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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 1,459 records · Page 81Linked to original sources

Chemotherapy administered using two-route infusion of cisplatin and sodium thiosulfate and intravenous infusion of vinblastine and peplomycin in patients with oral cancer.

The therapeutic effects of neo-adjuvant chemotherapy administered by two-route infusion of cisplatin and its antidote, sodium thiosulfate, and intravenous infusion of vinblastine and peplomycin were studied in 22 patients with previously untreated squamous cell carcinoma of the oral cavity or maxillary sinus. The overall response rate to chemotherapy was 90.9%, with a complete response in 12 patients (54.5%), a partial response in 8 patients (36.4%), and no change in 2 patients (9.1%). Histologic assessment showed a grade V response in 7 patients (31.8%), grade IV in 3 patients (13.6%), grade III in 5 patients (22.7%), grade II in 4 patients (18.2%), and grade I in 3 patients (13.6%). The cumulative 5-year survival rate, including 3 patients who died of another disease, was 72.2%. Leukocytopenia, an important side effect apparently induced by vinblastine, was seen, but no life-threatening complications occurred. Renal toxicity by cisplatin was minimal because of the use of sodium thiosulfate and fosfomycin. These data indicate that this mode of chemotherapy may be more effective for treating head and neck cancer than ordinary chemotherapy, from clinical and histologic standpoints. The high complete-response rate is especially noteworthy. No serious side effects or reductions in treatment period occurred. The results are preliminary and additional studies using a larger patient population are needed.

Adult↗

Proton magnetic resonance spectroscopy on childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA).

To evaluate brain dysfunction of childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA), three children with progressive myoclonus epilepsy, who were diagnosed as having DRPLA by DNA analysis, for the first time, underwent a study of proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS obtained from both the parietal and basal ganglia regions disclosed markedly reduced ratios of N-acetylaspartate to both choline and creatine. Especially regarding the basal ganglia region, the latter (ratio of N-acetylaspartate to creatine) closely correlated to severity of genetic abnormality, i.e. number of expanded CAG repeats, suggesting that the degree of neuronal loss in the region strongly depends on genetic factors. 1H-MRS must be a valuable tool to clarify the pathophysiology of DRPLA.

Adolescent↗

Unruptured interstitial pregnancy: a pitfall of MR imaging.

We report two cases with interstitial pregnancy, which showed completely different MR appearances. In case 1, a gestational sac was demonstrated and the diagnosis of ectopic pregnancy was straightforward. In case 2, a hypervascular mass was shown without demonstration of a gestational sac, the findings usually seen in gestational trophoblastic disease (GTD). MR imaging may play some role in the diagnosis of interstitial pregnancy when sonography is insufficient or equivocal. If GS is visualized, diagnosis is easy. However, if not, the appearance may have a spectrum and can be similar to GTD.

Adult↗

Mid-term clinical results of Graf stabilization for lumbar degenerative pathologies. a minimum 2-year follow-up.

BACKGROUND CONTEXT: Spinal fusion has some adverse effects, such as nonunion and pain at the site of grafted bone, and fusion with rigid spinal instrumentation especially may have the possibility of increasing mechanical stress on the segments adjacent to the site of fusion. The theory of the Graf system is that it will decrease adjacent disc deterioration because of maintenance of regional lordosis with flexibility and restriction of the motion of unstable segments without rigid spinal fusion. PURPOSE: To assess the clinical and radiologic results of Graf stabilization for lumbar degenerative disorders with minimal or mild instability. STUDY DESIGN: This is a retrospective study examining the mid-term results of Graf stabilization. PATIENT SAMPLE: In total, 59 patients underwent Graf ligamentoplasty and adequate decompression from April 1993 to September 1997. The subjects were 30 men and 29 women, and the mean age at the time of surgery was 60.6 years, ranging from 23 to 82 years. The average follow-up period was 3 years and 5 months, ranging from 2 years to 5 years and 10 months. OUTCOME MEASURES: We evaluated the surgical results using a scoring system, a visual analog scale, and radiological measurements. METHODS: The results were assessed according to a clinical scoring system established by the Japanese Orthopaedic Association (JOA score) and ratings based on a visual analog scale. Through analysis of x-ray images, the sagittal alignment (regional lordosis) and the range of motion (ROM) of the stabilized segments were measured in all cases, and the percentage of segments slipping and posterior disc height were determined for 29 patients with degenerative spondylolisthesis. RESULTS: Clinical scores and low back pain ratings based on a visual analog scale were significantly improved at the time of final follow-up compared with the preoperative values. Regional alignment of the operative segments was maintained in lordosis at the time of final follow-up. Preoperative ROM was significantly reduced at the time of final follow-up. There were no statistical differences in percentage of slippage or percentage of posterior disc height between the final follow-up values and the preoperative values. CONCLUSIONS: Our clinical results indicate that the Graf system is a suitable treatment option for mild and early lumbar degenerative diseases with minimum flexion instability of less than 10 degrees.

Adult↗

High-dose chemotherapy with hematopoietic stem cell transplantation is effective for nasal and nasal-type CD56+ natural killer cell lymphomas.

CD56+ natural killer (NK) cell lymphomas occur frequently in the nasal and nasopharyngeal regions and carry a poor prognosis. We have studied seven cases with NK-cell lymphomas. These lymphomas showed the following immunophenotype: CD56+, CD2+, sCD3- and Epstein-Barr virus-encoded small RNAs (EBERs)+. Six patients had localized (stage I or II) disease involving the nasopharyngeal region, while one had stage III disease. One patient with stage I disease achieved a complete remission (CR) after treatment with involved-field irradiation, but subsequently relapsed and died. The remaining six patients received combination chemotherapy as primary treatment: five patients with localized stage I or II disease and one patient with advanced stage III disease. Responses to initial chemotherapy were generally poor. These six patients received a variety of salvage chemotherapy regimens, but never achieved a CR. Subsequently, four of six patients showed a highly aggressive clinical course and died of disseminated disease within 1 year from the diagnosis. Three of six patients received high-dose chemotherapy supported by syngeneic, autologous or allogeneic peripheral blood stem cell transplantation. Two of the three transplant patients achieved a CR and are now surviving in continuous CR. Our clinical experience suggests that myeloablative high-dose chemotherapy and bone marrow rescue by hematopoietic stem cell transplantation may be an effective salvage treatment modality for refractory NK-cell lymphomas and could be considered as a part of the initial therapy for these patients.

Adolescent↗

Melanoma-Reactive CD8+ T cells recognize a novel tumor antigen expressed in a wide variety of tumor types.

An autologous melanoma cell line selected for loss of expression of the immunodominant MART-1 and gp100 antigens was initially used to carry out a mixed lymphocyte tumor culture (MLTC) in a patient who expressed the human leukocyte antigen (HLA)-AI and HLA-A2 class I major histocompatibility complex alleles. Ten clones identified from this MLTC seemed to recognize melanoma in an HLA-A1-restricted manner but failed to recognize a panel of previously described melanoma antigens. The screening of an autologous melanoma cDNA library with one HLA-Al-restricted melanoma-reactive T-cell clone resulted in the isolation of a cDNA clone called AIM-2 (antigen isolated from immunoselected melanoma-2). The AIM-2 transcript seemed to have retained an intronic sequence based on its alignment with genomic sequences as well as expressed sequence tags. This transcript was not readily detected after Northern blot analysis of melanoma mRNA, indicating that only low levels of this product may be expressed in tumor cells. Quantitative reverse transcriptase-polymerase chain reaction analysis, however, demonstrated a correlation between T-cell recognition and expression in HLA-A1-expressing tumor cell lines. A peptide that was encoded within a short open reading frame of 23 amino acids and conformed to the HLA-A1 binding motif RSDSGQQARY was found to represent the T-cell epitope. The AIM-2-reactive T-cell clone recognized a number of neuroectodermal tumors as well as breast, ovarian, and colon carcinomas that expressed HLA-A1, indicating that this represents a widely expressed tumor antigen. Thus, AIM-2 may represent a potential target for the development of vaccines in patients bearing tumors of a variety of histologies.

Amino Acid Sequence↗

Microdensity of solitary bone cyst after steroid injection.

The change of bone density in five patients with solitary bone cysts (SBC) was directly measured by microdensitometry (MD). Standard plain radiographs could not always predict the strength of the bone, but with MD, smaller changes in bone density could be found quantitatively. The density of the lesion temporarily decreased just after steroid injection and began to increase to maximum level in approximately 4 or 5 months. However, in two patients, the density decreased gradually to the first MD levels and refractured. In this article we stress the usefulness of direct MD in detecting the strength of the lesion.

Absorptiometry, Photon↗

Immunohistochemical analysis of human lung cancers with anti-ras p21 monoclonal antibodies.

The expression of ras oncogene product p21 in human malignant pleurisy and primary lung cancer was studied immunocyto-histochemically with monoclonal antibodies (MoAbs) rp-28 and rp-35 against ras p21. In pleural effusion cells, cancer cells revealed more intensively positive reaction with MoAb rp-35 than with MoAb rp-28, especially in the plasma membrane, and no positive reaction was obtained in any kind of inflammation cells with the exception of faintly positive reaction in the cytoplasm of macrophages. In primary lung cancers, well or moderately differentiated adenocarcinoma tissues showed higher reactivity with MoAb rp-28 than those of poorly differentiated adenocarcinoma or any other histological subtype of lung cancer. With MoAb rp-35, intensively positive reaction was obtained in most of cases with all different histological subtypes of lung cancer. The staining in cancer cells was usually localized intensively to the plasma membrane and weakly to the cytoplasm with both MoAbs. Normal bronchial epithelial and glandular tissues showed only cytoplasmic staining. These two MoAbs, especially MoAb rp-35, may be useful in clinicopathological applications for the diagnosis of malignant pleurisy and primary lung cancer.

Antibodies, Monoclonal↗

[Methylmercury human exposure in riverside villages of Tapajos basin, Pará State, Brazil].

Evaluation of total human exposure to mercury and methylmercury was effected in riverine villages along the Tapajos river and in the metropolitan area of Belem city, state of Para, Brazil, by using total mercury and methylmercury concentrations in hair samples in 1994 and 1995. It was observed that average concentrations of total mercury are in a range from 2 +/- 1 microg/g-1 to 20.5 +/- 12. 1 microg/g-1. While methylmercury average concentration varies from 1. 4 +/- 0.7 microg/g-1 to 18.5 +/- 11 microg/g-1. These results confirm mercury contamination in the Tapajos river and possible appearance of mercury intoxication symptoms, and recommends the monitoring of compounds in hair samples as well as the need for epidemiological and clinical studies for human health prevention and control of mercury intoxication.

Adult↗

A case of hybrid phenotypic chronic myelomonocytic leukemia transformed from aplastic anemia.

A case of hybrid phenotypic chronic myelomonocytic leukemia (CMMoL) transformed from a hematological remission state of severe aplastic anemia is reported. A 63-year-old woman was admitted to our hospital with complaints of easy fatigability and dizziness in December 1978. A diagnosis of aplastic anemia was made from findings of pancytopenia and hypoplastic marrow without dysplasia, and she was treated successfully with mepitiostane. Seven years later, anemia and thrombocytopenia reappeared with monocytosis. On the second admission, the peripheral blood showed a white blood cells count of 3.5 X 10(3)/microliters with 54% monocytes. The bone marrow was hypercellular with monocytosis, and dysplasia of three cell lineages was noted. A diagnosis of CMMoL was made. Cytogenetic analysis of bone marrow cells revealed a karyotype of 45 XX, -7, 11q-, and surface markers were polyphenotypic, including CD20+, CD14+ and CD13+. This is the first report of CMMoL with biphenotype which was transformed from aplastic anemia.

Anemia, Aplastic↗

Increased DNA synthetic potency of hepatocytes in cirrhotic patients may indicate a super-high risk for hepatocellular carcinoma.

Bromodeoxyuridine (BrdU) labeling indices (LI) of liver biopsied specimens from 27 control liver cirrhosis patients (control LC) without hepatocellular carcinoma (HCC), 26 cirrhotic patients with HCC, and from 6 control subjects were examined using an in vitro BrdU labeling technique. The mean BrdU LI +/- S.E. of HCC cancerous portion, HCC non-cancerous cirrhotic portion, control LC, and control subjects were 6.6 +/- 0.8%, 2.7 +/- 0.3%, 1.7 +/- 0.3% and 0.25 +/- 0.09%, respectively. Interestingly, there was a significant difference (p less than 0.025) between the non-cancerous LC portion and control LC. While 25 of 26 non-cancerous LC portion of HCC patients were in the high LI group (greater than or equal to 1.4%), 15 of 27 in the control LC were in the low LI group (less than 1.4%) (p less than 0.001). Of the 12 control LC with high LI, 6 developed HCC within 2 years, whereas only one of the 15 control LC with low LI developed HCC (p less than 0.05). In conclusion, HCC may develop in cirrhotic patients with high DNA synthetic potency.

Adult↗

Danazol treatment for paroxysmal nocturnal hemoglobinuria.

Danazol was administered to two patients with paroxysmal nocturnal hemoglobinuria (PNH) with a dramatic effect on the hematological findings. The patients, 31- and 41-year-old females, were initially diagnosed as having aplastic anemia, and were initially treated with anabolic steroid and immunosuppressive therapy, respectively. Sugar water and Ham tests turned positive at the start of danazol therapy in the former patient and after two months in the latter patient. This drug produced a dramatic improvement in the hemoglobin level and the platelet count and showed few side effects in the patients. A possible mechanism of action of danazol for PNH is briefly discussed.

Adult↗

Immune deficiency of cataract Shionogi (CTS) mouse. II. Impaired in vivo T cell-mediated immune response.

Our previous study demonstrated that cataract Shionogi (CTS) mice, an inbred strain related to non-obese diabetic (NOD) mice, are T lymphocytopenic and that their T cell-mediated in vitro reactions, such as proliferative responses of spleen cells to T cell mitogens and alloantigens or production of IL 2 and IL 2 receptors after stimulation of spleen cells with Con A, are greatly reduced. To confirm these in vitro characteristics, in vivo immune responses of CTS mice to T-dependent and T-independent antigens were compared with those of some reference strains including NOD mice. Antibody responses of CTS mice after one injection of a high dose (10(8)) or one or two injections of a low dose (10(5)) of sheep red blood cells (SRBC) were markedly lower than those of the reference strains. The decrease was particularly striking in the IgM antibody production at primary response to both high and low doses, and the IgG antibody production at the secondary response to low dose. Similar lower antibody production was observed in CTS mice against bovine serum albumin (BSA). Little production of IgE antibody was observed from 1 through 3 weeks after an injection of BSA plus Bordetella pertussis. IgG1 response was observed at high incidence but lower in titer than those in the reference strains. Unexpectedly, in spite of the poor antibody production to BSA, potent systemic sensitization for anaphylactic shock was easily established; incidence of lethal shock being comparable with those in the reference strains. This suggests that CTS mice are highly susceptible to the effector phase of active anaphylactic shock. Cell-mediated immunity was also impaired. Delayed type of hypersensitivity to SRBC was low, and the rejection of the skin graft from NOD mouse did not occur. In contrast to the reduced T cell-mediated responses, no difference was found between CTS and reference strains with regard to the antibody production to LPS, a T-independent antigen. These in vivo findings are consistent with the previous in vitro study.

Anaphylaxis↗

Two distinct P70 interleukin-2 receptors on a murine large granular lymphocyte clone Y479.

A continuous cloned cell line (Y479) was established by culturing normal mouse spleen cells in a high concentration of interleukin-2 (IL-2). Y479 cells showed morphological characteristics of large granular lymphocyte with the phenotypes of Thy-1.2+, T3+, Lyt-1-, Lyt-2-, L3T4-, B220-, AsGM1+, LFA-1+, and TcRV beta 8-. The Y479 cells required a high concentration of IL-2 for their growth but did not express detectable p55 IL-2 receptor (IL-2R) although they bound IL-2 with high and low affinities. Analysis of the IL-2 binding proteins on the Y479 cells revealed that both the high and low affinity receptors consisted only of 70 kDa protein. Analysis of the 70 kDa protein was performed using five monoclonal antibodies (L15, L20, L23, L34, and L61) against human recombinant IL-2. Although they recognized different epitopes, all monoclonal antibodies immunoprecipitated 70 kDa IL-2R that was cross-linked with radioiodinated IL-2. The supernatant after immunoprecipitation with L61 still contained IL-2/IL-2R complex that was L23-reactive, and the supernatant after immunoprecipitation with L23 contained L61-reactive IL-2/IL-2R complex, whereas L15 immunoprecipitated almost all the complex. Limited digestion of IL-2-cross-linked Y479 cells with trypsin caused the liberation of 45 kDa IL-2R fragment cross-linked with IL-2. This complex was immunoprecipitated by L15 or L61 but not by L23. These results suggest that there are at least two distinct 70 kDa IL-2R on the surface of Y479 cells.

Animals↗

Age-dependent difference in susceptibility to IgE antibody- and IgG1 antibody-mediated passive anaphylactic shock in the mouse.

The age dependence of the susceptibility to passive anaphylactic shock was studied in the mouse. Anti-BPO IgE monoclonal antibody produced potent systemic sensitization sufficient for provocation of lethal shock in most aged (6 to 10 months) CTS, DS and C57BL/6J mice but only in a very few young (1.5 to 2.5 months) mice. A similar trend was found in the NOD strain, though it was not as definite as in the above three strains. Age-dependent potentiation of the IgE antibody-mediated anaphylactic shock was not found in both sexes of five other strains, C3H/He, DBA/2, NON, BALB/c and B6D2F1. However, the potentiation became obvious even in these strains, when they were treated with Bordetella pertussis before the antigen challenge. Age-dependent potentiation was also clear with IgG1 antibody-mediated anaphylactic shock in DS females and NON males. In contrast, no age-dependent difference was seen for the shock induced by PAF which is estimated to be the main mediator for anaphylactic shock in the mouse. This suggests that the age-dependent potentiation of anaphylactic shock does not seem to be due to elevated susceptibility to the mediator but to its increased release. The sex-dependent differences was also studied and found to be particularly clear in the case of IgG1 antibody-mediated anaphylactic shock in young DS and aged NON mice.

Aging↗