[A case of IGF-II producing rectal cancer with recurrent hypoglycemia].
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Biomedical subjects
Publications and source records attributed to T Yano.
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Intratracheal instillation of bleomycin produces pulmonary fibrosis in rats. Alveolar type II cell proliferation is thought to minimize the fibrotic response after lung injury. Because keratinocyte growth factor (KGF) stimulates type II cell proliferation in the rat, we designed experiments to evaluate whether intratracheal KGF before or after intratracheal bleomycin would prevent pulmonary fibrosis. Intratracheal bleomycin without KGF resulted in moderate to severe lung injury and subsequent fibrosis. Conversely, intratracheal KGF pretreatment at 48 or 72 hr before bleomycin resulted in minimal to no visible lung injury. Rats pretreated with phosphate buffered saline before bleomycin had significantly more neutrophils and protein in bronchoalveolar lavage fluid at 4 and 6 days and higher hydroxyproline levels after bleomycin as compared to KGF-pretreated rats. Pretreatment with KGF at 48 hr protected against bleomycin-induced alterations in pulmonary physiology and increased surfactant protein C-positive (SP-C)-positive cells and SP-A, SP-B, SP-C, and SP-D mRNA levels after bleomycin instillation when compared to saline pretreated rats on day 1 or day 7. KGF posttreatment protocols did not prevent bleomycin lung injury and fibrosis. We conclude that KGF pretreatment attenuates bleomycin lung injury and increases type II cell proliferation and surfactant protein gene expression after bleomycin instillation in the rat.
A case of brain stem glioma, presenting with impairment of contralateral pain-temperature sense of ascending nature, is reported. A 38-year-old woman with documented neurofibromatosis type 1 (NF-1) was admitted to our hospital for treatment, complaining of diminished pain-temperature sense in the left lower extremity. On admission, the symptom was first evaluated to be due to cervical myelopathy although motor involvement was absent. An MRI, myelography and CT-myelography of the cervical spine were done, demonstrating no abnormality. Shortly after the admission the sensory impairment progressed to the upper chest level and then to the upper extremity on the left. Because of her documented NF-1 a brain CT was checked, revealing a small mass with ring enhancement in the dorsal midbrain on the right. On MRI, the tumor location was at the right dorsolateral tectal region of superficial situation. Under the diagnosis of midbrain glioma the tumor was partially removed by the occipital transtentorial approach. At operation, the tumor has grown intraaxially, having pinkish-gray color and central necrosis. Histologically the tumor was diagnosed as glioblastoma multiforme. Postoperatively she presented a definite improvement of the sensory impairment in the reverse order, that is from upper extremity and then to the lower extremity. Progression and post-treatment improvement of the impaired pain-temperature sense in this case suggested that the topography and lamination of the lateral spinothalamic tract might be present even in the dorsal midbrain, namely the posterior-superficial layer to be sacral segment and the anterior-deep layer to be cervical one.
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UNLABELLED: We compared the acetazolamide challenge test using 99mTc-ECD SPECT and 123I-IMP SPECT images in patients with chronic occlusive cerebrovascular disease. We also evaluated the usefulness of linearization correction for acetazolamide challenge test of 99mTc-ECD SPECT. METHODS: Twenty patients with unilateral chronic occlusive cerebrovascular disease (10 patients had middle cerebral arterial lesion and 10 had internal carotid lesion) were included in the study. Split-dose (a dose fractioning was 1:2), and sequential SPECT technique was used for 99mTc-ECD SPECT studies while only acetazolamide challenge test studies for 123I-IMP SPECT were performed. Permeability surface area product model (PS model) and back-diffusion model (Lassen's correction) were used for linearization correction of acetazolamide challenge with 99mTc-ECD SPECT. RESULTS: Six of 16 patients with reduced vasodilatory capacity in 123I-IMP SPECT were underestimated by 99mTc-ECD SPECT acetazolamide challenge test. Relative ECD uptake normalized by cerebellar uptake compared with IMP uptake showed a nonlinear relationship, indicating relatively less uptake in high flow range. The underestimations of limited vasodilatory capacity observed in 99mTc-ECD SPECT without linearization correction was modified by linearization algorithm. However, the effect of correction based on PS model was superior than that of Lassen's correction. The corrected 99mTc-ECD uptake ratio, based on PS model, and IMP uptake ratio demonstrated a better linear relationship than that of Lassen's correction. CONCLUSION: Technetium-99m ECD SPECT corrected based on the PS model is a better method of linearization for evaluating cerebrovascular reserve using acetazolamide challenge.
A single-institution phase II study indicated that combination chemotherapy using UFT (tegafur and uracil) plus cisplatin (Platinol) in patients with non-small-cell lung cancer was active with less host toxicity than other cisplatin-based therapies. To confirm these observations, the Japan JFT Lung Cancer Study Group conducted a multi-institutional phase II trial. The number of patients planned for this trial is 110. Eligibility includes previously untreated stage IIIB or IV non-small-cell lung cancer and a good performance status. UFT 400 mg/m2 in two divided doses is administered orally on days 1 through 14, and cisplatin 80 mg/m2 is injected IV on day 8. This treatment is repeated every 3 or 4 weeks. Between April 1995 and May 1996, 67 patients were enrolled, and all 67 were considered eligible for an interim analysis performed in October 1996. Among 63 patients evaluable for response, there was an overall response rate of 30% (95% confidence interval, 19% to 41%), with one complete response and 18 partial responses. With a median follow-up duration of 44 weeks, the median survival time was 32 weeks and the 1-year survival rate was 25%. Grade 3 leukopenia occurred in only 1 of 67 patients (1.5%), and there was no thrombocytopenia of grade 3 or greater. Vomiting, the most common nonhematologic toxicity observed, reached grade 3 or 4 in only 6 patients (9%). This interim analysis seems to support the observations of the previous single-institution phase II trial.
To clarify the clinical features of severe community-acquired pneumonia, we retrospectively studied 121 patients treated at our hospital. We divided the patients into three groups, based on the severity, of their disease. Patients were put in the "mild" group (n = 56) if they recovered after treatment with antimicrobial agents only, they were put in the "moderate" group (n = 34) if the required oxygen therapy and recovered, and they were put in the "severe" group (n = 31) if they required mechanical ventilation. Age and underlying disease were recorded, as well as signs, symptoms, and laboratory data obtained during the first 24 hours after admission. The data indicated that the following nine findings were associated with the severity of disease: age of at least 65 years, an underlying disease of (31) the respiratory or central nervous system, dyspnea, a pulse rate of at least 90 beats per minute, a respiratory rate of at least 25 breaths per minute, an albumin concentration no greater than 3.5 g/dl, a blood urea nitrogen level of at least 20 mg/dl, a PaO2 no greater than 60 mmHg or an SaO2 no greater than 90%, and a high score on a scale of the extent of roentgenographic evidence of pulmonary infiltrates. Patients in whom these are found be managed carefully.
We investigated the long-term survival and quality of life (QOL) of patients after abdominal aortic aneurysm (AAA) repair, in a retrospective study of 216 patients who underwent surgery at Nagoya University Hospital between 1980 and 1992. There were 189 elective operations and 27 emergency operations (22 ruptures and 5 impending ruptures). Complete follow-up information was available for 91% of the 200 patients who survived the surgery. Excluding operative deaths there was no significant difference in survival between patients who underwent elective or emergency surgery. The survival for both groups was close to that of age- and sex-matched cohorts. A significantly shorter survival time was found in patients over 75 than in those who were 74 or less (p<0.05). Preoperative heart disease or hypertension did not affect long-term survival rate. At the time of the last follow-up, 70% of the patients were quite healthy, and approximately 20% continued to work. We conclude that long-term survival after AAA repair is as good as that of the general population, and that survivors enjoy a good quality of life. However, there may have been preoperative selection for low risk patients in this study.
High-resolution CT (HRCT) scans of thirty-two patients (60 ears) with the clinical diagnosis of fenestral otosclerosis were evaluated retrospectively. HRCT was performed with 1-mm-thick targeted sections and 1-mm (36 ears) or 0.5-mm (10 ears) intervals in the semiaxial projection. Seven patients (14 ears) underwent helical scanning with a 1-mm slice thickness and 1-mm/sec table speed. Forty-five ears (75%) were found to have one or more otospongiotic or otosclerotic foci on HRCT. In most instances (30 ears), the otospongiotic foci were found in the region of the fissula ante fenestram. No significant correlations between CT findings and air conduction threshold were observed. We found a significant relationship between lesions of the labrinthine capsule and sensorineural hearing loss. We conclude that HRCT is a valuable modality for diagnosing otosclerosis, especially when otospongiotic focus is detected.
To investigate the relationship between the modulation of topoisomerase II activity and its phosphorylation state during the cell cycle, a monoclonal antibody against C-terminal peptide (residues 1335-1350) of topoisomerase IIalpha containing a consensus sequence of casein kinase II, TDDE and its phosphorylated threonine were prepared. In an enzyme-linked immunosorbent assay, the antibody, named PT1342, recognized the immunogenic phosphopeptide but not the non-phosphorylated form of the peptide. The PT1342 antibody reacted only with a 170-kDa protein from HeLa cells and recognized anti-topoisomerase IIalpha immunoprecipitants. Furthermore, the antibody did not react with the human topoisomerase IIalpha mutated at codon 1342 from threonine to alanine, showing that PT1342 was directed against the phosphorylated threonine 1342. To examine the level of phosphorylation of threonine 1342 of topoisomerase IIalpha through the cell cycle, HeLa cells were stained simultaneously for phosphorylated topoisomerase IIalpha and DNA and analyzed by flow cytometry. Cells in the G2-M phase contained about double the PT1341-reacted topoisomerase IIalpha than did cells in G1 or S phases. The antibody stained the nuclei in interphase and mitotic chromosomes and its periphery, as seen with anti-topoisomerase IIalpha antibody. Thus, threonine 1342 in topoisomerase IIalpha is phosphorylated throughout the cell cycle.
The ALL-1 gene is involved in human acute leukemia through chromosome translocations and fusion to partner genes, or through partial tandem duplications. ALL-1 is the human homologue of Drosophila trithorax which transregulates the homeotic genes of the Antennapedia and bithorax complexes controlling body segment identity. ALL-1 encodes a very large protein of 3968 amino acids which presumably interacts with many proteins. Here we applied yeast two hybrid screening to identify proteins interacting with the N-terminal segment of ALL-1. One protein obtained in this way was the product of the unr gene. This protein consists of multiple repeats homologous to the cold shock domain (CSD), a motif common to some bacterial and eukaryotic nucleic acids-binding proteins. The minimal region on unr required for the interaction with ALL-1 included two CSD and two intervening polypeptides. The interaction was confirmed by in vitro binding studies, and by coimmunoprecipitation from COS cells overexpressing the relevant segments of the two proteins. These results suggest that unr is involved in an interaction of ALL-1 with DNA or RNA.
To clarify the exact timing of K-ras gene mutational activation in lung tumorigenesis of mice, we applied a sensitive mutant allele specific amplification (MASA) method to pulmonary DNA from urethane-treated mice. The activation of K-ras gene with 61st codon AT mutation was detected in the lungs of mice at day 14 but not day 7 after urethane treatment by MASA. The mutation of MASA products was also checked by XbaI restriction fragment length polymorphism analysis and DNA sequencing. These data suggest that the mutation of K-ras gene in the lungs of mice treated with urethane occurred at the early stage of lung tumorigenesis.
BACKGROUND: Although lung carcinoma is the most common cause of tumor-induced hypercalcemia (TIH), the precise incidence of TIH remains obscure. Furthermore, the role of parathyroid hormone-related protein (PTHrP) has not been clearly elucidated. METHODS: This study included 690 consecutive patients who were newly diagnosed as having lung carcinoma between 1989 and 1994 (379 adenocarcinomas, 207 squamous cell carcinomas, 75 small cell carcinomas, and 29 large cell carcinomas). All patients were treated for lung carcinoma and were also periodically monitored for their serum level of calcium (Ca). Hypercalcemia was defined as a serum Ca concentration higher than 11 mg/dL. The serum levels of PTHrP (109-141) were measured by a C-terminal-region-specific radioimmunoassay. RESULTS: TIH was observed in 17 of 690 patients (2.5%). All 17 patients demonstrated an advanced stage of lung carcinoma (Stage III or IV), 10 squamous cell carcinomas, 5 adenocarcinomas, 1 small cell carcinoma, and 1 large cell carcinoma. In 15 patients, the serum level of C-PTHrP (109-141) was substantially high, ranging from 99 pmol/L to 890 pmol/L (normal range, 21-50.7 pmol/L). There was no significant difference in the serum PTHrP level between patients with or without bone metastasis. The reduction of tumor burden decreased both the serum level of PTHrP and that of Ca in parallel. The median survival time after diagnosis of TIH was only 27 days. CONCLUSIONS: TIH in lung carcinoma was most likely attributable to PTHrP, and its occurrence appears to be an ominous prognostic sign.
To elucidate the atherogenicity of lipoprotein(a) (Lp(a)), we examined its growth-stimulating activity in rat resident peritoneal macrophages. When macrophages were incubated with Lp(a), cell numbers were increased 1.5-fold as compared with control macrophages. Furthermore, apolipoprotein(a) (apo(a)), a plasminogen-like glycoprotein which is covalently attached to a low density lipoprotein-like particle (Lp(a)), also induced macrophage growth, while the growth-stimulating effect of Lp(a-) was negligible. These results suggest that apo(a) plays an active role in the mitogenic activity of Lp(a). Lp(a)-induced macrophage growth was inhibited by exogenously added active transforming growth factor-beta (TGF-beta) dose-dependently, and also by the addition of plasmin, which converts latent TGF-beta to an active form. Moreover, the amounts of endogenous active TGF-beta in the medium were significantly reduced by the incubation with Lp(a). It is evident from these results that Lp(a) induces macrophage growth by inhibiting TGF-beta activation. The capacity of Lp(a) to stimulate macrophage growth shown here could be novel atherogenic function of Lp(a).
The proton-translocating NADH-quinone oxidoreductase (NDH-1) of Paracoccus denitrificans is composed of at least 14 unlike subunits and contains one FMN and at least five EPR-detectable iron-sulfur clusters. The 14 subunits are designated NQO1 through NQO14. The expression and partial characterization of the NQO4, -5, and -6 subunits have been performed. The NQO4, -5, and -6 subunits were individually expressed in Escherichia coli. The NQO4 subunit was expressed in both the cytoplasmic phase and membrane fraction, the NQO5 subunit in the cytoplasmic phase only, and the NQO6 subunit in the membrane fraction only. The NQO4 and NQO5 subunits were purified from cytoplasmic phase. Neither subunit contains non-heme iron or acid-labile sulfide, suggesting that the NQO4 or NQO5 subunit is not an iron-sulfur subunit. The antibodies against the NQO4, -5, and -6 subunits cross-reacted with their counterpart subunits in bovine heart complex I. The NQO4, -5, and -6 subunits in membrane-bound P. denitrificans NDH-1 were extracted by treatment at alkaline pH ( > or = 10) or with chaotropes (NaBr, Nal, and urea), suggesting that these subunits are localized in the peripheral part (not in the membrane sector) of the enzyme complex similar to the NQO1, -2, and -3 subunits. In addition, the subunit stoichiometry of NQO1 through -6 of the membrane-bound P. denitrificans NDH-1 has been determined by radioimmunoassays. There is 1 mol each of the NQO1 through -6 subunits per mol of the P. denitrificans NDH-1.
We reported earlier that phosphorylation in vitro of keratin filaments reconstituted from rat type I keratin 18 and type II keratin 8 by cAPM-dependent protein kinase induces disassembly of the keratin filament structure. Keratin 8 rather than keratin 18 was the major target of the kinase. We have now identified the sites on rat keratin 8 for cAMP-dependent protein kinase. Sequential analysis of the purified phosphoropeptides, together with the known primary sequence, revealed that four major sites, Ser-12, Ser-23, Ser-36, and Ser-50, and three minor sites, Ser-8, Ser-33, Ser-42, are located in the amino-terminal head domain, while three minor sites, Ser-416, Ser-423 and Ser-425 locate in the carboxyl-terminal tail domain.
Enterotoxigenic Escherichia coli (STa+) strains were isolated from adult bovine with diarrhea. These strains did not express any known ETEC-specific adhesins. Although hemagglutination with rat and sheep erythrocytes was observed in the presence of D-mannose (MRHA), these strains also showed mannose-sensitive hemagglutination (MSHA) with guinea-pig erythrocytes. Electron microscopic studies revealed the presence of fimbria-like structures (provisionally called "F43ms") on bacterial cells grown at 37 degrees C but not on cells grown at 18 degrees C. However, it was observed by SDS-PAGE that the J-1 strain (F43ms+) produces a protein similar to F1 fimbriae, and this strain hybridized with a DNA probe for F1 fimbriae. Immunogold-labelling techniques indicated that a rabbit anti-serum is specific for F43ms fimbrial structures, but not for Type 1 fimbriae. The immunofluorescence test carried out with semipurified F43ms on bovine brush borders suggests that the fimbria-like structures are responsible for the adhesion to bovine epithelial cells.
The ALL-1 gene is involved in translocations with many partner genes in different types of the acute leukemias, but it is not clear whether it acts as an oncogene or whether the fusion proteins resulting from the translocations have dominant negative effects. To distinguish between these two possibilities, we analyzed the ability of wild-type AB2.1 embryonal stem (ES) cells and of single or double ALL-1 gene knockout cells derived from them to differentiate along hematopoietic lineages after withdrawal of leukemia inhibitory factor, using in vitro colony formation assays. All-1 double knockout ES cells formed a significantly greater number of colonies with faster kinetics than wild-type and ALL-1 single knockout ES cells. Parental ES cells formed lineage-restricted colonies, whereas single and double knockout ES cells developed, at high frequency, immature and/or "biphenotypic" colonies, mimicking the aberrant hematopoiesis typical of leukemic patients. These data are consistent with the possibility that loss of function of the ALL-1 gene is important in leukemogenesis.