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Biomedical subjects

K Kawabata

Publications and source records attributed to K Kawabata.

At least 235 records · Page 13Linked to original sources

Immunomodulation by orally administered protein-bound polysaccharide PSK in patients with gastrointestinal cancer.

The present study was designed to assess the effects of the protein-bound polysaccharide PSK on the immunological status of patients with gastrointestinal cancer. Twenty-nine gastric and 18 colorectal cancer patients were randomly assigned to either the control or PSK group. Patients in the PSK group were given 3.0 g of PSK orally before surgery, either daily or every other day. Patients in the control group received no PSK. The data of peripheral blood lymphocytes (PBL) were compared before and after administration of PSK, and those of the regional node lymphocytes (RNL) were compared between the control and the PSK group. The results indicate that the effects of PSK were significantly influenced by the duration of administration, but not by the frequency of administration. In the patients belonging to the short term PSK group (administration less than 14 days), the response of the PBL to PSK and Con A become significantly stronger compared to before the administration of PSK, whereas the cytotoxicity against K562 and KATO-3, and the proportion of CD16+ cells increased significantly in those patients belonging to the long term PSK group (greater than or equal to 14 days). In addition, the proportion of CD9 + 11b + suppressor T cells decreased in the RNL of the short term PSK group, whereas the proportion of CD4 + Leu8 - helper T cells in the RNL increased in the long term PSK group. These results suggest that the oral administration of PSK leads to the suppression of suppressor cells in the RNL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Islet amyloid polypeptide (IAPP) and pancreatic islet amyloid deposition in diabetic and non-diabetic patients.

Twenty pancreata of non-diabetic patients and 17 pancreata of diabetic patients, including two patients with insulin-dependent diabetes mellitus, were immunohistochemically studied using antiserum against human islet amyloid polypeptide (IAPP). The islet beta cells in non-diabetic patients were immunoreactive for both IAPP and insulin. Amyloid deposition immunoreactive for IAPP was detected in six of 20 pancreata of non-diabetic patients. The plasma glucose level of three of these six patients was elevated to more than 200 mg/dl, and that of the other three ranged from 143 to 162 mg/dl; all six were receiving intravenous hyper-alimentation and had no history of diabetes prior to treatment. Amyloid deposition was present in all patients with non-insulin-dependent diabetes mellitus (NIDDM). The deposition was absent in the pancreata of two secondary diabetic patients, one of whom had received steroid hormone for bronchial asthma and the other of whom had liver cirrhosis with hepatocellular carcinoma; deposition was also absent in the pancreas of a patient with impaired glucose tolerance diagnosed on a 75-g oral glucose load. Heterogeneous expression of immunoreactivities of beta cells for insulin and for IAPP was present, suggesting independently regulated production and secretion of the peptides. Immunoreactivity of beta cells was more sensitively decreased for IAPP than for insulin in the islets of NIDDM patients. The decreased immunoreactivity for IAPP suggested an initial stage of disturbed beta-cell function, even if the immunoreactivity for insulin was apparently intact or the amyloid deposition in the islets was insignificant. The degree of amyloid deposition immunoreactivity for IAPP did not necessarily reflect the severity of diabetes mellitus. Amyloid deposits were seen at the narrow spaces beneath the insular capsule of connective tissues and the perivascular region or, in some cases, occupying the whole of the islet. The diabetogenic role of IAPP is unclear, but the deposition might be an accelerating factor which disturbs beta-cell function.

Adult↗

A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice.

5'-Deoxy-5-fluorouridine (5'-DFUR) is one of the oral fluoropyrimidines widely used in the treatment of gastric, colorectal and breast cancers in Japan. 5'-DFUR is converted to 5-fluorouracil by pyrimidine nucleoside phosphorylase in the tumor. 5'-DFUR has toxic effects on the intestine and may cause severe diarrhea. Trimethoxybenzoyl-5'deoxy-5-fluorocytidine (Ro09-1390) is a prodrug of 5'-DFUR, which was developed to reduce the intestinal toxicity of 5'-DFUR. The present study was designed to assess the antitumor activity and spectrum of Ro09-1390, and to compare its efficacy with that of 5'-DFUR. Six digestive organ cancer xenograft lines (two gastric, one esophageal, one colorectal, one gall bladder and one bile duct cancers) were s.c. transplanted into nude mice. The agents were orally administered daily for 14 days at doses of 0.08-0.64 mmol/kg (1-8 times the maximal clinical dose of 5'-DFUR). Both 5'-DFUR and Ro09-1390 significantly inhibited the growth of two gastric cancer lines, and the IC50's for Ro09-1390 in both lines were lower than the respective values for 5'-DFUR. The esophageal, colorectal, gall bladder and bile duct cancer lines, however, were resistant to both agents. 5'-DFUR at 0.64 mmol/kg significantly inhibited the growth of these cancers, but with high mortality, and most mice receiving this dose died within 14 days after the start of therapy, suffering from severe diarrhea and body weight loss. Ro09-1390 at the same dose resulted in low mortality, but evidenced similarly low antitumor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Slowly progressive limb-kinetic apraxia with a decrease in unilateral cerebral blood flow.

We report two patients with slowly progressive motor disorders, whose principal manifestations were asymmetric limb-kinetic apraxia and muscle rigidity. In both patients MRI revealed no responsible lesion, whereas single photon emission computed tomography (SPECT) showed a decrease in cerebral blood flow (CBF) in the unilateral hemisphere. One patient with mainly right-sided apraxia had a decreased CBF in the left central region between the frontal and parietal cortices, and the other patient with left-sided apraxia in the right parietal cortex. In agreement with asymmetric clinical symptoms, the regional CBF decrease in the unilateral cortical areas including the frontal and parietal cortices may suggest a degenerative disease, presumably diagnosed as having cortico-basal degeneration.

Aged↗

[Correlation of visual evoked potentials with dementia in Parkinson's disease].

There has been some debate regarding abnormalities in visual evoked potentials (VEP) in Parkinson's disease (PD). To elucidate the mechanism causing abnormal VEP, we investigated the relationship between VEP and mental function in PD patients. Pattern reversal VEP was recorded in PD patients (n = 27) and age-matched control subjects (n = 14). PD patients consisted of two subgroups; PD without dementia (nD-PD; n = 17) and PD with dementia (D-PD; n = 10). Dementia was evaluated according to the criteria for dementia assigned in DSM III-R, and mental faculties were estimated by using the mini-mental state examination (MMSE). In pattern VEP recordings, P100 latency and amplitude were measured for each eye stimulated. No patient or control subject had impairment of corrected visual acuity or ophthalmological disease. There was no significant difference in age among the three groups (D-PD, nD-PD and control subjects). D-PD patients showed significantly prolonged P100 latency compared to nD-PD patients and control subjects (p less than 0.05). With respect to P100 amplitude, no significant difference was shown among the three groups. In PD patients, there was a rough correlation between P100 latency and MMSE score. No correlation was found between P100 amplitude and MMSE score. In control subjects, P100 latency did not correlate with advancing age. In PD patients, nD-PD patients showed a significant correlation between P100 latency and age, whereas D-PD patients presented no correlation. Abnormal VEP in PD has been mostly ascribed to dopaminergic deficiency in the retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A retrospective analysis of surgical operations on malignancies of the ear].

In the past 20 years from 1970 to 1990, 21 patients with malignancies of the ear were treated at Cancer Institute Hospital. The primary sites were the auricle and cartilaginous external auditory canal (group 1: n = 8), the bony external auditory canal (group 2: n = 6) and the middle ear (group 3:n = 7). In group 1, pathological types were squamous cell carcinoma in four patients and basal cell carcinoma in the other four patients. Seven patients were treated by surgery alone, and the remaining patient was treated by interstitial implant radiotherapy. No recurrence have been noted up to today in this group. In group 2, pathological types were squamous cell carcinoma in four patients and adenoid cystic carcinoma in the other two patients. All of the six patients underwent external canal resection or subtotal temporal resection. Two patients received postoperative radiotherapy. A five year survival rate of group 2 was 60%. In group 3, pathological types were squamous cell carcinoma in six patients and undifferentiated carcinoma in the remaining patient. Most of them underwent radical mastoidectomy followed by irradiation. However, all the patients died within two years after treatment. In group 2 and 3, cytodiagnosis was useful for early discovery. In group 2, temporomandibular joint seemed to be a key point in surgical treatment. In group 3, the combination of conservative surgery with radiotherapy was not a radical treatment. This suggested it necessary to perform subtotal temporal resection to treat malignancy of the middle ear.

Adult↗

[Three-dimensional surface display with 123I-IMP in corticobasal degeneration].

A 65-year-old right-handed woman was admitted due to gait disturbance. She had suffered from progressive motor clumsiness in the left-sided limbs for four years. On admission, she was mildly demented, but not aphasic. Neurological examination disclosed constructional disability, limb-kinetic apraxia on the left side, and parkinsonism. Brain CT and MRI showed no responsible lesion. Three-dimensional surface display with 123I-IMP demonstrated decreased cerebral blood flow mainly in the right angular gyrus, and mildly in the right central region. She was clinically diagnosed as having corticobasal degeneration. Hypoperfusion in the angular gyrus and central region may account for constructional disability and limb-kinetic apraxia, respectively. Three-dimensional surface display with 123I-IMP appears to be useful for detecting the cortical region.

Aged↗

ONO-5046, a novel inhibitor of human neutrophil elastase.

ONO-5046, N-[2-[4-(2,2-Dimethylpropionyloxy)phenylsulfonylamino] aminoacetic acid, competitively inhibited human neutrophil elastase (IC50 = 0.044 microM, Ki = 0.2 microM). It also inhibited leukocyte elastase obtained from rabbit, rat, hamster and mouse. However, ONO-5046 did not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 microM. In in vivo studies, ONO-5046 suppressed lung hemorrhage in hamster (ID50 = 82 micrograms/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil elastase.

Animals↗

Effects of splenectomy on pulmonary metastasis and growth of SC42 carcinoma transplanted into mouse liver.

The carcinoma SC42 was transplanted into the liver of its syngeneic mice DS, and the immunological integrity of the spleen and the effects of splenectomy on the growth and pulmonary metastasis of the liver tumor were assessed. On day 7 after liver tumor transplantation, the natural killer (NK) activity of the splenocytes was significantly elevated; it subsequently decreased at a later stage of the tumor. The response of the splenocytes to PHA and Con-A decreased significantly from the early stage of the tumor. However, the mixed lymphocyte-tumor cell reaction increased significantly from day 14 to day 28. The survival rate of the mice, which had undergone simultaneous splenectomy and liver tumor transplantation, was significantly lower than that of sham-operated control mice. The number of pulmonary metastases in splenectomized mice was significantly greater than in the control mice. There was, however, no difference between the two groups in the weight of the liver tumor. By contrast, splenectomies performed 14 days before or 14 days after tumor transplantation had no significant influence on the survival of the mice. Splenectomies performed on day 0 and on day 3 after tumor transplantation significantly increased the number of pulmonary metastases. Furthermore, the intravenous injection of anti-asialo GM1 antisera on day 0 and day 3 significantly increased the number of pulmonary metastases, but injection of anti-Thy 1.2 antisera had no effect. These results suggest that splenic NK cells may play an important role in the suppression of pulmonary metastasis at early stages of the liver tumor.

Animals↗

Combining independently effective anticancer agents may not augment the independent antitumor effects: a study using human digestive organ cancer xenograft lines in nude mice.

Five human digestive organ cancer xenograft lines were subcutaneously transplanted in nude mice, and 7 anticancer agents (ACAs) were intravenously administered singly or in combinations at 4 times the standard clinical doses. Cisplatin (P) was effective in 4 lines and 5-fluorouracil (F) was effective in 3 lines. A total of 8 combinations with 2 effective ACAs were assessed in 4 lines and only 1 combination (FP) resulted in an augmented antitumor effect in a single line. A total of 11 combinations with 1 effective ACA plus 1 ineffective ACA were assessed in 2 lines, and only 1 combination (F + carboquone [CQ; Esquinon]) resulted in an augmented effect in a single line. A total of 5 combinations with independently ineffective ACAs were assessed in 1 line, and 1 combination (FP) resulted in augmented antitumor activity. No 2-ACA combinations showed enhanced side effects. Two combinations with 3 effective ACAs were assessed in 2 lines and 1 combination (FP + mitomycin C) resulted in an augmented effect with a greater mortality rate. A total of 12 combinations with both effective plus ineffective ACAs were assessed in 2 lines, and 3 combinations (FP + Adriamycin or FP + CQ or FP + etoposide) resulted in an augmented effect in 1 line with enhanced side effects. These results indicate that the combination of independently effective ACAs does not always cause an augmented antitumor effect, and may sometimes result in augmented side effects. According to this study, the 3-ACA combinations with FP + 1 effective agent appear to be the best regimens for digestive organ cancer.

Animals↗

In vivo effects of human recombinant tumor necrosis factor alone and in combination with other biological response modifiers on human digestive organ cancer xenografts transplanted in nude mice.

The present study was designed to evaluate the effect of rTNF alone or in combination with other BRMs on human digestive organ cancers. Six kinds of human digestive organ cancer xenografts (esophageal, stomach, colonic, pancreatic, bile duct, and liver cancers: EC-YO, GC-YN, CC-KK, PC-HN, BDC-SN and Li-7, respectively) were transplanted in nude mice, and rTNF was administered at 10(3), 5 x 10(3), or 10(4)U/head directly into the tumor 3 times a week for 2 weeks. EC-YO was the most sensitive to rTNF, and intratumoral administration of rTNF at 10(3) U/head caused tumor regression. PC-HN, CC-KK and GC-YN were relatively sensitive to rTNF, and their growth was significantly inhibited by rTNF at 5 x 10(3) U/head, however, the tumors regrew after treatment. Li-7 and BDC-SN were resistant to rTNF. The effects of rTNF in combination with recombinant interferon-gamma (rIFN-gamma), recombinant interleukin-2 (rIL-2), or streptococcal preparation OK-432 were assessed in mice transplanted with GC-YN. All combinations of rTNF at 5 x 10(3) U/head and other BRMs were more effective than rTNF alone, and GC-YN tumors were completely regressed after treatment with a combination of rTNF and rIFN-gamma or rTNF and OK-432. However in all cases, the combination of rTNF at 10(3) U/head and any other BRM did not improve the effect. Furthermore, the adverse effects of the combinations were more serious than those of rTNF alone. TNF may still be a useful cytokine, because it can induce the regression of tumors. However, for its clinical application, a method should be developed to reduce its side effects.

Animals↗

Enhancement by propofol of epinephrine-induced arrhythmias in dogs.

Although propofol is a widely used intravenous anesthetic, its effect on epinephrine-induced arrhythmias remains unknown. This study examined the possible interaction between propofol and epinephrine that might affect the induction of ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with halothane alone, propofol alone, etomidate alone, or etomidate plus varying doses of propofol. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during propofol anesthesia (blood propofol concentration 18.0 +/- 0.98 micrograms/ml) were 2.52 +/- 0.43 micrograms.kg-1.min-1 and 23.6 +/- 8.5 ng/ml, respectively. During halothane anesthesia (end-tidal 1.3 MAC), they were 2.66 +/- 0.21 micrograms.kg-1.min-1 and 35.7 +/- 1.9 ng/ml, respectively. During etomidate anesthesia, they were 9.67 +/- 1.06 micrograms.kg-1.min-1 and 205 +/- 27.5 ng/ml, respectively. The dose-effect relationship for propofol was examined during etomidate plus propofol anesthesia. Propofol reduced the arrhythmogenic plasma concentration of epinephrine in a concentration-dependent manner: at blood propofol concentrations of 2.33 +/- 0.46, 5.46 +/- 0.71, and 11.2 +/- 0.81 micrograms/ml, the corresponding plasma epinephrine concentrations were 182.6 +/- 52.5, 89.0 +/- 28.8, and 26.6 +/- 6.9 ng/ml, respectively. These results suggest that propofol enhances epinephrine-induced arrhythmias in a dose-dependent manner in dogs.

Anesthesia↗

Comparative study on various combination chemotherapies against human gastric cancer xenograft lines of well- and poorly-differentiated adenocarcinomas transplanted in nude mice.

Two human gastric cancer xenograft lines (GC-YN and GC-SF) transplanted in nude mice were employed to evaluate and compare the anticancer effect of seven single anticancer agents and their various combinations. Mitomycin C, cisplatin (Briplatin) (CDDP) and 5-fluorouracil (5-FU) were screened out to be effective against GC-YN and only epirubicin (Farmorubicin) (EPIR) was effective against GC-SF. Combinations of two of these 'effective' agents revealed that FP (5-FU + CDDP) is the most effective two-agent combination regimen against both lines, and some of those 'ineffective' single agents showed synergistic effects against both lines when combined with 5-FU. Moreover, three-agent combinations composed of FP and one of the other five agents were also evaluated to select out the most effective regimen. All the combinations showed higher inhibition on the tumor growth of GC-YN than FP regimen, and FP + adriamycin (Adriacin) (ADR) and FP + EPIR were more effective against GC-SF than FP. However, taking toxic effects into consideration, the results suggest that CDDP + 5-FU + EPIR (FPEPIR) may be the regimen most worthy of clinical trial in the chemotherapy against human gastric cancer.

Adenocarcinoma↗

Low uracil concentration in the liver might be responsible for the decreased antineoplastic activity of fluoropyrimidines in mice with CCl4-induced chronic liver dysfunction.

Some fluoropyrimidines are considered to be metabolized in liver microsomes. The present study was designed to assess the effect of chronic liver dysfunction on the antineoplastic activity of fluoropyrimidines. Chronic liver dysfunction was induced in BALB/c mice by 8 weeks of CCl4 injections. The 5-fluorouracil (5-FU)-sensitive MOPC-104E and 5-FU-resistant Meth-A cells were inoculated subcutaneously into the mice and then various fluoropyrimidines were administered intragastrically. The antitumor activity of the fluoropyrimidines decreased in mice with chronic liver dysfunction, although the concentration of 5-FU in the tumor of normal mice did not differ from that of mice with liver dysfunction. However, the concentration of uracil in the liver was decreased in mice with chronic liver dysfunction. On the other hand, the percent conversion of Tegafur [1-(2-tetrahydrofuryl)-5-FU] to 5-FU in the normal liver did not differ from that in the dysfunctional liver. These results suggest that low uracil concentrations in the liver may result from chronic liver dysfunction and lead to decreased antitumor efficacy of fluoropyrimidines.

Animals↗

[Effect of maternal postural change on maternal hemodynamics in late pregnancy--supine hypertension].

The purpose of this investigation was to ascertain the effect of postural change in late pregnant women from the left lateral recumbent position to the supine position on their blood circulation. Patients in whom the blood pressure at the right upper limb in the supine position increased by at least 20mmHg or more (diastolic and/or systolic pressure) were classified as the supine hypertensive group. Patients in whom the blood pressure of the right upper limb decreased by at least 20mmHg or more were classified as the supine hypotensive group. And other patients were classified as the no blood pressure change group. The results were as follows. 1. The incidence of supine hypertension was 48% in primigravidas and 38% in multigravidas. Supine hypertension was especially common in PIH (pregnancy induced hypertension) complicated women (75%). 2. Maternal cardiac function: With postural change from the left lateral recumbent position to the supine position, CO (cardiac output) decreased and SVR (systemic vascular resistance) was increased in both the supine hypertensive and the no blood pressure change groups by the thermodilution method (n = 14). CVP (central venous pressure) and PCWP (pulmonary capillary wedge pressure) shows different pattern of change in the supine hypertensive group and the no blood pressure change group. In the former group, CVP was decreased by 45 +/- 16% and PCWP was increased by 21 +/- 9% in the supine position compared with in the left lateral recumbent position. However, in the latter group, CVP decreased by 87 +/- 69% and PCWP decreased by 53 +/- 46% as the result of the same postural change.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

[Electrophysiological comparison between patients with Binswanger's encephalopathy and Alzheimer's disease].

Short-latency somatosensory (SSEPs), brainstem auditory evoked potentials (BAEPs) and event-related potentials (ERPs) were studied in 7 patients with Binswanger's encephalopathy, 12 patients with Alzheimer's disease and 17 normal subjects. Patients with Binswanger's encephalopathy showed significantly prolonged central conduction time (CCT) and P300 latency, and prolonged tendency of I-V IPL compared to those of normal subjects. In particular, CCT showed significant prolongation compared to that of patients with Alzheimer's disease. In patients with Alzheimer's disease, I-V IPL and P300 latency were significantly prolonged compared to those of normals although there was no significant difference in CCT between Alzheimer's disease and normal subjects. These results indicate some difference between Binswanger's encephalopathy and Alzheimer's disease from the electrophysiological aspects although both of these entities are characterized by progressive mental deterioration.

Aged↗