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Biomedical subjects

H Kodama

Publications and source records attributed to H Kodama.

At least 343 records · Page 19Linked to original sources
PubMed1993

Intrapleural adaptive immunotherapy for breast cancer patients with cytologically-confirmed malignant pleural effusions: an analysis of 67 patients in Kyoto and Shiga Prefecture, Japan.

Sixty-seven breast cancer patients with cytologically-confirmed malignant pleural effusion, who required intrapleural treatment, were analyzed retrospectively. The patients received their first thoracentesis between 1980 and 1990. Among them, 29 patients received intrapleural administration of OK-432, a streptococcal preparation, followed by the transfer of autologous pleural effusion lymphocytes cultured with interleukin-2. Other intrapleural treatments consisted of OK-432 alone (12 patients), chemotherapeutic agents alone (n = 9), a combination of OK-432 and chemotherapy (n = 16), or others (n = 1). Twenty-six of the 29 patients given OK-432 plus cultured effusion lymphocytes responded, while only 15 of the 38 patients who received other treatments did (p < 0.01). Median survival time and 5-year survival rate of patients who received OK-432 and cultured lymphocytes was 12 months and 36%, while those of the patients who received other treatments was 3 months and 0%, a significant (p < 0.001) difference in survival. Multivariate analysis using Cox's proportional hazard model revealed that the treatment (adoptive immunotherapy) was the most significant (p < 0.005) factor to prolong the survival of the patients among several prognostic factors. Thus, OK-432 and adoptive immunotherapy is a promising therapy that should be further evaluated in a prospective study.

Adult↗
PubMed1993

Relationship between immunological parameters and survival of patients with liver metastases from breast cancer given immuno-chemotherapy.

We treated 33 patients with liver metastases from breast cancer by immuno-chemotherapy including adoptive cell transfer between 1987 and 1992. In this study, we examined the change of immunological parameters in the peripheral blood lymphocytes and interleukin-2 (IL-2)-cultured lymphocytes, in primary vs. metastatic breast cancer patients and before vs. after treatment. Moreover, we examined their correlation with therapeutic response and survival after treatment. The immunological parameters used were in vitro natural killer cell activity (% lysis of K562), in vitro autologous tumor-killing activity (% lysis against autologous freshly isolated tumor cells), and proliferation of lymphocytes stimulated with IL-2 and autologous sonicated tumor extract antigen in mixed culture (IL-2-enhanced MLTR). When compared with primary breast cancer patients, patients with liver metastases showed a significant decrease in % lysis of K562 and autologous tumor cells. After treatment, the stimulation index in IL-2-enhanced MLTR increased significantly from the pretreatment level and correlated with survival after treatment. Moreover, non-specific immunological parameters (performance status, lymphocyte count, and transferred cell count and proliferation rate of cultured lymphocytes) were significantly associated with response and prognosis.

Adult↗
PubMed1993

Identification of N-acetyl-alpha-aminoadipic acid in the urine of a patient with alpha-aminoadipic and alpha-ketoadipic aciduria.

A 3.5-year-old Japanese boy with a mild speech disturbance excreted a large amount of alpha-aminoadipic acid into the urine. The amino acid analysis using an amino acid analyser confirmed the presence of alpha-aminoadipic acid in both urine and plasma. We detected alpha-aminoadipic acid in the hydrolysate of the effluent and washwater fraction through cation exchange resin. This suggested the presence of acetylated derivatives and we identified N-acetyl-alpha-aminoadipic acid using liquid chromatography-atmospheric pressure ionization mass spectrometry (LC-API-MS). The concentrations of alpha-aminoadipic acid and N-acetyl-alpha-aminoadipic acid in the urine of a patient with alpha-aminoadipic aciduria were 376.9 nmol/mg creatinine and 18.1 nmol/mg creatinine, respectively. We also detected alpha-ketoadipic acid in the urine of this patient using LC-API-MS.

2-Aminoadipic Acid↗
PubMed1993

Recent developments in Menkes disease.

Recent studies on Menkes disease are reviewed, focusing especially on copper transport in the cells. A large amount of copper accumulated in the organelle-free cytoplasm, whereas mitochondria were in a state of copper deficiency, indicating that Menkes mutation probably affects copper transport from the cytosol to the organelles in the cells. Microscopic observation of the brain of the macular mouse showed that copper accumulates in the blood vessels. Observation of the brain tissue of the macular mouse after intraventricular administration of copper revealed that copper accumulates in the glia as well as the blood vessels. Copper accumulation was also observed in cultured astrocytes, a type of glial cell, indicating that the affected astrocytes accumulate blood-borne copper and release little of it in the patients with Menkes disease. Thus the effective treatment of Menkes disease could possibly be to release trapped copper from the blood vessels and glia into the neurons.

Animals↗
PubMed1993

Cellular interaction against autologous tumor cells between IL-2-cultured lymphocytes and fresh peripheral blood lymphocytes in patients with breast cancer given immuno-chemotherapy.

In patients with Stage II or III breast cancer and in patients with liver metastases from breast cancer, we examined cellular interaction in the cytotoxicity against autologous tumor cells by interleukin-2(IL-2)-cultured lymphocytes (CL) and fresh peripheral blood lymphocytes (FPBL) treated with immunochemotherapy including OK-432 and cyclophosphamide. In flow cytometric analysis, CD8+CD11b+ and CD16+ cells significantly decreased after immuno-chemotherapy in both groups of patients. A protocol study in Stage II or III breast cancer patients showed suppressive activity of FPBL on the cytotoxic activity of CL in 3/9 of the non-treatment group but no suppressive activity and enhancing activity in 3/7 in the immuno-chemotherapy group. Moreover, in 19 patients with liver metastases from breast cancer treated with immuno-chemotherapy including adoptive immunotherapy, FPBL in 6/19 showed enhancing activity, and in 8/19 suppressive activity in the lysis of autologous tumor cells. In assays in vitro using autologous and allogeneic tumor cells, FPBL showed a partial specificity in cellular interaction against autologous tumor cells. CD4-depleted FPBL inhibited cytotoxicity of CL, while CD8-depleted FPBL enhanced cytotoxicity of CL in patients with liver metastases. These results suggest that immuno-chemotherapy eliminates the suppressive population in FPBL and may induce tumor regression if combined with adoptive immunotherapy using CL.

Adjuvants, Immunologic↗
PubMed1993

Bone metastasis as a prognostic factor in breast cancer patients with liver metastasis given OK-432-combined adoptive immunotherapy via the hepatic artery.

The outcome in 31 patients with liver metastases from breast cancer given OK-432-combined adoptive immunotherapy via the hepatic artery was analyzed. Patients received intraarterial OK-432, a streptococcal preparation, followed by the transfer of autologous lymphocytes cultured with autologous tumor extract and interleukin-2 for 9-13 days. Liver lesions were evaluable in 11 of the 12 patients with bone metastasis (group A) and in 16 of the 19 patients without bone metastasis (group B). Complete response (CR) in the liver was attained in 8 patients in group A, but in only 1 in group B (p < 0.01). In group A, radiological features of all metastatic foci of bone improved after CR in the liver. Moreover, the median survival time (MST) of group A (20 months) was longer (p = 0.06) than that of group B patients with extra-hepatic metastasis (n = 12; MST = 6 months), while group B patients with liver metastasis alone (n = 7) showed a MST similar to that of group A. Thus, loco-regional immunotherapy via the hepatic artery was found to be useful in controlling both liver and bone metastasis from breast cancer. Moreover, in breast cancer patients with liver metastasis, bone metastasis appears to be a prognostic factor associated with good response to this immunotherapy.

Adult↗
PubMed1993

Sibling cases of a degenerative neurological disease associated with hypocupraemia and hypobetalipoproteinaemia.

We describe two siblings, a boy and his younger sister, with degenerative neurological disturbances, hypocupraemia and hypobetalipoproteinaemia. The neurological features in both cases were developmental delay, dysarthria, hyperkinetics with an attention deficit, dysdiadochokinesis, night blindness, myoclonic jerks and convulsions. Their serum cooper levels did not increase despite administration of copper sulphate both orally or intravenously. The copper contents of the cultured fibroblasts in the patients were 1.5-fold that of controls. Although neurological disorders associated with abnormal copper metabolism and inherited in an X-linked manner have been previously reported, this is the first report of a neurodegenerative disease concurrent with abnormal copper metabolism and hypobetalipoproteinaemia.

Adolescent↗
PubMed1993

Pentoxifylline-enhanced acrosome reaction correlates with fertilization in vitro.

To evaluate the possible effect of pentoxifylline on the acrosome reaction (AR) and its correlation with in-vitro fertilization (IVF), sperm samples obtained from 51 patients who underwent IVF treatment were studied. Acrosome reactions were evaluated as spontaneous, pentoxifylline-treated and calcium ionophore (A23187) induced, before and after treatment. The correlation of AR with fertilization in vitro in spermatozoa pre-treated with pentoxifylline was sought. In cases with failure or very low fertilization rate (< or = 10%) in their previous trials, spermatozoa after swim-up were treated before insemination. Spontaneous acrosome loss remained low even after treatment (mean +/- SD: 8.18 +/- 1.74%). Response to A23187 was enhanced significantly (P < 0.001) by pre-treatment with pentoxifylline in 33 control cases (group A) in which fertilization in vitro was previously successful without this treatment. Patients with at least two episodes of failed fertilization were divided into two groups. In 11 cases (group B), the IVF rate was improved significantly (P < 0.001) by the treatment. This was not observed in seven cases (group C) in which the treatment induced no increase in IVF rate. We achieved nine (27.3%) pregnancies in group A and five (45.4%) pregnancies in group B. This study demonstrated that pentoxifylline enhanced A23187 induced the acrosome reaction and this effect was correlated with improvement in IVF rate.

Acrosome↗
PubMed1993

[Morphological studies on liver in septic state by mice with E. coli injection into the abdominal cavity].

The purpose of this study is to elucidate morphological changes in septicemic mice induced by an injection of E. coli into the abdominal cavity and to discuss the relationship between the clinical findings and morphological ones. The liver of septicemic mice was morphologically demonstrated, a) Kupffer cells entrapped bacteria and erythrocytes, and large lysosomes were found in Kupffer cells, b) hepatocytes with low dense cytosol increased, and in the hepatocytes, many conglomerations of lysosome and cytolysome, and degeneration of rER, sER and mitochondria were identified, c) intercellular bile canaliculus became narrow. The conclusion is as follows: 1) the increase of the serum level of T. bili is caused by the increase of the phagocyte of erythrocytes by Kupffer cells and by the dysfunction of bile transformation and transportation in hepatocytes, 2) the increase of the serum level of GOT, GPT and LDH is caused by the degeneration of mitochondria in hepatocytes, 3) the decrease of the capacity to synthesize protein and lipid is due to the degeneration of cell organelles in hepatocytes.

Animals↗
PubMed1993

Cloning and sequencing of agaA, a unique agarase 0107 gene from a marine bacterium, Vibrio sp. strain JT0107.

An agarase gene (agaA) was cloned from genomic DNA of Vibrio sp. strain JT0107. An open reading frame of 2,985 nucleotides gave a primary translation product composed of the mature protein, agarase 0107 (975 amino acid residues, with a molecular weight of 105,271) and a signal peptide of 20 amino acid residues at the N terminus. Comparison of the deduced amino acid sequence of agarase 0107 with those of Streptomyces coelicolor and Pseudomonas atlantica suggests that these enzymes share two regions in common. The AgaA protein which was expressed in Escherichia coli had the agarase activity. Agarase 0107 hydrolyzes not only agarose but also neoagarotetraose [O-3,6-anhydro-alpha-L-galactopyranosyl (1-->3)-O-beta-D-galactopyranosyl(1-->4)-O-3,6-anhydro-alpha-L-galact opy ranosyl (1-->3)-D-galactose] to yield neoagarobiose [O-3,6-anhydro-alpha-L-galactopyranosyl(1-->3)-D-galactose]. This is a quite unique characteristic for a beta-agarase.

Amino Acid Sequence↗
PubMed1993

ADP-ribosylation of rainbow trout (Oncorhynchus mykiss) actin by botulinum C2 toxin.

Intracellular actin of rainbow trout macrophages was ADP-ribosylated by botulinum C2 toxin, which is composed of two nonlinked protein components, component I and trypsinized component II. The actin in the supernatants of various tissue homogenates of the trout was also directly ADP-ribosylated by component I of C2 toxin, indicating that fish actin other than those of land vertebrates is susceptible to enzymatic modification by component I of C2 toxin.

Actins↗
PubMed1993

Histochemical localization of copper in the intestine and kidney of macular mice: light and electron microscopic study.

Menkes' disease is an X-linked recessive disorder characterized by accumulation of copper in various organs and cells, such as the intestine, kidney, and cultured fibroblasts. Light and electron microscopic localization of Cu was investigated in the intestine and kidney of macular mice, an animal model of Menkes' disease, by a modified sulfide-silver method. Cu was accumulated in the cytoplasm of the absorptive epithelial cells, the vascular endothelium, and secretory granules of the Paneth cells. In kidney the distal tubule cells and glomeruli of both macular and control mice stained faintly, whereas the organelle-free cytoplasm in the proximal tubule cells of macular mice stained more intensely than those of controls. The nuclei, mitochondria, and lysosomes of the cells of macular mice hardly stained at all. These findings indicate that Cu is concentrated in the organelle-free cytoplasm of the affected cells of macular mice. This suggests that the Menkes' mutation affects Cu transport from the cytosol to the organelles in the cell.

Animals↗
PubMed1993

Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo.

The protooncogene c-kit encodes a receptor type tyrosine kinase and is allelic with the W locus of mice. SLF, the c-Kit ligand which is encoded by the Sl locus, has growth promoting activity for hemopoietic stem cells. Previous studies demonstrated that c-Kit is functionally required for the proliferation of hemopoietic progenitor cells at various differentiation stages in adult bone marrow. However, the absence of functional SLF and c-Kit in fetuses with mutant alleles of Sl and W loci produces only minor effects on the myeloid and early erythroid progenitor cells in the fetal liver, although the level of the late erythroid progenitor cells is significantly affected. We used an anti-c-Kit monoclonal antibody to investigate the expression and function of c-Kit in murine fetal hemopoietic progenitor cells. Flow-cytometric analysis showed that hemopoiesis in the yolk sac and fetal liver started from cells that express c-Kit. The c-Kit expression decreased upon maturation into erythrocytes in each organ. By fluorescence activated cell sorting, the c-Kit+ cell population was enriched with the hemopoietic progenitor cells clonable in vitro (CFU-E, BFU-E and GM-CFC). To elucidate whether c-Kit functions in these progenitor cells in vivo, we took advantage of the antagonistic anti-c-Kit monoclonal antibody, ACK2, which can block the function of c-Kit. Administration of ACK2 after 12.5 days of gestation rapidly eliminated BFU-E and GM-CFC as well as CFU-E from the fetal liver. However, the number of these progenitor cells in the yolk sac and fetal liver was less affected when the fetuses were given ACK2 before 12.5 days of gestation. Our results provide evidence that there are two waves of hemopoiesis in murine embryos relative to c-Kit dependency. The c-Kit has an essential role on the growth of hemopoietic progenitor cells in the fetal liver after 12.5 days of gestation, whereas the progenitor cells in the liver and yolk sac of the earlier embryo do not depend on c-Kit and its ligand SLF.

Animals↗
PubMed1993

The use of liquid chromatography-mass spectrometry for the identification and quantification of urinary iminodipeptides in prolidase deficiency.

It has been reported that the urine of patients with prolidase deficiency contains various iminodipeptides with a carboxyl-terminal proline (hydroxyproline). These iminodipeptides have hitherto been detected indirectly by acid hydrolysis or enzymatic digestion, followed by amino acid analysis. In the present study, it was shown that X-Pro could be distinguished from Pro-X when the iminodipeptides were analysed directly by liquid chromatography coupled with atmospheric pressure ionization mass spectrometry (LC/API-MS), with scanning of the protonated molecule ions ([M+H]+). The same procedure also successfully quantified urinary iminodipeptides from patients with prolidase deficiency. A quantitative investigation of two siblings with prolidase deficiency revealed that the patient with severe clinical symptoms excreted more iminodipeptides than the other who did not have serious symptoms. LC/API-MS also revealed iminodipeptides (Gly-Hyp and Pro-Hyp) in the urine of the mother of the patients and in normal volunteers. Patients excreted much more Pro-Hyp than normal volunteers, whereas no quantitative differences were found between the mother and controls. In patients, the excretion of large quantities of X-Pro is due to their very low prolidase activity towards this type of substrate. In the erythrocytes of patients, prolidase activity towards X-Hyp was extremely low; even in the mother and normal volunteers, it was remarkably low in comparison with the activity against X-Pro.

Amino Acid Sequence↗
PubMed1993

Fate of orally administered triethylenetetramine dihydrochloride: a therapeutic drug for Wilson's disease.

Triethylenetetramine dihydrochloride (TETA) is a therapeutic drug for Wilson's disease. We developed a simple fluorometric method for detection of TETA in biological fluids by using high-performance liquid chromatography (HPLC), and examined TETA concentrations in the serum and urine of two healthy adults who were given TETA orally. No TETA peak was detected in the serum. The amount of TETA in the urine of the two adults was only 1.6 and 1.7% of the dose administered. However, a large unidentified peak appeared in the urine after oral administration. This peak was not observed in a mixture of TETA and control urine or in urine before TETA administration. When the urine after TETA administration was analyzed after hydrolysis with HCl, the unidentified peak disappeared, while the TETA peak increased. These findings indicate that the substance which yielded the unidentified peak is a metabolite of TETA, suggesting that most of the TETA administered is metabolized and then excreted in the urine.

Adult↗
PubMed1993

[Role of surface tension lowering substances in the function of normal and diseased eustachian tubes of guinea pigs].

To examine the role of surface tension lowering substances (STLSs), we measured changes in passive opening pressure (OP) and closing pressure (CP) in eustachian tubes of guinea pigs before and after washing the tubes with various solutions (saline solution, artificial pulmonary surfactant, synthetic phospholipids, and detergent)). The percent decreases in OP and CP in tubes washed with artificial surfactant were significantly higher than those washed with saline solution. Those washed with synthetic phospholipids or detergent (Triton X-100) did not differ from those washed with saline solution. In guinea pigs with experimental otitis media produced by inoculation of formalin-killed Haemophilus influenzae into the middle ear cavity, the percent decreases in OP and CP in tubes washed with artificial pulmonary surfactant were significantly higher than in those washed with saline solution. Artificial pulmonary surfactant was injected into the middle ear cavity of the guinea pigs with otitis media. At 5 days after inoculation, the inflammatory changes of the middle ear were much milder in animals with intratemporal application of artificial pulmonary surfactant than in those with saline application. These results suggest the possible efficacy of treatment with artificial pulmonary surfactant for otitis media.

Animals↗
PubMed1993

[Effect of extended thymectomy in myasthenia gravis of pure ocular type].

The effect of extended thymectomy in myasthenia gravis of pure ocular type was investigated in 13 patients, who were divided into the surgical group of nine and the conservative group of four. In the surgical group, the onset was at 47 +/- 20 years old. The preoperative duration of symptoms was 4 +/- 6 years. The age at the time of operation was 51 +/- 16 years old. Three patients had thymomas, including one malignant thymoma. Acetylcholine receptor antibody titer was over normal range with 34.0 +/- 49.7 nmol/l. No postoperative crisis occurred. The palliation rate of the surgical group was more higher through the whole period than that of the conservative group, and increased with progress of the course. The remission occurred in the surgical group, but did not in the conservative group. It took 7 months to improve the symptom in the surgical group, while 18 months in the conservative group. We conclude extended thymectomy is reasonable for patients with myasthenia gravis of pure ocular type.

Adult↗