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Biomedical subjects

T Kasamatsu

Publications and source records attributed to T Kasamatsu.

At least 73 records · Page 4Linked to original sources

An INTERSALT study investigation: relationship between body mass index and blood pressure in the combined populations of three local centres in Japan.

Body mass index was positively and strongly correlated with BP in the INTERSALT study. Because the average body mass index in Japan, although low relative to other developed countries, has been increasing recently it would be useful, particularly from the public health viewpoint, to investigate the impact of body mass index on BP in Japanese populations. In this study, the relationship between body mass index and BP was investigated taking into account age, alcohol intake and sodium and potassium excretion in 24h urine. Data were obtained from 274 men and 284 women, aged 20-59 years, who were not taking antihypertensive medication. Random selection of participants took place at three local centres as outlined in the 1985 INTERSALT study in Japan. It was found that body mass index was positively and significantly correlated with BP in men and women, respectively, but was independent of age, alcohol intake and urinary sodium/potassium ratio. Both SBP and DBP were significantly higher by > or = 5 mmHg in participants whose body mass index (kg/m2) was in the highest quartile compared with participants in the lowest or the next lowest quartile category in men and women. In this study, it was suggested that the body mass index in Japanese men and women was directly correlated with BP independent of other confounding factors. Accordingly, the maintenance of a moderate body mass index may be important in achieving and maintaining a desirable BP level.

Adult↗

Altered fluidity of liver plasma membranes following partial hepatectomy in rats.

The fluidity of liver plasma membranes was assessed during regeneration following partial hepatectomy in rats. Fluorescence polarization was measured using 1,6-diphenyl-1,3,5-hexatriene to evaluate the fluidity of liver plasma membranes. The fluorescence polarization value of liver plasma membranes of control rats was 0.189 +/- 0.005 (mean +/- SEM). The fluorescence polarization values decreased initially after a 70% hepatectomy [0.176 +/- 0.003 at 3 hr and 0.174 +/- 0.004 at 6 hr (P < 0.01)] at 3 and 6 hours, but then recovered to preoperative levels (0.181 +/- 0.004, 0.189 +/- 0.004, 0.189 +/- 0.003, 0.193 +/- 0.003, 0.200 +/- 0.002, 0.208 +/- 0.007, and 0.190 +/- 0.003 at 12, 24, 36, 48, 72, 96 hr, and 7 days, respectively). Flow cytometric analysis using anti-bromodeoxyuridine (BrdU) monoclonal antibody was used to investigate the cell kinetics of the regenerating liver after 70% hepatectomy. The proportion of S-phase incorporating BrdU was not increased at 6 or 12 hr, but it then increased to peak of 27.9 +/- 1.9% at 24 hr. Subsequently, at 48, 72, and 168 hr, the proportion decreased to 8.5 +/- 0.6, 5.9 +/- 0.3, and 1.0 +/- 0.1%, respectively. The ratio of phospholipid to cholesterol contents of liver plasma membranes following partial hepatectomy did not significantly change in spite of markedly altered membrane fluidity. Thus, the alteration of membrane function occurs in conjunction with the initiation of the regeneration process following partial hepatectomy. It is suggested that the alteration of membrane fluidity plays an important role in the homeostatic response for cell proliferation.

Animals↗

Effect of anticancer agents on cell cycle of regenerating hepatocytes in rats.

The effect of three anticancer agents, cisplatin, doxorubicin, and mitomycin, on liver regeneration after 70% partial hepatectomy in rats was investigated by total DNA content of the liver and flow cytometric analysis of hepatocyte nuclei using two-color staining of anti-bromodeoxyuridine monoclonal antibody and propidium iodide. Total DNA content of regenerating liver 7 days after hepatectomy showed significant suppression of regeneration by these agents (P less than 0.01). The inhibitory effects of the agents on the cell cycle of hepatocytes by flow cytometric analysis were (1) a delay of the peak or a decrease in the proportion of S phase nuclei and/or (2) polyploidization of the nuclei, demonstrated by accumulation of 8c and occasionally 16c nuclei, of which the DNA contents were four and eight times as much as that of diploid (2c) cell nuclei, respectively. The former (1) suggests G0 or G1 phase block, and the latter (2) G2 phase block. In terms of total DNA content of regenerating liver, the inhibitory effect was most prominent in the cisplatin-administered groups. The polyploidization of nuclei was most remarkable in the mitomycin-administered groups. Although the total DNA content recovered to the level of control at 6 weeks after hepatectomy, the polyploidization effect persisted in the drug-administered groups. These agents had no cytocidal action on proliferating hepatocytes as can be seen from the aspartate aminotransferase and alanine aminotransferase serum levels. We conclude that in a short-term observation, the anti-cancer agents significantly inhibit liver regeneration, although the inhibitory effect on DNA synthesis does not last long.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cell kinetics of regenerating liver after 70% hepatectomy in rats--2-color flow cytometric analysis.

Two-color flow cytometric (FCM) analysis using anti-bromodeoxyuridine (BrdU) monoclonal antibody (MoAb) was used to investigate the cell kinetics of regenerating liver after 70% partial hepatectomy in rats. Three peaks were seen in DNA histograms of rat hepatocyte nuclei, corresponding to diploid(2c), tetraploid(4c), and octaploid(8c). These proportions changed in the course of regeneration which were clearly demonstrated by DNA histograms using flow cytometry. The proportion of diploid, tetraploid, and octaploid nuclei in control liver were 49.3 +/- 1.6%, 45.0 +/- 7.4%, and 1.7 +/- 0.7%, respectively. A significant change occurred at 24 hours after hepatectomy, as FCM revealed 25.9 +/- 1.1% diploid, 54.5 +/- 1.2% tetraploid, and 9.0 +/- 0.9% octaploid. This shift to polyploid nuclei persisted until 72 hours, and then gradually returned to the pattern of control liver. The S-phase nuclei which incorporated BrdU increased rapidly at 24 hours to a peak of 11.3 +/- 0.9%, and gradually decreased to 5.8 +/- 0.8%, 5.3 +/- 0.8%, 2.4 +/- 0.6%, 2.9 +/- 1.1%, and 1.2 +/- 0.6%, at 48, 72, 96, 120, and 168 hours, respectively. This 2-color FCM analysis made a detailed analysis of the cell kinetics in regenerating hepatocytes possible, and may be applied in investigations of various aspects of liver regeneration.

Animals↗

Clinical effect of sizofiran combined with irradiation in cervical cancer patients: a randomized controlled study. Cooperative Study Group on SPG for Gynecological Cancer.

To evaluate the clinical effect of a biological response modifier (BRM), sizofiran (SPG), combined with irradiation, a randomized controlled study was performed in patients with stage II or III cervical cancer involving the collaboration of 52 institutes throughout Japan. Patients were randomly allocated to the control group (radiotherapy only) and the SPG group (radiotherapy + SPG). SPG was given intramuscularly, 40 mg once and 20 mg twice, a week concomitantly with radiotherapy. A total 315 patients were enrolled for the study but 23 were excluded from analysis. Of the remaining 292 patients, 121 were of stage II (43 controls and 78 SPG) and 171 of stage III (49 controls and 122 SPG). The results were as follows. (1) The complete response (CR) rate among stage II patients was higher in the SPG group (91.0%) than in the control group (79.1%); also the CR rate among stage III patients was significantly higher in the SPG group (77.9%) than in the control group (61.2%). (2) The SPG group showed a significantly rapid recovery from the decreased lymphocyte counts due to radiotherapy (P less than 0.05). (3) Side effects, probably associated with SPG administration, were observed in 11 cases (5.2%).

Adult↗

Lithium reduces ocular dominance plasticity in kitten visual cortex.

Activity-dependent processes within the visual pathway play a crucial role in the expression of ocular dominance plasticity in immature visual cortex. The necessity of non-retinal, modulatory afferents to the regulation of ocular dominance plasticity has been recognized. Among a few chemically defined signaling systems, the noradrenaline-activated beta-adrenoreceptors seem to have a prime role in this matter. The involvement of acetylcholine afferents was also proven. We looked for plausible molecular mechanisms which integrate the contribution of the two neuromodulator systems to ocular dominance plasticity. At the first step, based on the rich literature on psychotropic action of lithium and the recent advancement in understanding of its molecular mechanisms, we physiologically studied visual cortex of kittens which had been repeatedly injected with the lithium solution intraperitoneally or the cortex directly infused with it. We found (1) that ocular dominance plasticity was significantly reduced in lithium-injected kittens, (2) that the decrease was directly correlated with plasma concentrations of lithium (i.e. the higher the lithium concentration, the lower the plasticity), and (3) that the comparable decrease in the plasticity was obtained from kitten visual cortex which had been directly infused with the lithium solution. The present results suggest that lithium-sensitive processes, through most likely reduced production of second messengers, underlie the regulation of ocular dominance plasticity.

Animals↗

Cortical recovery from effects of monocular deprivation caused by diffusion and occlusion.

Two forms of visual deficit were induced in 12 pairs of kittens (4-6 weeks of age) by monocular lid suture combined with either an opaque soft contact lens ('occlusion' amblyopia) or a clear lens ('diffusion' amblyopia) which had been kept behind the sutured eyelids for 5-9 weeks. The kittens were then reverse-sutured at the age of 9-15 weeks, and the previously open eye was occluded with an opaque lens for the next 5-7 weeks. We compared across the two groups the proportion of binocularly driven cells (group 2-6) and cells predominantly activated by stimulation of the initially deprived eye (groups 1-3). Both values were significantly higher in the 'occlusion' kitten, though the difference was small, compared to the 'diffusion' kitten. In addition, we measured visual acuity and peak contrast sensitivity for the two eyes in 4 of the 12 pairs, using the sweep VEP method applied under anesthesia and paralysis. The 'occlusion' kitten showed consistently better acuity and higher peak contrast sensitivity than the 'diffusion' kitten, when the initially deprived eye was tested. Taken together, the present results suggest that there is a difference in the depth of amblyopia caused by monocular 'occlusion' and monocular 'diffusion'. The cortical effects of the latter are more difficult to reverse than those of the former.

Amblyopia↗

Second cancer after radiation therapy for cancer of the uterine cervix.

Radiation-induced cancers after radiation therapy for cancer of the uterine cervix were investigated on 11,855 patients including 5725 patients treated with radiation therapy alone, 1969 postoperative radiation therapy and 4161 surgery alone. The observed-to-expected ratios of the second primary cancer was 0.933 for the patients with radiation therapy alone and 1.074 for the patients with postoperative radiation therapy, respectively. No significant increase was observed in the risk of second primary cancers when all sites were combined. However, assessing on site by site basis, significant excess was noted for the rectum cancer, leukemia, and bladder cancer for the radiation therapy group but not for the surgery group. A significant excess of lung cancer was observed in both radiation therapy and surgery groups, which was attributed to some other causative factors. Radiation-induced cancers were suggested to develop apparently in organs involved in the irradiated field.

Adult↗

Ocular dominance plasticity restored by NA infusion to aplastic visual cortex of anesthetized and paralyzed kittens.

We studied the ocular dominance distribution in visual cortex of kittens which had been monocularly exposed to moving-pattern stimuli under anesthesia and paralysis. 1. We did not obtain any discernible changes in ocular dominance, confirming the previous reports that anesthesia and paralysis prevent ocular dominance plasticity from occurring. 2. The plasticity, however, was restored under the acute experimental condition by a cortical infusion of 1-noradrenaline (1-NA). In the 1-NA-infused visual cortex, the ocular dominance distribution was clearly shifted to the open eye after monocular exposure for about 20-24 h. 3. We also studied how quickly and to what extent the changes were induced when the duration of the combined treatment was varied. The results were: (i) the earliest change was observed in approximately 12 h with disappearance of binocular cells, (ii) the treatment was most effective after 20-24 h in inducing the shift of ocular dominance, and (iii) the treatment longer than 24 h (up to 45 h) did not necessarily enhance the shift, though the state of reduced binocularity was sustained throughout. 4. The effects of the cortical 1-NA infusion combined with monocular exposure became less with increasing the age of experimental animals, suggesting the presence of the "susceptible period" in the acute experiments. 5. The effects seemed to become smaller toward the end of a given recording session, suggesting that the restored plasticity wanes with time. The present results further support the idea that the direct activation of the NA system enhances cortical plasticity, in principle, independent of general conditions of experimental animals.

Aging↗

Adrenergic regulation of visuocortical plasticity: a role of the locus coeruleus system.

Noradrenaline-beta-adrenoceptor-mediated neural plasticity in cat visual cortex exemplifies clearly established roles of the locus coeruleus system in brain function. The prime role of the noradrenaline-beta-adrenoceptor system in the regulation of ocular dominance plasticity is discussed in this chapter and includes a newly invented paradigm of ocular dominance changes under anesthesia and paralysis without benefit of visual attention. Based on our recent findings, we have sought to integrate positive contributions of muscarinic cholinergic receptors to the beta-adrenoceptor-mediated regulatory processes. The issue of "activity dependency" is important and we recognize the necessity of designing new studies in which relationships between activity dependency within the visual pathway and global neurochemical/cellular factors can be tested directly. Further, we critically reviewed the involvement of gamma-aminobutyric acidA type receptors and N-methyl-D-aspartate receptors in the regulation of ocular dominance plasticity.

2-Amino-5-phosphonovalerate↗

Protein kinase C activity and substrate (F1/GAP-43) phosphorylation in developing cat visual cortex.

Protein kinase C (PKC) and substrate proteins such as F1/GAP-43 have been previously implicated in the synaptic plasticity of long-term potentiation (LTP). As a first step in determining whether they participate in the plasticity observed during the critical period of visual cortex development, we have studied cytosol and membrane PKC activity as well as the endogenous phosphorylation of visual cortical proteins in cat cortical areas 17, 18 at postnatal days 1 and 3, weeks 1, 3, 5, 7, 9, 13, 28 and 51, and adult year 5. There was an 8.4 to 10.9 fold increase in cytosolic PKC activity relative to day 1 level during the critical period of synaptic plasticity (weeks 3-13) which then dramatically decreased back to 2.5-fold of day 1 level by week 51. This was near the adult level of cytosolic PKC. Since there was an increase of 1.8- to 2.1-fold in membrane PKC activity during the critical period, this argues against a PKC translocation event and for an increase in enzyme synthesis. Endogenous phosphorylation in the same visual cortex tissue revealed an increase in protein F1 phosphorylation during the critical period. This level of PKC substrate activity was maintained in the adult providing a mechanism for plasticity in adult cat visual cortex.

Aging↗

Noradrenergic control of ocular dominance plasticity in the visual cortex of dark-reared cats.

In the visual cortex of cats which had been dark-reared for several months since the time before natural eye opening, a cortical infusion of 6-hydroxydopamine (6-OHDA), a noradrenaline (NA)-related neurotoxin, partially suppressed a usual shift in ocular dominance following brief monocular lid suture, causing a significant loss of binocular cells. This partial shift in ocular dominance (U-shaped histogram) was also observed typically in the control hemisphere of cats which were subjected to dark-rearing for more than a year. Furthermore, the expected shift in ocular dominance following monocular deprivation was blocked by a direct cortical infusion of D,L-metoprolol, a selective beta 1-adrenergic receptor antagonist. The blockade was not obtained by D-metoprolol, a biologically inert stereo-isomer, under the comparable condition. In contrast, exogenous L-NA gave rise to an obvious shift in ocular dominance toward the non-deprived eye. The present results suggest that the NA-beta 1 adrenoreceptor system was necessary to maintain the ocular dominance plasticity in the visual cortex of dark-reared cats.

Animals↗

Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate.

Following a previous report we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan. Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.

Antineoplastic Agents↗

Interaction of noradrenergic and cholinergic systems in regulation of ocular dominance plasticity.

We studied interactions among the noradrenergic (NA) and the muscarinic cholinergic (ACh) systems in the regulation of ocular dominance plasticity in kitten visual cortex. The cortex was bilaterally infused with 6-hydroxydopamine (6-OHDA) for a week. Upon termination of the 6-OHDA infusion, one hemisphere was infused with a muscarinic ACh agonist, bethanechol, through the same, chronically implanted cannula for the second week together with monocular lid suture. The other hemisphere received an infusion of the vehicle solution alone. (1) Only in the hemisphere infused with bethanechol at relatively high concentrations did we obtain a clear shift in ocular dominance. We also found that the effect of bethanechol was concentration-dependent. (2) By comparing necessary concentrations of bethanechol and NA for the respective maximal effects, we noted that the former was at least 100-fold less effective than the latter in restoring the plasticity. (3) The cortical infusion of bethanechol did not restore the plasticity to the propranolol-pretreated cortex; the ocular dominance distribution remained virtually unchanged. This result was interpreted as suggesting that functioning beta-adrenoreceptors are needed for the cortical effect of activating the muscarinic ACh receptors to become detectable. (4) The expected shift in ocular dominance following monocular deprivation was partially suppressed, when highly concentrated scopolamine, a muscarinic ACh antagonist, was used, indicating that the involvement of the ACh system in this matter was indirect. The concentration of scopolamine needed for the half-maximum effect was 172-fold higher than that of propranolol. We thus conclude that the involvement of the muscarinic ACh system in ocular dominance plasticity is secondary to that of the NA-beta-adrenoreceptor system.

Aging↗

[The significance of serum specific IgA antibody to Chlamydia trachomatis in the diagnosis and treatment of chlamydial infection in female genital tract].

Chlamydia trachomatis IgA and IgG antibody titers were determined by indirect immunoperoxidase assay in sera of 88 female patients with C. trachomatis-positive cervicitis and 55 C. trachomatis negative healthy controls. Serial serum samples obtained until 66 weeks after treatment were also studied for IgA and IgG antibodies in 28 of the 88 patients with chlamydial cervicitis. In the 88 patients, the presence (94.3%) of antibody (titer greater than or equal to 16) was comparable to that (100%) of IgG antibody (titer greater than or equal to 32), but in healthy controls the presence (5.4%) of IgA antibody was lower than that (30.6%) of IgG antibody. Serum IgA antibody decreased gradually and was undetectable (titer less than or equal to 8) at 20 weeks after treatment in 78.6% of the 28 patients. Serum IgG antibody persisted at stable levels within the same period. These data suggest that the presence of serum IgA antibody to C. trachomatis is correlated with active C. trachomatis infection of the female genital tract.

Adolescent↗

Urinary sodium and potassium excretion, body mass index, alcohol intake and blood pressure in three Japanese populations.

Standardised data on blood pressure, 24 hour urinary electrolyte excretion and other lifestyle factors were obtained in three Japanese populations as part of the INTERSALT study. Urinary sodium excretion and sodium/potassium ratio were significantly (P less than 0.01) higher in Toyama (a semi-rural area in central Japan) than in Tochigi (a rural area 100 km north of Tokyo) and Osaka. There were also significant (P less than 0.01) differences between the centres in diastolic blood pressure (highest in Toyama), although systolic pressure was similar in all three centres. Average potassium excretion was low (46 mmol/day), and the prevalence of both heavy alcohol drinking (greater than or equal to 300 ml/week) and smoking was high in men (33% and 61% respectively); compared with other countries, there were favourable levels of body mass index (mean 22.4 kg/m2). Despite a recent decline in sodium consumption in Japan, which has been accompanied by a fall in blood pressure levels, in the prevalence of hypertension and also in stroke mortality, average sodium excretion in the three centres was high compared to other countries (187 mmol/day). Applying overall INTERSALT regression coefficients to the Japanese data, suggested that further falls in sodium intake together with a modest increase in potassium intake and a reduction (in men) in the prevalence of heavy alcohol drinking could have an important impact on average blood pressures and the prevalence of hypertension. It can be expected that these nonpharmacological approaches to improved blood pressure levels will be accompanied by continued reductions in mortality from stroke.

Adult↗