Physicians and biological warfare agents.
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Bioethics↗
Biomedical subjects
Y Tokuda
Publications and source records attributed to Y Tokuda.
Un-cross-linked fibrin substrates inhibit keratinocyte spreading and replication: correction with fibronectin and factor XIII cross-linking.
Wound repair is characterized by the presence of a fibrin-rich matrix, but the effect of fibrin on re-epithelialization remains unclear. In this study, we determined the effects of different fibrin matrices on cultured human neonatal keratinocytes. Using purified fibrinogen and fibrin gels generated by the enzymatic action of thrombin, batroxobin (it leads to retention of fibrinopeptide B), or Agkistrodon contortrix thrombin-like enzyme (ACTE; it leads to retention of fibrinopeptide A), we determined the effect of each of these matrices on keratinocyte morphology, attachment, spreading, and replication as compared to tissue culture plastic. Morphologically, keratinocytes seeded on fibrin surfaces were more rounded and formed three-dimensional structures. Specific cell attachment, as measured at either 37 degrees C or 4 degrees C, was not altered on the different fibrin substrates (P > .05) but was increased on fibrinogen and factor XIII cross-linked fibrin (P < .01). However, keratinocytes seeded on fibrin, regardless of the presence or absence of fibrinopeptides A or B, showed a marked decrease (up to 71%) in cell numbers by days 5 (P = .0357) and 10 (P = .0114). Keratinocyte spreading was decreased by 78.8% (P = .0006), 80.3% (P = .0001), and 89.2% (P = .0001) on thrombin-, batroxobin-, and ACTE-generated fibrin, respectively, but not on fibrinogen-coated dishes. However, either the addition of fibronectin or cross-linking of fibrin with factor XIII allowed full keratinocyte spreading to occur (P = .0002 and P = .0013, respectively). We conclude that fibrin inhibits keratinocyte spreading in the absence of other matrix or plasma proteins or cross-linking by factor XIII.
Cell Adhesion↗
Immunohistochemical detection of tumor cells in the bone marrow of breast cancer patients.
BACKGROUND: Contamination of bone marrow and peripheral blood stem cells with tumor cells is a problem that may be encountered when autologous hematopoietic stem cell transplantation is conducted concurrently with high-dose chemotherapy. METHODS: Using monoclonal antibodies to a variety of tumors, the detection of tumor cells in the bone marrow of breast cancer patients was studied by immunohistochemistry. RESULTS: KL-1 and CAM5.2 were strongly reactive with breast cancer cells, but not with normal bone marrow cells. The reactivity of the tumor cells with EMA was not strong, and DF-3 and 115D8 yielded only slightly positive reactions. These latter antibodies also exhibited some reactivity to normal bone marrow cells. When tumor cells were admixed with normal cells, the sensitivity of CAM5.2 and EMA permitted the detection of one cell in 10(4), but with KL-1, the detection of one in 10(5) cells was possible. When immunohistochemical staining was used in testing 40 patients with advanced or recurrent breast cancer, positive reactions were obtained in four of 27 patients (14.8%) with KL-1, four of 26 (15.4%) with CAM5.2, and nine of 37 (23.7%) with KL-1 + CAM5.2, figures similar to those reported by others who studied stage IV patients. CONCLUSIONS: Immunohistochemical staining with KL-1 and CAM5.2 is therefore considered to be a useful technique for detecting contamination by tumor cells.
Antibodies, Monoclonal↗
Ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate: case report.
OBJECTIVE AND IMPORTANCE: We report a rare case of a ruptured de novo aneurysm induced by ethyl 2-cyanoacrylate. CLINICAL PRESENTATION: A 44-year-old woman had undergone microvascular decompression for a right-sided facial spasm. The preoperative vertebral angiogram did not show any aneurysmal dilation. The right anteroinferior cerebellar artery, which was compressing the exit zone of the facial nerve, was detached and fixed to the dura mater with ethyl 2-cyanoacrylate. Nine years later, the patient suffered a subarachnoid hemorrhage caused by the rupture of a newly developed aneurysm of the right anteroinferior cerebellar artery. INTERVENTION: The aneurysm was clipped 2 days after onset of the subarachnoid hemorrhage. It consisted of two bulges in the arterial wall on the proximal side of the meatal loop. One bulge was stuck to the dura mater of the pyramis by ethyl 2-cyanoacrylate, which had been used in the microvascular decompression 9 years previously. CONCLUSION: This is the first reported clinical case of a de novo aneurysm induced by a cyanoacrylate adhesive. Ethyl 2-cyanoacrylate can damage the arterial wall and induce a de novo aneurysm.
Aneurysm, Ruptured↗
Usefulness of MR angiography in detection of persistent trigeminal arteries.
OBJECTIVES: To examine the usefulness of magnetic resonance angiography (MRA) in detection of persistent trigeminal arteries (PTA). MATERIAL AND METHODS: 3D-time-of-flight (TOF)-MRA images obtained from 1100 patients (798 males and 302 females aged 6-75 years with a mean of 55 years) at our and related institutions were examined retrospectively for PTA. The course of the PTA was classified into the posteromedial type and posterolateral type. Charts of the patients were also examined retrospectively for clinical symptoms related to PTA. RESULTS: PTA was observed in 5 (0.45%) of the 1100 patients, and no aneurysm or arteriovenous malformation was noted in any of these 5 patients. PTA was the posteromedial type in 2 and posterolateral type in 3. PTA was possibly related with clinical symptoms in only 1 patient with oculomotor paresis. CONCLUSION: MRA is useful for non-invasive screening for PTA.
Adolescent↗
A case of an inflammatory variant of epidermolysis bullosa acquisita: chronic bullous dermatosis associated with nonscarring mucosal blisters and circulating IgG anti-type-VII-collagen antibody.
A 42-year-old man showed prominent blistering lesions of the mouth and esophagus in addition to a few bullous lesions of the skin. Direct immunofluorescence microscopy revealed distinct linear deposition of IgG and C3 at the epidermal basement membrane zone where slight deposition of IgA and IgM was also observed. In direct immunoelectron-microscopic examination, antibody was detected in the sublamina densa of the basement membrane zone. Immunoblot analysis with dermal extracts demonstrated that the patient's serum contained circulating IgG antibodies against the 290-kD protein, which comigrated with type VII collagen. The lesions healed without any scars. The results of these studies corresponded to the laboratory findings in epidermolysis bullosa acquisita (EBA), although the clinical features were distinct from classic EBA.
Adult↗
[Treatment of advanced breast cancer: current issues].
Because the great majority of patients with advanced breast cancer have been traditionally placed under the care of surgeons, therapeutic planning is usually done by making operative management the key even at the present time when operable breast cancer is appropriately recognized to represent a systemic disease. For advanced breast cancer to be treated more effectively, systematically planned multimodality treatment must be undertaken. The development of G-CSF and stem cell transplantation to counter hematopoietic toxicity have allowed the safe use of high-dose intensity chemotherapy, which has also been applied in the neoadjuvant setting. Recent experience with neoadjuvant chemotherapy (NACT) has shown promise and indeed some good responders have been offered breast conserving surgery. NACT also serves as an in vivo chemosensitivity test, the results of which are to be exploited in chemo-hormonal therapy after locoregional treatment. Although further studies are required to evaluate this treatment more precisely, multicycle dose-intensified chemotherapy can now be safely and liberally incorporated into systematically planned multimodality treatment for advanced breast cancer.
Antineoplastic Combined Chemotherapy Protocols↗
High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in breast cancer.
Since 1981 we have conducted four studies of the treatment of metastatic and postoperative high-risk breast cancer with high-dose chemotherapy supported by autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56 metastatic cancer patients, proved that induction chemotherapy produces a lasting complete response (CR) in only a few cases despite the achievement of a CR rate higher than that expected from standard chemotherapy. Study II was designed to examine consolidation chemotherapy in metastatic cancer patients responding to induction chemotherapy. At a median follow-up of 26 months (range 2-66), consolidation therapy produced a 5-year progression-free survival rate of 27.1% in 30 patients showing a CR or a partial response to induction therapy and 58.6% in 13 patients showing a CR to consolidation therapy. No treatment-related death occurred during study II. The same regimen used in study I was employed for 58 postoperative high-risk patients in study III. The 10-year disease-free survival rate recorded for patients with > or = 10 positive axillary lymph nodes was significantly higher (P < 0.05) in the AHSCT-supported chemotherapy group than in the conventional chemotherapy group. A double high-dose regimen was adopted for 21 postoperative high-risk patients in study IV. The 3-year disease-free survival rate recorded for 9 patients with > or = 10 positive axillary lymph nodes was 71.4% at a median follow-up of 25 (range 8-45) months. No treatment-related death occurred during study IV. Peripheral blood stem-cell transplantation shortened the duration of bone marrow suppression more effectively than did bone marrow transplantation, thereby optimizing high-dose chemotherapy.
Adult↗
New immunodeficient (nude-scid, beige-scid) mice as excellent recipients of human skin grafts containing intraepidermal neoplasms.
Engraftment of normal or lesional human skin onto nude or SCID (severe combined immunodeficiency) mice has been used as an in vivo experimental model. However, this model has some limitations, such as shrinkage and loss of the grafted skin over time. To improve the experimental model, we have produced two new SCID-lineage mouse strains, BALB/cA-nude-scid (nu/nu, scid/scid) and BALB/cA-beige-scid (bg/bg, scid/scid) mice, by the method of cross intercross. Intraepidermal neoplastic lesions such as Bowen's disease were grafted onto the back of the mice of these strains. The rate of reduction in the size of the grafts was lower on nude-scid and beige-scid mice than on SCID mice. Rates of survival of neoplastic cells in the grafts were higher in nude-scid mice than in SCID and beige-scid mice (SCID mice 38%, nude-scid mice 55%, beige-scid mice 38%). Neoplastic cells of Bowen's disease grafted onto a beige-scid mouse proliferated and invaded the dermis during 233 days of observation, confirming the progression to invasive squamous cell carcinoma from carcinoma in situ. The present study revealed that nude-scid and beige-scide mice newly produced by us provide a very useful in vivo experimental model for the investigation of carcinogenesis and tumor progression in human skin.
Animals↗
A case of angiosarcoma of the breast.
This is a case report of a 20-year-old woman who had primary angiosarcoma of the left breast, with metastases to the spleen and ovary. Eight months after detecting a mass in her breast, she underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes, splenectomy and bilateral oophorectomy. Five months after the operation, the patient succumbed to lung metastases. Angiosarcoma of the breast is a rare condition with a poor prognosis, and there are no established chemotherapeutic regimens as yet. Immunohistochemical staining for endoglin, known to be expressed mainly on the surface of endothelial cells, was positive. This suggests the possibility of treating angiosarcoma with anti-endoglin monoclonal antibodies.
Adult↗
A case of multiple endocrine neoplasia type 2B.
A sporadic case of multiple endocrine neoplasia type 2B in a twenty-six year old man who manifested medullary thyroid carcinoma, multiple mucosal neuromas of the tongue and a marfanoid habitus is reported. At the time of diagnosis, he also had multiple liver and lung metastases. Genetic analysis of his lymphocytes revealed a point mutation in exon 16 of the RET proto-oncogene. Since multiple endocrine neoplasia type 2B has a relatively poor prognosis because of the occasional aggressive behavior of medullary thyroid carcinoma, the necessity of the genetic diagnosis of multiple endocrine neoplasia in the early stage is suggested.
Adult↗
[A case of multiple gastric carcinoid tumors associated with type A gastritis, diabetes insipidus and Hashimoto's disease].
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Autoimmune Diseases↗
[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↗
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↗
Unscientific speculation.
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Disease Outbreaks↗
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↗
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↗
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↗