[Multicenter study of combined modality treatment of esophageal cancer,with special reference to surgical treatment].
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Combined Modality Therapy↗
Biomedical subjects
H Ide
Publications and source records attributed to H Ide.
[Effective combined injection method of fluoropyrimidine and platinum--application for advanced esophageal cancer].
In patients with esophageal cancer, combined chemotherapy is usually given as a part of multimodality treatment and therefore undesirable toxicity should be diminished. Recently, the most standard protocol against esophageal cancer has been Cisplatin/5-FU combination, of which the response rate is 40-60%. We showed the development of chemotherapy and chemoradiotherapy using Cisplatin/5-FU for esophageal cancer. In recent Japanese protocols, continuous infusion of Cisplatin for several days or bolus injection of low-dose Cisplatin are supposed to be mainstream. The supra additive effect of leucovorin to Cisplatin +5-FU considering biochemical modulation is confirmed, and Cisplatin/5-FU/adriamycin protocol study is ongoing.
Antineoplastic Combined Chemotherapy Protocols↗
[Pediatric psychiatry during disasters--future planning].
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Adolescent Psychiatry↗
Cloning of the cDNA encoding a novel rat mast-cell proteinase, rMCP-3, and its expression in comparison with other rat mast-cell proteinases.
A cDNA encoding a novel rat mast-cell proteinase (MCP) named rMCP-3 was successfully cloned and sequenced from the peritoneal cells of Lewis rats infected with the intestinal nematode Nippostrongylus brasiliensis by using the combination of reverse transcription-PCR and rapid-amplification-of-cDNA-ends ('RACE') methods. The cDNA was 979 bp long and included a 741 bp open reading frame. When the deduced amino acid sequence was compared with those of other known mast-cell proteinases, rMCP-3 was considered to be translated as a preproenzyme with a 19-amino-acid signal peptide, a two-amino-acid activation peptide and a 226-amino-acid mature enzyme. The amino acid identity in the mature enzyme was 52.9% and 55.1% with rMCP-1 and rMCP-2 respectively. The rMCP-3 mRNA was not detected in the peritoneal cells of mast-cell-deficient Ws/Ws rats, though it was strongly detected in those of littermate +/+ and Lewis rats, indicating the mast-cell origin of rMCP-3 In addition to being present in peritoneal mast cells, the rMCP-3 mRNA was strongly detected in the skin, tongue, and RBL2H3 rat basophilic leukaemia cells and weakly in the jejunum of N. brasiliensis-infected rats by RNA blot analysis using a rMCP-3 gene-specific probe. By reverse transcription-PCR, the rMCP-3 mRNA was also detected in the lung. While the expression of rMCP-1 and rMCP-2 are clearly restricted in connective-tissue mast cells and mucosal mast cells respectively, rMCP-3 was widely expressed in both types of mast cells with a predominance in connective-tissue mast cells.
Amino Acid Sequence↗
Molecular cloning of mouse intestinal trefoil factor and its expression during goblet cell changes.
A cDNA encoding mouse intestinal trefoil factor (mITF) was successfully cloned and sequenced from the small intestine of C57BL/6 mouse by using the combination of reverse transcription-PCR and rapid amplification of cDNA ends methods. The gene was, similar to rat and human ITFs, mainly expressed in the small and large intestine. The mITF expression was up-regulated during the recovery phase after depletion of goblet cells in acetic acid-induced colitis. On the other hand, the expression in the jejunum was not altered, while goblet cell hyperplasia was induced by Nippostrongylus brasiliensis infection. These results suggest that the mITF expression did not simply correlate with the number of goblet cells. The mITF may play an important role in the maintenance and repair of mucosal function of the rectum. Additionally, the mITF in the jejunum may play a role in alteration of the physicochemical nature of goblet cell mucins, thereby affecting the establishment of intestinal helminths.
Acetates↗
Cloning of the cDNA encoding mast cell tryptase of Mongolian gerbil, Meriones unguiculatus, and its preferential expression in the intestinal mucosa.
By using the combination of reverse-transcription PCR and rapid amplification of cDNA ends methods, a cDNA encoding mast cell tryptase was successfully cloned from the small intestine of Mongolian gerbil, Meriones unguiculatus, infected with Nippostrongylus brasiliensis. The cDNA was 1219 bp long including 810 bp of an open reading frame. Based on the deduced amino acid sequences of known mast cell tryptases of other species, the gerbil mast cell tryptase (gMCT) was highly similar to mouse mast cell protease (mMCP)-7, and seems to be translated as a prepro-enzyme with 25 amino acids of signal and activation peptides and 245 amino acids of mature enzyme. The gMCT mRNA was preferentially transcribed in the intestinal mucosa and to a far lesser extent in the connective tissue such as skin and tongue. Moreover, kinetic study after infection revealed that the amount of gMCT mRNA in the small intestine correlated well with the degree of intestinal mastocytosis. Throughout the course of infection, enzyme-histochemically detectable tryptase activity was limited to mucosal mast cells. Since mucosal mast cells of other rodents, including mice and rats, do not express tryptases, this is the first report of rodent mast cell tryptase expressed in the intestinal mucosa.
Amino Acid Sequence↗
Influence of alpha-deoxyadenosine on the stability and structure of DNA. Thermodynamic and molecular mechanics studies.
The alpha anomer of deoxyadenosine (alpha) and an abasic site (tetrahydrofuran, F), which are DNA lesions produced by free radicals, were site-specifically incorporated in 9-mer duplexes d(TGAGXGTAC).d-(GTACNCTCA), where X = alpha or F and N = A, G, C, or T. Their influence on thermodynamic stability and structure of DNA was assessed by UV-melting measurements and molecular mechanics calculations. UV-melting studies revealed that a duplex containing an alpha T pair was as stable as the parental duplex containing an AT pair at the same site. Furthermore, the stability of duplexes containing alpha varied depending on the base opposite this lesion, with the Tm decreasing in the following order: alpha T > alpha C approximately alpha A > alpha G. On the contrary, an abasic site introduced in the same site showed a significantly greater destabilizing effect than alpha, but variation of Tm with the bases opposite F was less evident. To delineate the molecular mechanism of thermodynamic effects of an alpha lesion, molecular mechanics calculations were performed for the same duplexes as used for UV-melting measurements. The results suggest that the structural perturbation introduced into DNA by an alpha N pair is alpha G > alpha A > alpha C > alpha T, showing a parallel correlation with the destabilizing effects of alpha N pairs. On the basis of these results, it is discussed how the perturbations introduced by these DNA lesions may influence the selection of nucleotides opposite the lesions by DNA polymerases and the interaction with DNA repair enzymes such as Escherichia coli endonuclease IV and exonuclease III.
Base Sequence↗
On the mechanism of preferential incorporation of dAMP at abasic sites in translesional DNA synthesis. Role of proofreading activity of DNA polymerase and thermodynamic characterization of model template-primers containing an abasic site.
DNA polymerase preferentially incorporate dAMP opposite abasic sites (A-rule). The mechanism of the A-rule can be studied by analyzing three dissected stages of the reaction including (i) initial nucleotide insertion, (ii) proofreading excision of the inserted nucleotide and (iii) extension of the nascent primer terminus. To assess the role of the stage (ii) in the A-rule, kinetic parameters of the proofreading excision of primer terminus nucleotides opposite abasic sites were determined using E.coli DNA polymerase I Klenow fragment. The relative efficiency of the excision (Vmax/Km) revealed that removal of A was the least favored of the four nucleotides, but the differences in the efficiencies between excision of A and the other nucleotides was less than 2-fold. In addition, in an attempt to reconcile kinetic data associated with the stage (i) or (ii), the differences in free energy changes (delta delta G degrees) for the formation of model template-primer termini containing XN pairs (X = abasic site, N = A, G, C or T) were determined by temperature dependent UV-melting measurements. The order of delta delta G degrees was XG > XA = XC > or = XT, with delta delta G degrees being 0.5 kcal/mol for the most stable XG and the least stable XT. Based on these data, the role of the stage (ii) and energetic aspects of the A-rule are discussed.
Base Sequence↗
MRC-5 cells induce the AER prior to the duplicated pattern formation in chick limb bud.
We have previously shown that MRC-5 cells induce the duplication of the chick limb bud following the implantation into the anterior limb bud only during pre-limb-bud stages. We now report the process of duplicated pattern formation caused by MRC-5 cells. The duplicated patterns are also formed following the implantation into the center of the limb bud and an excess apical ectodermal ridge (AER) with Msx2 expression is induced prior to these duplicated pattern formulations. Only after the implantation into the anterior leg bud, the shh gene is expressed additionally in the anterior leg bud and the mirror-symmetric duplication along the anteroposterior (A-P) axis is formed. The map of the polarizing activity in stage 21 embryo suggests that the high polarizing activity of the normal flank region is responsible for the changes in the A-P polarity when MRC-5 cells are grafted into the anterior leg bud. These results indicate that MRC-5 cells induce the AER and that the excess AER produces the duplicated cartilage pattern of the limb bud.
Animals↗
Expression of p53 protein related to human papillomavirus and DNA ploidy in superficial esophageal carcinoma.
We examined the p53 protein and human papilloma virus (HPV) by immunohistochemistry and DNA ploidy by cytofluorometry in paraffin-embedded esophageal carcinoma tissue specimens. Sixty-one patients with superficial esophageal carcinoma were operated on between 1983 and 1991 without any prior treatment. Immunostaining of the anti-p53 protein antibody (CM1) was positive in 32 carcinomas (52%). Patients with p53-positive tumors had a poorer outcome than those with p53-negative tumors (P < 0.05). In addition, patients with p53-positive tumors did not have any characteristic site of relapse. Only 5 of the 61 patients (8.2%) had HPV-positive tumors. One of these 5 carcinomas expressed both p53 protein and HPV. Three patients with HPV-positive tumors which had invaded the submucosal layer died of relapse. A determination of DNA ploidy revealed 30 patients with aneuploid tumors, 13 with polyploid tumors and 18 with diploid tumors. The outcome of the patients with aneuploid tumors was worse than that of the patients with diploid tumor (P < 0.05). p53 protein expression was not associated with DNA ploidy; however, the 16 patients who had both p53-positive and aneuploid tumors had a worse prognosis than patients with p53-negative and aneuploid tumors (P < 0.01). These findings suggest that p53 protein expression in conjunction with DNA ploidy may be a useful indicator in evaluating the prognosis of patients with superficial esophageal carcinoma.
Adult↗
Effect of mannitol on focal cerebral ischemia evaluated by somatosensory-evoked potentials and magnetic resonance imaging.
BACKGROUND: Mannitol has been used in routine neurosurgical practice for the control of increased intracranial pressure. The effect of mannitol on focal cerebral ischemia was evaluated by somatosensory-evoked potentials (SEP) and magnetic resonance imaging (MRI). METHODS: The left middle cerebral artery (MCA) was exposed via the superomedial transorbital approach and occluded proximal to the origin of the perforating arteries. Ten cats received mannitol (0.5 g/kg IV) immediately, 6, 12, and 18 hours after MCA occlusion. The other 10 cats received saline solution and served as control. The animals were initially prepared to measure SEP before and 15, 30, and 60 minutes after MCA occlusion. Following SEP measurement, all cats were prepared for MRI. Sequential MRI of both intravoxel incoherent motion (IVIM) and T2-weighted spin echo techniques were obtained at 2, 4, 6, and 24 hours after MCA occlusion. The animals were sacrificed after the last MRIs for histologic study. RESULTS: The SEP amplitude decreased to about 10% at 15 minutes after MCA occlusion and then gradually recovered to 38% at 60 minutes in the mannitol group, and 21% in the control group. In MRI study, IVIM imaging demonstrated ischemic cerebral injury as a sharply demarcated area at 2 hours after MCA occlusion, while T-2 weighted imaging failed to show clear evidence of injury until 2-6 hours. High-signal intensity areas on both IVIM and T2-weighted images were smaller in the mannitol group than those in the control group. Histologic study demonstrated that infarction size was 36.9% +/- 7.7% of the left hemisphere in the mannitol group and 57.3% +/- 5.3% in the control group (p < 0.05). CONCLUSIONS: Mannitol is effective for acute cerebral ischemia, and SEP and MRI are useful for monitoring it.
Animals↗
cDNA sequencing and expression of rat mast cell tryptase.
A cDNA encoding rat mast cell tryptase (rMCT) was successfully cloned, and sequenced, from peritoneal cells of Lewis rats infected with Nippostrongylus brasiliensis by the reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends methods. The cDNA was 1,097 base-pairs long, and included 822 base-pairs of an open reading frame. As judged from the deduced amino acid sequence, rMCT is highly homologous to mouse mast cell protease-6, and is considered to be translated as a prepro-enzyme with a 19-amino acid signal peptide, a 10-amino acid activation peptide, and a 245-amino acid mature enzyme. The rMCT mRNA was not detected in peritoneal cells of mast cell-deficient Ws/Ws rats, though it was strongly detected in ones of littermate +/+ and Lewis rats. In addition to in peritoneal mast cells, the rMCT mRNA was detected in the tongue. However, mRNA signals were not detected in the small intestine regardless of N. brasiliensis infection. Nor were mRNA signals detected in RBL2H3 rat basophilic leukemia cells. In the lung, the rMCT mRNA was strongly detected after infection with N. brasiliensis, though it was only faintly detected before infection. These results suggest that the rMCT is basically specific for connective tissue mast cells, but not for mucosal mast cells and that it is up-regulated in the lung during the inflammatory process of a parasitic infection.
Amino Acid Sequence↗
[Clinico-pathological study of preoperative chemotherapy of esophageal cancer by combined use of three drugs--cisplatin, 5-FU and leucovorin].
We compared the clinical and pathological effects of preoperative combination chemotherapy using CDDP, 5-FU, and response rate for the primary lesion, an 81.8% response rate for intramural metastasis, 100.0% for intraepitherial spread, and a low response rate of 40.7% for lymph node metastasis. Pathological examination showed a 55.2% response rate for the primary lesion. There were seven cases in which the clinical assessment indicated that treatment was effective and pathological examination showed that it was ineffective, and three cases in which pathological examination showed a better response than clinical assessment. Cases showing a better clinical response included in which necrotic cancer lesion had disappeared due to absorption by the time of pathological examination, those with tumor regrowth after preoperative evaluation, those evaluated as showing a poor response due to residual cancer at the margin. Cases showing a better pathological response included those having remaining necrotic tissues and those having myoma beneath tumor. For intramural metastatic lesions, the pathological response rate was 42.9%, being lower than the clinical response rate. Metastasis to 209 lymph nodes showed a 23.0% response rate, with the abdominal nodes showing a poor response in comparison with those of the cervix and mediastinum. In 26 patients receiving preoperative radiotherapy, there was a significantly higher frequency of such changes as fibrous scar tissue, foreign body giant cells, vacuolation of tumor cells, and hyaloid degeneration of the lesion in comparison with the group receiving chemotherapy. Another difference was that the radiotherapy group showed a higher response of tumors with venous and lymphatic involvement.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[A case of agranulocytosis which occurred several hours after the readministration of D-penicillamine accompanied by shivering-chillness].
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Agranulocytosis↗
Structure and stability of DNA containing alpha-deoxyadenosine.
The alpha-anomer of 2'-deoxyadenosine (alpha) is a major adenine lesion produced by hydroxyl radicals. This lesion was specifically incorporated in duplexes d(TGAGXGTAC).d(GTACNCTCA), where X = alpha and N = A, G, C, or T. The thermodynamic and structural perturbations introduced into DNA by alpha were assessed by UV-melting measurements and molecular mechanics calculations.
DNA↗
Sequencing of cDNAs encoding alpha 1-microglobulin/bikunin of Mongolian gerbil and Syrian golden hamster in comparison with man and other species.
Complementary DNAs (cDNAs) encoding alpha 1-microglobulin (alpha 1mG)/bikunin, also known as inter-alpha-inhibitor (I alpha I) light chain, were cloned from liver extracts of the Mongolian gerbil, Meriones unguiculatus, and the Syrian golden hamster, Mesocricetus auratus, by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends methods. From the deduced amino-acid sequences of alpha 1mG/bikunin of gerbil and hamster, the basic molecular structure of the proteins seemed to be well-conserved. However, near the proposed sequence of proteinase inhibitory sites of two Kunitz domains in the bikunin part, variable regions composed of three amino acids each were observed between species, including rodents. Since the second half of bikunin is genetically identical with the mast cell proteinase inhibitor, trypstatin, the bikunin of each animal may have distinct inhibitory activity against mast cell proteinases.
Alpha-Globulins↗
Radiotherapy for superficial esophageal cancer.
PURPOSE: The results of definitive radiotherapy for superficial esophageal cancer is presented. METHODS AND MATERIALS: Twenty-one patients with superficial squamous cell carcinoma of the esophagus were treated by definitive radiotherapy with megavoltage x-rays in Tokyo Women's Medical College from 1975 to December 1990. Eight patients refused surgery and 13 patients were considered to be unsuitable for surgery due to advanced age or morbid conditions such as severe pulmonary dysfunction, myocardial infarction, liver cirrhosis, and other cancer. Radiotherapy was performed using 1.8-2.2 Gy fraction dose, 5 times a week and with a total dose of 50-76 Gy/5-7 weeks (median; 70 Gy). Three patients received intraluminal radiotherapy in addition. Combined chemotherapy was performed in four cases, and three cases received it before radiotherapy and one case after radiotherapy. RESULTS: Overall survival rate was 40.8%, and the cause-specific 5-year survival rate was 61.7%. The 5-year survival rate of the group with morbid conditions was 17.5%, but that of the group without morbid conditions was 60.6%. Seven patients developed recurrence (primary site: 3, lymph nodes: 3, lung: 1) and one patient revealed multicentric cancer of the hypopharynx with wide submucosal spread of the esophagus at 28 months after radiotherapy. No patient developed severe side effect due to radiotherapy. CONCLUSION: Definitive radiotherapy with or without chemotherapy can be applied as an alternative therapy to surgery for superficial esophageal cancer, even for the operable patients under good general condition.
Aged↗
Interaction of alpha-deoxyadenosine in template DNA with DNA polymerase. A novel mutational spectrum induced by alpha-deoxyadenosine.
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Base Sequence↗