[A case of advanced hepatocellular carcinoma treated by repeated arterial infusion chemotherapy of 5-FU, LV, CDDP with an implanted reservoir].
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Biomedical subjects
Publications and source records attributed to H Taniguchi.
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A 19-year-old man presented with an acute febrile illness and progressive dyspnea. He had begun smoking two weeks before admission. A chest X-ray film revealed Kerley B lines and diffuse infiltration in both lungs. Analysis of bronchoalveolar lavage fluid showed 21% eosinophils. The patient had no history of hypersensitivity to drugs, nor was there any evidence of infectious disease. Acute eosinophilic pneumonia was diagnosed, and his condition improved without steroid treatment. A smoking challenge test was performed. After the test, the patient's body temperature rose to 38.0 degrees C, computed tomograms of the chest showed increased density, and elevated eosinophil levels were again detected in bronchoalveolar lavage fluid. These findings supported the view that beginning to smoke can be a cause of acute eosinophilic pneumonia.
A 49-year-old woman was diagnosed with local recurrence and cervical lymph node and bone metastases 55 months after surgery for breast cancer. She was treated with goserelin acetate and tamoxifen but the disease was assessed as progressive after 8 months. Five courses of CMF therapy were performed but lung, pleural and mediastinal lymph node metastases were detected. Then, five courses of CAF therapy were carried out, but a contralateral breast metastasis was detected and the patient complained of shortness of breath. The CAF therapy was assessed as PD. We attempted administration of doxifluridine (5'-DFUR) and mitomycin C (MMC) on an outpatient basis. After 6 months, no progressive disease was detected and she was relieved of her shortness of breath. The combination therapy was assessed as long NC. Combination therapy with 5'-DFUR and MMC is thus a useful treatment for adriamycin- and methotrexate-resistant breast cancer, especially in terms of quality of life.
Twenty-five cases with unresectable metastatic liver cancers were experienced in our hospital over the past five years who underwent weekly 24-hour continuous hepatic arterial infusion chemotherapy using 5-FU and CBDCA. The response rate was 20%, the median survival was 23 months, and the one/two year overall survival rates averaged 81.3/45.5%. In 77% of patients, this therapy prevented death from hepatic metastases. Moreover, since adverse effects were limited compared with bolus infusion, weekly 24-hour continuous hepatic arterial infusion chemotherapy was thought to be a favorable method.
We reported five cases of cerebral and/or cerebellar embolism after insertion of a heparin-coated catheter from the left thoracoacromial artery for multiple liver metastases. They were one patient with multiple liver metastases from the angiosarcoma of the scalp, and 4 others with gastrointestinal cancer liver metastases. The first case suffered a cerebeller embolism just after removal of a catheter that had been obstructed. In this case, it is possible that the thrombus quickly migrated into a cranial vessel from around the catheter. In the others with patent catheters, the cerebral embolisms occurred more than a month after insertion of the catheters. In the latter cases, it is thought that embolisms did not occur because of catheter insertion maneuver. However, a thrombus that grew around the catheter migrated into the left common carotid artery or the left vertebral artery. The anti-coagulation therapy should be considered for prophylactic treatment.
A 47-year-old woman was referred to our hospital because of cough and an abnormal shadow in the left lung field. The infiltrate reduced without therapy and another infiltrate appeared in the right lung field. Bronchiolitis obliterans organizing pneumonia was clinically suspected due to the absence of signs of eosinophilia in peripheral blood and bronchoalveolar lavage fluid (BALF). Open lung biopsy specimens disclosed alveolitis with mononuclear cell infiltration and organization within the air spaces of bronchioli and alveolar ducts. The observation of pronounced eosinophil infiltration in the alveolar spaces of some specimens yielded a diagnosis of eosinophilic pneumonia. After steroid therapy, the abnormal shadows disappeared. BALF lymphocyte surface marker analysis detected no decrease in the CD4/CD8 ratio; activated CD4 and CD8 lymphocytes were notably higher than the corresponding levels in peripheral blood. IL-5, IL-3, and GM-CSF values in BALF were not significantly elevated. This was a case of borderline eosinophilic pneumonia that was difficult to diagnose on the basis of clinical parameters alone.
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In mandibulectomy patients who have not undergone surgical reconstruction, the remaining mandibular segment is unstable and often deviated. Its movements have low reproducibility during mastication, deglutition and speech. The purpose of this study was to clarify three-dimensionally the differences in mandibular movements for each of these oral functions in mandibulectomy patients with and without mandibular continuity. Four mandibulectomy subjects (Group I) without mandibular continuity and three subjects (Group II) with mandibular continuity were selected. Their mandibular movements were recorded using a jaw movement tracking device with six degrees of freedom. Each movement was assessed graphically at the virtual incisor point and the rotational angles of the mandible in the frontal, sagittal and horizontal plane were analyzed. The findings were as follows; 1. In Group I, the border movements at the virtual incisor point exhibited an irregular and asymmetric envelope deviated to the resected side in the frontal plane, whereas Group II exhibited a smooth and symmetric envelope. 2. In Group I, the rotational angles in the frontal plane during border movements and mastication, in all planes during speech, and in the frontal and horizontal plane during deglutition were significantly larger than in Group II. A comparison among border and all functional movements in mandibulectomy patients revealed characteristic movements in the rotation of the mandible in the frontal plane. It is suggested that the rotational angle of the mandible is a useful parameter for assessment of mandibular movements in mandibulectomy patients.
Obturator prostheses have been extensively used in the functional rehabilitation of maxillectomy patients. The purpose of this study was to evaluate in vitro the vibration movements of three types of obturator prostheses. Three types of bulbs were used: the solid type, the buccal flange type, and the hollow type. Modal analysis was performed to identify the better form. The three types of obturator prostheses were excited by a shaker, and the frequency response functions were recorded on an FFT analyzer to identify their modal shapes. In addition, transient response simulations were carried out, and decay rates of the resultant transient response waves were compared to evaluate the energy absorption after the obturator prosthesis had experienced an impact. The results showed that the modal shapes were closely similar, while the amplitudes at the rests and clasps of the hollow type bulb were the smallest. In the transient response simulation, the decay rates of the hollow type were significantly the highest (p < 0.01). In this study, modal analysis demonstrated that the hollow type obturator prosthesis showed the steepest vibration decay slope, indicating that it might be the best among the three types of bulbs for use in clinical treatments.
HAP2 forms a capping structure, which binds very tightly to the distal end of flagellar filaments and still allows insertion of flagellin subunits below the cap by an unknown mechanism. Terminal regions of HAP2 from Salmonella typhimurium were found to be quickly degraded by various proteases, indicating that HAP2 also possesses disordered terminal regions like other axial proteins of bacterial flagellum. Removal of these portions by trypsin results in a fragment of 40 kDa (HP40), which lacks 42 NH2-terminal and 51 COOH-terminal residues. HAP2 in solution readily associates into a decameric structure without any significant population of intermediate oligomeric forms. The HP40 fragments, however, do not form decamers, while they can assemble into pentamers, as revealed by chemical cross-linking and analytical ultracentrifugation. Decameric HAP2 also dissociates into pentamers and smaller oligomers upon a heat induced conformational transition around 36 degreesC. While the highly mobile terminal regions are immobilized in decameric HAP2 complexes, they are still largely disordered in the pentameric state. These results demonstrate that the intersubunit interactions within the pentamers are mainly through the HP40 portions, whereas the terminal regions are responsible for association of pentamers into decameric complexes. Several observations indicate that HAP2 performs its capping function as a pentamer. We suggest that binding of the pentameric HAP2 cap to the filament is mediated by the highly flexible terminal regions. Indeed, HP40 fragments are unable to cap the end of filaments, while removal of about 30 residues from both terminal regions of HAP2 results in a highly reduced capping ability. A model is presented to explain the molecular mechanism of capping, in which conformational entropy in the disordered terminal regions moderates the otherwise too tight HAP2-filament interactions to allow insertion of flagellin subunits below the cap.
To assess the role of ORL1 (opioid receptor-like 1) receptor in the bowel movement, we investigated the effect of nociceptin on colonic contraction and transit in rats. Nociceptin (0.1-100 nM) concentration-dependently caused an immediate tonic contraction followed by rhythmic waves of contractions in the isolated colon. The response to nociceptin (10 nM) was not affected by the classical opioid receptor antagonists, naloxone, naltrindole and nor-binaltorphimine. Suppression of effect of inhibitory neurotransmitters using pituitary adenylate cyclase activating polypeptide(6-38) (PACAP-(6-38); 3 microM), vasoactive intestinal polypeptide(10-28) (VIP-(10-28); 3 microM) and N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 microM) did not influence the nociceptin-induced contractions. In anesthetized rats, intravenous administration of nociceptin (1 microg/kg) or morphine (1 mg/kg) caused phasic contractions in the proximal colon. Pretreatment with naloxone (300 microg/kg, i.v.) abolished the contractions induced by morphine, but not by nociceptin. The rate of large intestinal transit was dose-dependently accelerated by nociceptin (0.03-3 microg/kg, s.c.), but was retarded by morphine (1.7-5 mg/kg, s.c.). These results indicate that stimulation of ORL1 receptor accelerates the colonic contraction and transit independently from opioid receptors.
Two fluorescent substrates for protein tyrosine phosphatase (PTPase) reaction were prepared by conjugation of commercially available O-phosphotyrosine and dansyl chlorides. They were hydrolyzed by CD45 tyrosine phosphatase, and proved to be useful for PTPase assay.
BACKGROUND: Mortality resulting from gastric carcinoma is decreasing. This is mainly due to vigorous endoscopic screening and the consequent higher incidence of early detection of the disease. In this study, to evaluate the effect of surgical treatment on the prognoses of patients with gastric carcinoma, the survival of 1579 patients who underwent gastrectomy between 1970 and 1994 was retrospectively analyzed. METHODS: The patients were divided into 5 groups at 5-year intervals. Postoperative survival was compared among the groups. RESULTS: Postoperative survival was significantly improved in the later groups for patients with Stage I, II, III, and IV disease. A multivariate analysis of prognostic factors revealed that the time period during which the gastrectomy was performed was an independent predictor of survival. CONCLUSIONS: It was concluded that survival has been improved by recent advances in the surgical approach to gastric carcinoma.
Liquid chromatography/electrospray mass spectrometry is one of the rapidly developing techniques with which mass of large hydrophilic polymers such as proteins and nucleic acids can be determined precisely. The technique was applied to studies on the modifications of tRNAs. Various tRNA species purified from Escherichia coli were directly injected into a capillary reversed-phase column and the desalted and concentrated tRNAs were analyzed on-line with an electrospray mass spectrometer. In some cases, small but significant differences were noted between the theoretical and observed molecular masses, suggesting that there exist still unknown modifications. Under high resolution measurements, multiple peaks corresponding to species modified to a varying extent were resolved. To study the structures in detail, the isolated tRNA species were digested with ribonuclease T1, and the resulting mixture of fragments were analyzed by the same liquid chromatography/mass spectrometry. In this way, most of the fragments were easily identified solely from their masses, and the positions where the expected and real structures differ were revealed. The results obtained showed the presence of micro-heterogeneity among tRNAs and demonstrated at the same time the power of the hyphenated technique for the structural analysis on nucleic acids.
MARCKS, the major protein kinase C substrate in various cells and tissues, binds to calmodulin, acidic membrane phospholipids, and actin filaments, and these interactions are regulated by protein phosphorylation. We have previously shown that MARCKS purified from bovine brain is phosphorylated not only by protein kinase C but also by so-called proline-directed protein kinases in the well conserved N-terminal half of the molecule (Taniguchi, H., Manenti, S., Suzuki, M., and Titani, K. (1994) J. Biol. Chem. 269, 18299-18302). Although the presence of other phosphorylation sites in the C-terminal peptide was also noticed, the ambiguity in the C-terminal domain of the bovine protein hampered a more detailed analysis. In the present study, we analyzed MARCKS purified from rat brain by electrospray ionization/ion trap mass spectrometry. The results obtained revealed two additional novel phosphorylation sites in the C-terminal region. Both phosphorylation sites (Ser291 and Ser299) are immediately followed by proline, suggesting that these sites are also phosphorylated by the proline-directed protein kinase(s). Since Ser299 is within the C-terminal domain, which is well conserved among various species, the function of the domain, whatever it is, seems to be controlled by phosphorylation.
OBJECTIVE: To examine the effects of the Kobe, Japan, earthquake, a life-threatening event, on stress and glycemic control in diabetic patients. PATIENTS AND METHODS: Hemoglobin A1c levels before and after the earthquake were evaluated in diabetic patients in Kobe (N = 157; magnitude, 7.2) and in Osaka, Japan, as a control (N = 277; magnitude, 4.2), where little damage to houses and traffic facilities occurred. Glycosylated hemoglobin levels were also compared with those of 2 years before and 1 year after the earthquake. The General Health Questionnaire (GHQ) and a self-administered questionnaire regarding damage to houses and relatives killed or injured were used to assess psychological and mental stresses on earthquake survivors. RESULTS: Glycemic control was aggravated in diabetic patients after the earthquake in Kobe but not in Osaka. THe GHQ scores were significantly higher in the patients in Kobe than those in Osaka. Increased hemoglobin A1c concentrations and high scores on the GHQ were especially evident in diabetic patients with severe damage to houses and/or with relatives killed or injured. CONCLUSION: These results suggest an association between chronic, life-threatening stress and the worsening of metabolic control in patients with diabetes mellitus.
MARCKS, a major cellular substrate for protein kinase C, plays important roles in various cellular functions and its functions are regulated by calmodulin. We have studied the conformational properties of recombinant human MARCKS in solution and in complex with calmodulin. Circular dichroism (CD) spectra showed a high content of random coil in physiological solution. When MARCKS or MARCKS-derived calmodulin-binding peptide was complexed with Ca2+-calmodulin, little change was observed in the CD spectra, suggesting that MARCKS binds with calmodulin in a non-helical conformation, which is unique among the calmodulin-binding proteins.
An efficient expression system of rat calmodulin in Escherichia coli is presented. To express rat calmodulin cDNA, we employed a pET expression vector which contains the T7 phage promoter and terminator. After transformation of E. coli BL21(DE3) strain which carries T7 phage RNA polymerase inducible with isopropyl-beta-D-thiogalactopyranoside, induction of the expression, and chromatography of soluble proteins on a phenyl-Sepharose column, about 250 mg of recombinant rat calmodulin was obtained from 1 liter of E. coli culture. The recombinant calmodulin lacked the N-terminal methionine, and posttranslational modifications such as Nalpha-acetylation and methylation. This system facilitates the large amount preparation of calmodulin and the mutant proteins required for the structural analysis by NMR spectrometry and/or X-ray crystallography.