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Biomedical subjects

Y Tokuda

Publications and source records attributed to Y Tokuda.

At least 109 records · Page 6Linked to original sources

[Chemotherapy for patients with recurrent breast cancer and quality of life].

Chemotherapy plays a major indispensable role in treating patients with recurrent breast cancer. Although standard regimens such as CAF, FAC or CMF yield approximately a 50% response rate, the response usually lasts only for 6 months or so on average. For those who have an unfavorable response to chemotherapy, significant portions of their remaining time are to be consequently lost with only identifying damaging effects of treatment, depressed quality of life. Because of this dismal outcome, many of the patients are deeply discouraged about the future, and there is a desperate need for better treatment. Autologous stem cell support, originally practiced in the form of autologous bone marrow transplantation, has been found instrumental in treating breast cancer, and our pilot study started some fifteen years ago showed a higher response rate and survival rate compared to conventional chemotherapy. Moreover, there have been some long-term disease-free survivors with probable cures among complete responders. This is because quality of life is not a mere rating of health status, and is something perceived by each patient individually, reflecting the way in which individual patients feel about their health status. Although high-dose chemotherapy with autologous stem cell support will cause quite a lower quality of life for a significant period of time, it has been fairly well accepted and tolerated by many patients who would be able to maintain some degree of hope. The need to incorporate patients' values, preferences and hopes is what distinguishes quality of life from all other health measures, and physicians' values ought to play no major role in the decision making process when the outcome is often palliation and treatments may be unpleasant.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of meningioma associated with intracerebral hemorrhage and acute deterioration].

We report a case of convexity meningioma associated with sudden onset of intracerebral hemorrhage followed by acute deterioration. A 76-year-old previously healthy male suddenly collapsed into coma and was admitted to our department. On admission, he was deeply comatose. Computerized tomography (CT) scan revealed intracerebral hemorrhage in the right frontal lobe, together with an isodense mass lesion of about 5 cm in diameter. The density on the fronto-medial side of the mass increased after administration of contrast medium, probably due to extravasation. However, there was no enhancement of the mass lesion. Cerebral angiography revealed marked prolongation in circulation time and extravasation via the right middle internal frontal artery. The right middle meningeal artery was dilated and elongated, but no tumor stain was found. The patient died on the following day. Autopsy disclosed massive hemorrhage in the right frontal lobe together with a convexity meningioma. Histological examination showed that the tumor was a fibroblastic meningioma. We review previously reported cases of convexity meningioma associated with intracranial hemorrhage, and discuss mainly the mechanism of bleeding.

Acute Disease↗

Coping styles among Japanese women with breast cancer.

In order to investigate changes in coping styles before and after diagnosis of cancer, and the relationship between coping styles and emotional states among Japanese women, we conducted a study using the Profile of Mood States (POMS) and Dealing With Illness-Coping Inventory. Coping methods such as active-cognitive, active-behavioral and avoidance were found to be more frequently used after the women were diagnosed with cancer than before (p < 0.001). There were also positive correlations between active-reliance behavior and tension-anxiety and depression, between cognitive-passive behavior and depression and lack-of-vigor, between passive-resignation behavior and anger-hostility and confusion, and between avoidance-solitary behavior and anger-hostility, fatigue, depression, lack-of-vigor and confusion. In conclusion, a diagnosis of cancer causes a patient to use more frequently avoidance behavior as well as active coping styles, and these passive/avoidance coping styles are often correlated with negative emotions. These results imply that patients with breast cancer need support considering the relationship between passive/avoidance coping styles and negative emotions.

Adaptation, Psychological↗

[A case of multiple cerebral arteriovenous malformations treated by gamma knife radiosurgery].

We reported a case of multiple cerebral arteriovenous malformations (AVMs) treated by gamma knife radiosurgery. A 6-year-old girl was admitted because of systemic tonic convulsion. At the first admission, we performed only vertebral angiography, which showed a 15 mm cerebral AVM. It was fed by the right posterior cerebral artery and drained into the great vein of Galen. Seven years after the first admission, the patient returned again with severe headache. Four-vessel cerebral angiograms showed another 7 mm AVM fed by the left frontopolar artery. We treated both cerebral AVMs bv gamma knife radiosurgery. Follow-up angiograms performed 2 years after radiosurgery confirmed the disappearance of both AVMs. We then discuss treatment of multiple cerebral AVMs.

Abnormalities, Multiple↗

Epithelial Proliferative Lesions and Carcinomas in Fibroadenomas of the Breast.

Sixteen cases of fibroadenomas with epithelial proliferative lesions (EP lesions) with histologic features resembling those of epithelial hyperplasia, sclerosing adenosis, and microglandular adenosis, and four cases of carcinomas in fibroadenomas (CA lesions) were studied histopathologically and immunohistochemically. The CA lesions included one intraductal carcinoma, two invasive ductal carcinomas, and one lobular carcinoma in situ. The histologic features of the EP lesions and CA lesions were fundamentally the same as those of carcinomas commonly observed in the mammary gland. Immunohistochemically, smooth muscle actin was useful in the detection of myoepithelial cells, particularly in EP lesions of the adenosis type (sclerosing adenosis or microglandular adenosis), and in distinguishing carcinoma. The differences between EP lesions and CA lesions of sites of immunoreactivity to CA15-3, CEA, and EMA were also helpful for differential diagnosis.

Journal Article↗

Cloning, nucleotide sequence, and expression of an isovaleryl pepstatin-insensitive carboxyl proteinase gene from Pseudomonas sp. 101.

A unique carboxyl proteinase (EC 3.4.23.33), insensitive to the classical inhibitor isovaleryl pepstatin and isolated from Pseudomonas sp. 101 (PCP), is the first example of a prokaryotic enzyme of this class. The gene coding for PCP was cloned, sequenced, and expressed in Escherichia coli. The gene consists of 1,761 base pairs encoding a protein of 587 amino acid residues. The NH2-terminal 215-amino acid preprosequence flanks the 372-amino acid mature protein, which is identical with the primary structure of an authentic PCP determined by chemical methods. E. coli carrying a plasmid containing the cloned wild-type PCP gene produced a 62-kDa protein. This molecule was processed and secreted into the periplasm as a 43-kDa protein, which converted to mature PCP under acidic conditions. This autocatalytic conversion was completely blocked by tyrostatin, a PCP-specific peptidic inhibitor from Kitasatosporia sp. 55. The purified recombinant PCP has the same characteristics as authentic PCP. When several preprosequence deletion mutants were expressed in E. coli, mutant proteins were accumulated as insoluble forms with no proteinase activities. These results suggest that the prepropeptide of PCP plays an essential role in the formation of functional PCP.

Amino Acid Sequence↗

cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor.

A novel human G-protein-coupled seven-transmembrane-type receptor gene, 24-1, has been cloned from THP-1 cells. The 24-1 was 56% and 34% identical to the macrophage inflammatory protein-1 alpha (MIP-1 alpha) receptor and the interleukin-8 (IL-8) receptors at the amino acid level, respectively. To examine the ligand specificity of the receptor, we have established a stable transfectant of this gene with human kidney 293 cells. Monocyte chemoattractant protein-1 (MCP-1) induced a rapid increase of Ca++ influx in the 24-1-transfectant, while other C-C chemokines tested did not. This indicates that the 24-1 encodes the human MCP-1 receptor.

Amino Acid Sequence↗

A rapid colorimetric assay for determination of leukocyte-mediated inhibition of mycelial growth of Candida albicans.

A staining method with crystal violet (CV) was demonstrated to be useful for a simple, quick and objective assessment of in vitro growth inhibitory activity of leukocytes against Candida albicans cells. Candida cells incubated with murine neutrophils or macrophages for 14 hr in microwells were stained with CV and, after washing with 0.25% sodium dodecyl sulfate (SDS), treated with isopropanol containing HCl (0.04 N) to extract Candida cell-bound CV. Then the absorbance at 590 nm of the isopropanol extract was photometrically measured. The results showed that the photometrical absorbance was proportional to the amount of 3H-glucose taken up by C. albicans cells, which reflected the number of viable Candida cells.

Animals↗

Bio-histochemical aspects of integrins (alpha 2 beta 1, alpha 6 beta 1) in invasive mammary carcinomas: an immunohistochemical study.

Immunohistochemical expression of integrins was examined in 39 human invasive mammary carcinomas, of which 34.2% and 43.6% expressed integrins alpha 2 beta 1 and alpha 6 beta 1, respectively. Immuno-electron microscopy clearly demonstrated that the integrins were in the cell membrane of the carcinoma cells. Similar expression of integrin alpha 2 beta 1 or alpha 6 beta 1 in both the intraductal component and invasive portion of the same tumor was seen in 76.9% and 85.7% of cases, respectively. This suggested that invasive carcinoma cells retained their integrin expression after invasion through the basement membrane. Reciprocal expression of integrins alpha 2 beta 1 and alpha 6 beta 1 was seen in 20 cases. Expression of alpha 2 beta 1 was seen significantly less frequently in scirrhous carcinoma than in the more differentiated papillotubular or solid tubular carcinoma (Chi-squared test, P < 0.05). Intraductal components of carcinoma were present more frequently in cases expressing integrin alpha 2 beta 1 than in those that were negative. This suggests the potential usefulness of integrins as clinical parameters in the surgical treatment of mammary carcinoma, since recent trials of conservative treatment for mammary carcinoma have focused on the intraductal spread of the tumor cells.

Antigens, CD↗

Chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.

Autoimmune hemolytic anemia is an autoimmune diseases which is reported to be caused by interferon treatment. A 33-year-old male with chronic hepatitis C developed Coombs-negative hemolytic anemia, probably due to administration of interferon-alpha 2b. This is, to our knowledge, the first report of chronic hepatitis C complicated by Coombs-negative hemolytic anemia during interferon treatment.

Acute Kidney Injury↗

Serum c-erbB-2 in breast cancer patients.

The c-erbB-2 oncogene product in serum (serum c-erbB-2) was measured by an enzyme-immunoassay kit. The 12 U/ml cut-off level was estimated as the mean plus two standard deviations for 250 healthy women. With this cut-off level increased serum c-erbB-2 was found in 12.0% of primary breast cancer cases (n = 25), in 4.9% of non-recurrent breast cancer patients (n = 82), and in 31.4% of patients with recurrent breast cancer (n = 35). In patients with primary and recurrent breast cancer, whose sera were assayed concurrently for serum c-erbB-2, CEA and CA15-3, the positive rates of these markers were fairly similar. However, their combined use significantly increased the sensitivity as compared to the use of any one marker alone.

Adult↗

[Chemotherapy with autologous stem cell support for breast cancer].

The importance of dose intensity in breast cancer chemotherapy has been stressed in recent years with clear correlations demonstrated between dose intensity and clinical outcome of the patients in both therapeutic and adjuvant settings. In addition to various and intense supportive care, autologous stem cell support (ASCS) has been used over the past 15 years in order to overcome myelotoxicity of cancer chemotherapy. ASCS was initially practiced in the form of bone marrow transplantation, and more recently peripheral stem cell transplantation has been combined in addition to administration of G-CSF. Our pilot study in patients with recurrent/advanced breast cancer showed a higher response rate and a higher survival rate as compared to conventional chemotherapy, and there have been some long-term disease-free survivors with probable cures among complete responders with ASCS-supported chemotherapy. In adjuvant settings for patients with a high risk for recurrence who had been given a high-dose, the ASCS-supported regimen showed a higher disease-free survival rate as compared to those who were treated with conventional adjuvant therapy. Whether these apparently better results in our pilot studies hold true generally remains to be seen with well-scheduled randomized clinical trials.

Antineoplastic Agents↗

Growth dynamics of acquired melanocytic nevi. Higher reactivity of proliferating cell nuclear antigen in junctional and compound nevi than intradermal nevi.

BACKGROUND: The histogenesis of acquired melanocytic nevi is still a matter of debate. OBJECTIVE: To provide data on the histogenesis, we investigated the lesional area of acquired melanocytic nevi and the proliferative activity of the nevus cells. METHODS: Proliferative activity was examined with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). The lesional area of the nevus was estimated in histologic sections. RESULTS: Intradermal nevus was the largest of the acquired melanocytic nevi but had few PCNA-positive nevus cells. In contrast, junctional nevi were smallest and showed the highest PCNA positivity. Statistical analysis showed a significant inverse correlation between the largest lesional area and PCNA positivity. CONCLUSION: The findings of the present study are in accordance with an epidermal melanocytic origin of acquired melanocytic nevi.

Antigens, Neoplasm↗

Immunomodulating activity of antifungal drugs.

1. The immunomodulating activity of antifungal drugs was reviewed. Although results are conflicting, all azole drugs tend to be immunosuppressive, except for fluconazole, which has no immunologic effect. In contrast, the polyene antibiotic amphotericin B (AMPH) is immunostimulatory. 2. AMPH induced host resistance to Pseudomonas aeruginosa infection in mice, whereas no azole drugs did so. 3. Polymorphonuclear leukocytes are activated by AMPH, but not by any azole drugs, in terms of the level of their adherence. 4. No azole drugs induce in vitro tumor necrosis factor alpha (TNF) production by macrophages, whereas AMPH slightly but substantially does so. 5. AMPH potently primes macrophages in vitro and in vivo so that they produce large amounts of TNF after the secondary stimulation (triggering) by bacterial lipopolysaccharides or a streptococcal preparation used for antitumor immunotherapy, OK432. 6. Viable or heat-killed Candida albicans cells are capable of inducing in vitro TNF production by macrophages. This activity of the fungal cells is enhanced by AMPH.

Adjuvants, Immunologic↗

The superoxide dismutase activities of cerebral tissues, assayed by the chemiluminescence method, in the gerbil focal ischemia/reperfusion and global ischemia models.

Superoxide dismutase is well known to act as an effective antioxidant enzyme against cellular damage caused by oxidative stresses including ischemia/reperfusion-induced cerebral injury. However, it is still controversial whether or not the activity of endogenous superoxide dismutase changes during cerebral ischemia and reperfusion. In order to elucidate this phenomenon, we assayed the superoxide dismutase activity in the cerebral tissues of gerbils using the chemiluminescence method with a Cypridina luciferin analog. This method was demonstrated to be a sensitive and specific assay for the enzymatic activity of superoxide dismutase in cerebral tissues, which was not subject to interference from proteins or ascorbate. After 3 h of focal and global ischemia, there were no changes in the cerebral tissue superoxide dismutase activities. After 24 h of reperfusion following 1 h of ischemia, the superoxide dismutase activity decreased only approx 20%, whereas the adenylate kinase activities, measured in the same cerebral tissues as those used for superoxide dismutase assay, started to decline 1 h after reperfusion commenced and were approx 50% of the control levels after 24 h. These results show that almost all the activity of endogenous superoxide dismutase is maintained and does not decrease significantly as a result of ischemia/reperfusion-induced cerebral injury.

Animals↗

Effective detection of plantar malignant melanoma.

BACKGROUND: As the sole of the foot is the most prevalent site of malignant melanoma in non-Caucasians, early detection of the neoplasm at this anatomical site is very important. In our previous study, we proposed a clinical guideline that acquired melanocytic lesions on the sole larger than 7 mm in maximum diameter should be examined histologically. METHODS: Eighty-one Japanese patients with the complaint of plantar pigmented lesions were screened at our dermatology clinic during 3 years using the 7-mm criterion. RESULTS: Of the total 80 melanocytic lesions on the sole, 14 lesions were larger than 7 mm in maximum diameter, excluding congenital lesions. Diagnoses of the 14 "large" lesions were as follows: advanced malignant melanoma, 8 lesions; early malignant melanoma (malignant melanoma in situ), 1 lesion; acquired melanocytic nevus, 4 lesions, and volar melanotic macule, 1 lesion. CONCLUSIONS: The present study confirmed the validity of the 7-mm criterion for the early effective detection of plantar malignant melanoma.

Adolescent↗