Biomedical subjects
Publications and source records attributed to H Hamada.
Some morphological characteristics of the Mexican hairless dog and their inheritance were investigated. The dogs examined were hairless and had defective teeth. From the results of mating experiments, an autosomal dominant semi-lethal gene was considered to be responsible for the hairlessness accompanied by defective teeth in the dog. The possible usefulness of the dog was also discussed.
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To examine the effect of spleen cell on host antitumor immunity, spleen cells from mice bearing large Methylcholanthrene-induced sarcoma (MCA-F) (F4w spc) were injected subcutaneously into mice which had been inoculated subcutaneously with MCA-F cells or intravenously with the subline from MCA-F cells which had high potential of metastasis (FLn2). F4w spc enhanced significantly the growth of subcutaneous MCA-F tumor in a dose-dependent fashion (p less than 0.05) and increased the number of metastatic lesions induced by intravenous FLn2, but not spleen cells from normal mice or spleen cells from mice bearing MCA-D tumor which is antigenically different from MCA-F. These results suggest that spleen cells of mice bearing a large tumor have a component suppressing specifically antitumor immunity. In this study, effects of spleen cells were assessed by the subcutaneous injection into tumor bearing mice instead of Winn's assay, and this method was thought to be useful for analysis of effector cells in tumor immunity.
A 51-year-old man was hospitalized with complaints of gross hematuria and terminal micturition pain. Cystoscopy revealed a low columnar tumor at the dome of the bladder. Ultrasonography and X-ray CT also demonstrated the same shape of tumor and no evidence of invasion to adjacent organs. Gastrointestinal examination, including upper gastrointestinal series and barium enema failed to reveal any primary tumor. The serum CEA level was 2.3 ng/ml, which was not elevated. Total cystectomy with ileal conduit and adjuvant chemotherapy consisting of cyclophosphamide, adriamycin and cisplatinum was performed. He died of a recurrent tumor 2 years and 2 months after the operation. Besides our experience of primary signet ring cell carcinoma of the urinary bladder, a review of the literature is reported.
We have examined the expression of P-glycoprotein in clinical leukemic cell samples by using a monoclonal antibody (MRK16) against P-glycoprotein. We found that leukemia cells isolated from 3 out of 6 patients with blast crisis of chronic myelogenous leukemia were reactive to MRK16. These 3 cell lines expressed high levels of mdr1 mRNA, which codes for P-glycoprotein. The present result indicates that the clinically refractory state of the tumor may be predicted in part by determining P-glycoprotein expression using the monoclonal antibody against P-glycoprotein, and the mdr1 probe.
The incidence of unexpected ureteral carcinoma on mapping and recurrence of upper urinary tract urothelial cancer was examined in 160 patients who had undergone total cystectomy for vesical cancer and complete mapping of the specimens between May, 1978 and June, 1986 at our Center. Unexpected carcinoma in the ureteral stump was found in 5 patients (3.1%) and recurrent cancer in the upper urinary tract developed in 2 (1.3%) of the 160 patients. The incidence was higher in the recurrent bladder cancer cases, and also higher in patients with non-visible, high grade and superficial tumors of the bladders.
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The subcapsular renal transplantation tumor model was explored to standardize the growth of rat RN6 neurinoma and RG2 glioma nitrosourea-induced clonal cell lines in syngeneic and allogeneic systems. Growth of RN6 and RG2 tumor spheroids was compared with that of solid subcutaneous tumor pieces transplanted under the renal capsule. Two morphometrical methods were applied to evaluate growth rates. Tumor specimens were examined histologically with regard to their morphology, extent of immune reactions, and development of tumor necroses. The take rate was 98%. In the syngeneic system linear progressive tumor growth was found, while in preirradiated allogeneic rats this was only the case up to 21 to 25 days post transplantation (p.t.). Strong rejection reactions in the allogeneic RN6 tumors were noted from 4 to 7 days p.t. resulting in total tumor rejection after 10 to 14 days. Both kinds of tumors, especially in the first days of growth, were characterized by strong desmoplastic reaction with rich reticulin fiber formation. However, after 10 days, in the center of RG2 subcapsular renal tumors (SRT) this kind of reaction was found only in the vicinity of tumor vessels, while RN6 SRT demonstrated reticulin fibers around tumor cells in all cases studied. The transplantation experiments revealed that the malignant RN6 and RG2 spheroids represent a suitable tool to study three-dimensional early tumor growth in both in vivo and in vitro cultures. The model of spheroid transplantation under the renal capsule is simple to handle and well reproducible. Compared with subcutaneous tumors the SRT model has advantages in early stages of tumor growth because the tumors are clearly visible grossly and can be easily submitted to adequate morphometry, indicating that this model may be suitable for experimental chemotherapy and radiotherapy studies.
An overexpression of the plasma membrane glycoprotein of relative molecular size 170-180 kDa is consistently found in different multidrug-resistant human and animal cell lines, although the functional role of the protein in multidrug resistance is not known. Two monoclonal antibodies that interfere with biochemical functions were generated against the human myelogenous leukemia K-562 cells resistant to adriamycin (K-562/ADM). These antibodies, designated MRK16 and MRK17, are specifically reactive to K-562/ADM and a human ovarian cancer cell line resistant to adriamycin (2780AD). MRK16 modulated vincristine and actinomycin D transport in the resistant cells, while MRK17 specifically inhibited the growth of the resistant cells. Both antibodies recognized the 170- to 180-kDa glycoprotein. These data indicate that the 170- to 180-kDa glycoprotein is involved, directly or indirectly, in the drug transport mechanisms and the proliferation of multidrug-resistant tumor cell lines.
Expression of enhancerless (E-) and enhancer-containing (E+) genes that are chromosomally integrated was examined. An E- plasmid (pE-cat) containing a chloramphenicol acetyltransferase (cat) gene linked to the simian virus 40 (SV40) early promoter or its E+ counterpart plasmid (pE+-cat) containing the SV40 enhancer was cotransfected into thymidine kinase (TK)-deficient L cells with a cloned tk gene. A number of TK+ transformants were isolated, and expression of the cointegrated cat gene in these cell lines was quantitatively determined by the assay of CAT activity. The results indicated unexpectedly that the E- cat gene was as actively expressed as the E+ cat gene. Analysis of CAT mRNA by primer extension indicated that the E- cat gene, as well as the E+ cat gene, was transcribed from the "native" initiation site contained in the SV40 early promoter region. The active expression of the E- cat gene was maintained in secondary TK+ transformants that arose by transfection with genomic DNA from the primary transformant. These results suggest that expression of the integrated E- cat gene is activated by endogenous enhancer elements.
Long-range-acting gene activator elements were randomly isolated from the human genome by functional selection. HeLa cells were transfected with an enhancer trap, a plasmid containing an enhancerless xanthine-guanosine phosphoribosyltransferase (gpt) gene transcribed from the simian virus 40 early promoter, and stably transformed GPT+ cells were selected. From several transformants, human DNA sequences flanking the enhancer trap were cloned. Two gene activators (GA1 and GA2) were found in the cloned human DNAs. GA1 and GA2 showed strong enhancer activity both in a stable transformation assay and in a transient expression assay. They had functional properties similar to those of other known enhancers: GA1 and GA2 activated the expression of a linked gene over distances of at least 5 kilobases both upstream and downstream in an orientation-independent fashion. GA1 may be required for the initial establishment of gene activation but was not essential for the maintenance of active expression. GA1 and GA2 were active not only in HeLa cells but also in other types of human cells, such as neuroblastoma cells. This indicates a limited but relatively broad cell type specificity. The HeLa genome contains multiple copies of GA1, while GA2 exists once in the genome.
An adriamycin (ADM)-resistant variant (K562/ADM) of human myelogenous leukemia K562 was established. K562/ADM was stable for 2 months in medium without ADM, and was 130-fold more resistant to ADM as compared to the parent K562. Twenty clones were isolated from K562/ADM by the limiting dilution technique. Five clones with different ADM sensitivity were selected and characterized further. The extent of clonal resistance to ADM was parallel to the extent of resistance to vincristine (VCR), except for one clone, KA-15. The majority of clones, including K562/ADM, accumulated far smaller amounts of daunomycin (DAU) or VCR as compared to the parent K562. However, a highly resistant clone did not necessarily accumulate less DAU in the cells, indicating that the mechanism of ADM resistance cannot be explained solely by a defect of ADM accumulation. All clones rapidly transported DAU and VCR from the cells. K562/ADM expressed on the cell surface three distinct glycoproteins with molecular weights of 180,000, 83,000 and 65,000 daltons. No change was detected in the actin and tubulin contents of K562 and clones. K562/ADM and its clones expressed double minute chromosomes and contained homogeneously staining regions in the chromosomes.
Thirty-two patients with osteosarcoma of the femur and the tibia were treated with systemic chemotherapy and radical surgery between 1976 and 1984. Adriamycin (ADR) alone, ADR plus high-dose methotrexate with citrovorum factor (HD-MTX-CF) (protocol A) and ADR plus HD-MTX-CF plus cis-platinum plus bleomycin, cyclophosphamide and actinomycin-D (BCD) (protocol B) were given as chemotherapeutic regimens. Twenty-nine out of 32 patients received chemotherapy both preoperatively and postoperatively, and eleven of 29 patients had a good response. Amputation was performed on 19 patients and en bloc resection on 13 patients. No local recurrence was detected in any of the 32 patients. The disease-free survival rate was 35%. Disease-free survival rate of patients treated with protocol A and protocol B was 25% and 91% respectively. Fourteen out of 17 patients who developed pulmonary metastasis underwent thoracotomy. Survival rate after thoracotomy was 50%. The overall survival rate of 32 patients with osteosarcoma was 56%.
It has already been noted that hemangioblastoma is occasionally complicated with various diseases, especially retinal angioma, cysts of kidney and/or pancreas, vascular disorders, and furthermore about 10% of hemangioblastoma are multiple. The authors report here a case of multiple cerebellar hemangioblastomas accompanied with congenital deafness, juvenile diabetes mellitus and retinal angioma. The patient, a 38-year-old man who complained of disturbance of consciousness, headache and vomiting, admitted to our hospital on October 6, 1982. He was born in consanguineous marriage family and his elder sister was also suffered from congenital deafness and juvenile diabetes mellitus, but no angiomas. CT and angiography showed a left side cystic and a right side small cerebellar lesions with remarkable ventricular enlargement. Ventriculo-peritoneal shunt and suboccipital craniectomy & removal of the tumors were performed on October 6, and November 8, 1982 succeedingly. From a point of view of hereditary occurrence, the authors investigated these complicated lesions recognized in this patient. It revealed that this case did not belong to any other categories of hereditary syndromes which were already reported and so authors considered that this was an extremely rare condition. Moreover, in case of multiple hemangiomas, cerebral angiography could be a more useful method than CT scan to detect multiplicity of the lesions in the posterior fossa.
As a rapid screening method for testing chemotherapeutic agents against human tumor explants, renal subcapsular assay has been established by Bogden et al (1978). The authors investigated the effectiveness of the technique of Bogden for rat glioma. Preselected 1 mm3 fragments of viable tumor tissue of rat (CDF) were implanted under the renal capsule of normal immunocompetent rats. Then initial and final tumor sizes (formula; see text) were measured in situ with an oculometer inserted into a surgical microscope, and evaluated the changes of tumor sizes. The experiments were divided into three groups. The first group was that tumor pieces of rat (CDF) were implanted under the renal capsule of the syngenetic rats (CDF). Non-irradiated and preirradiated (400 rad) heterogenetic rats (Wistar) were used as the second and third groups. The explanted tumor pieces grew rapidly in the first group (syngenetic rats). On the other hand, poor growth of the second group (non-irradiated heterogenetic rats) was seen within 7 days after implantation, and rejected completely until 15 days after implantation. Explanted tumor pieces in the third group (pre-irradiated heterogenetic rats), however, grew enough big, though the change of tumor sizes was less than that of the first group. Histological examination was also performed. In the first and third group, proliferation of glioma cells was remarkable under the renal capsule, and neovascularization in the explanted tumor tissue was provided from the capsule, first, and then parenchym of the kidney. Even necrosis and hemorrhage were seen in the tumor tissue 15 days after implantation.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to detect the serum immunosuppressive factors of tumor bearer, the effects of normal C3H/He mice serum (NMS), serum from methylcholanthrene induced fibrosarcoma bearing mice (F4w serum) and sera fractionated by high performance liquid chromatography (HPLC) using anion exchange column were examined on mitogen-induced blastogenesis of normal murine spleen cells (Nspc). The addition of 5% of NMS suppressed the blastogenesis of Nspc. Less than 0.6% of F4w serum suppressed the blastogenesis. NMS was applied to HPLC and was separated to four peaks (A,B,C,D). In HPLC pattern of F4w serum, peak B was higher than that of NMS and new peak (E) was observed next to peak D. Peak D of NMS suppressed the blastogenesis. Not peak D but peak E of F4w serum suppressed the blastogenesis. The properties of those blastogenesis-suppressive fractions were discussed.
The direct antitumoral effect of interferon-alpha on human glioma was suggested in a study involving tissue culture, and scanning and transmission electron microscopy. Consequently, intratumoral local administration of interferon-alpha for four cases of human glioma was performed, and each survival period from the initiation of its application was seven, eight, three and two months. Slight direct antitumoral effect of interferon was observed in the findings of both CT scan and autopsy in our series, but the survival time was not as great as we had expected. One of the reasons for this was thought to be insufficient permeability of interferon-alpha into the residual infiltrating tumor tissue. Therefore, the use of systemic administration of interferon or another adjuvant therapy with local administration of interferon would be expected to produce better results.
Bone morphogenetic activity of osteosarcomas from 20 patients was assayed. The activity was demonstrated as ectopic bone formation on implantation of a lyophilized fraction of the tumor into athymic nude mice in 8 of 20 cases. Osteosarcomas producing bone morphogenetic protein (BMP) differed in clinical features from those not producing BMP. They were characterized radiologically by perpendicular spicules, histologically by osteoblastic type cells, and clinically by an increased serum alkaline phosphatase level, relative resistance to preoperative chemotherapy with Adriamycin (doxorubicin) plus high-dose methotrexate, and a tendency to metastasize to other bones and the lungs.