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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 469 records · Page 26Linked to original sources

Results of the combination of external-beam and high-dose-rate intracavitary irradiation for patients with cervical carcinoma.

We retrospectively analyzed 220 patients with squamous cell carcinoma of the uterine cervix treated by the combination of external-beam and high-dose-rate intracavitary brachytherapy between 1978 and 1986. Five-year survivals for Stage Ib (n = 15), IIa (n = 18), IIb (n = 107), IIIb (n = 50), and IVa (n = 18) were 72.3, 88.9, 68.9, 64.0, and 16.7%, respectively. The incidences of recurrence outside the pelvis in Stage IIb and IIIb patients (15.0 and 24.0%) were higher than those of local recurrences (10.3 and 12.0%). Eighteen patients (8.2% of the total) had serious intestinal complications. These serious complications were closely correlated with the external-beam dosages. External-beam therapy was performed at 1.8-2.0 Gy/day, and high-dose-rate brachytherapy using a remotely controlled afterloading system (RALS) was performed once a week with 6.0-7.5 Gy at points A/fraction. Treatment dosages to the whole pelvis (WP), with central shieldings (CS), and with RALS according to FIGO stage were as follows: Stages Ib, IIa, 30-40 Gy (WP) plus 24-30 Gy (RALS); Stages IIb, IIIb, 40 Gy (WP) plus 10-20 Gy (CS) plus 24-30 Gy (RALS); Stage IVa, 40-50 Gy (WP) plus 10-20 Gy (CS) plus 20-30 Gy (RALS). From these data, the combination of external-beam and high-dose-rate intracavitary irradiation is an effective therapy for cervical cancer. It is also suggested that an additional combined chemotherapy is necessary to control metastic lesions outside the pelvis for Stages IIb and IIIb.

Adult↗

Electron beam intraoperative radiation therapy (EBIORT) for localized pancreatic carcinoma.

Treatment results for 37 patients with localized pancreatic carcinoma treated using electron beam intraoperative radiation therapy (EBIORT) with curative intent from 1978 to 1990 in National Shikoku Cancer Center Hospital and the related hospitals were presented in comparison with those of a control group comprising 40 patients treated with no use of EBIORT. With additional treatment of EBIORT, 37 patients survived longer than the control 40 patients (p less than 0.05 during the 19th and 31st month). In the macroscopically total or partial resection, patients treated with EBIORT survived slightly longer than the controls. In the unresectable lesions, patients treated with EBIORT survived longer than the control patients (p less than 0.05 during the 7th month). In this group, there was one 5-year survivor who received EBIORT plus postoperative external radiation therapy (ERT) to the unresectable pancreatic head lesion but died 5 years later of massive bleeding from the duodenal ulcerations. Patients with unresectable carcinoma treated by EBIORT plus ERT survived longer than patients treated with EBIORT alone (p = 0.065). Pain relief was obtained in 95.0% of the unresectable patients with pain. Major adverse effects caused by irradiation were gastrointestinal troubles in five patients (leakage of choledochojejunostomy, gastric ulcerations, duodenal stenosis, gastric ulcerations and duodenal stenosis, duodenal perforation and ulcerations). EBIORT proved to be effective in the relief of serious pain and in the improvement of the survival of patients with localized pancreatic carcinoma.

Adult↗

Patterns of failure and survival in locally advanced carcinoma of the uterine cervix treated with high dose-rate intracavitary irradiation system.

We retrospectively analyzed 71 patients with locally advanced carcinoma of the uterine cervix treated by irradiation using high dose-rate intracavitary brachytherapy between 1978 and 1985. Seven patients were Stage IIIa, 46 Stage IIIb, and 18 Stage IVa. Five-year survivals for Stage IIIa, IIIb, and IVa were 71.4, 60.9, and 16.7%, respectively. An analysis of patterns of failure demonstrated that loco-regional recurrences were observed in 1 (14.3%) for Stage IIIa, 6 (13.0%) for Stage IIIb, and 9 (50.0%) for Stage IVa. The incidence of recurrence outside the pelvis observed in Stage IIIb patients (7 para-aortic nodes, 5 distant metastases) was much higher than that of local recurrence. Five patients (7.0% of the total: 1 with Stage IIIa, 3 with Stage IIIb, 1 with Stage IVa) required surgery to manage the complications. These data suggest that a high dose-rate intracavitary irradiation system is an effective tool for the treatment of cervical cancer. Further efforts to control metastatic lesions outside the pelvis are required for patients with Stage IIIb. To increase a loco-regional control rate for patients with Stage IVa disease, it is important to give additional treatment such as chemotherapy in conjunction with radiation therapy.

Adult↗

4-Borono-2-[18F]fluoro-D,L-phenylalanine: a possible tracer for melanoma diagnosis with PET.

The potential of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), a flurodinated derivative of a target compound for boron neutron capture therapy, for melanoma imaging by positron emission tomography (PET) was studied using animal models. A high uptake of [18F]FBPA was found in murine B16 melanoma or in Greene's melanoma No. 179, a melanotic cell line in hamsters, for the first 6 h after injection. Whole body autoradiography using [18F]FBPA gave a clear image of the B16 tumor. The acid-insoluble 18F in the B16 increased to 27% by 6 h, and most of the free 18F was detected as [18F]FBPA in both B16 and plasma. In the hamster models, No. 179 showed a 1.7 times higher uptake than amelanotic Greene's melanoma No. 178 at 6 h post-injection, although both melanomas indicated similar metabolic activities when examined by a tracer uptake study using L-[14C]methionine, 2-deoxy-D-[14C]glucose and [3H]thymidine. [18F]FBPA may be a very promising PET tracer for melanoma imaging.

Animals↗

Pure word deafness due to left hemisphere damage.

We report the case of a 55 year-old right-handed man who presented with a long lasting pure word deafness following left thalamic bleeding. There was no sign of aphasia. The auditory deficit was specific for language, while recognition of music and environmental sounds was normal. CT, MRI and PET examinations showed that the lesion was anatomically and functionally confined to the left cerebral hemisphere, mainly the white matter of the temporal and parietal lobes. Wernicke's area was largely preserved. It is proposed that pure word deafness was consequent to the isolation of Wernicke's area from incoming auditory information due to the interruption both of the association fibers from the right auditory area traveling across the corpus callosum and of the left auditory radiations.

Brain Injuries↗

Angiotensin II does not increase renal prostaglandin E2 in response to pressure reduction.

Whether angiotensin II (Ang II) stimulates renal secretion of prostaglandin E2 (PGE2) synthesized in response to pressure reduction was examined. PGE2 and Ang II in aortic and renal venous plasma were measured before and during renal arterial constriction in anesthetized dogs, with or without an intrarenal arterial infusion of an Ang II antagonist, losartan potassium (1 mg/min), or saralasin (3 micrograms/min). In other anesthetized dogs, two doses of Ang II (30 and then 300 ng/min) were infused into the renal artery, and plasma Ang II levels and renal PGE2 secretion were measured. When renal perfusion pressure was reduced to 75 and 45 mm Hg by constriction, the renal secretion of PGE2 increased seven- and fourfold, respectively. Ang II levels in the renal venous plasma increased from 6.6 +/- 1.8 to 21.7 +/- 7.4 and then 48.1 +/- 15.3 pg/ml (both P less than 0.05) as the pressure decreased. Neither losartan nor saralasin suppressed the response of renal PGE2 secretion to the pressure reduction. The intrarenal infusion of Ang II (30 ng/min) elevated the Ang II level in the renal venous plasma from 9.8 +/- 4.6 to 33.7 +/- 4.2 pg/ml (P less than 0.01), but did not increase PGE2 secretion. The higher dose (300 ng/min) of Ang II increased it, but the Ang II level in the renal venous plasma was 166 +/- 63 pg/ml. These results suggest that the greater part of the increased renal synthesis of PGE2 in response to pressure reduction is not mediated by Ang II.

Angiotensin II↗

Can the chest tube draining the pleural cavity with persistent air leakage be removed?

The pleural drain with persistent air leak in six selected patients after pulmonary surgery was clamped or removed without causing pulmonary collapse. In all the patients, air leak through the chest tube was present when speaking or coughing but not seen when breathing normally at rest or taking deep breaths. The fact that the chest tube could be removed in selected patients is explained by supposing the air leakage through an alveolopleural fistula is dependent on pressure difference between the alveoli and the pleural cavity, and this was confirmed in a rethoracotomy case for persistent air leak. Removal of the chest tube following the above-mentioned rationale would reduce the number of rethoracotomy cases for air leak and facilitate early removal of the chest tube in some patients.

Aged↗

Ga-67 citrate scintigraphy for the early detection of radiation pneumonitis.

To evaluate the usefulness of Ga-67 citrate scintigraphy in the early detection of radiation pneumonitis, scintigrams from 103 patients who were treated with radiation therapy for lung cancer were retrospectively analyzed with regard to abnormal Ga-67 uptake after radiation therapy in sites other than the original or recurrent tumors. Sixteen (20%) of the 80 asymptomatic cases showed positive Ga-67 scintigrams. All of the other 23 symptomatic cases showed positive Ga-67 scintigrams. Thirteen (57%) of these 23 cases had negative chest radiographs although their Ga-67 scintigrams were positive. Detection of radiation pneumonitis by Ga-67 scintigraphy was significantly earlier than that possible by chest radiography (P less than 0.01). These data suggest that Ga-67 scintigraphy is more useful and sensitive than chest radiography for the early detection of radiation pneumonitis.

Aged↗

Infection of macaque monkeys with a chimeric human and simian immunodeficiency virus.

Two macaque monkeys were inoculated with a chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu and env genes of human immunodeficiency virus type 1. Infectious virus was recovered from one of the monkeys at 2 and 6 weeks post-infection. The hybrid nature of the isolated viruses was verified by Southern and Western blotting analyses. Both of the monkeys infected with the chimera elicited a humoral antibody response against the virus.

Animals↗

Sequences responsible for efficient replication of simian immunodeficiency virus SIVMND in cells of the monocyte/macrophage lineage.

We determined the susceptibility of monocytic cell lines to infection with viral strains derived from two infectious clones of simian immunodeficiency virus isolated from a mandrill. One of the strains, which replicates poorly in T cell lines, was found to grow more rapidly than the other in these cells. The viral determinant for this property was genetically mapped within the env gene encoding a surface protein. Six amino acid substitutions identified appeared to be located outside of the domains corresponding to human immunodeficiency virus type 1 env functional domains such as the CD4-binding and V3 loop regions.

Animals↗

Sodium and noradrenaline in cerebrospinal fluid and blood in salt-sensitive and non-salt-sensitive essential hypertension.

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.

Adult↗

Circulating angiotensin II levels under repeated administration of lisinopril in normal subjects.

1. To examine the effect of chronic administration of angiotensin I-converting enzyme (ACE) inhibitor on circulating angiotensin II (AII) concentration, 20 mg of lisinopril was administered once daily for 7 consecutive days to eight healthy volunteers. 2. Plasma ACE activity was inhibited to less than approximately 30% of the pretreatment level during the repeated administration. 3. Mean arterial pressure (MAP) was slightly but significantly reduced during the administration period. Plasma AII concentration measured by an established method using high performance liquid chromatography combined with a radioimmunoassay, however, was maintained at approximately the pretreatment level when it was measured at 24 h intervals after each administration of lisinopril. 4. With the gradual recovery of ACE activity following discontinuation of administration, the plasma AII concentration correlated with AI concentration (r = 0.46), and also with the product of AI and ACE activity (AI x ACE; r = 0.80), corresponding to the formula obtained from the kinetics of ACE activity. No correlation was observed between MAP and AII levels throughout the study period. 5. We conclude that in normal subjects repeatedly administered with ACE inhibitor, the AII level in the circulation is still determined by an elevated level of AI and any remaining ACE activity, thus maintaining AII at pretreatment levels. We confirmed that it is not necessary to achieve a decrease in plasma AII concentration through the chronic administration of ACE inhibitor in order to effectively lower blood pressure.

Adult↗

The posttranslational processing of ras p21 is critical for its stimulation of yeast adenylate cyclase.

Mammalian ras genes substitute for the yeast RAS gene, and their products activate adenylate cyclase in yeast cells, although the direct target protein of mammalian ras p21s remains to be identified. ras p21s undergo posttranslational processing, including prenylation, proteolysis, methylation, and palmitoylation, at their C-terminal regions. We have previously reported that the posttranslational processing of Ki-ras p21 is essential for its interaction with one of its GDP/GTP exchange proteins named smg GDS. In this investigation, we have studied whether the posttranslational processing of Ki- and Ha-ras p21s is critical for their stimulation of yeast adenylate cyclase in a cell-free system. We show that the posttranslationally fully processed Ki- and Ha-ras p21s activate yeast adenylate cyclase far more effectively than do the unprocessed proteins. The previous and present results suggest that the posttranslational processing of ras p21s is important for their interaction not only with smg GDS but also with the target protein.

Adenylyl Cyclases↗

Intracellular free magnesium of red blood cells in patients with renal disease.

While serum magnesium (Mg) level is increased in patients with end-stage renal disease (ESRD), it is decreased in renal transplant recipients (TR) receiving ciclosporin. This study was performed to examine the cation metabolism of red blood cells (RBC) in these patients. Intracellular free Mg was measured with 31P-nuclear magnetic resonance spectrometry, and ouabain-sensitive sodium (Na) efflux rate (Eos) was measured from the increase in RBC-Na concentration when RBC were incubated in the presence of ouabain. The ouabain-sensitive Na efflux rate constant (ERCos) was obtained by dividing Eos by RBC-Na concentration. RBC free Mg and ERCos were significantly higher in the TR group than in the ESRD group. There was a significant correlation between RBC free Mg and ERCos (r = 0.474, p less than 0.01). These results support the views that the regulation mechanism for intracellular free Mg is different from that for extracellular Mg in patients with renal disease, and intracellular free Mg modulates Na pump activity of RBC.

Adenosine Triphosphate↗

Morphological studies on cataract and small lens formation in neonatal rats treated with monosodium-L-glutamate.

Changes in the transparency and size of lenses in rats were investigated following administration of monosodium-L-glutamate (MSG). MSG (5 mg/g b.w.) was injected subcutaneously on the 9th and 10th day after birth. Ophthalmoscopically, localized opacity was apparent at the posterior pole of the lens corresponding to the attached site of the hyaloid vessels at the 1-month stage. The incidence of cataract increased with age, reaching more than 75% at 4 months. Morgagnian globules were histologically detected in the opacity of the posterior lens cortex. The size and weight of the lens were smaller than those of the control rats. These findings indicate that the administration of MSG could be an etiologic factor in cataract formation in the developing rat.

Animals↗

Apolipoprotein E prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Apo E plays an important role in plasma lipoprotein metabolism through its high affinity binding to cell surface LDL receptor. In the present study, we studied the effects of apo E on the atherogenic process in Watanabe heritable hyperlipidemic rabbits which are deficient in LDL receptor and an animal model for familial hypercholesterolemia. We isolated apo E from plasma of 1% cholesterol-fed rabbits and administered 10 mg of purified apo E intravenously into five Watanabe heritable hyperlipidemic rabbits three times a week from their age of 2.5 months to 11 months for 8.5 months. After sustained administration to apo E, we found a significant reduction in the accumulation of cholesterol ester in aortae (1.55 +/- 0.07 mg/g tissue) as compared to control rabbits (4.32 +/- 0.61 mg/g tissue). Supporting this, the percentage of the surface area of the aorta with macroscopic plaque was remarkably decreased in apo E-treated animals (18.8 +/- 5.1% vs. 38.8 +/- 8.0% in control). Thus, apo E definitely prevented the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Animals↗

Critical degree of renal arterial stenosis that causes hypertension in dogs.

The minimum degree of renal arterial stenosis needed to cause hypertension was identified by renal arterial angiography of anesthetized dogs. The effects of renal nerves and prostanoids on the critical stenosis were also examined. The left renal artery was constricted concentrically by a radiolucent constrictor device, and the stenosis of the artery was evaluated by cineangiography with the kidney either innervated or denervated. At this time, renal blood flow, renal perfusion pressure, and systemic blood pressure were serially monitored. In another group of dogs, renal venous and aortic blood samples were taken as the stenosis increased; these were assayed for prostaglandin E2 and plasma renin activity. The same experiments were done again after treatment with a cyclooxygenase inhibitor, aspirin DL-lysine (54 mg/kg). With the kidney either innervated or denervated, systemic blood pressure began to increase when the stenosis was more than 70% of the diameter of the renal artery; the renal blood flow decreased when the stenosis was more than 75% of the diameter. Aspirin treatment attenuated the increase in blood pressure but did not affect the autoregulation of the renal blood flow when stenosis was 70% or less. Prostaglandin E2 production increased in the stenotic kidney when the stenosis was more than 70%; aspirin inhibited prostaglandin synthesis and suppressed the stimulation of renin release. These results suggest that whether there is innervation or not, the critical degree of renal arterial stenosis that causes hypertension is more than about 70% of the diameter in the presence of renal prostaglandins; in their absence, the critical point above which hypertension occurs is 75% or more.

Animals↗

Development of a highly cardioselective ultra short-acting beta-blocker, ONO-1101.

A novel, highly cardioselective ultra short-acting beta-blocker, ONO-1101, has been developed for application in the emergency treatment of tachycardia and better control of heart rate in surgery. This agent is approximately nine times more potent in beta-blocking activity in vivo and eight times more cardioselective in vitro than esmolol. This beta-blocking drug has a short duration of activity, enabling rapid recovery after cessation of administration if side effects occur. It can be used safely in patients suffering from acute heart disease and represents a major therapeutic advance in the treatment of heart disease.

Adrenergic beta-Antagonists↗