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M Yoshimoto

Publications and source records attributed to M Yoshimoto.

At least 55 records · Page 3Linked to original sources

[Sentinel node detection of patients with breast cancer by radionuclide method: consideration of radiation safety].

Sentinel node was detected by 99mTc labeled nanocolloid in five patients with breast cancer. Surgery of breast cancer was done at 16 hours after the administration of 74 MBq of 99mTc labeled nanocolloid. Sentinel node was searched by scintigraphy prior to surgery and by gamma-probe during surgery. Radioactivity of injected site, sentinel nodes, blood contaminated gauze, and other garbage was measured by GM detector. Radiation to medical staffs was monitored by a pocket radiation detector and film batches. Sentinel nodes were successfully detected both by scintigraphy and gamma-detector. More than 70% of radioactivity remained in the administered site at 16 hours. Small amount of radioactivity was detectable in the sentinel node. Almost no radioactivity was detectable in blood-contaminated gauze and other garbage. Radiation dose to the main surgeon was 4 to 6 microSv per surgery by a pocket radiation detector. Radiation dose to the assistant surgeon was 2 microSv per surgery. Radiation dose by labeling or injection was 0 to 1 microSv per procedure. No detectable radiation was measured by film batches. It is concluded that the detection of sentinel node by 99mTc labeled nanocolloid is a safe procedure from the point of radiation safety consideration.

Breast Neoplasms↗

Allelic losses of loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 correlate with postoperative recurrence in breast cancer.

We previously defined 18 chromosomal regions in which frequent allelic losses were observed in breast cancers (T. Sato et al., Cancer RES:, 50: 7184-7189, 1990; Y. Harada et al., Cancer (PHILA:), 74: 2281-2286, 1994; I. Ito et al., BR: J. Cancer, 71: 438-441, 1995; K. Tsukamoto et al., Cancer (PHILA:), 78: 1929-1934, 1996; S. Matsumoto et al., Genes Chromosomes Cancer, 20: 268-274, 1997; T. Yokota et al., JPN: J. Cancer RES:, 88: 959-964, 1997; K. Tsukamoto et al., Cancer (PHILA:), 82: 317-322, 1998; A. Iida et al., Genes Chromosomes Cancer, 21: 108-112, 1998; K. Fukino et al., Genes Chromosomes Cancer, 24: 345-350, 1999; T. Yokota et al., Cancer (PHILA:), 85: 447-452, 1999; Y. Utada et al., JPN: J. Cancer RES:, 91: 293-300, 2000). To identify specific allelic losses that might correlate with postoperative recurrence, we examined tumors from a cohort of 504 breast cancer patients, who were followed clinically for 5 years postoperatively, for allelic losses of 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 8p22, 13q12, 17p13.3, or 22q13 had significantly higher risks of recurrence than those whose tumors retained both alleles at those loci; at 3p25.1, the 5-year recurrence rate was 27% among patients with losses versus 18% with retention (P = 0.0131); at 8p22, 27% versus 14% (P = 0.0129); at 13q12, 28% versus 15% (P = 0.0109); at 17p13.3, 27% versus 20% (P = 0.0482); and at 22q13, 29% versus 20% (P = 0.0477). These data indicate that loss of heterozygosity at any one of these five specific loci is a significant predictor of postoperative recurrence among patients who have undergone surgery for breast cancer. These allelic losses can serve as negative prognostic indicators to guide postoperative management of patients.

Adult↗

[Effect of probucol on the concentration of cyclosporin A in patients with nephrotic syndrome].

The first choice of therapy for nephrotic syndrome is steroid, and cyclosporin A(CyA) or other immunosuppressants are selected for steroid resistant or recurrent cases. Nephrotic syndrome accompanies hyperlipidemia for which HMG-CoA reductase inhibitors are mainly used. On the other hand, probucol is used in cases showing inadequate effects or some adverse reactions under treatment with HMG-CoA reductase inhibitors. Recently, we experienced several cases whose blood levels of CyA were decreased to about half that before the combined use of probucol, and concomitant administrations were discontinued. Based on these cases, we considered that the use of probucol should be prescribed in patients with nephrotic syndrome accompanying hyperlipidemia giving preference to CyA treatment. In cases of unavoidable usage of probucol, CyA dose adjustments are required on the basis of frequent CyA blood level monitoring.

Adult↗

Immobilized liposome chromatography for refolding and purification of protein.

Small unilamellar liposomes were utilized as a kind of aqueous two-phase system and artificial chaperone which specifically recognize protein conformation with fluctuated structure. Liposomes showed highly selective binding ability to conformationally changed proteins treated with various concentrations of guanidinium hydrochloride, as evaluated by immobilized liposome chromatography (ILC). In refolding of proteins, liposomes bound to refolding intermediate of proteins and prevented them from forming intermolecular aggregates. Refolding of bovine carbonic anhydrase, lysozyme and ribonuclease A was significantly improved in the presence of liposomes. Furthermore, by utilizing ILC, refolding of proteins was also successfully and simply carried out with considerable high reactivation yield.

Animals↗

Neurotoxicity after hypoxia/during ischemia due to glutamate with/without free radicals as revealed by dynamic changes in glucose metabolism.

Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake in the slices were obtained on imaging plates. The fractional rate constant of [18F]FDG (proportional to the cerebral glucose metabolic rate) from pre-loading of ischemia (O(2) and glucose deprivation)/hypoxia (O(2) deprivation) to the reperfused/reoxygenated post-loading phase was quantitatively evaluated by applying the Gjedde-Patlak graphical method to the image data. Against ischemia an N-methyl-D-aspartate antagonist and hypothermia, but not a free radical scavenger, showed a protective effect when administered during ischemia, whereas no such effect was achieved with any of the above agents when administered after reperfusion. Against hypoxia, there was no protective effect with any of the above agents when administered during hypoxia, although an effect was noted with each when administered after reoxygenation. Excitatory amino acids during ischemia loading were found to be the main factor in the neuronal damage associated with ischemia, while in hypoxia, excitatory amino acids working in tandem with free radicals immediately after reoxygenation were implicated.

Animals↗

Posthypoxic reoxygenation-induced neurotoxicity prevented by free radical scavenger and NMDA/non-NMDA antagonist in tandem as revealed by dynamic changes in glucose metabolism with positron autoradiography.

Using a positron autoradiography technique, dynamic changes in the cerebral glucose metabolic rate (CMRglc) induced by hypoxia/reoxygenation were investigated in living brain slices. After incubating fresh rat brain slices (300 microm thick) with [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, serial two-dimensional time-resolved images of [(18)F]FDG uptake in the slices were obtained on imaging plates. As compared to the unloaded control values, with hypoxia-loading [(18)F]FDG uptake increased markedly, suggesting enhanced glycolysis. The net influx constant (K) of [(18)F]FDG at pre-hypoxia-loading and after reoxygenation with loading hypoxia for various periods of time was quantitatively evaluated by applying the Patlak graphical method to the image data. Regardless of the brain region, with hypoxia of </=10-min duration, the K value returned to the preloading level, whereas with hypoxia of >/=20 min duration only partial or no recovery was seen, indicating irreversible neuronal damage. The 30-min administration of either N-methyl-D-aspartate (NMDA)/non-NMDA antagonist or a free radical scavenger at the same time as reoxygenation after 20 min hypoxia showed a neuroprotective effect inhibiting the decrease in the post-hypoxia-loading K value. In contrast, no such neuroprotective effect was evident with administration of either of these agents only during hypoxia loading, possibly indicating that immediately after reoxygenation neuronal damage was induced mediated by excitatory amino acids and free radicals in tandem. These results demonstrate that serial quantitative evaluation of CMRglc using this technique may be of use in investigating the brain tissue injury associated with hypoxia/reoxygenation as well as clarifying the underlying mechanisms and protective effect of various drugs against such injury.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Surgery for ductal carcinoma in situ.

BACKGROUND: Ductal carcinomas in situ (DCIS) are sometimes treated too aggressively by surgery. We discuss minimal invasive surgery for DCIS on the basis of our experience at the Cancer Institute Hospital in Tokyo. METHODS: We performed surgery for 667 cases of DCIS between 1987 to 1998. This twelve year period we divided into three periods; 1987-1990,1991-1994, and 1995-1998. RESULTS: DCIS comprised 10% of all breast cancers, and tended to increase in incidence over time. The number of minimally invasive procedures such as breast conserving treatment (BCT), surgery without axillary dissection, and day surgery increased in later periods. In BCT for DCIS the surgical margin status is the most important factor, the rate of negative surgical margins was higher in DCIS than invasive cancer, and especially high in cases of mammographically detected nonpalpable cancer, the incidence of which is increasing yearly. The outcome of the 667 cases was very good. No distant metastases were observed, and the incidence of ipsilateral breast cancer(including second primary cancer) in these cases was 5% CONCLUSIONS: Because small cancers, including nonpalpable cases, will be detected more frequently, minimal invasive surgery will become more common for DCIS.

Axilla↗

Intratumoral pyrimidine nucleoside phosphorylase (PyNPase) activity predicts a selective effect of adjuvant 5'-deoxy-5-fluorouridine (5'DFUR) on breast cancer.

BACKGROUND: Pyrimidine nucleoside phosphorylase (PyNPase) is the enzyme that converts 5'-deoxy-5-fluorouracil (5'DFUR) to 5-fluorouracil (5FU). Its activity in cancer tissue may correlate with the selective antitumor activity of 5'DFUR in breast cancer. METHODS: Two hundred and sixteen T2 breast cancer patients were treated consecutively with surgery followed by 5'DFUR (600 mg/body/day) + tamoxifen (20 mg/body/day) for 2 years. PyNPase activity in breast cancer tissue, determined by high-performance liquid chromatography, ranged from 4.2-626.0 micrograms FU/mg protein/hr (mean +/- SD, 203.5 +/- 122.4), and the examined patients were divided into two groups: group A (high PyNPase group), cases with the PyNPase activity equal to or more than the mean value of 203.5 micrograms FU/mg protein/hr, and group B (low PyNPase group), cases with activity less than the mean value. RESULTS: Although there was no difference in relapse-free survival (RFS) between groups A and B, among node-positive patients (n = 83) those in group A tended to have a longer RFS. When divided into subgroups according to estrogen receptor (ER) status, among node-positive and ER-positive tumors (n = 49), the RFS was significantly better in group A than in group B (p < 0.05). CONCLUSION: Intratumoral PyNPase activity might be of use as a predictor of the effect of adjuvant 5'DFUR on breast cancer.

Adult↗

Mammographic and clinicopathological features of mucinous carcinoma of the breast.

BACKGROUND: We attempted to improve the effectiveness of diagnostic techniques in mammographic imaging of mucinous carcinoma of the breast by defining the characteristics of mammographic images and investigating correlations between these images and various clinicopathological findings. METHODS: Clinicopathological investigations of 92 lesions in 90 cases of mucinous carcinoma of the breast were made. Mammography demonstrated 80 lesions with identical tumor shadow characteristics and these were divided into three patterns, circumscribed, indistinct and blended. Correlations between clinicopathological findings and mammographic images were investigated. RESULTS: Patients with mucinous carcinoma of the breast usually present with a palpable mass. The lymph node metastasis rate in this study was low and prognosis in the early postoperative period was satisfactory. On mammograms, the circumscribed pattern was the most frequent. The investigation of the correlation between histological sub-type and mammographic pattern showed a high percentage of pure type lesions exhibited in the circumscribed pattern while those of mixed histologic type often showed the indistinct pattern. Calcification frequency demonstrated on mammography was 75% for the indistinct and mixed patterns, and approximately 50% for the circumscribed pattern. A high rate of calcification seen outside the tumor shadow suggested a high frequency of invasion and the spread of cancer to neighboring tissues. The circumscribed pattern was least frequently associated with lymph node metastasis, followed by the indistinct and blended patterns in that order. CONCLUSION: Investigation of clinicopathological factors and mammographic findings in mucinous carcinoma of the breast suggests that mammography provides clinically valuable information for the treatment of this disease. These findings indicate the importance of careful mammographic observation at the time of diagnosis.

Adenocarcinoma, Mucinous↗

NACP/alpha-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson's disease brains.

The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP), also called alpha-synuclein, is a major component of Lewy bodies in Parkinson's disease (PD) as well as of neuronal and oligodendroglial cytoplasmic inclusions in multiple system atrophy. We previously reported argyrophilic, tau-negative glial inclusions in the midbrains of patients with PD and have now conducted immunocytochemical and ultrastructural examinations. The PD glial inclusions also are immunoreactive for NACP/alpha-synuclein, but not for beta-synuclein, and ultrastructurally are composed of filamentous structures about 25-40 nm in diameter. Double immunolabeling showed that the inclusions were present in both astrocytic and oligodendroglial cells. They were located within the substantia nigra in 13 of 30 patients with PD and outside the nigra in 24. The number of inclusions was correlated with the severity of nigral neuronal loss. These findings indicate that abnormal accumulation of NACP/alpha-synuclein in glial cells is a pathological feature of PD related to its progression.

Aged↗

Juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease) with diffuse neurofibrillary and lewy body pathology.

We describe an unusual case of Hallervorden-Spatz disease (HSD). After presenting with limb rigidospasticity at the age of 9 years, our patient developed progressive dementia, spastic tetraparesis and myoclonic movements, leading to akinetic mutism. He died of pneumonia at the age of 39 years. Autopsy revealed a severely atrophic brain, weighing 510 g. Histologically, there were iron deposits in the globus pallidus and substantia nigra pars reticulata, and numerous axonal spheroids throughout the brain and spinal cord. Neurofibrillary tangles were abundant in the hippocampus, cerebral neocortex, basal ganglia and brain stem. Neuritic plaques and amyloid deposits were absent. Lewy bodies and Lewy neurites, which were immunolabeled by anti-alpha-synuclein, were found in the brain stem, cerebral cortex and spinal gray matter. Sarkosyl-insoluble tau extracted from the temporal cortex resolved on immunoblots into three major bands of 60, 64 and 68 kDa and a minor band of 72 kDa, as reported for Alzheimer's disease. The present case, together with a few similar cases reported previously, may represent a particular subset of neuroaxonal dystrophy, i.e., HSD associated with extensive accumulation of both tau and alpha-synuclein.

Adolescent↗

Identification of Rad51 alteration in patients with bilateral breast cancer.

The human Rad51 gene, HsRAD51, is a homolog of RecA of Escherichia coli and functions in recombination and DNA repair. BRCA1 and BRCA2 proteins form a complex with Rad51, and these genes are thought to participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Additionally, we have shown that the pattern of northern blot analysis of the RadS gene is closely similar to those of the BRCA1 and BRCA2 genes. It is therefore possible that alterations of the Rad51 gene may be involved in the development of hereditary breast cancer. To investigate this possibility, we screened Japanese patients with hereditary breast cancer for Rad51 mutations and found a single alteration in exon 6. This was determined to be present in the germline in two patients with bilateral breast cancer, one with synchronous bilateral breast cancer and the other with synchronous bilateral multiple breast cancer. In both patients, blood DNAs showed a G-to-A transition in the second nucleotide of codon 150, which results in the substitution of glutamine for arginine. As this alteration was not present in any patients with breast or colon cancer examined, we assume that this missense alteration is likely to be a disease-causing mutation.

Blotting, Northern↗

Effect of single intracerebroventricular injection of alpha-interferon on monoamine concentrations in the rat brain.

The effect of a single intracerebroventricular (i.c.v.) injection of alpha-IFN on levels of central monoamines and their metabolites in six brain regions (frontal cortex, striatum, hypothalamus, hippocampus, mid brain and medulla) of the rat was investigated. Wistar rats (n=10) were decapitated 2 h after i.c.v. injection of alpha-IFN. The brain tissues were homogenized, and monoamine concentrations were measured by high-performance liquid chromatography with an electrochemical detector. The levels of 5-hydroxytryptamine (5-HT) were significantly reduced in the frontal cortex in a dose-dependent manner, and the levels of both 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) were reduced in the mid brain and the striatum. The levels of noradrenaline (NA) were also significantly reduced in a dose-dependent manner in the frontal cortex. Some neurophysiological changes that affect activity of the noradrenergic or/and the serotonergic neuron system may occur during IFN therapy.

3,4-Dihydroxyphenylacetic Acid↗

Oxidative refolding of lysozyme assisted by negatively charged liposomes: relationship with lysozyme-mediated fusion of liposomes.

Oxidative refolding of denatured/reduced lysozyme was examined in the presence of charged liposomes composed of neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG). Surface charge density of liposomes had a marked effect on the interaction between liposomes and reduced lysozyme which is observed in the early stage of the refolding. It was found that there was a critical level of surface charge density of liposomes (-0.15 C/nm2) at which the interaction between liposomes and lysozyme drastically changed. At the surface charge density of liposomes ranging from -0.15 to -1.4 C/nm2, the interaction between liposomes and lysozyme resulted in aggregate formation. In contrast, at the surface charge density ranging from 0 to -0.15 C/nm2, no aggregate formation was observed if the lysozyme/liposome molar ratio was less than 600. On the basis of the experimental results, a model for the interaction between charged liposomes and lysozyme was proposed, focusing on the mechanism of protein-induced fusion of charged liposomes as well as protein refolding on liposomes. Then, the optimal condition for oxidative refolding of lysozyme was examined in the presence of charged liposomes by controlling the lysozyme-liposome interaction. The reactivation yield of lysozyme was improved up to 85% in the presence of liposomes with a surface charge density of -0.14 C/nm2.

Journal Article↗

Surgical treatment of hepatic metastases from breast cancer.

We have performed a retrospective study to evaluate whether surgical treatment is beneficial in patients with hepatic metastases from breast cancer. Between September 1985 and September 1998, 25 patients with hepatic metastases (14 solitary and 11 multiple), eight of whom had extrahepatic metastases, underwent hepatectomy. All of the detectable liver metastasis were resected in all of the cases. There were no severe postoperative complications. All but one of the patients received adjunctive polychemotherapy after the hepatectomy. After the hepatectomy, recurrent tumors were detected in 18 of the patients, being located in the liver in 12 (67%) of them. Overall, however, hepatectomy ensured that the liver was clinically recurrence-free for a median of 24 months (range 2-132 months). Eleven patients died of recurrent tumors, two died of other causes and the remaining 12 are currently alive. The 2- and 5-year cumulative survival rates after hepatectomy were 71% and 27%, respectively, and the median survival duration was 34.3 +/- 3.2 months, much better than the period of 8.5 months for another series of patients treated with standard or non-surgical therapies at our institution. The number and the size of hepatic metastases, the interval between treatment of the primary lesion and hepatectomy, and the existence of extrahepatic metastasis were not adverse prognostic factors. In conclusion, our data, although limited and highly selective, suggest that surgical treatment of hepatic metastases from breast cancer may prolong survival in certain subgroups of patients to a greater extent than standard or non-surgical therapies.

Adult↗

Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats.

The effects of antibiotics and anti-inflammatory drugs on the promotion stage of lung carcinogenesis initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated in two experiments with a similar protocol. In experiment 1, rats received tap water containing 2000 p.p.m. BHP for 12 weeks followed by basal diet or basal diet containing 0.02% erythromycin (EM), 0. 04% ampicillin (ABPC), 1.5% sho-saiko-to, 0.02% EM plus 1.5% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administration. The development of adenocarcinomas (AC), squamous cell carcinomas (SqC) and adenosquamous carcinomas (ASqC) was completely inhibited in rats given ABPC plus sho-saiko-to and the numbers of lung lesions including alveolar hyperplasias, adenomas and carcinomas were decreased in rats given EM plus sho-saiko-to or ABPC plus sho-saiko-to. Neutrophil and macrophage infiltration into alveolar spaces of the lung were also markedly suppressed. In experiment 2, rats received BHP in the same manner as in experiment 1 and basal diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks. The incidence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon. Bacteria, mainly Escherichia coli, were detected in broncho-alveolar lavage of rats receiving BHP. The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may therefore be useful as a chemopreventive strategy in lung cancer clinics.

Adenocarcinoma↗

Association between complement regulatory protein factor H and AM34 antigen, detected in senile plaques.

BACKGROUND: We have previously shown that monoclonal antibody AM34, which is reactive with senile plaques, may recognize the C terminus of complement factor H. In this study, we investigated the expression of factor H in tissue from a human brain and the relation between AM34 antigen and factor H. METHOD: Total ribonucleic acid (RNA) was extracted from a normal human brain. A reverse transcriptase-polymerase chain reaction method was employed for detecting messenger RNAs coding for factor H and related proteins. Protein extracts from a normal human brain were also analyzed to detect factor H and related proteins by means of Western blotting. The cerebrospinal fluid from an Alzheimer's disease patient was immunoprecipitated with AM34 and anti-factor-H antibodies, and then it was subjected to gel electrophoresis followed by immunoblotting with AM34 and anti-factor-H antibodies. RESULTS: 26 clones of complementary DNA fragment were obtained by reverse transcriptase-polymerase chain reaction. Among them, seven clones were identical to factor H, and the others were related proteins and unreported sequences. A Western blot analysis of protein extracts from the normal brain tissue exhibited a 150-kd band, indicating the presence of factor H. AM34 was immunoreactive with the 150-kd molecule contained in the immunoprecipitates with anti-factor H antibodies, and vice versa. These results suggest that AM34 antigen could be identical to complement factor H. CONCLUSIONS: The results of our experiments indicate that factor H is possibly detected in the human brain, and that the AM34 antibody could recognize factor H. Because AM34 is capable of staining senile plaques positively, factor H is suggested to be associated with senile plaques in the human brain.

Aged↗