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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 415 records · Page 23Linked to original sources
PubMed1995

Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy--an MR analysis.

PURPOSE: The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. METHODS AND MATERIALS: Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The data were examined to elucidate the influential ones of five factors (patients' age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted literature review. RESULTS: Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. CONCLUSION: Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient's age and CRT dose.

Adolescent↗
PubMed1995

Inhibitory effects of cadmium ion on extracellular Ca(2+)-independent contraction of rat aorta.

In vitro effects of cadmium ion on vasoconstriction, particularly on vasoconstriction independent of extracellular Ca2+, were investigated using isolated rat aorta. Aorta incubation with CdCl2 (0.01, 0.1 mM) significantly attenuated contractile responses to KCl and phenylephrine in the medium containing normal Ca2+ (2.5 mM). The contractile response to phenylephrine in the presence of calcium channel antagonists, nifedipine (1 microM) or verapamil (1 microM), was markedly inhibited by CdCl2 (0.1 mM). In the medium without Ca2+, phenylephrine (10 microM) induced a phasic contraction, which was markedly inhibited by CdCl2 (0.1 mM). In the medium without Ca2+, phorbol 12-myristate 13-acetate (1 microM) and okadaic acid (10 microM) caused tonic contractile responses, which were strongly attenuated by CdCl2 (0.1 mM) pretreatment. Contractile response to sodium fluoride (5 approximately 15 mM) in the absence of extracellular Ca2+ was strongly attenuated by CdCl2 (0.1 mM) pretreatment. These results suggest that cadmium ion depresses an extracellular Ca(2+)-independent component of agonist-induced vasoconstriction by hindering an intracellular contractile mechanism(s).

Animals↗
PubMed1995

A new cytochrome P450 form belonging to the CYP2D in dog liver microsomes: purification, cDNA cloning, and enzyme characterization.

A new form of cytochrome P450 (P450 DUT2) was purified from untreated male dog liver microsomes. The final preparation (a specific content of 19.1 nmol P450/mg protein) showed a single band with an apparent monomeric molecular weight of 50,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but was further separated into two apoproteins (P450 DUT2a and P450 DUT2b) by reverse-phase HPLC. Both proteins had identical NH2-terminal amino acid sequences, but the first three amino acids of P450 DUT2b were truncated in P450 DUT2a. Purified P450 DUT2 showed 5 to 18 times higher catalytic activities than did hepatic microsomes toward desipramine, metoprolol, and dextromethorphan. These activities in dog liver microsomes were strongly inhibited by anti-P450 DUT2-IgG. A 1.7-kilobase pair cDNA (cDUT2) encoding a male dog liver P450 of 500 amino acid residues (molecular weight 56,400) was isolated and sequenced. The first 35 NH2-terminal amino acid sequence of P450 DUT2b coincided with the deduced amino acid sequence of cDUT2 at 2-36. The deduced total amino acid sequence of cDUT2 shared high similarity with the reported 2D forms (with 2D6, 74.6%; 2D14, 75.4%; 2D1, 65.4%; and 2D9, 63.6%). Moreover, the expressed P450 DUT2 in COS-7 cells had catalytic activities similar to those of purified P450 DUT2. Therefore, this paper is the first report about dog CYP2D. Furthermore, Northern and Western blot analyses indicated that the expressed levels of mRNA and protein were almost equal between male and female dogs. Western blot analysis suggested that P450 DUT2 is a constitutive and major (approximately 20% of the total P450) form, indicating that the 2D subfamily P450 in dog liver is quite unique from CYP2D members of other species.

Amino Acid Sequence↗
PubMed1995

Protein L-isoaspartyl methyltransferase: developmentally regulated gene expression and protein localization in the central nervous system of aged rat.

We have cloned a cDNA encoding protein L-isoaspartyl methyltransferase (PIMT) and characterized gene expression in the development, maturation, and the aging process of the central nervous system by RNA blot analysis, western blot analysis, and immunohistochemistry. PIMT transcript was detected in rat embryonic brain and showed a linear up-regulation during the maturation of the brain and maintained its level in aged rat brain. Immunoblot analysis also supported a linear increase in the amount of PIMT in the maturation process of rat brains. An immunohistochemical study showed that PIMT is strongly expressed in neurons and weakly but definitively in glial cells and oligodendrocytes. These immunoreactivities significantly increased in some neurons of the hippocampus, cerebral cortex, and the brain stem of aged rat brain. The present results suggest that the expression of PIMT is associated with the amount of racemized/isomerized proteins accumulated during the developmental and aging process of the central nervous system.

Age Factors↗
PubMed1995

Infantile subdural fluid collection: diagnosis and postoperative course.

The authors reviewed 47 cases of infantile subdural fluid collection with regard to diagnosis and postoperative course after placement of a subdural-peritoneal shunt. CT scan with contrast enhancement proved to be an important diagnostic modality, showing vessels in the subarachnoid space as high-density spots. Utilizing this technique, we were able to differentiate the following varieties of fluid collection: (1) subdural fluid collection, in which enhancing vessels were seen on the brain surface, (2) subarachnoid fluid collection, in which vessels were on the inner table of the cranium, and (3) coexistence of subdural and subarachnoid fluid collections, in which vessels were between the inner table of the cranium and the brain surface. The postoperative course of subdural fluid collection was characterized as follows: (1) the subdural fluid collection decreased first, with increased subarachnoid fluid collection; (2) the subarachnoid fluid collection remained after the disappearance of subdural fluid collection; and (3) the brain expanded again later. Subdural fluid collection disappeared about 1 month after the shunt operation, which could lead occlusion of the shunt system. Postoperative enlargement of the subarachnoid space was an early indicator of the efficacy of the subdural-peritoneal shunt.

Cerebral Angiography↗
PubMed1995

Prevention of glomerular hyperfiltration in rats with streptozotocin-induced diabetes by an atrial natriuretic peptide receptor antagonist.

The contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration in diabetes was investigated by examining the effects of HS-142-1, a non-peptide antagonist of biological receptors for ANP, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in rats with streptozotocin-induced diabetes. Three to four weeks after streptozotocin injection, the plasma concentration of ANP, urinary cyclic GMP excretion rate, GFR, and RPF were significantly higher in diabetic rats than in control rats. The increase in GFR and RPF in diabetic rats was significantly reduced, in a dose-dependent manner, by a single intravenous injection of HS-142-1; the maximal effect was apparent at a dose of 10 mg per kg of body weight. Continuous subcutaneous administration of HS-142-1 with an osmotic minipump for 3 to 4 weeks, beginning 2 days after streptozotocin injection, prevented the increases in urinary cyclic GMP excretion rate, GFR, and RPF observed in untreated diabetic rats. These results highlight the importance of ANP in the development of diabetic glomerular hyperfiltration and indicate that this condition can be prevented by continuous inhibition of the action of ANP.

Animals↗
PubMed1995

Suppression of in vivo tumor growth by the transfection of the interleukin-5 gene into colon tumor cells.

To investigate the influence of tumor producing interleukin-5 (IL-5) on growth kinetics of tumors, we transduced the murine IL-5 gene into murine colon C26 tumor cells. Two IL-5-secreting clones, low-level IL-5 producer C26-8B and high-level IL-5 producer C26-6F, were established. Both tumors, C26-6F and C26-8B, grew more slowly than the mock C26 tumor, although the in vitro growth rate of these IL-5 transfectants was much the same as that of the mock C26 cells. There was a significantly decreased number of colonies in the lung of mice given C26-6F or C26-8B tumors i.v. than in mice given mock C26 tumors i.v. Moreover, in mice given C26-6F cells i.v., a smaller number of tumor colonies in the lung was observed, as compared to the case with C26-6B cells. While the growth rate of C26-8B tumors in mice treated with anti-IL-5 mAb was more rapid than that seen in control mAb-treated mice, growth of C26-6F tumors in anti-IL-5-mAb-treated mice was slightly more rapid compared to findings in control mAb-treated mice. The isotype-matched mAb did not alter the in vitro growth of mock-C26 cells or of the IL-5-gene-modified C26 cells. Growth of IL-5-secreting C26 tumors transplanted in nude mice was also inhibited. These results suggest that tumor-producing IL-5 inhibits growth of colon tumors mediated through T-cell-independent protective mechanisms of the host.

Animals↗
PubMed1995

MR findings of avulsive cortical irregularity of the distal femur.

Avulsive cortical irregularity, a benign condition occurring only among children and adolescents, has been known to simulate malignancy not only radiologically but also microscopically. Therefore, in addition to plain radiographs, further studies including by magnetic resonance (MR) imaging may occasionally be required. MR images of seven cases of avulsive cortical irregularity of the femur were reviewed. In all cases, the lesion appeared hypointense on T1-weighted images and hyperintense on T2-weighted images, with a dark rim on both sequences at or near the sites of the bony attachment of the medial head of the gastrocnemius muscle. In all cases, bilateral involvement was demonstrated by plain radiography, computed tomography, and/or MR imaging. The authors suggest that avulsive cortical irregularity involves both femora much more frequently than has been reported previously.

Adolescent↗
PubMed1995

Potential application of human interferon-alpha in microbial infections of the oral cavity.

We have been evaluating the potential use of interferon-alpha (IFN-alpha) against fungal infections of the oral cavity. IFN-alpha has been reported to enhance the antifungal activity of neutrophils. This cytokine is also known to synergize with interleukin-1 in enhancing a number of immunomodulatory responses. To study cytokine involvement in oral defense mechanisms against microbial infection, we first demonstrated the presence of antimicrobial interleukins (IL)-1 alpha, IL-1 beta, and IL-8 in the saliva, which can all augment the microbicidal activity of neutrophils, and the presence of epithelial cells and neutrophils in oral lavage fluid from healthy volunteers. Immunostaining for cytokines produced by these cells showed that the candidate producers of both IL-1 alpha and IL-8 are epithelial cells, but those of IL-1 beta remained inconclusive. We next found that IFN-alpha enhanced IL-1 alpha-augmented neutrophil-mediated anticandidal action while marginally enhancing IL-8- and IL-1 beta-mediated reactions. These results suggest that IFN-alpha is a potential agent for treating oral mycosis by cooperating with endogenous cytokine(s) in the saliva, in addition to its intrinsic antiviral action.

Adult↗
PubMed1995

Collaborative study of interlaboratory variability in Salmonella typhimurium TA102 and TA2638 and Escherichia coli WP2/pKM101 and WP2 uvrA/pKM101. Association of Microbial Mutation Testing Laboratory C.O.

A collaborative study of interlaboratory variability in bacterial mutagenicity induced by mitomycin C (MMC) and bleomycin (BLM) was performed using the four strains Salmonella typhimurium TA102 and TA2638 and Escherichia coli WP2/pKM101 and WP2 uvrA/pKM101. Thirteen laboratories participated in this study. The four strains and two chemicals were sent from a central source to each laboratory. Each strain was cultured in nutrient broth containing antibiotics and laboratories were requested to ensure that the spontaneous counts for marker check fell within a specified range in the preparation of the original stock culture. Concerning the response to the chemicals, most interlaboratory variability was within a 4-fold range for tests with TA102, TA2638 and WP2/pKM101. From the results of the statistical analysis using the linear regression test, positive results in TA102, TA2638 and WP2/pKM101 and negative results in WP2 uvrA/pKM101 were obtained by MMC testing in all of the laboratories. On the other hand, with BLM testing, considerable interlaboratory variability was observed between the strains, largely because of the variation in results of the repeat experiments. Overall mean spontaneous revertant counts in all laboratories were within acceptable ranges for all four bacterial strains. In conclusion, it is judged that among Japanese laboratories, there is excellent agreement in the tested response of these bacterial strains to a strong mutagen such as MMC, as well as uniformity in the spontaneous reversion rates. However, for chemicals such as BLM that induce a weak response, it may be necessary to repeat experiments several times to obtain clear results. In this study, TA102 was shown to be a useful strain for routine mutagenicity testing. This necessitated control over culture maintenance by the addition of tetracycline and strict selection in the preparation of the original stock cultures.

Bleomycin↗
PubMed1995

An intracranial wooden foreign body without neurological findings: case report.

We encountered an unusual case of an intracranial wooden stick penetrating through the frontal bone, without remarkable neurological findings. That foreign body was shown to be a low-density area similar to an intracranial air pocket by a standard computed tomogram. Here we discuss the potential hazards of intracranial wooden foreign bodies and emphasize the necessity for special attention to them during radiologic examination.

Brain Injuries↗
PubMed1995

Blockade by ONO-NT-012, a unique prostanoid analogue, of prostaglandin E2-induced allodynia in conscious mice.

1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice was reported to induce allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli through prostaglandin E receptor subtype EP1 and hyperalgesia through prostaglandin E receptor subtypes EP2 and/or EP3. In the present study, we investigated the effects of an EP1 antagonist on these sensory disorders by use of ONO-NT-012 or AH6809. 2. ONO-NT-012 dose-dependently antagonized the PGE2-induced allodynia but had no effect on the PGE2-induced hyperalgesia by the hot plate test. On the other hand, AH6809 blocked the PGE2-induced hyperalgesia at the highest dose examined (50 micrograms kg-1) but had no effect on the PGE2-induced allodynia. The i.t. injection of AH6809 or ONO-NT-012 alone did not have any effect on the response to noxious or innocuous stimuli. 3. Increasing doses (5 pg kg(-1)-500 ng kg-1) of ONO-NT-012 produced parallel shifts to the right of the dose-response curves to PGE2. The Schild plot regression line was linear and the slope was close to unity. The pA2 value against PGE2 was calculated to be 9.96. 4. The present study demonstrates that i.t. administration of PGE2 exerts allodynia through EP1 in the mouse spinal cord and that ONO-NT-012 is a highly potent, simple competitive antagonist for the PGE2-induced allodynia.

Analysis of Variance↗
PubMed1995

Mechanisms in inhibitory action of aclarubicin on contractility of rat aorta.

The effects of aclarubicin on vasocontractile response and 45Ca2+ influx were investigated using rat isolated aorta. KCl-induced contractile force in medium containing 2 center dot 5 mM calcium and calcium-induced contractile force in high K+ (60 mM)-depolarized aorta were both markedly attenuated by aclarubicin (70 microM) pretreatment. 45Ca2+ influx stimulated by 60 mM KCl was significantly lower in the aclarubicin (70 microM)-pretreated aorta compared with the control. Aclarubicin pretreatment attenuated phorbol 12, 13-dibutyrate (1 microM)-induced contraction both in the presence and absence of calcium in the medium. Aclarubicin pretreatment also attenuated caffeine (20 mM)-induced transient contraction. These results suggest that aclarubicin attenuates vasoconstriction by inhibiting both Ca2+ entry through the voltage-dependent calcium channel and the intracellular contractile pathway after elevation of intracellular free calcium in vascular smooth muscle, in addition to the known mechanism of inhibition of phosphoinositides hydrolysis.

Aclarubicin↗
PubMed1995

Serial proton magnetic resonance spectroscopy in a patient with the interval form of carbon monoxide poisoning.

Serial proton magnetic resonance spectroscopy (1H-MRS) studies were performed from immediately after the appearance of sequelae in a patient with the interval form of carbon monoxide (CO) poisoning. The volume of interest was set over the frontal lobe white matter. In the early period a persistent increase in choline was found, which was thought to reflect the course of progressive demyelination. The appearance of lactate and decrease in N-acetylaspartate reflected the point at which neuron injury became irreversible. These were followed later by the finding of irreversible changes on MRI and single photon emission computed tomography. The findings suggest that 1H-MRS may be a useful modality to determine neuron viability and prognosis early in the course of the interval form of CO poisoning.

Brain Diseases↗
PubMed1995

A longitudinal follow-up study of seasonal affective disorder.

OBJECTIVE: The purposes of this study were to evaluate the long-term stability of a seasonal pattern of recurrent depression, identify possible factors associated with alteration of the seasonal pattern, and determine whether atypical vegetative symptoms during early seasonal depressive episodes predict future seasonal relapses. METHOD: The subjects were 41 patients satisfying the criteria used in the Japanese multicenter study of seasonal affective disorder who were consistently treated at the same outpatient clinic. Their longitudinal courses were evaluated by using case records and the Schedule for Affective Disorder and Schizophrenia--Life-time Version; the mean follow-up period was 10.4 years. RESULTS: Nine subjects (22.0%) consistently showed a fall-winter pattern of recurrence throughout follow-up. Seventeen patients with an initial fall-winter pattern subsequently tended to shift seasons or show less seasonality. This alteration in pattern was possibly associated with antidepressant therapy or life events. Eleven patients with an initial diagnosis of nonseasonal affective disorder subsequently developed seasonal affective disorder; no specific factors were associated with this change. Atypical vegetative symptoms were significantly more common in patients with stable seasonal patterns of recurrence than in those who lost seasonality. CONCLUSIONS: Although seasonal affective disorder appeared to be altered by antidepressant treatment, the presence of a core group of patients with a consistent seasonal pattern of recurrent depression suggests the validity of seasonal affective disorder as a distinct subtype of recurrent affective illness. The findings also suggest that atypical vegetative symptoms during early seasonal depressive episodes predict the subsequent seasonality of depression.

Adult↗