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Biomedical subjects

Y Tokuda

Publications and source records attributed to Y Tokuda.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Late phase reaction in atopic dermatitis--immunological parameters and immunohistological analysis].

We studied the correlation between late phase reaction (LPR) and laboratory data in atopic dermatitis (AD) and evaluated the pathological findings in LPR. We studied the correlation between LPR and the severity of AD, total IgE, specific IgE, total IgG4, specific IgG4 and eosinophils. There were correlations between immediate reaction (IR) and some laboratory data, but not between LPR and laboratory data. Pathological findings at 15 min 24 hrs and 48 hrs after dermal injection showed edema at 15 min, followed by epidermal eczematous changes in almost all cases at 24 hrs, edema and degeneration of dermal endothelial cells and surrounding connective tissue, and leukocytoclasia in half of the cases and deposition of C3 and IgG in parts. We found CD4+ cells in all layers of dermis, a greater ratio of EG2+ cells in deeper layers of dermis as time passed, and decrease of CD23+ cells after 24 hrs throughout the dermis. These changes were found in cases of IR-LPR+, too. It appears that the mechanism of LPR is complex and that IR is not indispensable, for LPR and that infiltration of CD4+ and EG2+ cells throughout all layers of dermis are important, and these condition were related to subsequent reactions.

Adolescent↗
PubMed1997

A study of 46 cumulative breast cancer autopsy cases.

Forty-six cases of breast cancer, autopsied at the Tokai University Hospital, between 1975 and 1993, were studied. Forty of the patients had undergone surgery, and 27 of them had been surgically treated in the Tokai University Hospital. The major causes of death were respiratory failure, cancer-related complications, and hepatic failure. Frequently involved organs were lymph node, lung, liver, and bone. The survival time after surgery ranged from 1 day to 137 months, with the patients being divided into two groups based on survival of more or less than three years after surgery. Frequently observed in individuals surviving less than 3 years were larger tumor sizes, extensive lymph node metastases, advanced stages, and negative reactions for estrogen and progesterone receptors, as compared to individuals surviving for more than 3 years. The patterns of tumor metastasis were also different in two groups. Local recurrences were more frequently observed in short-term survivors whereas disseminated spreading was encountered in the long-term survivors. These findings seem to indicate that not only survival time but also pattern of recurrence are related to the status of the original tumor.

Autopsy↗
PubMed1996

In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product.

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers overexpressing the c-erbB-2 gene. In vitro and in vivo anti-tumour effects of a humanised antibody against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 was less effective than its murine counterpart, mu4D5, for the direct antiproliferative activity against the c-erbB-2-overexpressing SK-BR-3 cell line. In vivo treatment of severe combined immunodeficient (SCID) mice carrying the c-erbB-2-overexpressing 4-1ST human gastric carcinoma xenograft with 4hu4D5 revealed that the recombinant protein had potent anti-tumour activity. Furthermore, cytotoxicity of human peripheral blood mononuclear cells against 4-1ST was significantly augmented with rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might perform better in patients than predicted from preclinical studies.

Animals↗
PubMed1996

Use of metronidazole gel to control malodor in advanced and recurrent breast cancer.

Intolerable malodor emanating from ulcerated tumors as a result of anaerobic infection is a serious problem in the management of advanced and recurrent breast cancer. Metronidazole can control this malodor, but its oral use may cause adverse reactions. We therefore formulated a metronidazole gel, since no equivalent preparation is commercially available in Japan, and used it in five female patients (four with advanced cancer and one with recurrent cancer) admitted to our hospital between March 1994 and July 1995. The patients were aged between 47 and 71 (median: 59) years, and the duration of morbidity in the four patients with advanced cancer ranged from 10 months to four years. In three patients, the tumors were larger than 10 cm x 10 cm. Metronidazole gel was applied to the surface of ulcerated tumors once or twice daily. Independent assessments by the patient, doctor and nurse were unanimous, and revealed that the malodor was alleviated in one patient after three days, and removed in four patients after two to five (median: four) days of metronidazole gel treatment. Culture of swabs showed a decrease or disappearance of anaerobic colonies. Adverse reactions characteristic of metronidazole did not occur. The topical use of metronidazole in a gel form will improve the quality of life for patients with malodorous ulcerated tumors and facilitate intensive treatment of the underlying disease.

Administration, Topical↗
PubMed1996

The role of DNase and EDTA on DNA degradation in formaldehyde fixed tissues.

Degradation and extraction of high molecular weight DNA from formaldehyde fixed tissues suitable for gene analysis are presented. We previously reported that DNase might play an important role in the degradation of DNA extracted from formaldehyde fixed tissues (Tokuda et al. 1990). In the present study, DNase activity of the supernatant from rat tissues fixed in buffered formaldehyde at room temperature was negligible within 3 hr. Analysis of DNA extracted from reconstituted chromatin revealed that the degradation increased in the absence of DNase depending on the duration of the formaldehyde fixation. Furthermore, high molecular weight DNA could be extracted from tissues devoid of DNase activity fixed in buffered formaldehyde containing EDTA. These results demonstrated that DNA degradation was due mainly to a mechanism other than DNAse which was inhibited by EDTA. For clinical application, v-H-ras gene was successfully detected by Southern blotting from rat spleen tissues fixed in buffered formaldehyde especially at 4 C. Fixation at low temperature is useful for gene analysis.

Animals↗
PubMed1996

[The management selection of renal angiomyolipoma].

BACKGROUND: Nephron-sparing surgery is ideal in the treatment of renal angiomyolipoma (AML). But, in fact, occasional cases are found in post-ruptured AML and/or in bilateral multiple AMLs, that is seen in tuberous sclerosis. And we cannot perform nephron sparing surgery so easily. We proposed the treatment selection in such complicated AML. METHODS: We experienced 10 cases (12 kidneys) for about ten years, and studied our treatment selection and prognosis on each cases retrospectively. RESULTS: Of the 5 kidneys with AML less than 4 cm in diameter, 4 have not encountered with rupture. Of the 7 kidneys with AML more than 4 cm in diameter, 4 kidneys had rupture. Of the 3 kidneys unruptured AML more than 4 cm in diameter, 2 kidneys were treated by enucleation and we performed preventive embolization for rupture in residual one kidney. The patients was suffered from tuberculosis sclerosis, and she had bilateral multiple AMLs. Of the 4 kidneys with ruptured AML, 2 kidneys were treated by enucleation, and the other 2 kidneys were entirely resected. We succeeded enucleation in 2 of 4 kidneys with ruptured complicated AML. In those cases, we did long term watching after rupture and in-situ perfusion technique at the operation. CONCLUSIONS: Active treatment of AML, that is more than 4 cm in diameter, might be recommended. Because most of those will be ruptured. The ideal treatment, nephron-sparing surgery is difficult in complicated situation, such as after rupture and bilateral multiple AMLs. In our opinion, the point of success of nephron-sparing surgery might be long term watching after rupture and in-situ perfusion technique at the operation.

Adult↗
PubMed1996

A case of microhepatoma associated with schistosomiasis japonica diagnosed by enhanced ultrasonography after hepatic intraarterial injection of carbon dioxide gas.

The patient was a 58-year old man whose complaints were generalized malaise and right epigastralgia. He had liver cirrhosis and schistosomiasis japonica, previously diagnosed by laparoscopy. Computed tomography (CT) showed a high density funicular shadow in the liver. However no tumorous lesions in the liver were visualized. Ultrasonography (US) of the liver showed a reticulate or scaly pattern, but no images of tumorous lesions. Hepatic angiography showed a single, deeply colored image about 1cm in diameter, in the segmentum anterosuperior. Preoperative and intraoperative enhanced US with hepatic intraarterial injection of carbon dioxide gas was performed. It showed a hyperechoic tumor shadow about 1cm in the segmentum anterior. The segmentum anterosuperior including the tumor was partially resected. Pathologically, the tumor was found to be a hepatoma of Edmondson type II, caused by cirrhosis and schistosomiasis japonica. The patient's postoperative course was uneventful. Enhanced US with hepatic intraarterial injection of carbon dioxide gas was useful for the diagnosis and treatment of the microhepatoma associated with schistosomiasis japonica.

Angiography↗
PubMed1995

Clinical and Histological Prognostic Factors in Axillary Node-Negative BreastCancer: Univariate and Multivariate Analysis with Relation to 5-Year Recurrence.

In the recent years several studies have shown that about 30% of cases with axillary node-nagative breast cancer suffer relapse of the disease. Our attempt was made to evaluate the most significant prognostic factors to predict this high risk group which may be benefited from adjuvant treatment. For this purpose, we selected 9 patients out of 80 cases of node-negative breast cancer who had been followed up at least for 5 years and had the recurrence of the disease. For comparison, 16 patients from the same group who did not have relapse were selected on a random basis. Histology, receptor status, AgNOR, DNA flow cytometry and various immunohistochemical parameters were compared between the groups with recurrence and that without recurrence. On univariate analysis, tumor size, immunohistochemical expressions of PCNA, MIB-1, c-erbB-2 and S-phase fraction were significantly different between the above two groups. By multivariate analysis, immunohistochemical c-erbB-2 expression (more than 50% of cancer cells) was an independent parameter. As a summary from our studies, c-erbB-2 immunohistochemical staining on paraffin sections might be the best independent prognostic factor in axillary node-negative breast cancers.

Journal Article↗
PubMed1995

Engraftment of precursor lesions of human cutaneous neoplasms onto C.B-17 SCID mice: a useful in vivo experimental model of carcinogenesis in human skin.

Using a full-thickness skin grafting technique, lesional skin from various human neoplastic and preneoplastic skin diseases was transplanted onto SCID (severe combined immunodeficiency) mice. Of 27 grafted lesions, 21 were successfully accepted by the mice and maintained in good condition. All these accepted grafts were finally excised 10-101 days after transplantation for histological examination. In most grafts, the characteristic histological configurations of each disease were well preserved. Immunohistochemical study using monoclonal antibodies to human blood group antigens ABH revealed that some elements of the grafts such as sweat glands were clearly positive, confirming that the tissue was from human skin. Neoplastic (atypical) cells were detected in 9 of 17 accepted grafts containing neoplastic cells from the beginning. The detection rates for neoplastic cells were very high (90%) in grafts from precursor lesions of squamous cell carcinomas such as Bowen's disease (5/5 specimens) and thermal keratosis (2/3). In contrast, no definite neoplastic cells were found in two grafts from extramammary Paget's disease and five grafts from the radial growth component of malignant melanoma. In most of the grafts from latter two diseases, characteristic histological configurations such as elongation of the rete ridges were maintained, suggesting that the neoplastic cells were selectively eliminated from the grafts. Split-thickness grafts of normal human skin were accepted and remained in a good condition for as long as 6 months. Engraftment of human lesional and non-lesional skin onto SCID mice therefore may well provide a useful in vivo experimental model of human skin diseases.

ABO Blood-Group System↗
PubMed1995

Intracerebral hematoma in patients with ruptured cerebral aneurysms.

BACKGROUND: Intracerebral hematoma from ruptured aneurysms is one of the unfavorable factors for outcome in patients with subarachnoid hemorrhage. In this study, the clinical characteristics of intracerebral hematoma in patients with ruptured aneurysms were examined. METHODS: The subjects were 512 patients who had been admitted by day 3 after aneurysmal rupture without episodes of rebleeding before the initial computed tomography (CT) scan. They were divided into two groups according to the findings of initial CT; groups 1 and 2 comprised patients with and without intracerebral hematoma, respectively. RESULTS: Of the 512 patients, intracerebral hematoma was observed in 98 (19%). The incidence of intracerebral hematoma was higher in patients with distal anterior cerebral and middle cerebral artery aneurysms, compared with those at other sites (both, p < 0.01). Interhemispheric, callosal, and temporal lobe/sylvian hematomas were observed more frequently in patients with anterior communicating, distal anterior cerebral, and middle cerebral artery aneurysms, respectively, than in those with aneurysms at other sites. The incidence of rebleeding was 22% in group 1 and 14% in group 2 (p < 0.05). Clinical grades on admission were higher and outcome at 6 months after onset was less favorable in group 1 than in group 2 (both, p < 0.01). The larger the intracerebral hematoma, the higher was the clinical grade and the less favorable the outcome. However, when comparing management and surgical outcome under the same clinical grades, there was no significant difference between the two groups. CONCLUSIONS: There was a close correlation between the site of hematoma and that of the ruptured aneurysm. Poor outcome in patients with intracerebral hematoma seems to be related to severity of clinical grade on admission.

Adult↗
PubMed1995

Prolonged survival of mice with human gastric cancer treated with an anti-c-ErbB-2 monoclonal antibody.

A monoclonal antibody (MAb), 4D5, specifically recognising an extracellular epitope of the c-ErbB-2 protein, inhibited the growth of human gastric cancer overexpressing c-ErbB-2 severe combined immunodeficient (SCID) mice. This antibody also reduced the mass of established tumours xenografted into SCID mice, whereas gastric cancer not expressing c-ErbB-2 exhibited no regression in response to 4D5 treatment. In addition, administration of 4D5 prevented colonisation of cancer cells and prolonged the survival of host SCID mice inoculated i.v. with c-ErbB-2-overexpressing tumour cells. This is the first reported study to show that treatment with a single antibody specific to c-ErbB-2 prolongs the survival of host SCID mice bearing xenotransplanted tumours.

Animals↗
PubMed1995

Failure of genotoxic carcinogens to produce tumors in human skin xenografts transplanted to SCID mice.

Chemical carcinogenesis of human skin was investigated using human skin xenografts (16 full thickness and 48 split thickness skin grafts) transplanted to CB-17-scid (SCID) mice. Topical application of a carcinogen, i.e. 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene, methylcholanthrene or N-methyl-N'-nitro-N-nitrosoguanidine, to the human skin xenografts once a week for 25-30 weeks failed to produce skin tumors. Both DMBA application plus UV-B irradiation and alternate applications of the above four carcinogens in combination with UV-B irradiation also failed to produce tumors. All of these treatments induced skin papillomas in skins of host SCID mice. DMBA induced skin papillomas in allogenic CD-1 mouse skin grafts transplanted to SCID mice. These results indicate that susceptibility of human skin to these carcinogenic stimuli is much lower than that of mouse skin.

Animals↗
PubMed1995

Interleukin-12 augments the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes from tumor-infiltrating lymphocytes.

Human tumor-infiltrating lymphocytes (TIL) were obtained from breast cancer, renal cancer or neuroblastoma to investigate the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes (CTL). When TIL were cultured with interleukin (IL)-2 (100 U/ml), the growth of TIL peaked around 8-10 days after the initiation of culture. In contrast, the proliferation of TIL cultured with IL-2 plus IL-12 peaked around 4-5 days after culture and tumor cells rapidly disappeared from the culture. To determine the generation of autologous tumor-reactive CD8+ CTL, TIL-derived CD8+ T cells were separated by FACStar. Both IL-2-activated and IL-2 plus IL-12-activated TIL-CD8+ T cells showed the same level of lymphokine-activated killer activity against a variety of tumor cells. However, TIL-CD8+ T cells activated with IL-2 plus IL-12 revealed greatly augmented cytotoxicity against autologous tumor cells compared with that induced by IL-2 alone. The autologous tumor cell-killing activity of TIL-CD8+ CTL was significantly inhibited by the addition of F(ab)2 anti-CD3 monoclonal antibody, indicating that these CTL recognize autologous tumor antigen through T cell receptor. These results imply that IL-12 is a novel cytokine which facilitates the generation of autologous tumor-reactive CD8+ CTL from TIL.

CD8-Positive T-Lymphocytes↗
PubMed1995

In situ perfusion by retrograde cannulation of a tumor artery for nephron-sparing surgery.

BACKGROUND: Although ice slush cooling or ex situ perfusion with bench surgery is most widely used for protecting ischemic renal damage which possibly accompanies complicated nephron-sparing surgery, each has its own disadvantages. The former does not allow excessively long ischemia and the latter requires complicated procedures as autotransplantation. In order to mitigate against these problems, we devised a novel method of in situ renal perfusion with intracellular hyperosmolar solution. METHODS: One renal segmental artery mainly supplying a tumor was isolated and cannulated with a small feeding tube. The tube was introduced through a small arteriotomy incision directed towards the proximal side, advanced until its tip remained in the main or first branch of the renal artery, and then it was anchored to that artery. After the main renal artery and vein were clamped, the kidney was perfused with cold Euro-Collins' solution through the tube, while the venous blood and perfusate were drained from the left gonadal vein or small venotomy incision of the right renal vein. RESULTS: In one case of renal cell carcinoma and three cases of angiomyolipoma, two of which ruptured, nephron-sparing surgery was carried out under in situ hyperosmolar perfusion. Ischemic time of these four cases was an average of 96 minutes, varying from 45 to 145 minutes. All the kidneys functioned well postoperatively. CONCLUSIONS: The method presented here is very simple, requires no unusual dexterity and safely allows for a long period of renal ischemia. This method is best indicated in cases where simple clamping of the renal pedicle with ice-slush cooling appears insufficient, yet ex situ surgery with autotransplantation seems excessive.

Angiography↗
PubMed1995

Study of aneurysmal subarachnoid hemorrhage in Izumo City, Japan.

BACKGROUND AND PURPOSE: Estimation of the actual incidence rate of subarachnoid hemorrhage and evaluation of the treatment require the inclusion of all patients in a defined geographic area. METHODS: During 1987 through 1992 in Izumo City, Japan, we estimated the incidence rate of subarachnoid hemorrhage by including dead-on-arrival patients and by further adding the results obtained after reviewing all death certificates registered in this city in the corresponding period. In addition, we compared the management and surgical outcomes in hospitalized patients from 1987 through 1992 with outcomes from 1980 through 1986. RESULTS: During 1987 through 1992, we diagnosed 123 patients as having subarachnoid hemorrhage. The crude and the age- and sex-adjusted incidence rates using the 1990 population statistics for Japan were 25 (95% confidence interval, 21 to 30) per 100,000/y and 23 (95% confidence interval, 19 to 28) per 100,000/y for all ages, respectively; these occurrences are the highest among those reported to date. Of these patients, 8% died before receiving medical attention, 27% in the first week, and 39% at 1 month. The survival curve for 2 years improved significantly from 1980-1986 to 1987-1992 in patients with admission grades 4 and 5 (P = .035) and in operated patients with preoperative grades 1 through 3 (P = .036). However, there was little improvement in the overall management results (P = .168), possibly because patients with high risk and/or old age were admitted and/or diagnosed more often in the latter period. CONCLUSIONS: The incidence rate of subarachnoid hemorrhage is much higher than that reported so far in the literature, and despite improvement of management and surgical therapy, the actual case-fatality rate is still high, mainly because of the high mortality rate directly associated with the primary bleeding.

Adult↗
PubMed1995

[A case of cranial metastasis of hepatocellular carcinoma].

A case of cranial metastasis of hepatocellular carcinoma is reported. A 77-year-old woman with an elastic hard tumor in the right temporal region was referred to our department on April 30, 1992. On admission, the patient had slight weakness of the left upper limb. Plain skull X-ray and computed tomography (CT) showed bone destruction in the right temporal region. Magnetic resonance images (MRI) showed that the tumor was hypo-intense with T1-sequences and hyper-intense with T2-sequences, and included hyper-intense spots on both T1- and T2-images. Right carotid angiography showed that the tumor was fed by the middle meningeal and accessory meningeal arteries. The patient became disoriented, and the left hemiparesis worsened on May 4, 1992. CT scan revealed an irregular high-density area in the tumor because of intratumoral hemorrhage. After embolization of the arteries feeding the tumor, surgery was performed on May 8, 1992, and the tumor was totally removed. Histological examination of the tumor specimen revealed that it was a metastatic hepatocellular carcinoma. The patient died 8 months after initial diagnosis because of hepatocellular carcinoma.

Aged↗