[Iron metabolism in iron deficiency anemia and anemia of chronic disease].
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Anemia↗
Biomedical subjects
Yoshiro Niitsu
Publications and source records attributed to Yoshiro Niitsu.
Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis.
We came across a rare case of acute megakaryocytic leukemia, the clinical course of which was relatively chronic and nonaggressive. This case was complicated with generalized severe osteosclerosis (OS). The medium in which blastic cells from the patient were cultured showed a strong activity to enhance the expression of an osteosclerotic cytokine, osteoprotegerin (OPG), as revealed by real-time quantitative RT-PCR and Western blot analysis. The OPG-inducing activity of the culture medium was neutralized by the anti-interleukin-11 (IL-11) antibody. These results indicate that IL-11 produced by the blasts was a causative factor of the OS observed in this patient.
Adult↗
Chemoprevention of colorectal cancer.
Colorectal cancer is a disease with a high mortality rate and it has been increasing in prevalence worldwide. Chemoprevention, as well as primary and secondary prevention, for colorectal cancer have attracted much attention. Many chemopreventive trials have been performed, and several agents, including nonsteroidal antiinflammatory drugs, such as aspirin and sulindac, cyclooxygenase-2 selective inhibitors, such as celecoxib, vitamin D, folate, and calcium, have been shown to have some effect. In these chemopreventive trials, the targeted lesions used for evaluation were mainly polyps. However, the chemopreventive effects of some agents on polyps may require several years to evaluate. Further, larger polyps may not be susceptible to chemopreventive agents. Aberrant crypt foci (ACF) are tiny lesions at the earliest stage of colorectal carcinogenesis, which consist of large, thick crypts identified by dense, methylene blue staining. We succeeded in identifying human ACF in situ using magnifying endoscopy and found that the number of ACF, particularly dysplastic ACF, increased significantly from normal subjects to adenoma patients and then to cancer patients. We also found that the number, size, and dysplastic features of ACF are significantly correlated with the number of adenomas in adenoma patients. Thus, it was surmised that ACF are precursor lesions of the adenoma-carcinoma sequence in humans and that ACF may be the most appropriate lesions as targets for chemoprevention. We have shown that the number of ACF was significantly reduced in patients treated with sulindac. We are currently proceeding with a randomized, double-blind, chemopreventive trial targeting ACF.
Animals↗
A significant reduction in serum alanine aminotransferase levels after 3-month iron reduction therapy for chronic hepatitis C: a multicenter, prospective, randomized, controlled trial in Japan.
BACKGROUND: Increasing evidence indicates that iron cytotoxicity plays an important role in the pathogenesis of chronic hepatitis C (CHC). However, the biochemical effects of iron reduction therapy on CHC remain to be confirmed in a controlled study. This study aimed to test whether iron removal by repeated phlebotomy improves serum alanine aminotransferase (ALT) levels in patients with CHC. METHODS: Patients were randomly assigned to an iron reduction therapy or control group. The patients in the treatment group received 3-month iron reduction therapy by biweekly phlebotomy, while the patients in the control group were followed up for 3 months with regular blood tests alone. RESULTS: Thirty-three patients completed the 3-month treatment, while 29 patients received the complete follow-up. The serum ALT levels were reduced from 118 +/- 79 to 73 +/- 39 IU/L in the treatment group, but did not change in the control group (106 +/- 45 versus 107 +/- 48 IU/L). Posttreatment enzyme activity was decreased significantly from the baseline. Furthermore, it was significantly lower than the 3-month control level. Although 5 patients withdrew from the study, none was affected by any side effects of repeated phlebotomy that required them to discontinue the treatment. CONCLUSIONS: This short-term controlled trial demonstrated the biochemical efficacy and safety of iron reduction therapy for patients with CHC.
Adult↗
In which step does the K-ras mutation occur in colorectal carcinogenesis?
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Adenocarcinoma↗
Wnt3 modulates the characteristics and cobblestone area-supporting activity of human stromal cells.
OBJECTIVE: Our objective was to investigate the expression and significance of Wnt proteins in adult human hematopoietic-supporting stromal cells. METHODS: Degenerate reverse transcription-polymerase chain reaction was performed to screen telomerized human stromal cells (hTERT-stromal cells) and multipotent mesenchymal cells (hTERT-MSCs) for expression of Wnt genes. We studied the actions of Wnt proteins by overexpressing them in stromal cells and MSCs by retrovirus-mediated gene transfer. RESULTS: The hTERT-stromal and primary stromal cells expressed Wnt5A, while hTERT-MSCs and primary MSCs expressed Wnt3 and Wnt5A. Gene transfer of Wnt5A slightly reduced the growth rate of hTERT-stromal cells, but did not affect their morphology. In contrast, gene transfer of Wnt3 into both hTERT-stromal cells and hTERT-MSCs enhanced Wnt-betacatenin signaling, and caused remarkable morphological changes and growth retardation. Upon 2-week co-culture, expansion of clonogenic cells on Wnt5A-stromal cells was superior to that on control stromal cells. However, expansion of CD34+ cells on Wnt3-stromal cells did not differ from that on control stromal cells. Moreover, there was a drastic reduction in the formation of cobblestone area (CA) underneath Wnt3-stromal cells compared with that underneath control stromal cells. CONCLUSION: These results suggest that Wnt3 plays an important role in regulating characteristics and CA support activity of stromal cells.
Antigens, CD34↗
Prolonged survival of mice with multiple liver metastases of human colon cancer by intravenous administration of replicable E1B-55K-deleted adenovirus with E1A expressed by CEA promoter.
Liver is the most preferential site for metastasis of colon cancer. We, in the present study, constructed a self-replicable adenovirus in which E1A is driven by a CEA promoter and E1B-55K is deleted from the E1B region (AdCEAp/Rep) and examined its effects on multiple metastases of a human colon cancer cell in a mouse xenograft model. We first showed effective replication of the virus in various CEA-producing human colon cancer cells (M7609, HT-29) and subsequent lysis of the infected cells in vitro. We then demonstrated that a single intratumoral injection of the virus (1 x 10(8) PFU/100 microl) induced a complete regression of subcutaneous tumors (M7609) inoculated into nude mice. Further, we demonstrated that systemic administration of the virus (1 x 10(8) PFU/100 microl) through the tail vein to nude mice, which 1 week prior had been inoculated with tumor cells (colon carcinoma cell line HT-29) via the spleen and showed apparent multiple metastases in the liver, effectively suppressed the metastasis formation. The mean survival time of the treated mice was significantly longer than that of the controls. Thus, the systemic administration of AdCEAp/Rep was considered to be effective on multiple liver metastases of CEA-positive colon cancer in a xenograft model.
Adenoviridae↗
Successful treatment with prostaglandin E1 of ischemic colitis complicated by colonic stricture.
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Alprostadil↗
Decrease of Smad4 gene expression in patients with essential thrombocythaemia may cause an escape from suppression of megakaryopoiesis by transforming growth factor-beta1.
Essential thrombocythaemia (ET) is characterized by the abnormal and sustained proliferation of megakaryocytes. The mechanism for this lineage-specific expansion in ET, remains unclear. We have previously reported that transforming growth factor-beta1 (TGF-beta1) is involved in negative feedback regulation of megakaryopoiesis in both healthy volunteers (HV) and patients with idiopathic thrombocytopenic purpura (ITP). The present study found that megakaryocyte colony-forming units (CFU-MK) of ET patients were less sensitive to TGF-beta1 than those of HV. The expression of Smad4 (Sma- and Mad-related protein-4) in CFU-MK of ET patients was reduced in comparison with that of HV. Finally, to confirm that the impaired TGF-beta1 sensitivity was caused by reduced expression of Smad4, we examined Smad4-transfected CFU-MK from ET patients in the presence of TGF-beta1, and verified that the transfectants were indeed as susceptible as CFU-MK from HV to TGF-beta1. Thus it was surmised that one of the mechanisms for impaired sensitivity of CFU-MK to TGF-beta1 is the reduced expression of Smad4.
Adult↗
Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid.
BACKGROUND & AIMS: Aberrant crypt foci, precursors of colonic adenoma, are frequently positive for glutathione-S-transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, we examined the possibility that aberrant crypt foci, through the cytoprotecting function of glutathione-S-transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. METHODS: Glutathione-S-transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochemistry and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively. Glutathione-S-transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to glutathione-S-transferase P1-1 was analyzed by circular dichroism and immunoprecipitation. Caspase activities were determined by colorimetric protease assay, and sulindac binding to glutathione-S-transferase P1-1 was determined by inhibition assay of glutathione-S-transferase P1-1 activity. RESULTS: Aberrant crypt foci showed positive immunostaining for glutathione-S-transferase P1-1 but negative staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the glutathione-S-transferase P1-1-specific inhibitor gamma-glutamyl-S-(benzyl)cysteinyl-R-phenylglycine diethylester. By transfection of glutathione-S-transferase P1-1, M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of glutathione-S-transferase P1-1 to deoxycholic acid was proven by circular dichroism and by immunoprecipitation. The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to glutathione-S-transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2-3 months. CONCLUSIONS: Glutathione-S-transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.
Adenoma↗
A case of Gardner syndrome with a mutation at codon 1556 of APC: a suggested case of genotype-phenotype correlation in dental abnormality.
A 25-year-old man with suspected Gardner syndrome was introduced to our hospital by a dentist who, during examination of the patient, had found dental dysplasias and multiple osteomas of the jaw. Radiographs, endoscopy and biopsies revealed adenomatous polyposis of the colon. Genetic analysis of peripheral lymphocytes revealed a one-base deletion at codon 1556 in exon 15 of APC, which caused a frame shift and a premature stop at codon 1564. The pedigree analysis demonstrated five patients in his family who presented with dental abnormality and osteomas in addition to adenomatous polyposis of the colon. Although the relationship between the location of APC mutations and dental abnormalities remains controversial, this case supports the hypothesis that a mutation at around codon 1556 of APC is closely associated with dental abnormality and osteomas.
Adult↗
Selective embolization of the splenic vein in patients with hepatic encephalopathy and splenorenal shunt.
Obliteration of portal-systemic shunts is effective for portosystemic encephalopathy but is often associated with complications such as retention of ascites and worsening of esophageal varices. Selective embolization of the splenic vein was performed on six patients with hepatic encephalopathy and splenorenal shunts. Hepatic encephalopathy was not observed in four patients after the procedure. Neither retention of ascites nor rupture of esophageal varices was observed because postoperative elevation of portal venous pressure was not as great as that seen when shunt obliteration is performed. This procedure can be an effective and safe treatment option for hepatic encephalopathy with a splenorenal shunt.
Aged↗
Recovery of neutrophil count by ganciclovir in patients with chronic idiopathic neutropenia associated with cytomegalovirus infection in bone marrow stromal cells.
Patients with chronic idiopathic neutropenia (CIN) usually show chronic inflammation in their bone marrow stromal cells, but the etiologies of this disorder are still unknown. We suspected viral infection of the bone marrow stromal cells and used polymerase chain reaction (PCR) analysis to test for cytomegalovirus (CMV) infection in 4 patients with CIN and in 6 healthy volunteers. Peripheral blood mononuclear cells did not yield signals in any of the patients or healthy volunteers, but PCR analysis for CMV DNA in bone marrow stromal cells showed positive signals in 2 of the patients with CIN. CMV DNA was not detected in the other 2 patients or in the healthy volunteers. The 2 patients who were positive for stromal CMV received 500 mg/day ganciclovir for 14 days. After this treatment, the PCR band showing the presence of stromal CMV disappeared, and the neutrophil numbers of the 2 patients who received this viral eradication therapy normalized 6 months after treatment. In conclusion, the etiology in some cases of CIN is speculated to be infection by CMV in bone marrow stromal cells, and treatment with ganciclovir may be effective in treating such patients.
Aged↗
A ride on the ferrous wheel.
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History, 20th Century↗
[Successful corticosteroid treatment of thrombocytopenia in a pregnant woman with myelodysplastic syndrome (refractory anemia)].
A 31-year-old pregnant woman was referred to our hospital due to anemia and thrombocytopenia, and was diagnosed as having myelodysplastic syndrome (refractory anemia) with autoimmune thrombocytopenia. Administration of high dose methylprednisolone and gamma-globulin did not raise her platelet count, and she subsequently delivered a healthy baby after the transfusion of a large amount of platelets. Although the anemia spontaneously improved after delivery, the platelet count remained unchanged. Prednisolone was thus administered a second time, which did finally increase the platelet count. This is the first reported case of a pregnant woman with myelodysplastic syndrome in whom corticosteroid administration was effective for thrombocytopenia.
Adult↗
[Successful induction and complete improvement of myelofibrosis and erythema nosodum with cladribine in a case of hairy cell leukemia].
The patient was a 45-year-old male who had been diagnosed with pancytopenia in 1998 at another hospital, where he continued treatment for idiopathic thrombocytopenic purpura (ITP) as an outpatient. After atypical lymphocytes were detected in his peripheral blood, he was admitted to our hospital for further examination in April 2002. Tests results revealed the additional existence of pancytopenia, splenomegaly, bone marrow fibrosis and erythema nodosum, in addition to the findings of surface marker. Tartrate resistant acid phosphatase (TRAP) staining and scanning electron microscopy of peripheral blood lymphocytes indicated hairy cell leukemia. After administration of cladribine (0.09 mg/kg) for 7 days, complete remission was obtained, with bone marrow fibrosis and erythema nodosum also being completely improved.
Antineoplastic Agents↗
[A case of cholangiocellular carcinoma complicated with intratumoral hemorrhagic necrosis].
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Bile Duct Neoplasms↗
[Targeting molecular mechanisms for cancer therapy].
Cancer development is considered by the dysregulated proliferation of transformed cells. In recent years, dramatic and remarkable insight into the molecular mechanisms of this phenomenon have come from basic cancer research. Detailed knowledge of the molecular mechanisms and pathophysiology of cancer allows therapeutic agents to be designed that specifically target aberrant cellular processes. There are currently a number of targeted treatment strategies with less toxicity being evaluated. In the future, it is likely that this mechanistic and targeted approach will have a significant impact on clinical oncology and the diagnostic evaluation of tumors.
Apoptosis↗