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Biomedical subjects

I Maekawa

Publications and source records attributed to I Maekawa.

At least 19 recordsLinked to original sources

Successful treatment with allogeneic peripheral blood stem cell transplantation and granulocyte transfusion for severe aplastic anemia with sinusitis.

A 43-year-old woman with severe aplastic anemia (SAA) received anti-thymocyte globulin and cyclosporin A (CyA) and achieved hematological remission. Although she had maintained hematological remission, the disease relapsed 10 months after arbitrary discontinuance of maintenance therapy with CyA. Resumption of CyA therapy was not effective, and her condition became complicated with progressive sinusitis with bone destruction, which was refractory to antibiotics, antifungal agents, granulocyte colony-stimulating factor, and surgical drainage. Because of the necessity for early neutrophil recovery (to resolve the infection), we proceeded with a combination therapy using allogeneic peripheral blood stem cell transplantation (PBSCT) promptly followed by granulocyte transfusion (GTX) from the same human leukocyte antigen-identical donor rather than carrying out a second immunosuppressive therapy. The patient showed temporal resolution of infection on the second day after a single GTX. Although the patient had pneumonia on day 11, it was resolved promptly after engraftment on day 16. This report suggests the clinical utility of a salvage therapy with allogeneic PBSCT followed by GTX in a particular case of recurrent SAA with refractory infections.

Adult↗

A novel splice site mutation of the thiazide-sensitive NaCl cotransporter gene in a Japanese patient with Gitelman syndrome.

Gitelman syndrome (GS, MIM 263800) is an inherited disorder characterized by metabolic alkalosis with hypokalemia, hypomagnesemia, and hypocalciuria. The genetic abnormalities causing GS are known to lie in the thiazide-sensitive NaCl cotransporter (TSC), which is expressed in the distal tubule of the kidney. The TSC gene, located at chromosome 16, consists of 26 exons and encodes the protein containing 12 putative transmembrane domains with long intracellular amino and carboxy termini. Most of the abnormalities identified in GS were missense mutations, distributed throughout the TSC gene without a hot spot. A 42-year-old Japanese man was introduced for close examination of hypokalemia. In renal clearance studies using furosemide or thiazide, chloride clearance was increased after furosemide but not after thiazide administration. Furthermore, the distal fractional chloride reabsorption was dramatically decreased by furosemide but not thiazide administration, suggesting a defect in the distal tubule. We then analyzed the TSC gene to confirm the diagnosis of GS, and identified a novel G to T mutation at the acceptor splice site preceding exon 14, resulting in disruption of a conventional 3'AG consensus splice site. Abnormal splicing by this mutation is predicted to cause the formation of truncated TSC with a partial deletion of the transmembrane domain, which will loose the function of transporter. In conclusion, we have identified a unique novel splice site mutation of the TSC gene in GS. The predicted structure of this mutant TSC can conceivably cause an impairment of the transporter activity and thereby be responsible for the development of GS in our patient.

Adult↗

Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan.

This pilot study evaluated the efficacy of a new combination chemotherapy with a newly developed nitrosourea derivative ranimustine and evaluated the efficacy of interferon alpha (IFN-alpha) maintenance in previously untreated patients with multiple myeloma (MM). The induction therapy (ROAD-IN) was a 6-week regimen consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan (Alkeran) and dexamethasone starting on day 1 and IFN-alpha, which was administered three times weekly for 3 weeks starting on day 22. This was repeated for three cycles. The responders were subsequently randomized into two groups that received or did not receive IFN-alpha as maintenance therapy. Of the 164 patients registered, 161 were evaluated. An objective response to induction therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and partial remission (PR) in 82 (51%). The median survival for all patients was 3.6 years from registration. The survival of responders (CR + PR) was significantly better than that of non-responders (median survival 4.3 years vs. 1.4 years; 7-year survival rate 32% vs. 9%; P < 0.0001). The IFN-alpha maintenance did not show any advantage for either response duration or survival. This pilot study demonstrated that a comparatively short period of induction therapy with the ROAD-IN regimen produced a rather high response rate and a similar survival rate to those achieved with other longer induction regimens, and that good responders to the initial therapy survived significantly longer than non-responders.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study.

The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge. In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF). The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS. Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML. The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy. No therapy-related death occurred. Some unique actions of M-CSF were suggested in this trial. It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.

Adult↗

[Collaterals after flow alternation in pelvic arteries: precondition for pelvic reservoir therapy].

To determine the best flow alternation in the internal iliac arteries for regional chemotherapy using a reservoir to treat pelvic malignancies, collateral arteries that arose after arterial flow alternation were evaluated on follow-up pelvic angiographies. Follow-up angiographies were obtained in 11 patients with 21 embolized arteries; six male and five female patients including three with urinary bladder cancer, two with prostate cancer, four with uterine cervical cancer and two with bone metastasis. The interval until follow-up angiography ranged from one to-28 months (mean 8.9 months). Three radiologists interpreted the angiographic results and evaluated collateral vessels. Among 21 embolized arteries, 19 were well occluded, while two were not blocked completely. The two arteries with incomplete embolization did not induce collaterals. Eight internal iliac arteries occluded at the proximal portion enhanced retrogradely via collaterals from the ipsilateral external iliac arteries. Collaterals between the bilateral internal iliac arteries were noted only in four of them. In conclusion, embolization at the proximal point of the internal iliac arteries usually induced collaterals from the ipsilateral external iliac arteries and did not always from collaterals between the bilateral internal iliac arteries, which were necessary for regional chemotherapy. This should be considered when pelvic malignancies are treated with reservoirs.

Adult↗

[Prognosis in 75 cases of chronic lymphocytic leukemia and second malignancies].

Clinical prognosis and analysis of causes of death of 75 CLL cases were evaluated. Median survival was 43.7 months. Major causes of death were infection (36%), primary CLL (16%), secondary malignancies (16%), cardiac failure (8%), brain hemorrhage (7%) and so on. There were 10 deaths (13%) with second or double cancers and 2 deaths with malignant lymphomas. In terms of deaths from CLL complicated by cancer, there were 4 deaths from stomach cancer, 3 from lung cancer, 1 from liver, pancreas, or prostata cancer. Cancer risk, which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis.

Aged↗

Primary biliary cirrhosis associated with idiopathic thrombocytopenic purpura.

A case of primary biliary cirrhosis (PBC) associated with idiopathic thrombocytopenic purpura (ITP) is reported. The patient is a 59-year-old man. When he was 49 years old, he was diagnosed with ITP and received steroid therapy that successfully increased platelet numbers. However, the steroid therapy failed to normalize the elevated gamma-glutamyl transpeptidase. Ten years after this episode, he suffered from general itching and malaise and exhibited a gradual increase of serum biliary enzyme levels. Immunologically, IgM was increased and anti-mitochondrial antibody was positive. Histological findings of liver needle biopsy showed chronic non-suppurative destructive cholangitis, confirming the diagnosis of PBC. To date, very few PBC cases associated with ITP have been reported. Our case is the second one in Japan. PBC and ITP in our patient seemed to develop simultaneously, but the effect of steroid therapy on the two conditions was different. This result suggests that the autoimmune process may have been different in PBC and ITP in the present patient.

Biopsy, Needle↗

Effects of rhG-CSF on infection complications and impaired function of neutrophils secondary to chemotherapy for non-Hodgkin's lymphoma. Hokkaido Study Group of Malignant Lymphoma, and rhG-CSF, Japan.

It has been previously demonstrated that the administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF) ameliorates the decrease of the polymorphonuclear neutrophils (PMNs) count after the cytotoxic chemotherapies, thereby reducing the infection complications associated with neutropenia. In this multi-center study, we studied the prophylaxtic effect of rhG-CSF administration on infection complications in patients with non-Hodgkin malignant lymphoma, who received cytotoxic chemotherapies (CHOP or ProMACE/CytaBOM). rhG-CSF administration reduced the frequency of infection complications, and there was no obvious difference in it's frequency between the CHOP-treated and the ProMACE/CytaBOM-treated groups when administered with rhG-CSF, thereby indicating that third generation therapy for NHL may be safely completed in Japanese in combination with rhG-CSF administration. Furthermore, we investigated both the in vitro and the in vivo effects of rhG-CSF on the function of PMNs in patients with NHL and healthy donors, and revealed that the administration of rhG-CSF for NHL patients receiving cytotoxic chemotherapy brought on an improvement of the production of active oxygen but did not affect serum levels of IFNs, IL-1-beta, and IL-6, inspite of a slight elevation of TNF-alpha. Consistent with these results, in vitro treatment of PMNs with rhG-CSF induced no significant production of these inflammatory cytokines and their mRNA expressions. Furthermore, rhG-CSF administration showed no significant effects in vivo on the expression of CD11a, CD11b and LECAM-1 on PMNs and integrins on platelets.

Adult↗

Administration of rhG-CSF increases complete remission rates after CHOP and ProMACE/CytaBOM for non-Hodgkin's lymphoma: a pilot study. Hokkaido Study Group of Malignant Lymphoma and rhG-CSF.

To evaluate the clinical effects of the administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy for patients with advanced-staged intermediate-grade or high-grade non-Hodgkin's malignant lymphoma (NHL), we conducted this multicenter study and compared the responses between both the regimens, CHOP as a first-generation chemotherapy and ProMACE/CytaBOM as a third-generation chemotherapy, when combined with the rhG-CSF administration. In this multicenter study, where forty patients were registered, patients in both the CHOP and ProMACE/CytaBOM groups were treated with the original regimen designs without the necessity of reducing drug dosages when combined with the administration of rhG-CSF. The administration of rhG-CSF post both of the cytotoxic therapies brought about much higher rates of complete remission in both the groups (CHOP, 75 percent; ProMACE/CytaBOM, 75 percent), as compared with those of the previous study without the rhG-CSF administration. Regarding response rates according to the International prognostic factor index, the CHOP group showed a lower rate of complete remission in patients with risk factors, compared with ProMACE/CytaBOM group. This result suggested that the administration of rhG-CSF may offer one important approach for improving the first-line therapy for aggressive NHL with high risk factors.

Adult↗

Establishment and characterization of a new Ph1-positive ALL cell line (ALL/MIK) presenting bcr gene rearrangement on bcr-2 and ALL-type bcr/abl transcript: suggestion of in vitro differentiation to monocytoid lineage.

A new Ph1-positive acute lymphoblastic leukemia cell line, designated as ALL/MIK, has been developed from a patient with Ph1-positive acute leukemia. The ALL/MIK cells showed an immunophenotype of common ALL with rearranged JH and Jk genes. The ALL/MIK cells showed no M-bcr rearrangement using Southern blot analysis with either 3' or 5' M-bcr probes, but had the bcr gene rearrangement on bcr-2 within the first intron of the bcr gene. Consistent with this result, the reverse transcriptase-dependent polymerase chain reaction (RT-PCR) assay revealed that the ALL/MIK cells contained the transcript derived fusion of the first exon of bcr gene and the second exon of abl gene. Although the ALL/MIK cells were defined as early pre-B cells by immunophenotypical and genotypical analyses, they were capable of differentiating into monocytoid lineage by when cultured with TPA. Furthermore, another Ph1-positive ALL cell line, (TOM-1), was investigated for its ability to differentiate to monocytoid lineage. TOM-1 was also induced to monocytoid lineage by TPA. Thus, the present study suggested that the leukemic transformation in some Ph1-positive ALL may occur at the level of multipotential hematopoietic cells capable of differentiating towards lymphoid and myelo-monocytoid lineage.

Aged↗

[The present status and the issues of the nosocomial infection at Asahikawa Municipal Hospital].

The prophylactic strategy against nosocomial infection at Asahikawa municipal hospital is discussed. The issues of the prophylactic strategy are; (1) Establishment of a bacterial surveillance system and a series of bacterial examination at fixed sites in the hospital organized by our own nosocomial infection committee. A quick response and a reaction by the committee according to the results obtained from a series of bacterial examinations, (2) Education of the practical guide of patient care, sterile technique and management method of disposed stuffs according to the anti-infection manual, (3) Improvement of the health care system for the hospital staffs, and (4) Planning and carrying out of the well-designed improvement plan of the hospital environment.

Cross Infection↗

The development of an enzyme immunoassay for placental tissue protein 17 (PP17) and its clinical significance.

We developed an enzyme immunoassay (EIA) for placental protein 17 (PP17) using avidin biotin binding, and measured the serum-PP17 levels of 37 healthy men, 103 nonpregnant women, 48 pregnant women, and 86 patients with gynecologic malignancies. The mean level was 12.8 ng/ml in healthy men and 44.2 ng/ml in nonpregnant women (p < 0.05). The calculated upper limit of normal was 97.8 ng/ml (mean + 2 sigma). The serum PP17 concentration was remarkedly reduced postmenopausally. Pregnant women showed a mean serum level of 19.2 ng/ml, which was significantly lower than that of nonpregnant women. Immunoserological results strongly suggest that PP17 is produced far more in the normal endometrium than in the placentae and decidua. Patients with gynecologic malignancies had obviously lower mean serum PP17 levels (8.3-19.9 ng/ml) than those found in healthy nonpregnant women. Measurement of the serum PP17 concentration might be useful in distinguishing gynecologic malignancies from various normal conditions.

Biomarkers, Tumor↗

Antitumor activity of acemetacin in mice bearing colon 26 carcinoma: a preliminary report.

The antitumor activity of acemetacin (ACM) was examined in mice bearing colon 26 carcinoma and its effect was compared with indomethacin (IND). The addition of ACM (0.001-0.003%) to drinking water prolonged the survival time of mice bearing colon 26. On the other hand, prostaglandin E2 (PGE2) reduced the effect of ACM. The results suggest that the antitumor activity of ACM may be associated with the reduction of PGE2 levels.

Animals↗

[Issues in the AIDS medicine based on the analysis of medical worker's recognition of the disease].

We analysed problems on the front line of the AIDS medicine through our experience of a with hemophilia A, who had HIV infection developed to ARC and the AIDS and in addition, had non-Hodgkin's lymphoma in his rectum and died of pneumonitis caused by pneumocystis carinii. We have learned from the poll on medical worker's recognition of the disease through the experience of this case that the nurses who were concerned with the care of this patient did not have opinions against acceptance of patients with AIDS, although they have a fear, from the professional point of view, to a possibility of infection of the virus from patients with AIDS. What should be done in the practical part of the AIDS medicine are (1) a repetitive education of accurate knowledge of the disease, (2) completion of practical guide lines for medical care of patients with AIDS and (3) legal establishment of an insurance system for accidental infections of HIV to medical or paramedical staffs.

Acquired Immunodeficiency Syndrome↗

[A case of gastric amyloidosis developing into Bence-Jones type multiple myeloma, treated effectively by cyclo-VAMP chemotherapy].

A 65-year-old man was admitted because of bleeding from gastric ulcer. A massive deposition of AL lambda type amyloid proteins in the gastric lesion was found. There were a few Bence-Jones (BJ) proteins in the urine, but serum M proteins and bone lesions were not found. Bone marrow puncture showed no dysplastic change of plasma cells. Moreover, there were no amyloid proteins deposited anywhere in the digestive tract examined, except for the stomach, nor were they found in the bone marrow, prostata, liver or kidney. Gastric amyloidosis was diagnosed. Gastrectomy was performed because of uncontrollable bleeding. Sixteen months later, bone swelling occurred in the sternoclavicular joint and the 3rd rib. At that time, plasma cells with dysplasia and increasing levels of urine BJ protein were revealed. BJ type multiple myeloma was finally diagnosed. For remission induction, cyclo-VAMP chemotherapy was given in 3 courses. Decreased levels of urine BJ protein, diminished bone lesion, normalization of bone marrow and fewer amyloid deposits were seen, and partial response was obtained. The patient is well with no signs of recurrence evident 42 months after treatment. This is an interesting case of initial gastric amyloidosis that developed into BJ type multiple myeloma and was effectively treated with cyclo-VAMP chemotherapy.

Aged↗

[Successful oral administration of etoposide therapy for refractory malignant lymphoma treated with frequent combination chemotherapy].

A 67-year-old man was diagnosed as non-Hodgkin lymphoma (diffuse, mixed cell type, B cell) with clinical stage IV in March 1989. He had been treated many times with salvage chemotherapy on admission including CHOP-etoposide and ProMACE-Cyta BOM. Recurrence, however, occurred in two or three months after any therapy. He had a therapeutic history of chronic daily administration of etoposide. In November 1991, recurrence was found in the peripheral lymph node and the colon. A new regimen of oral administration of etoposide, 50 mg/day four times a week, was employed. Two months later, the peripheral lymph node swelling disappeared. Seven months later, the patient showed no signs of recurrence by Ga-scintigraphy. This therapy is being continued. It is suggested that anti-neoplastic activity of etoposide is dependent on the schedule of administration. This regimen is suggested to be effective in the treatment of patients with refractory malignant lymphoma.

Administration, Oral↗