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Biomedical subjects

M Kitagawa

Publications and source records attributed to M Kitagawa.

At least 325 records · Page 18Linked to original sources

Relationship between antisaccades and the clinical symptoms in Parkinson's disease.

We studied voluntary control of saccadic eye movement in 32 parkinsonian patients using the antisaccade task (the subjects were instructed not to look at the target but to look in the opposite direction). Mean latencies and error rates in the antisaccade task were significantly increased in advanced parkinsonian patients. The latencies of the antisaccades correlated with the severity of bradykinesia as well as the results of the Wisconsin Card Sorting Test. Patients taking anticholinergics showed significantly higher error rates. These results suggest that disturbance in the initiation of voluntary saccades in advanced patients may be associated with frontal lobe dysfunction, while anticholinergics may affect the inhibitory control of reflexive saccades.

Analysis of Variance↗

[A cooperative study on the incidence of bacteriuria in patients with benign prostatic hypertrophy].

The incidence of bacteriuria in patients with benign prostatic hypertrophy was studied at 8 National Hospitals. Among 1,542 patients, urinary infection was the reason of visit in 63 patients (4.1%). After open and transurethral prostatectomy, one-third of patients developed bacteriuria (30 of 59 subcapsular enucleations, and 252 of 776 transurethral resections). When a catheter is placed without prophylactic antimicrobial, all patients developed bacteriuria within 10 days, and within 30 days even if they received antimicrobials. The incidence of bacteriuria increased with age.

Aged↗

[Early detection of pancreatic cancer by serum markers].

Serum markers such as pancreatic enzymes and tumor markers are useful for the diagnosis of pancreatic cancer. Among 40 cases of pancreatic cancer, elevated values were observed for immunoreactive elastase (IRE) in 70% and for CA19-9 in 73%. Elevated serum IRE was observed more frequently in head cancer and resectable cancer, whereas elevation in CA19-9 occurred more often in body-tail cancer and unresectable cancer. Elevation of serum IRE and CA19-9 are useful for diagnosis of pancreatic cancer but it is not specific for pancreatic cancer. Therefore, we studied the clinical usefulness of a combination assay of various serum markers such as CA19-9, lipase, serum iron, amylase, albumin globulin ratio, tissue polypeptide antigen, immunoreactive trypsin, and CA125 using the logistic regression analysis. This assay showed higher sensitivity and high specificity for pancreatic cancer than CA19-9. This combination assay may be very useful for the diagnosis of pancreatic cancer.

Amylases↗

Bone marrow transplantation from Fv-4-resistant donors rescues Friend leukemia virus-infected mice from leukemia: a model of bone marrow transplantation therapy against retroviral infection.

Bone marrow transplantation experiments were conducted in mice in order to develop an experimental bone marrow transplantation therapy model, with which to investigate possible means to cure retrovirus-infected hosts with bone marrow or stem cells from virus-resistant donors. In one experiment, lethally irradiated Friend leukemia virus (FLV)-sensitive C3H/He (C3H; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s Rfv-3s) mice were transplanted with (i) bone marrow cells from FLV-resistant BALB/c-Fv-4Wr (C4W; Fv-2s, Fv-4r, Rfv-1s, Rfv-2s, Rfv-3s) mice (C4W --> C3H) or (ii) a mixture of bone marrow cells from C4W and C3H mice (C4W + C3H --> C3H). They were then inoculated with FLV 3-4 months later and leukemia development was examined. The results indicated that C4W --> C3H chimeras were completely resistant to FLV-induced leukemogenesis and that C4W + C3H --> C3H mixed chimeras that contained as low as 30% C4W-derived cells, or as high as 70% C3H-derived cells, did not develop leukemias. In another experiment, bone marrow cells from C57BL/6 (B6; Fv-2r, Fv-4s, Rfv-1r, Rfv-2r, Rfv-3r) or C4W donors were grated to FLV-sensitive DBA/2 mice (DBA; Fv-2s, Fv-4s, Rfv-1s, Rfv-2s, Rfv-3s) that had been infected with FLV 6 days earlier (DBA-FLV). The results indicated that most, if not all, FLV-infected DBA mice which received bone marrow transplantation from B6 donors developed B6-derived leukemias, although the survival time of these mice was dramatically prolonged as compared to that of untreated DBA-FLV mice. In contrast, bone marrow transplantation from Fv-4r-bearing C4W donors successfully rescued FLV-infected DBA mice from leukemic deaths. Thus, the bone marrow transplantation therapy against retroviral infection of hemopoietic cells was shown to be feasible, provided that donor cells carry a resistant allele that functions via receptor blockade as in the case of Fv-4r, but less effective when the roles of the resistant alleles partially interfered with the virus replication, leukemic transformation and/or cycling of target cells as suggested for Fv-2r gene action, or to resist virus infection by immunological means as are known for Rfv-1r, Rfv-2r and Rfv-3r genes which are also carried by B6-strain mice. Implication of these findings on the somatic gene therapy against retrovirus infection diseases in man are discussed.

Animals↗

Current status of pancreatic stone protein.

Pancreatic stone protein (PSP) has been argued to play a crucial role in intraductal pancreatic stone formation in chronic pancreatitis. PSP was initially reported to inhibit calcium carbonate precipitation from human pancreatic juice and to be decreased in pancreatic secretions from patients with chronic pancreatitis. Recent clinical investigations have further demonstrated elevation of PSP in the serum and urine of patients with renal disease as well as pancreatic disease. However, the PSP reduction in pancreatic secretion in chronic pancreatitis remains controversial. Therefore, we review the current concept of PSP.

Calcium-Binding Proteins↗

Accelerated exon skipping of IRF-1 mRNA in human myelodysplasia/leukemia; a possible mechanism of tumor suppressor inactivation.

The transcription factor IRF-1 has been shown to function as a tumor suppressor. Here we report that a significant proportion of the IRF-1 mRNA detected in normal human hematopoietic cells and cultured cell lines lacks exon 2 (containing the AUG initiation codon) and 3 as a result of exon skipping. Surprisingly, when we examined the bone marrow and peripheral mononuclear cells from patients with myelodysplastic syndrome (MDS) or leukemia secondary to MDS, we could still detect the exon-skipped form but little or none of the intact IRF-1 mRNA. This appears to be the result of accelerated exon skipping since we could find no mutations within the exons and splicing junctions from these patients. The exon-skipped form of IRF-1 lacking exons 2 and 3 displayed neither DNA binding nor tumor suppressive activities. Thus this accelerated exon skipping may cause the inactivation of IRF-1 and thereby contribute to the development of human hematopoietic malignancies.

Cell Line↗

[Spontaneous regression of small cell lung cancer].

An 82-year-old man was admitted for evaluation of dry cough and low grade fever. A chest roentgenogram obtained on admission revealed an abnormal mass shadow at the left hilus. Trans-bronchial lung biopsy was used to make a diagnosis of small cell lung cancer. This tumor regressed spontaneously.

Aged↗

p53 expression in myeloid cells of myelodysplastic syndromes. Association with evolution of overt leukemia.

To assess p53 expression in the hematopoietic cells of the bone marrow in premalignant as well as malignant conditions, we examined immunohistochemically bone marrow biopsies from patients with myelodysplastic syndromes (MDS, n = 51), acute myeloid leukemia (n = 42) and as a nonneoplastic condition, aplastic anemia (n = 20) and samples from individuals who had no hematological disorder (control, n = 12). Nuclear accumulation of p53 protein was found in seven of 51 patients with MDS (14%) and two of 42 acute myeloid leukemia patients (5%), whereas patients with aplastic anemia and control subjects were uniformly negative for p53 protein. In the bone marrow of patient with MDS, p53-positive cells constituted about 5 to 30% of the total bone marrow cells. Two-color immunohistochemical analysis revealed that the p53-positive cells were also positive for the myeloid cell marker. Half of the MDS cases that evolved to overt leukemia (seven of 14) exhibited positive p53 reaction in the bone marrow at the time of initial diagnosis. This frequency (50%) was significantly higher than that in de novo acute myeloid leukemia cases. All of the seven MDS cases that exhibited p53 expression at the time of initial diagnosis developed overt leukemia later, and p53 expression was maintained throughout the progression of MDS. The results suggest that p53 mutations that occur in the myeloid cells in MDS may confer a growth advantage to these cells resulting in the progression to overt leukemia. Thus, immunohistochemical examination for p53 is very useful for predicting the evolution to overt leukemia from MDS.

Acute Disease↗

A cyclin-dependent kinase inhibitor, butyrolactone I, inhibits phosphorylation of RB protein and cell cycle progression.

Butyrolactone I is a selective inhibitor of the cyclin-dependent kinase (cdk) family. It inhibits both cdk2 and cdc2 kinase, but scarcely affects C-kinase, A-kinase, casein kinases, MAP kinase or EGF receptor-tyrosine kinase (Kitagawa et al., 1993, Oncogene, 8, 2425-2432). We studied the effects of butyrolactone I on the cell cycle as well as on phosphorylation of retinoblastoma protein (pRB). Butyrolactone I inhibited phosphorylation of pRB catalyzed by cyclin A-cdk2 produced by baculovirus in vitro. Furthermore, it inhibited phosphorylation of pRB and cell cycle progression from G1 to S phase in WI38 cell cultures. WI38 cells arrested at the G0 phase by serum starvation progressed in the cell cycle after serum stimulation. pRB was phosphorylated after 10 h serum stimulation. Incorporation of [3H]thymidine into the cells began to increase after 16 h serum stimulation. These processes were inhibited by butyrolactone I. Flow cytometric analysis showed that exposure to butyrolactone I inhibited progression of the cell cycle from G1 to S phase. These data suggested that initiation of DNA synthesis was inhibited by butyrolactone I and that the cell cycle was arrested in the G1 phase. Butyrolactone I also inhibited H1 histone phosphorylation in human WI38 cells and their G2/M progression. tsFT210 cells, a temperature-sensitive cdc2 mutant cell line, were synchronized at G2/M at a nonpermissive temperature, butyrolactone I inhibited the cell cycle progression of these cells at G2/M at the permissive temperature. Thus butyrolactone I, a cyclin-dependent kinase family inhibitor, which prevented the phosphorylations of the cell cycle-regulating proteins pRB and H1 histone, inhibited the cell cycle at G1/S and G2/M, respectively. These results suggest that the phosphorylations of pRB and H1 histone may play crucial roles in G1/S and G2/M progression, respectively, although it is possible that phosphorylations of other proteins by cdks are involved in G1/S and G2/M progression.

4-Butyrolactone↗

[Clinicopathologic analysis of ossification in spinal meningioma].

Calcification such as psammoma body is sometimes found especially in spinal cord meningioma but ossification of the meningeal tumor was rarely observed. Two cases of ossificated spinal cord meningiomas, located extramedullary intradurally apart from spinal bone, were clinicopathologically analyzed. The patients were 75-year-old female with meningioma at T9-10 level and 60-year-old female with one at T6-8 level. With pathological examination, concentration of psammoma bodies is not related to the formation of bone tissue. Metaplasia of arachnoid cell is seemed to be the origin of the bone structure.

Aged↗

[A case report of rounded atelectasis on MRI].

A 73-year-old man was admitted to Toyama Red Cross Hospital, because of productive cough and right flank pain. His chest X-ray film and computed tomography (CT) showed pleural effusion and a mass shadow in the right lung area. On CT vessels and bronchi were seen curving toward the mass (comet tail sign), suggesting rounded atelectasis. Transthoracic lung biopsy under CT and echo guidance revealed suppurative pleuritis. MRI also showed the comet tail sign. Moreover, in the lesion, curling hypointense lines were observed on various slices. We describe how MRI facilitates the diagnosis of rounded atelectasis.

Aged↗

[A case of mediastinal cystic lymphangioma: with special reference to ultrasonographic findings].

We reported a rare case of mediastinal cystic lymphangioma, which happened to be discovered on chest X-ray. CT density level of the mediastinal tumor was 20 HU and the tumor was homogeneous cystic lesion. Multilocularity of the cyst and the relationship to the adjacent inferior vena cava were clarified by pre-operative transesophageal and intraoperative ultrasonographic examination, and the tumor was successfully excised without mishap.

Humans↗

Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development.

Interferon regulatory factor 1 (IRF-1), a transcriptional activator, and its antagonistic repressor, IRF-2, were originally identified as regulators of the type I interferon (IFN) system. We have generated mice deficient in either IRF-1 or IRF-2 by gene targeting in embryonic stem cells. IRF-1-deficient fibroblasts lacked the normally observed type I IFN induction by poly(I):poly(C), while they induced type I IFN to similar levels as the wild type following Newcastle disease virus (NDV) infection. In contrast, IRF-2-deficient fibroblasts showed up-regulated type I IFN induction by NDV infection. A profound reduction of TCR alpha beta+CD4-CD8+ T cells in IRF-1-deficient mice, with a thymocyte developmental defect, reveals a critical role for IRF-1 in T cell development. IRF-2-deficient mice exhibited bone marrow suppression of hematopoiesis and B lymphopoiesis and mortality following lymphocytic choriomeningitis virus infection.

Animals↗

Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2.

Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon and interferon-inducible genes. The IRF-1 gene is itself interferon-inducible and hence may be one of the target genes critical for interferon action. When the IRF-2 gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice. This transformed phenotype was reversed by concomitant overexpression of the IRF-1 gene. Thus, restrained cell growth depends on a balance between these two mutually antagonistic transcription factors.

3T3 Cells↗

Enzyme immunoassay and characterization of pancreatic stone proteins in human urine.

An enzyme immunoassay of pancreatic stone protein (PSP) in human urine was developed. Mean analytical recovery of pure PSP-S2-5 added to urine was 102.3% (SD 5.9%), and the precision of the assay was 2.0-2.7% within an assay and 2.5-2.9% between assays. In healthy volunteers (age 20-55 years), the mean value of the PSP concentration, expressed as ratios to urine creatinine, was 129 +/- 88 (mean +/- SD) micrograms/g without any differences for sex. Urine PSP correlated with urine N-acetylglucosaminidase (NAG) (r = 0.354). The molecular forms of immunoreactive PSP in urine were characterized by using cation exchange chromatography (Mono S), SDS-PAGE, N-terminal sequence, and enzyme immunoassay analysis. The urine PSP, eluted at the position corresponding to PSP-S2-5 on cation exchange chromatography, was converted to PSP-S1 by trypsin digestion. The difference in mobility on SDS-PAGE between urine PSP and PSP-S2-5 seems to be due to a glycosylated undecapeptide (N-terminal 1-11). The proposed method offers a sensitive, specific, and reproducible tool for laboratory analysis of human urine PSP levels.

Acetylglucosaminidase↗

Dynamic changes in stress fiber expression in rat uterine vein endothelial cells associated with pregnancy.

En face endothelial preparations of rat uterine vein were stained with rhodamine-phalloidin to investigate the dynamics of stress fiber expression during pregnancy. In prepregnant animals, somewhat plump, spindle-like endothelial cells of the uterine vein had only a few short stress fibers. With the progress of pregnancy, however, many long stress fibers appeared within the elongated endothelial cells. Within 2 hr after delivery, these stress fibers became dramatically decreased in number as the cells reverted from an elongated to a plump shape and returned to the prepregnancy level by 14 days postpartum. The uterine vein showed a significant increase in length during pregnancy and quickly shortened after delivery. Thus, expression of stress fibers in endothelial cells of the uterine vein seems to be related to the tension loaded on this vessel during its elongation in parallel with the marked growth of the uterine body during pregnancy. This study shows that stress fibers are dynamic structures that may serve to maintain endothelial cell integrity during the exertion of tensile stress on the vessel wall.

Actins↗