Biomedical subjects
Publications and source records attributed to K Hori.
We report a neonate with angio-oedema following fetal hydrops caused by maternal parvovirus B19 infection. Levels of complement components, including total haemolytic complement activity and C1 inhibitor concentration, were within normal ranges in cord blood. Neonatal angio-oedema might be included in the clinical spectrum of parvovirus B19 infection in pregnancy.
Electrolyzed water accelerated the healing of full-thickness cutaneous wounds in rats, but only anode chamber water (acid pH or neutralized) was effective. Hypochlorous acid (HOCl), also produced by electrolysis, was ineffective, suggesting that these types of electrolyzed water enhance wound healing by a mechanism unrelated to the well-known antibacterial action of HOCl. One possibility is that reactive oxygen species, shown to be electron spin resonance spectra present in anode chamber water, might trigger early wound healing through fibroblast migration and proliferation.
BACKGROUND AND STUDY AIMS: Photodynamic therapy (PDT) has proved effective in the treatment of gastric cancer, but there is room for improvement. To achieve the technical goal of carrying out endoscopic PDT, endoscopists need to determine the precise area for laser irradiation at adequate dosages. This report describes the use of a shapememory alloy (SMA) loop snare as a useful tool in endoscopic PDT. PATIENTS AND METHODS: Eleven patients with biopsy-proved early gastric cancer were treated with endoscopic PDT after intravenous injection of Photofrin II (2 mg/kg b.w.). Five patients underwent PDT using the SMA loop snare, and six underwent PDT without the use of the device. Cancer lesions smaller than 2 cm in diameter were irradiated with an excimer-dye laser (4 mJ, 80 Hz, 630 nm) for 20 min. RESULTS: All five patients (100%) treated with PDT using the SMA loop snare, and four of the six patients (67%) treated with PDT without use of the SMA loop snare, showed complete remission. CONCLUSIONS: The SMA loop snare routinely forms a circle 2 cm in diameter, covering an area of 3.14 cm2, and makes it possible to mark and calculate the precise area of cancerous lesions for irradiation at appropriate dosages. The findings of this study suggest that the SMA loop snare is an effective tool for PDT in early gastric cancer.
BACKGROUND: Recent studies have shown that hepatocyte growth factor (HGF) has a mitogenic and motogenic activity for gastric mucosal cells. The aim of this study is to ascertain the clinical significance of the expression of HGF and its receptor (c-met) during the course of gastric ulcer healing. METHODS: Ten patients who underwent endoscopic mucosal resection (EMR) and developed acute gastric ulcer and 20 patients with peptic ulcer of the stomach were enrolled in this study. Tissue samples were serially obtained from both the edge of the ulcer and its neighboring mucosa 0, 2, and 8 weeks after EMR or diagnosis. Gene expression of HGF, c-met, c-myc, and proliferating cell nuclear antigen (PCNA) was semiquantitatively examined by reverse transcription polymerase chain reaction (RT-PCR) using beta-actin as an internal control. In addition, expression of HGF and c-met mRNA with regard to the presence or absence of Helicobacter pylori infection was studied. RESULTS: In patients after EMR HGF, c-met, c-myc, and PCNA mRNA in the ulcer lesion at 0 week was at the peak of its expression and then decreased with time (P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively). In patients who underwent EMR the intensity of HGF mRNA was correlated with that of c-met, c-myc, and PCNA mRNA (P < 0.0001, P = 0.0095, and P = 0.0009, respectively) and that of c-met mRNA was correlated with that of c-myc and PCNA mRNA (P = 0.012 and P < 0.0001, respectively). In patients with peptic ulcer, expression of HGF mRNA decreased with time (0 week versus 8 weeks, P < 0.05; 0 week versus 8 weeks, P < 0.01). c-Met expression was lower at 8 weeks than at 0 week (P < 0.05). The intensity of c-met mRNA was correlated with that of PCNA mRNA (P < 0.0001). H. pyiori-infected mucosa had a higher level of HGF mRNA than non-infected mucosa. CONCLUSION: The present study suggests that HGF is one of the growth factors acting together during healing of gastric ulcer.
To enhance chemotherapeutic efficacy against cancer, it is important to deliver anticancer drugs preferentially to cancer cells and to retain the drugs there for a prolonged time. The in vivo prolongation of the exposure time of anticancer drugs in tumors can be accomplished by decreasing tumor tissue blood flow (tBF) after anticancer drug administration. The present study demonstrated that temocapril hydrochloride, an angiotensin converting enzyme inhibitor, decreases tumor tBF markedly in LY80 tumor, a subline of Yoshida sarcoma in the rat, without affecting the blood flow in liver, kidney, bone marrow, and brain. In tumor areas with flow of above 20 ml/min/100 g, the tBF decreased by approximately 50% due to temocapril. In tumor areas with tBF of about 20 ml/min/100 g, it became less than 3 ml/min/100 g with temocapril and did not recover during the 2 h experiment. These findings were obtained not only in large tumors, but also in microfoci growing within a transparent chamber. Furthermore, even when temocapril was administered under the condition of increased tumor tBF by administering angiotensin II, tumor tBF decreased immediately. Using this technique, it should be possible to trap anticancer drugs selectively in tumor tissue for an extended period of time.
We examined the differentiation-inducing effects of extracts of 49 wild plants, 25 types of seaweed and 26 mushrooms in Akita on the human leukemia cell line HL60 and a B16 mouse melanoma-derived sub-clone with high differentiation capability (B16 2F2). Differentiation inducers of HL60 cells such as retinoic acid, showed no effects on the differentiation of B16 2F2 cells. Furthermore, chemical compounds known to be inducers of B16 cells, did not induce differentiation of HL60 cells. Screening tests showed that the differentiation of HL60 cells was induced by extracts of 28 wild plants, 10 types of seaweed and 2 mushrooms, and melanogenesis of B16 2F2 cells was increased by extracts of 21 wild plants, 8 types of seaweed and 7 mushrooms. All of the alcoholic extracts of plants belonging to the subfamily Cichorioideae of the family Compositae caused cell differentiation of the melanoma cell line. The extracts of Chinese dandelion root, also inhibited cell growth and induced melanogenesis of B16 2F2 cells. We isolated the active compound from ethanol extracts of the crude drug. Chemical and physical data for the active compound were identical with those for lupeol, a lupane-type triterpene.
Fungicidal activity of widely used imidazole antifungal drugs in topical applications is not so strong in spite of their fungistatic activities against dermatophytes and pathogenic yeasts. In order to improve fungicidal activity of imidazole antifungal agents, a series of novel imidazole derivatives having a hydrophobic substituent derived from isoprenoid were synthesized. The efficacy of these compounds was evaluated with respect to direct cell-membrane damaging activity, ergosterol biosynthesis inhibition, minimum growth-inhibitory concentration (MIC) and therapeutic effect for experimental dermatophytosis of guinea pigs. Among the newly synthesized compounds, the geranyl derivative named AFK-108 (2a) showed the highest in vivo fungicidal activity with both cell membrane damaging activity and ergosterol biosynthesis inhibition in vitro.
A case of adult Bochdalek hernia in a naturally healthy 49-year-old woman is described. She was seen at our hospital because of cough lasting for about one month. The chest X-ray film revealed a gastrointestinal gas image in the left thoracic cavity. In addition, the CT scan and upper gastrointestinal series showed prolapse of the stomach, small intestine and a part of transverse colon. Operation was performed through a mini-thoracotomy using a thoracoscope assistedly. No hernia sac was observed and the diaphragmatic defect was 6 x 5 cm in size. After the organs was restored, the defect was closed with continuous over-and-over suture and the diaphragm was enhanced by PROLEN MESH.
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BACKGROUND: Under systemic hypertension induced by angiotensin II (AII) infusion, an attenuated vasoconstrictive response to the infusion in tumours was observed and a marked increase in tumour blood flow was observed in comparison with that in normal tissues. The results show a parallel circuit that connects the vascular bed of the pre-existing tissue to that of the tumour. The phenomenon was absent when hypertension was provoked by other vasoconstrictive agents such as norepinephrine or endothelin-1. However, the biological basis for this attenuated vasoconstrictive response to angiotensin II observed in tumours has not been fully elucidated. METHODS: We assessed this response to characterise the angiotensin II receptor density and affinity in normal and tumour tissues. AH109A and LY80 tumour cell lines were transplanted to the skin in nude rats. Four weeks later, the rats were sacrificed. 125I-[Sar1, Ile8] angiotensin II was used to map its receptors in rat tissues using in vitro computerised autoradiography. Operated human gastric cancer tissues from a 49-year-old and a 66-year-old male patients were also investigated. RESULTS: The numbers of angiotensin II receptors were markedly reduced in tumour tissues without a change of affinity. The numbers in AII-R in tumours were shown to be mainly AT1 by the marked reduction in radioligand binding achieved by losartan but not by PD123177. The same results were observed in human gastric cancer. CONCLUSIONS: These results suggest that the decrease in angiotensin II receptors in tumours may explain the haemodynamic effect of angiotensin II-induced hypertension on tumour blood flow. This condition for drug delivery to tumour tissue may play a major role in enhancing the therapeutic effects of chemotherapy.
A 59-year-old woman with recurrent seizures and progressive dementia is reported. Her past history and familial history were unremarkable. She became short-tempered at 56 years old (Oct. 1991). She had the first seizure attack and was admitted to a hospital at March 4, 1993, with prolonged disturbance of consciousness and subsequent mental deterioration. Her brain CT showed multiple small calcifications in the subcortical white matter and pons. The laboratory data including blood count, serum chemistry, serological studies and CSF was normal. MRI and digital subtraction angiography of the cranial vessels were unremarkable. There was a decrease in accumulation in the right cerebral hemisphere on 123I IMP SPECT. Despite anti-convulsant therapy, she had recurrent seizures several times, with gradual worsening of her mental state. She had the latest seizure attack and was transferred to Matsusaka Chuo Hospital, on August 29, 1993. After the attack she had been in the apallic state, and died on Nov. 13, 1995. This case was discussed in a neurological CPC. The discussants suggested that the isolated angiitis of the central nervous system caused secondary seizures and cerebral infarctions. Post-mortem examination revealed the CNS findings of vasculitis at various stages, calcification or mineralization mainly in the subcortical white matter and pons, massive cerebral infarctions with massive exudate, fresh and old small bleedings and exudate around the inflamed or calcified vessels. The white matter degeneration resembled that of Binswanger leukoencephalopathy. The final pathological diagnosis was isolated angiitis of the central nervous system since there was no inflammatory changes or atherosclerotic change of the blood vessels in the extracranial organs.
Tumor tissue is composed of cancer cells (parenchyma) and tumor vessels (interstitium). Many investigators have pointed out that blood flow in tumors has a very inhomogenous distribution, and that this inhomogeneity in blood flow increases as tumors grew. This would be a certain cause of insufficient drug delivery to tumor tissues. Among the experimental evidence using Yoshida Sarcoma and Ascites Hepatomas, functional differences in microcirculation between tumor and normal tissues were found by Suzuki et al. (1977). Under hypertensive state induced by the continuous infusion of angiotensin II, tumor blood flow increased remarkably, while there was no change or decrease in blood flow in normal tissues such as the brain, bone marrow, liver and kidney. Moreover, the increase in blood flow in tumors was selective, as the mean blood pressure remained at the level of 150 mmHg. Increases were confirmed not only in many growing sites such as in the liver, muscle, subcutis, and even microfoci, but also in various kinds of xenografted human tumors and autochthonous tumors. Augmentation of the anti-tumor effects of angiotensin II-induced hypertension chemotherapy (IHC) for advanced gastric carcinoma was revealed in two randomized controlled trials (RCT-1 & 2) of collaborative study groups in Japan. The response rates were 42.9% vs 10.5% in RCT-1 and 31.3% vs 6.7% in RCT-2. The frequencies of toxicities were not statistically different. In the results of phase II studies from 1978 to 1994 (OPN-1) and 1995 to 1999 (OPN-2) for advanced gastric carcinoma (GC), the response rates were 37.9% and 35.7%. Down staging in which the conclusive stage score was lower than the score of the clinical stage, was observed in 8 out of 94 cases (19%) with primary lesions in total and in 30 patients (63%) receiving reduction surgery after IHC, since 1978. It is very important for exact evaluation after chemotherapy to understand or estimate the pathohistological changes in the tumor and its degenerated or repaired tissues, which present various clinical images. In the present study, the actual administered dose intensity of adriamycin (aDIadm) was 5.9 +/- 2.4 mg/sqm/w, and the ratio of aDIadm to the proposed DIadm of reported FAM/FAP schedules was 0.78 +/- 0.32. IHC with smaller DI could lead to a reduction in the accumulation of toxicities of anti-cancer drugs in the host. In conclusion, IHC might be applied to all kinds of tumors to enhance the chemotherapeutic effects through selective increase of drug delivery to tumors.
PURPOSE: To examine the retina of basigin (Bsg) knockout mice by electrophysiological and histologic methods and thereby to determine the possible function of Bsg in phototransduction and retinal development. METHODS: Scotopic and photopic electroretinograms (ERGs) were recorded from 11 wild-type, 12 heterozygous, and 8 homozygous Bsg gene knockout mice of different ages. The retinas were also examined by histologic and immunolabeling methods. RESULTS: Bsg knockout mice of 5 to 41 weeks of age showed a decrease in the amplitude of all components of both the photopic and scotopic ERGs. In contrast, the fundus and the fluorescein fundus angiography and morphology of the retina at the light microscopic level appeared to be normal until 8 weeks of age in Bsg knockout mice. Thereafter, the length of outer segment and outer nuclear layers decreased with increasing age. Immunohistochemical analysis localized Bsg protein in a variety of cells in the retina, especially in the pigment epithelium, the upper outer plexiform layer and the inner segments of photoreceptor cells. CONCLUSIONS: The results demonstrated that both rod and cone function were severely affected from an early age by the targeted disruption of the Bsg gene. In spite of abnormal ERGs, the photoreceptor cells maintained normal morphology up to 8 weeks. Thereafter, the photoreceptor cells degenerated gradually and were almost ablated by 41 weeks.
To clone the genes encoding lysis protein from a Chlorella virus, water samples were collected from 13 aquatic environments located in the Kanto area of Japan. Eight water samples contained plaque-forming viruses on Chlorella sp. NC64A, but no virus was detected in the other five samples. A novel Chlorella virus, CVN1, was isolated from the Inba-numa marsh sample. CVN1 genomic DNA was partially digested and shotgun cloned into pUC118 to identify the genomic region responsible for the lytic phenotype on Chlorella sp. NC64A. A DNA fragment which encoded two ORFs, ORF1 and ORF2, was obtained by antialgal assay. The ORF2 gene product, CL2, consisted of 333 amino acids showing antialgal activity not only on the original host of Chlorella sp. NC64A, but also on the heterogeneous hosts of Chlorella vulgaris C-27 and C. vulgaris C-207. CL2 showed a weak homology (19.8% amino acid identity) to mannuronate lyase SP2 from Turbo cornutus. CL2 in Escherichia coli cells was purified using a nickel chelate column. Lyase activity of purified CL2 on alginic acid was observed in an enzyme assay. The specific activity of purified CL2 was 2.1x10(-2) U mg(-1), the optimum pH for enzymatic activity was 10.5, and Ca(2+) was required for enzyme activity. This is the first report of a Chlorella virus protein with lyase activity.
DNA polymerase beta (polbeta) is one of mammalian DNA polymerases and is known to be involved in a G:T/G:U mismatch repair. In order to investigate an involvement of this enzyme in a base excision repair, we searched a mutation of human polbeta in human gastric cancer and studied a function of the mutation. We observed cancer-specific missense mutations in 6 of 20 samples. All of these mutations were, however, heterozygous. We further analyzed the base excision repair activity of these mutants to know whether these mutants cause an error of mismatch repair. One of these mutants, which resulted in an amino acid substitution of Glu for Lys at codon 295, showed an inhibitory effect by in vitro base excision repair assay, suggesting that this mutation might play some role in carcinogenesis of the gastric mucosa.
The L8 protein complex consisting of L7/L12 and L10 in Escherichia coli ribosomes is assembled on the conserved region of 23 S rRNA termed the GTPase-associated domain. We replaced the L8 complex in E. coli 50 S subunits with the rat counterpart P protein complex consisting of P1, P2, and P0. The L8 complex was removed from the ribosome with 50% ethanol, 10 mM MgCl(2), 0.5 M NH(4)Cl, at 30 degrees C, and the rat P complex bound to the core particle. Binding of the P complex to the core was prevented by addition of RNA fragment covering the GTPase-associated domain of E. coli 23 S rRNA to which rat P complex bound strongly, suggesting a direct role of the RNA domain in this incorporation. The resultant hybrid ribosomes showed eukaryotic translocase elongation factor (EF)-2-dependent, but not prokaryotic EF-G-dependent, GTPase activity comparable with rat 80 S ribosomes. The EF-2-dependent activity was dependent upon the P complex binding and was inhibited by the antibiotic thiostrepton, a ligand for a portion of the GTPase-associated domain of prokaryotic ribosomes. This hybrid system clearly shows significance of binding of the P complex to the GTPase-associated RNA domain for interaction of EF-2 with the ribosome. The results also suggest that E. coli 23 S rRNA participates in the eukaryotic translocase-dependent GTPase activity in the hybrid system.
Intraphagosomal viability of wild type E. coli and lycopene (a powerful (1)O(2) quencher)-producing transformant E. coli was investigated using human polymorphonuclear leukocytes as the cells for phagocytosis of opsonized viable bacteria. While the viability of both wild type and the transformant E. coli decreased very rapidly in the phagosome, but the viability of the lycopene-transformant in phagosomes was about 1.7 times higher than that of wild type E. coli after 5 min of incubation. The results were very similar to the results obtained when E. coli strains were exposed to (1)O(2) generated in myeloperoxidase-H(2)O(2)-Br(-) system (a pure (1)O(2) generating system) at pH 4.5. The reason for HOCl, which may be generated in the myeloperoxidase-H(2)O(2)-Cl(-) system under physiological conditions but does not become involved in bactericidal action, could be explained by the near neutral pH in phagosomes at which bacterial killing by chlorination is extensively attenuated. This is the first report which proved (1)O(2)-mediated bacterial killing in neutrophil-bacterial phagosomal system.