruled out. However, there have been no reports concerning early changes in bone mineral metabolism due to radiation. The bone mineral density was measured by QCT (Quantitative Computed Tomography) in 30 normal non-radiated cases and 14 radiated cases to investigate the changes in bone mineral metabolism due to radiation. The bone mineral density (QCT-Value: QCT-V) in the 3rd lumbar vertebra (L3) of normal non-radiated subjects decreased linearly with age (Y = 291.114447-3.01473X). The QCT-V of the 5th lumbar vertebra (L5) of normal cases also decreased linearly with age (Y = 309.641397-3.03986X), resembling that of L3. The ratio of the QCT-V of L5 to L3 (L5/L3, expressed as a percentage) definitely increased with age (Y = 86.5657441 + 0.58885064X). In radiated cases, the QCT-V of L3 in the non-radiated field did not change appreciably. The QCT-V of L5 in the radiated field was decreased from 20GY and reached 53.08 +/- 17.37% of the pre-radiation value after 50GY. The L5/L3 ratio was also decreased from 20GY and reached 55.47 +/- 15.32% of the pre-radiation value after 50GY. It becomes apparent that the QCT-V of the radiated lumbar vertebra is decreased during radiation. It is suggested that bone mineral metabolism may be disturbed in the early phase of radiation.

Bone Density↗

[Early diagnosis of acute mesenteric artery occlusion--clinical and experimental study].

This study was undertaken for the purpose of making early diagnosis of acute superior mesenteric artery occlusion (SMAO). (Clinical Study) This study included 16 patients with SMAO. The early diagnoses by clinical, laboratory, echographic and radiologic findings which were commonly obtained in the cases of abdominal emergency, were difficult. Angiography was useful method for its diagnosis. But in its early stage, we could hardly determine which patient was subject to angiography, therefore non-invasive and simple screening modelity is needed for its early diagnosis. (Experimental Study) Portal blood flow (PVF) is considered to decrease when superior mesenteric artery (SMA) is occluded, because SMA is a main feeder of portal vein. If SMAO has specific portal hemodynamics, its early diagnosis will be possible by non-invasive PVF measurement using an ultrasonic duplex system (PD). We investigated the portal hemodynamic changes in experimental SMAO, peritonitis and ileus using 24 mongrel dogs. Our results showed that PVF to cardiac output ratios (PCR) of SMAO models were under 10% and in contrast, those of others were over 10%. So SMAO models were distinguishable from others. These suggested that PCR measured by PD and echocardiography was an useful indicator of early diagnosis of SMAO.

Acute Disease↗

[Combined treatment in patients with carcinoma in situ of the urinary bladder using intravesical pirarubicin, irradiation and hyperthermia].

The treatment with hyperthermia in combination with radiation and intravesical pirarubicin (THP-ADM) was preliminary investigated in 5 patients with urinary bladder carcinoma in situ. Following intravesical administration of 30 mg THP-ADM, external irradiation of 3.0 Gy was delivered to the urinary bladder. Immediately then, hyperthermia using Thermotron RF-8 was performed for 50 min (intravesical temperature: 42-43 degrees C for 35 min). After five courses of the treatment, complete response has been maintained for 6, 8, and 9 months in 3 patients. However, in a patient with complete response, urinary cytology became positive in the 6th month after the treatment. In the remaining patient treatment was interrupted after only 3 courses due to urinary irritation, urinary cytology didn't become negative. The side effects of the combined treatment were limited to the transient symptoms of bladder irritation in all patients and thermal burn in 2 patients. These preliminary results suggest that this combined treatment may represent an effective conservative therapy for patients with urinary bladder carcinoma in situ.

Administration, Intravesical↗

[Radiation therapy for unresected gastric lymphoma].

Six consecutive patients with unresected gastric lymphoma which were treated by radiation therapy between November, 1976 and March 1989 were reviewed. Radiation therapy was performed using involved fields, total radiation dosages of which ranged from 25.2 to 36 Gy (mean, 29.3 Gy). Five out of the 6 patients were treated with chemotherapy combined with radiation. Regimen of the chemotherapy was CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) in most cases. Three out of the 6 underwent probe laparotomy, but the tumors were diagnosed as unresectable due to locally invading the adjacent structures. They were treated by chemo-radiotherapy and 2 of them are surviving as of the present study (40 and 116 months). The other 3 patients were diagnosed as with clinical stage IV disease and 2 of them were successfully treated with chemo-radiotherapy (21 and 66 months, surviving). These data suggest that unresected gastric lymphomas, which are locally advanced or stage IV disease, are treated by chemoradiotherapy with high curability without any serious complications.

Adult↗

[Role of CT and ultrasonography in acute blunt trauma of the abdomen].

From March 1985 to April 1989, one hundred thirty-one patients were examined using computed tomography (CT) and/or ultrasonography (US) in the evaluation of acute blunt trauma of the abdomen (CT and US in 36 patients, CT in 25 US in 70). Twenty-three out of the 131 cases (17.6%) showed positive findings of abdominal trauma on CT and/or US. Sixteen of the 23 patients with positive findings underwent therapeutic laparotomy, while all of the other 108 patients with negative findings were successfully managed conservatively. This fact suggests that one of the roles of CT and/or US is to pick up patients with negative findings who do not have any laparotomy. Free fluid collection was demonstrated in all of the 23 patients with positive findings in: all 22 on CT (100%), and 13 of 14 on US (92.9%). In all of the 23 patients but one with an injured mesenterium, injured organ was demonstrated by CT and/or US in: 21 of 22 by CT (95.5%), and 11 of 14 by US (78.6%). In one of the 11 patients, not an immediate US but a follow-up on the next day revealed an injured organ. In 6 out of the 12 patients who underwent both plain and contrast enhancement (CE), CT, CE-CT demonstrated the injured organ more clearly than plain CT. US with sector probe was also useful for demonstrating the injured lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗