Biomedical subjects
H Imai
Publications and source records attributed to H Imai.
[Treatment of cancer ascites by combined intraperitoneal administration of low-dose CDDP and reinfusion of ultra-filtrated and concentrated ascitic fluid in patients].
Ascites due to carcinomatous dissemination is a severe problem for end-stage cancer patients. We attempted treating patients on an outpatient basis with the administration of low-dose CDDP-i.p. and reinfusion of ultrafiltrated and concentrated ascites. From 1995, we performed this therapy on 16 patients with concentrated ascites 6-8 fold and reinfusion, combined with low-dose CDDP-i.p. and drip infusion of 5-FU intravenously. The ascitic fluid was significantly decreased after treatment in 8 patients, and 2 patients had lasting low concentrations of CA 125. CA 125 decreased in 83.3% of patients, who tended to have extended survival times after remarkable ascites pooling and treatment with low-dose CDDP-i.p. and reinfusion therapy. This treatment is a useful cant method for decreasing ascites and improving QOL.
[Severe peripheral neuropathy, cardiac hypofunction, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a patient with Churg-Strauss syndrome].
A 64-year-old Japanese male was admitted to Kotoh General Hospital because of fever and cough on July, 14, 1997. Laboratory data showed hypereosinophilia (11,500/microliter) and high titer of anti-myeloperoxidase antineutrophil cytoplasmic antibody (319 EU). A physical examination revealed progressive peripheral neuropathy. He had been diagnosed as having bronchial asthma since November, 1996. Therefore, he was diagnosed as having Churg-Strauss syndrome (CSS). He was treated with methylprednisolone pulse therapy (500 mg/day for 3 days) and oral prednisolone (PSL, 60 mg/day). However, peripheral neuropathy was rapidly progressive, and echocardiogram revealed cardiac hypofunction (ejection fraction (EF); 39%). He was refereed to Akita University Hospital for further examination. On admission, laboratory data showed hyponatremia (125 mEq/l) with inappropriate secretion of antidiuretic hormone (ADH, 13.0 pg/ml). Atrial natriuretic peptide was normal (26 pg/ml). Urinary osmorality was 488 mOsm/l, and urinary sodium excretion was 86 mEq/l. Renal, adrenal, and thyroid functions were normal. From these data, his hyponatremia was caused by syndrome of inappropriate secretion of ADH (SIADH). After cyclophosphamide-pulse therapy (500 mg) and oral administration of cyclophosphamide (50 mg/day) and PSL (50 mg/day), peripheral neuropathy improved gradually, and his serum sodium returned to normal, but cardiac hypofunction continued. A possible relationship between SIADH and CSS is discussed.
An EM-type Algorithm for Ordered Restriction Map Alignment.
Constructing restriction maps is one of the important steps towards the determination of DNA sequences. Recently, the single-molecule approaches to constructing restriction maps, such as Optical Mapping by D. Schwartz et al., have developed. In practice, with the single-molecule approach like Optical Mapping, the identification of the restriction sites is complicated by several error factors due to resolving power of biological experiments. The ordered restriction map alignment problem is a problem to estimate the actual restriction sites from many imprecise copies of map from single molecule. In this paper, we formulate the problem on the basis of the statistical maximum likelihood estimate, and propose a new efficient local search algorithm for this problem, by applying the Expectation-Maximization (EM) algorithm along with the concept of two-clustering. Our algorithm works well for a lot of sets of simulated data, some of which we believe more difficult than the actual cases.
A Greedy Algorithm for Minimizing the Number of Primers in Multiple PCR Experiments.
The selection of a suitable set of primers is very important for polymerase chain reaction (PCR) experiments. Most existing algorithms for primer selection are concerned with producing a primer pair for each DNA sequence. However, when all the DNA sequences of the target objects are already known, like the approximately 6,000 yeast ORFs, we may want to design a small set of primers to PCR amplify all the targets, which can then be resolved electrophoretically in a series of experiments. This would be quite useful, because decreasing the number of primers greatly reduces the cost of an experiment. This paper extends the problem of primer selection for a single experiment presented in Doi and Imai (Genome Informatics, 8:43-52, 1997) to primer selection for multiple PCR experiments, and proposes algorithms for the extended problem. The algorithms design primer sets one at a time. We extend the greedy algorithm for one PCR experiment in (Genome Informatics, 8:43-52, 1997) by handling amplified segments in DNA sequences that have been identified by primer pairs already selected and by changing the priorities in the greedy algorithm. This algorithm is applied to real yeast data. The number of primers equaled 85% of the number of identified DNA sequences, which represented more than 90% of all the target DNA sequences. This is 42% the number of primers needed for multiplex PCR. Furthermore, the length of each primer is less than half the length of multiplex PCR primers so the cost of producing the primers is reduced to 20% of the cost in the multiplex PCR case.
[Problems in treatment of kidney failure (discussion)].
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Identification of a new intermediate state that binds but not activates transducin in the bleaching process of bovine rhodopsin.
Using time-resolved low-temperature spectroscopy, we have examined whether or not bovine rhodopsin has a unique transducin-binding state, meta Ib, previously detected from chicken rhodopsin. Unlike chicken meta Ib, bovine meta Ib was detected only by detailed kinetics analysis of the bleaching process, but it was stabilized by transducin and visualized in the observed spectral changes. From the effect of GTPgammaS, it was revealed that meta Ib induced no GDP-GTP exchange reaction in transducin. Thus meta Ib is a common intermediate of vertebrate rhodopsin and transducin is activated in two steps by meta Ib and meta II.
Stereoselective synthesis of 11Z-9-demethyl-9-benzyl- and 9-phenyl-retinals and their interaction with bovine opsin.
11Z-9-Demethyl-9-benzyl- and 9-phenyl-retinals were synthesized stereoselectively from the beta-ionone analog-tricarbonyliron complexes and their interaction with bovine opsin was investigated.
Suppression of leukotriene formation in RBL-2H3 cells that overexpressed phospholipid hydroperoxide glutathione peroxidase.
The overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) by RBL-2H3 cells was used as the basis for an investigation of the effects of PHGPx on the formation of leukotrienes. The rates of production of leukotriene C4 (LTC4) and leukotriene B4 (LTB4) in cells that overexpressed PHGPx were 8 times lower than those in a control line of cells. The reduction in rates of production of leukotrienes apparently resulted from the increase in the PHGPx activity since control rates of formation of leukotrienes could be achieved in PHGPx-overexpressing cells upon inhibition of PHGPx activity by diethyl malate. The conversion of radioactively labeled arachidonic acid to intermediates in the lipoxygenase pathway, such as 5-hydroxyeicosatetraenoic acid (5-HETE), LTC4, and LTB4, was strongly inhibited in PHGPx-overexpressing cells that had been prelabeled with [14C]arachidonic acid. PHGPx apparently inactivated the 5-lipoxygenase that catalyzed the conversion of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid (5-HPETE) since 5-HPETE is a common precursor of 5-HETE, LTC4, and LTB4. The rates of formation of LTC4 and LTB4 in PHGPx-overexpressing cells returned to control rates upon the addition of a small amount of 12-HPETE. Flow cytometric analysis revealed that the rapid burst of formation of lipid hydroperoxides induced by A23187 was suppressed in PHGPx-overexpressing cells as compared with the control lines of cells. Subcellular fractionation analysis showed that the amount of PHGPx associated with nuclear fractions from PHGPx-overexpressing cells was 3.5 times higher than that from the control line of cells. These results indicate that PHGPx might be involved in inactivation of 5-lipoxygenase via reductions in levels of the fatty acid hydroperoxides that are required for the full activation of 5-lipoxygenase. Thus, in addition to its role as an antioxidant enzyme, PHGPx appears to have a novel function as a modulator of the production of leukotrienes.
Visual pigment: G-protein-coupled receptor for light signals.
The visual pigment present in photoreceptor cells is a prototypical G-protein-coupled receptor (GPCR) that receives a light signal from the outer environment using a light-absorbing chromophore, 11-cis-retinal. Through cis-trans isomerization of the chromophore, light energy is transduced into chemical free energy, which is in turn utilized for conformational changes in the protein to activate the retinal G-protein. In combination with site-directed mutagenesis, various spectroscopic and biochemical studies identified functional residues responsible for chromophore binding, color regulation, intramolecular signal transduction and G-protein coupling. Extensive studies reveal that these residues are localized into specific domains of visual pigments, suggesting a highly manipulated molecular architecture in visual pigments. In addition to the recent findings on dysfunctional mutations in patients with retinitis pigmentosa or congenital night blindness, the mechanism of intramolecular signal transduction in visual pigments and their evolutionary relationship are discussed.
Management of recurrent pilocytic astrocytoma with leptomeningeal dissemination in childhood.
Two cases of recurrent pilocytic astrocytoma with leptomeningeal dissemination (LMD) are described. A 6-year-old boy presented with a cerebellar tumor, which was subtotally removed. Tumor recurrence with LMD occurred 4 years later. Reoperation for tumor removal followed by craniospinal irradiation stabilized the LMD over 5 years. A 4-year-old girl presented with a chiasmatic-hypothalamic tumor. Partial removal of the tumor was followed by radiation therapy. Tumor regrowth with LMD occurred 4 years later and was managed by reoperation, chemotherapy and radiotherapy. Tumor recurrence with LMD can be stabilized by multimodal treatment without tumor progression.
Staging and treatment for patients with pancreatic cancer. How small is an early pancreatic cancer?
To determine the tumor size that constitutes early pancreatic cancer, we reviewed and analyzed the English-language and Japanese literature (a total of 25 publications) on small pancreatic cancers less than 2 cm in diameter and/or stage 1 cancers. Reports on in situ carcinoma and intraductal carcinoma of the pancreas were also evaluated. The results were: (1) A total of 302 cases of small pancreatic cancer less than 2 cm in diameter reported at separate institutions were pooled from 15 reports. The rates for patients in stage I and those with no lymph node metastasis averaged 41.7% and 57.9%, respectively. The 5-year postoperative cumulative survival rate (5Y-PCR) was less than 50% in almost all these reports. Similar data were shown in the 7 collective reviews. (2) Another 33 cases of small pancreatic cancer of 1 cm or less in diameter were collected from three reports. The rates for stage I tumor and 5Y-PCR at one institution with two reports were 100% and 100% and the rates in the other report were 85% and 78%, respectively. (3) Twelve cases of in situ carcinoma and intraductal carcinoma of the pancreas were collected from four reports. All of the patients were stage I and were alive with no evidence of tumor recurrence for periods ranging from 6 to 78 months. Small pancreatic cancer less than 1 cm in diameter is better viewed as an early pancreatic cancer, and in situ carcinoma and intraductal carcinoma of the pancreas with minimal invasion to the pancreatic parenchyma may be defined as early pancreatic cancer, regardless of size.
Clinical application of hepatitis C virus core protein in early diagnosis of acute hepatitis C.
A fluorescence enzyme immunoassay (FEIA) for the quantitative measurement of hepatitis C virus (HCV) core protein has recently been developed. In this study, we studied the clinical usefulness of this measurement in patients with acute hepatitis C. Eighteen patients with post-transfusion acute hepatitis C were enrolled in the study; 5 patients showed resolution of hepatitis with disappearance of HCV viremia, while the remaining 13 patients did not. A second generation HCV antibody, HCV RNA, and HCV core protein were measured in serial serum samples taken within 1 month of the onset of acute hepatitis and 3, 6, 12, 24, and 36 months after onset. Within the first month after disease onset, the positivity rates of HCV RNA (100%; P = 0.0014) and HCV core protein (89%; P = 0.0300) were both significantly higher than that of HCV antibody (56%). Six months after disease onset, the positivity rate of HCV antibody had increased, to 100%, and the positivity rates of HCV RNA and HCV core protein began to decrease. HCV core protein levels did not differ between patients with resolved and unresolved disease in the first month after disease onset. These findings indicate that FEIA, a simple assay, for the measurement of HCV core protein was useful for the early diagnosis of acute hepatitis C.
The diagnostic problem associated with blunt traumatic azygous vein injury: delayed appearance of right haemothorax after blunt chest trauma.
Azygous vein injury (AVI) associated with blunt chest trauma is rare, but it can become a very serious problem if diagnosis and treatment are delayed. However, in 13 reported cases of AVI, including the present case, right hemothorax was not found on the initial chest X-ray film, even though its delayed appearance was confirmed in 3 out of 13 patients (23.1%). Thus, the diagnosis of AVI can be hampered because of delayed right hemothorax (DRH).
Clinical application of the Personal Dialysis Capacity (PDC) test: serial analysis of peritoneal function in CAPD patients.
BACKGROUND: Peritoneal damage has been reported since the beginning of CAPD therapy. METHODS: To clarify the change of peritoneal function in CAPD patients, we used the Personal Dialysis Capacity (PDC) test in 22 patients with 49 serial studies and 14 patients with single studies. The data were expressed at the condition of 2.5% (2.27 g/dl of glucose), four times at 2,000 ml/day. RESULTS: In the mass analysis, the urea generation rate, creatinine generation rate, PNA/PCR, and water removal via the peritoneum (PD) were kept at the same level for almost eight years, and then gradually decreased. Urine volume and residual renal creatinine clearance (CCr) became zero at six years. On the other hand, PD CCr increased gradually with the time course of CAPD, and therefore the total CCr remained at the level of 6.0 ml/min even after six years. Weekly urea KT/V decreased gradually from almost 2.800 to 2.000. The protein loss remained approximately 7.0 g/day for the initial five years, then became 6.0 g/day, except in five patients who showed levels above 10.0 g/day on the first test of PDC. Weekly urea KT/V was correlated with residual renal CCr (P < 0.005), and significantly correlated with total CCr (weekly urea KT/V = -0.2798 + 0.3720 x total CCr; r = 0.915, P < 0.001). In the serial analysis, when the first and the last tests were compared, the urea generation rate increased significantly (mean +/- SD, 2.800 +/- 3.204 vs. 3.882 +/- 3.382; P < 0.0001); however, water removal via PD (1364 +/- 887 vs. 813 +/- 609; P = 0.021), total ultrafiltration (1762 +/- 841 vs. 1124 +/- 843; P = 0.042), and weekly urea KT/V (2.285 +/- 0.486 vs. 2.112 +/- 0.512; P = 0.026) decreased significantly. The delta water removal via PD/ duration became negative (-10.03 +/- 6.59 ml/week) in all 7 patients after more than four years, however, it was positive (+14.40 +/- 7.84 ml/week) in 6 of 10 patients after less than one year. CONCLUSION: These results suggest that water removal via PD increases within one year, then decreases after four years. The PDC test is useful to evaluate the change of peritoneal function in mass and serial analyses.
Crescentic glomerulonephritis accompanied by myeloperoxidase-antineutrophil cytoplasmic antibodies in a patient having myelodysplastic syndrome with trisomy 7.
A 63-year-old woman developed rapidly progressive glomerulonephritis syndrome with serum myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA). A renal biopsy showed diffuse crescentic glomerulonephritis. Immunofluorescence and electron microscopic studies showed no significant deposits in the glomeruli. The morphological findings were consistent with pauci-immune type crescentic glomerulonephritis. In addition, the patient had erythropoietin-resistant anemia and subsequent pancytopenia. Bone marrow was normocellular without an excess of blasts. However, multinuclear erythroblasts, hypersegmented neutrophils, and megakaryocytes without platelet formation were observed. Chromosome analysis of the bone marrow showed 47,XX,+7. This is the first case of MPO-ANCA-related crescentic glomerulonephritis in a patient with myelodysplastic syndromes (MDS). A possible relationship between MPO-ANCA and MDS is discussed.
Glomerulopathy due to chronic infection of Propionibacterium acnes in a patient with Felty's syndrome.
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Human parathyroid hormone does not influence human erythropoiesis in vitro.
BACKGROUND: Although renal anaemia is associated with secondary hyperparathyroidism, the relationship of both conditions remains obscure. Previously it was reported that high levels of bovine parathyroid hormone (PTH) did not inhibit in vitro human erythropoiesis, but whether human PTH inhibits in vitro human erythropoiesis has not been determined. METHOD: To clarify the direct effects of human biologically active N-terminal (1-34) PTH and intact (1-84) PTH on human haematopoietic progenitor growth, we investigated colony assays of human erythropoiesis and granulomonopoiesis. RESULTS: Neither N-terminal PTH (300 ng/ml) nor intact PTH (5000 pg/ml) inhibited haematopoietic progenitor growth. CONCLUSION: Our findings confirm that human PTH does not directly inhibit human erythropoiesis.