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Biomedical subjects

Y Niitsu

Publications and source records attributed to Y Niitsu.

At least 199 records · Page 11Linked to original sources

Ectopic choroidal calcification of the eyes of a patient with parathyroid adenoma.

A 39-year-old man was admitted to our hospital complaining of general malaise, polyuria, disturbance of ocular movement and right cervical tumor. Blood examination revealed increased parathyroid hormone, hypercalcemia and hypophosphatemia, suggestive of hyperparathyroidism. Histology of the resected tumor revealed a benign parathyroid adenoma. Ectopic calcifications in the choroid and sclera were noted by computed tomography and further ophthalmological examination. Although ocular calcification in conjunctiva and cornea associated with hyperthyroidism is not unusual, sclerochoroidal calcification has not been reported previously in Japan. The possible cause of this unusual condition in this patient is discussed.

Adenoma↗

Recombinant human granulocyte colony-stimulating factor can mobilize sufficient amounts of peripheral blood stem cells in healthy volunteers for allogeneic transplantation.

Peripheral blood stem cells (PBSC) are a good source for bone marrow reconstitution after intensive chemotherapy. The ability to transplant PBSC between allogeneic subjects would be a key step forward in the application of this procedure. For this purpose, we examined the mobilization and recovery of PBSC in healthy volunteers who were given recombinant human granulocyte colony-stimulating factor (G-CSF). Three informed healthy volunteers were injected with G-CSF subcutaneously at a dose of 2.5 micrograms/kg for 6 successive days and at 5.0 micrograms/kg for the following 4 days. The concentration of PBSC was assessed daily by CFU-GM and BFU-E assays, both of which peaked on the sixth to seventh day of G-CSF administration. Comparison between colony assays and hematological parameters revealed that flow cytometry analysis of CD34+ cells by mononuclear cell gating is a rapid and convenient method to quantify mobilized stem cells. The maximum numbers of CFU-GM were 432, 665, and 1386 colonies/ml blood. It is calculated that sufficient amounts of stem cells for transplantation (at least 1.0 x 10(5) CFU-GM/kg) could be obtained by leukapheresis of 5 to 201 blood when the peak was attained. This trial confirmed the feasibility of allogeneic transplantation using PBSC from healthy volunteers who have received G-CSF.

Adult↗

[A case of advanced mediastinal choriocarcinoma showing complete remission for two years by high-dose chemotherapy with peripheral blood stem cell transplantation].

A twenty-six-year-old male patient with advanced choriocarcinoma originated from mediastinum was treated by high-dose chemotherapy with peripheral blood stem cell (PBSC) transplantation. He had massive tumors in the cervical, mediastinal and bilateral lung fields. After 3 kur of PVeBV therapy (CDDP 60 mg x day 1-3, etoposide 160 mg x day 1-3, BLM 30 mg x day 1, VBL 12 mg x day 1), he obtained complete remission. PBSC was collected at the time of hematopoietic recovery and high-dose chemotherapy with PBSC transplantation was conducted because of the high possibility of recurrence. The hematopoietic recovery was rapid, and the patient remained well with no sign of recurrence for 24 months.

Adult↗

[Effects of rHuEPO on aplastic anemia: results of a phase II clinical study].

The safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in adult aplastic anemia patients whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha was given subcutaneously every day at a dose of 3,000IU/body for two weeks, and the dosage was increased to 6,000IU, 12,000IU and 24,000IU every two weeks when the increment of Hb was insufficient. In cases in whom Hb concentration increased by more than 1g/dl or whose transfusion requirements reduced to less than 50%, treatment was judged to be effective. The whole rate of efficacy was 34.5% (10/29). Response to epoetin alpha treatment was better in patients whose symptoms were relatively mild. Mild cases responded to the treatment with 6,000IU/body/day, although a dosage of 24,000IU/body/day was required in moderate or severe cases. Neither serious adverse effect nor abnormal laboratory findings were observed. These results suggest that high dose subcutaneous epoetin alpha treatment is effective for the aplastic anemia in terms of increasing Hb concentration and reducing blood transfusions.

Adolescent↗

CD33, CD4-double positive blastic transformation in a patient with chronic myelogenous leukemia.

We report a 19-year-old female with blastic transformation of chronic myelogenous leukemia whose blasts had CD33 and CD4 phenotypes, although no significant characteristics were detected by morphological and histochemical analysis. In a colony assay with hematopoietic growth factors, the blasts proliferated and differentiated into myelo-monocytic lineage, particularly in the presence of GM-CSF or IL-3 + G-CSF. The blasts transformed from CML were assumed to be myelo-monocytic progenitor cells, corresponding to GM colonies. Blastic transformation expressing such a phenotype has not been reported previously.

Adolescent↗

Glutathione S-transferase pi levels in a panel of lung cancer cell lines and its relation to chemo-radiosensitivity.

The human placental form of glutathione S-transferase pi (GST-pi) was measured by a sandwich enzyme-linked immunosorbent assay in lung cancer cell lines established in our laboratories. In classic-type small cell lung cancer (SCLC), variant-type SCLC and non-small cell lung cancer (NSCLC), the respective mean GST-pi values were 0.83 +/- 0.88, 3.27 +/- 2.85 and 2.40 +/- 0.76 micrograms/mg protein. Cell lines with high GST-pi content had low levels of neuron specific enolase, which is known as a representative tumor marker for SCLC. This suggests that GST-pi may also be used as a potential marker for NSCLC. The lines with low GST-pi content were more sensitive to radiation than those with high GST-pi content. Cell lines not subjected to prior therapy also showed a good correlation between GST-pi levels and chemosensitivity to cisplatin. The findings suggest that GST-pi can be used as an adjunctive marker for lung cancer.

Carcinoma, Non-Small-Cell Lung↗

[Phase II clinical study of recombinant human erythropoietin on the anemia associated with multiple myeloma].

Safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in anemic patients with multiple myeloma whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha (3,000IU/body) was given subcutaneously daily for two weeks and the dosage was increased to 6,000IU, 12,000IU and 24,000IU every two weeks when the increment of Hb was insufficient. Cases in which Hb concentration increased by more than 1g/dl or in which blood transfusion requirements decreased by more than 50% were judged to be effective. The overall rate of efficacy was 52.6% (10/19). Response to epoetin alpha treatment was better in patients whose blood erythropoietin level was relatively low. The majority of patients responded to the treatment with up to 6,000IU/body/day but a dosage of more than 12,000IU/body/day was required in some cases. No serious adverse effects or abnormal laboratory findings were observed. These results suggest that high-dose subcutaneous epoetin alpha treatment is effective for anemia associated with multiple myeloma in terms of increasing Hb concentration and reducing blood transfusion.

Aged↗

[Phase II clinical study of recombinant human erythropoietin on the anemia of myelodysplastic syndrome].

The safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in anemic patients with myelodysplastic syndrome (MDS) whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha was given subcutaneously daily at a dose of 3,000IU/body for two weeks and the dosage was increased to 6,000IU, 12,000IU, and 24,000IU at two week interval when the increment of Hb was insufficient. Patients in whom the Hb concentration increased by more than 1g/dl or whose blood transfusion requirement reduced to below 50% were considered to be cases of effective treatment. The overall rate of effectiveness was 20.6% (7/34). Response to epoetin alpha treatment was better in patients with refractory anemia (RA) or RA with ringed sideroblasts (RARS). The high dose epoetin alpha (12,000-24,000IU/body/day) was required for the patients to respond. These results suggest that the high dose subcutaneous epoetin alpha treatment is effective for the anemia associated with MDS in terms of increasing Hb concentration and reducing blood transfusion.

Adolescent↗

[Successful treatment with combination chemotherapy of BHAC-AMP in a case of acute myelofibrosis developed from myelodysplastic syndrome with multiple chromosomal aberrations].

A 62 year old male patient was previously admitted to another hospital in February 1989 because of palpitation. Peripheral blood examination revealed pancytopenia. Although the number of nucleated cells in the bone marrow aspirate was in the normal range. It contained 2.2% of blastic cells and dysplastic cells. He was diagnosed to be myelodysplastic syndrome with refractory anemia. He subsequently received repeated blood transfusions and other symptomatic treatments as an outpatient until 1990. When he was admitted to our hospital because of severe pancytopenia. The numbers of WBC, RBC, and platelets were 2,000/microliters, 134 x 10(4)/microliters, 2.9 x 10(4)/microliters respectively. Bone marrow aspiration resulted in dry tap, and biopsy at the iliac bone showed remarkable fibrosis with marked decrease of normal hematopoietic cells. Chromosome analysis revealed multiple aberrations such as 47XY, +8, 13q-, 14p+, 48XY, +8, +9, 13q+. The patient was treated with BHAC-AMP combination chemotherapy. After 3 cycles of the therapy, pancytopenia was improved and chromosomal aberration disappeared. This case was considered to be an acute myelofibrosis developed from myelodysplastic syndrome and worth to reporting with a review of literature, because drastic combination chemotherapy was extremely effective.

Aclarubicin↗

[Follicular lymphoma associated with t(14;18)(q32;q21) chromosome translocation and bcl-2 gene rearrangement: report of a case].

A 31-year-old Japanese male who complained of low-grade fever, fatigue and generalized lymphadenopathy had shown an increase in peripheral white cell count, and 84% of peripheral blood cell and 76% of nuclear bone marrow cells consisted of small cleaved lymphoblastic abnormal cells with or without barely visible nucleoli. Cytogenic study of cervical lymph node biopsy specimens showed a t(14;18)(q32;q21) chromosome translocation. Histologically the lymph node cells were classified according to the International Working Formulation as follicular small cleaved-cell lymphoma. Molecular analysis of DNA fragments of peripheral lymphocytes revealed both J-H gene and bcl-2 oncogene rearrangements. Immunophenotypes of peripheral lymphocytes, bone marrow cells and lymph node cells expressed a clonally distinct B-cell population bearing surface immunoglobulin-G, kappa-chain, CD-10, CD-19, CD-20, CD-21 and OKIa-1 antigens. We diagnosed this case as follicular lymphoma in the leukemic phase,

Adult↗

Significance of glutathione S-transferase-pi as a tumor marker in patients with oral cancer.

BACKGROUND: The authors analyzed the clinical usefulness of glutathione-S-transferase-pi (GST-pi) as a tumor marker in patients with oral cancer. METHODS: GST-pi levels in plasma of 61 patients with oral squamous cell carcinomas, 65 patients with benign oral diseases, and 78 healthy subjects were investigated with the sandwich enzyme-immunoassay (EIA) system. RESULTS: Elevated GST-pi levels in plasma were observed in patients with oral cancer, but patients with benign oral diseases had normal GST-pi levels. More than 70% of patients with Stage III or IV oral cancer and more than 50% of those with Stage I and II disease had elevated levels of GST-pi in plasma. Elevated levels of GST-pi in plasma were also discovered in most patients with tumor recurring after surgery before recurrence was detected clinically. GST-pi also was found to be a useful marker for evaluating the response to chemotherapy, for monitoring postoperative tumor resectability or tumor burden, and for predicting the recurrence of tumor in patients with oral cancer. CONCLUSIONS: GST-pi is considered to be a useful aid for early diagnosis, predicting tumor extent, and determining parameters of treatment efficacy and prognosis for oral cancer.

Antigens, Neoplasm↗

Endogenous tumor necrosis factor functions as a resistant factor against hyperthermic cytotoxicity.

One of the mechanisms of cytotoxicity by tumor necrosis factor (TNF) is the induction of reactive oxygen molecules. Cells producing endogenous tumor necrosis factor (enTNF) show resistance to the cytotoxicity of exogenous TNF by scavenging the reactive oxygen molecules. The intracellular hydroxyl radical production is also known to be involved in the heat-induced cytotoxicity. In the present study, we therefore examined the possibility that enTNF may act as a protective protein against the heat-induced cytotoxicity in a manner similar to that of exogenous TNF. Heat-sensitive L-M (mouse tumorigenic fibroblast) cells, originally expressing no enTNF, were transfected with a human TNF expression vector to produce enTNF. The stable transfectants showed apparent resistance to heat treatment. Conversely, when HeLa (human uterine cervical cancer) cells, originally producing an appreciable amount of enTNF, were transfected with an antisense TNF mRNA expression vector to inhibit enTNF synthesis, their heat sensitivity was enhanced. Furthermore, L-M cells which were transfected with nonsecretory human TNF expression vector also acquired resistance to heat treatment. In these cells, heat resistance correlated well with expression of enTNF and intracellular levels of manganous superoxide dismutase. These results indicate that enTNF exerts its intracellular protective effect against the heat-induced cytotoxicity by scavenging reactive oxygen with induced manganous superoxide dismutase in a manner similar to that found in cells treated with exogenous TNF.

Animals↗

Endogenous tumor necrosis factor exerts its protective function intracellularly against the cytotoxicity of exogenous tumor necrosis factor.

Based on the findings that expression of endogenous tumor necrosis factor (enTNF), which is not present in TNF-susceptible cells, was generally observed in TNF-resistant cells and that TNF gene transfection gives rise to TNF resistance, the assumption was made that enTNF may be a protective protein against the cytotoxicity of exogenous TNF. However, it remains unknown whether the protection by enTNF is exerted in an intracellular or extracellular (autocrine) manner. We therefore transfected a nonsecretory human TNF gene (pTNF delta pro) into highly TNF-sensitive mouse tumorigenic fibroblasts (L-M cells) and investigated their TNF susceptibility. The transfectants expressed enTNF which was not secreted into the medium and acquired an appreciable degree of resistance to exogenous TNF. A significant increase in the manganous superoxide dismutase level was also noted in the transfectants. These findings suggest that enTNF exerts its protective function intracellularly by inducing manganous superoxide dismutase production.

Animals↗

Induction of synthesis of manganous superoxide dismutase in L-M(pNTnF) cells carrying an inducible TNF gene.

Based on findings that the cytotoxic effects of tumor necrosis factor (TNF) are closely related to levels of intracellular oxygen radicals, and on the results of TNF gene transfection studies, the hypothesis was made that endogenous TNF (enTNF) acts as a protective factor against exogenous TNF by inducing inhibitors or scavengers of oxygen radicals. In order to test this hypothesis, we investigated the intracellular levels of manganous superoxide dismutase (MnSOD) and glutathione (GSH) in L-M(pNTnF) cells carrying a TNF gene induced by dexamethasone (DM). When L-M(pNTnF) cells were treated with DM they expressed enTNF, and acquired resistance to exogenous TNF. There was no change in the GSH concentration after enTNF induction, but a 1.9- to 3.9-fold increase in MnSOD levels was noted. Our findings suggest that enTNF exerts its protective function against the cytocidal effect of exogenous TNF by inducing MnSOD production.

Animals↗

Altered expression of E-cadherin in gastric cancer tissues and carcinomatous fluid.

Expression of E-cadherin in 21 patients with various histological types of gastric carcinomas was studied by immunoperoxidase staining. Intercellular boundaries of almost all cancer cells in well and moderately differentiated adenocarcinomas stained as deeply for E-cadherin as normal gastric mucosa. However, singly infiltrating cells of those histological types were poorly stained. In poorly differentiated adenocarcinomas, cancer cells forming clusters stained lightly and those infiltrating singly stained even less. In signet ring cell carcinomas, hardly any staining was observed. In each histological type, the staining patterns and intensity at different layers of the gastric wall, were essentially the same. Cancer cells from carcinomatous ascites of gastric adenocarcinomas and pancreatic adenocarcinomas, and those from pleural effusion of lung adenocarcinomas were also studied by immunofluorescence staining. Of 11 specimens, ten were negative and only one from a lung adenocarcinomas was positively stained. By phase-contrast microscopic observations, none of these cancer cells including those from the lung adenocarcinomas, formed obvious cell-cell contacts. Cell aggregation assays confirmed the above results. The molecular weight of E-cadherin of cancer cells of lung adenocarcinomas was less than intact E-cadherin as revealed by Western blot analysis. These results suggest that depressed expression and/or impaired function of E-cadherin in cancer cells, facilitates their liberation from primary sites to infiltrate freely into tissue or fluid.

Adenocarcinoma↗