[Etoposide, pirarubicin and cisplatin(ETP) combined therapy of inoperable head and neck cancer].
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Biomedical subjects
Publications and source records attributed to S Tamura.
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We investigated incidence of pulmonary tuberculosis for 31 years (from 1960 to 1990) by sex and age among workers of NTT (Nippon telegraph and telephone corporation) in Tokyo area. Annual transition of recent years was mainly analyzed and following results were obtained. (1) Incidence in male of the twenties, thirties and forties decreased smoothly from 1960 to around 1980, then came to standstill and increase tendency was suspected, that is to say, 1) incidence in male of the twenties was minimum in 1976 (21 per 100,000 persons). Annual reduction rate (minus means decrease, plus means increase) from 1960 to 1976 was -11.7% and that from 1977 to 1990 was -0.4%. 2) incidence in male of the thirties was minimum in 1983 (0 per 100,000 persons). Annual reduction rate from 1960 to 1982 was -8.8% and that from 1984 to 1990 was +6.8%. 3) incidence in male of the forties was minimum in 1981 (0 per 100,000 persons). Annual reduction rate from 1960 to 1980 was -11.5% and that from 1982 to 1990 was +1.3%. (2) Incidence in male of the fifties decreased gradually from the 1960's and no tendency of increase was observed. (3) Incidence in female of the twenties, thirties and forties decreased almost continuously from 1960 to 1990 and no tendency of increase was observed in each age group, but total incidence in female (from the teens to the sixties) seemed to be leveling off after 1979. From these results, stagnant or increase tendency of pulmonary tuberculosis in young and middle-aged male was noticed.
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Cross-protection against influenza virus infection was examined in mice, immunized intranasally with a nasal site-restricted volume of inactivated vaccines together with cholera toxin B subunit (CTB) as an adjuvant. The mice were challenged with either a small or a large volume of mouse-adapted virus suspension, each of which gave virgin mice either a predominant upper or lower respiratory tract infection. A single dose of a monovalent influenza A H3N2 virus vaccine with CTB provided complete cross-protection against the small-volume challenge with a drift virus within the same subtype, but a slight cross-protection against the large-volume challenge. A second dose of another drift virus vaccine increased the efficacy of cross-protection against the large-volume challenge. Similar cross-protection against H1N1, H3N2, or B type drift virus challenge was provided in the mice having received a primary dose of a mixture of H1N1, H3N2, and B virus vaccines with CTB and a second dose of another trivalent vaccine. The degree of cross-protection against the small- and the large-volume infection paralleled mainly the amount of cross-reacting IgA antibodies to challenge virus hemagglutinin in the nasal wash and that of cross-reacting IgG antibodies in the bronchoalveolar wash, respectively. On the other hand, in mice immunized subcutaneously with the trivalent vaccines having no cross-reacting IgA antibodies, the efficacy of cross-protection was not so high as that of nasal vaccination. These results suggest that the nasal inoculation of trivalent vaccines with CTB provides cross-protection against a broader range of viruses than does the current parenteral vaccination.
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A nuclear protein(s) from rat or pig stomach recognized a conserved sequence in the 5'-upstream regions of the rat and human H+/K(+)-ATPase alpha subunit genes. A gel retardation assay suggested that part of the binding site was located in the TAATCAGCTG sequence. No nuclear proteins capable of the binding could be detected in other tissues of rat (liver, brain, kidney, spleen and lung) or pig liver. The sequence motif (GATAGC) located 5'-upstream of the beta-subunit gene also seemed to be recognized by the same protein, because the binding of nuclear protein to the sequence motifs in the alpha and beta subunits was mutually competitive. Considering the sense-strand sequence of the binding motif in the alpha-subunit gene, we conclude that (G/C)PuPu(G/C)NGAT(A/T)PuPy is a core sequence motif for the gastric specific DNA binding protein (PCSF, parietal cell specific factor).
E-cadherin (ECD) is one of subclasses of the cadherin family which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. An immunohistochemical study of ECD expression was performed on gastric adenocarcinoma from 103 patients using our monoclonal antibody for human ECD (HECD-1). ECD was strongly expressed in normal gastric epithelium without exception; however, various staining patterns were observed in cancer tissues. The frequency of tumours with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 42% and 58% respectively. Tumours with a high frequency of Rd-type expression particularly included: undifferentiated tumours (85%, 46/54), Borrmann's type 4 (90%, 9/10), tumours larger than 2.6 cm in diameter (65%, 53/81), tumours invading beyond the subserosa layer (78%, 46/59), and tumours with infiltrative growth (87%, 41/47). Furthermore, the frequency of Rd-type expression in cases with peritoneal dissemination (82%, 9/11) or lymph node metastasis (73%, 43/59) was significantly higher than that in cases without dissemination or metastasis. These results suggest that ECD might play a key role in the genesis of histological differentiation, and that the reduction of ECD expression may affect the mode of invasion and metastasis of human gastric cancer cells.
The intracellular transport of mucus glycoprotein precursor (apomucin) from endoplasmic reticulum (ER) to Golgi was quantitated by the immunoprecipitation with 3G12 antimucin monoclonal antibody and by estimation of the apomucin glycosylation using UDP-[3H]galactose. The assembly of the entities carrying apomucin to Golgi was assessed by electron microscopy and by quantitation of the incorporation of [14C]choline, [14C]ethanolamine, and [14C]oleic acid into their lipids. The microscopic image of the isolated transport components revealed a population of 80- to 100-nm vesicles with occasional membranes of the ER used for their synthesis. On the average, the vesicles contained 82 ng apomucin/microgram of protein and 80-90% of the total incorporated lipid precursors. From that, 91% of [14C]choline was detected in phosphatidylcholine, and 9% in phosphatidylethanolamine, lysophosphatidylcholine, and sphingomyelin. With [14C]oleate, 54% of the label was incorporated into ceramide, diglyceride, and phosphatidic acid, 35% to phosphatidylcholine, 7% in phosphatidylethanolamine, and 2% in sphingomyelin. After incubation of the vesicles with Golgi, the apomucin was found glycosylated and the lipids of the transport vesicles incorporated into Golgi membranes. The fusion of the vesicular membranes was accompanied by the synthesis of sphingomyelin. In the Golgi, 39-55% of the radiolabeled phosphatidylcholine of transport vesicles was converted to sphingomyelin. The results indicate that the newly synthesized membranes of apomucin transporting vesicles are enriched in phosphoglycerides and ceramides. Upon fusion with the Golgi, the membranes of the vesicles are replenished with sphingomyelin by exchange reaction between phosphatidylcholine and ceramide.
Human NADPH-P450 oxidoreductase (OR) is an intrinsically membrane-bound flavoprotein that serves to transfer electrons from NADPH to cytochrome P450. OR is also involved in the metabolic activation of chemotherapeutic alkylating agents. The human OR cDNA was engineered into baculovirus and the recombinant virus was used to infect Spodoptera frugiperda (Sf9) cells. Approximately 3.3% of total protein of infected cells was human OR. The enzyme was purified by ion exchange and affinity chromatography to a specific activity of 20 units/mg protein. Baculovirus-expressed OR displayed an absolute spectrum typical of the protein purified from tissue sources. The purified enzyme was able to support P450 activity in a reconstituted lipid vesicle system where maximal P450 activity was achieved at an OR/P450 ratio of 2. When recombinant OR and P450 DNA-containing baculoviruses were used to coinfect Sf9 cells, the OR/P450 ratio needed to achieve half maximal P450 catalytic activity was less than 0.5. These studies demonstrate the utility of baculovirus to analyze the functional and structural relationship of OR and P450.
1. Analysis of the submandibular saliva revealed that the secretion consists of mucin complexed with 150 kDa fibronectin fragment and DNA. 2. The kallikreins, secreted by the submandibular gland, appear to be responsible for the fibronectin fragmentation, since an identical peptide was also generated when fibronectin was subjected to incubation with the submandibular saliva or the purified enzyme. 3. The results provide evidence that the 150 kDa glycopeptide so-called salivary mucin "link" component is neither an integral part of the mucin molecule, nor linked to mucin subunits by disulfide bonds, but is a fibronectin fragment which associates with mucin. 4. Using mucin monoclonal antibody (3G12), it was revealed that the nonglycosylated (naked) 8-12 kDa fragment of the mucin molecule is responsible for the interaction of mucin with other components of saliva. 5. Under physiological conditions, the interaction of mucin with fibronectin on the luminal surfaces may be relevant in building mucous barrier and protection of the delicate oral epithelium from damage.
Type 2C protein phosphatase (PP2C) is one of four major serine-threonine specific phosphoprotein phosphatases which modulate various intracellular activities. By in situ hybridization analysis of the adult rat, expression signals of mRNA for PP2C were observed most highly in the granule cells and Purkinje cells of the cerebellum, the pyramidal cells of the hippocampus and granule cells of the dentate gyrus, and plexus choroideus of the lateral ventricle, whereas moderate levels of its expression were observed in the medial habenula, piriform cortex and the pineal body. Several discrete nuclei of the brainstem including pars compacta of the substantia nigra, the pontine nuclei, and the locus ceruleus expressed the mRNA moderately. Weak expression of PP2C mRNA was observed in mitral and internal granule cells of the olfactory bulb, spinal cord gray matter, the cerebral neocortex, thalamic and hypothalamic nuclei. Only faint expression was detected in the caudate putamen. These patterns of expression are different from that of calcineurin/PP2B reported by other immunohistochemical studies and it is suggested that various neuronal proteins are differentially dephosphorylated by the different types of PP.
Secretory antibodies in mucosal surfaces are known to play an essential role in protection against various infectious diseases. To enhance the production of such antibodies, influenza HA vaccine was inoculated intranasally into rabbits, together with cholera toxin B subunit (CTB) which is known to augment antibody response to an unrelated antigen. This combination resulted in high levels of serum IgG antibody responses against HA and CTB molecules, 3-4 weeks after inoculation, compared with the inoculation of HA vaccine alone. The adjuvant mechanism for CTB was studied by using Ussing chambers, in which nasal mucosa from rabbits were mounted. CTB was found to enhance the transepithelial flux of HA vaccine, from the mucosal side (lumen) into the serosal side (lamina propria), indicating that the permeability of the membrane was changed by CTB. Moreover, to achieve effective flux of HA vaccines, some interactions between the vaccine and CTB across the membrane were found, which may effect the effectiveness of the vaccine formulation. The results suggest that one of the mechanisms by which CTB enhances the production of mucosal antibody response is to enhance the transepithelial influx of vaccine into the nasal mucosa, where the cells involved in the antibody production are located. CTB may be used as a potent adjuvant to induce antibody response, by nasal vaccination, against pathogens impinging on mucosal surfaces.
Right anterior caudocranial oblique (RACCO) projections were evaluated for transarterial portography with digital subtraction angiography. For RACCO projection, the image intensifier was tilted 25 degrees caudally and 30 degrees to the patient's right with the patient in the supine position. The abnormal findings imaged in 20 patients were analyzed by types of abnormalities and their locations in the portal venous systems by comparing RACCO and PA projections. The RACCO view was superior to the PA projection for demonstrating either encasements or tumor thrombi in relatively proximal segments of the portal venous branches. Two encasement lesions and a tumor thrombus were imaged only on the RACCO projection. However, the RACCO projection had no definite advantage over the PA view for showing encasements or tumor thrombi in the distal segmental branches. The RACCO projection was superior to the PA view for demonstrating defects in the hepatograms of some hepatic segments (S5 and S8). We concluded that the RACCO view is extremely useful and is indicated for angiographic work-ups of hepatic or biliary lesions when abnormalities are suspected in proximal portal venous branches.
The effect of dietary fiber on the induction of cytochrome P450IA1 in rat colonic mucosa after a single intragastric injection of 3-methylcholanthrene (3MC, 20 mg/kg) was investigated by examining the drug-metabolizing enzyme activity, immunoblotting for cytochrome P450IA1 and immunohistochemistry. 7-Ethoxycoumarin-O-deethylase activities were approximately 20-fold higher in microsomes from both proximal and distal portions of the colonic mucosa of control diet-fed 3MC-treated rats compared with those of control diet-fed untreated rats. Strong immunofluorescence for cytochrome P450IA1 was localized in the cytoplasm of the colonic mucosa surface epithelium from the control diet-fed 3MC-treated rats. 7-Ethoxycoumarin-O-deethylase activity and cytochrome P450IA1 content determined by immunoblotting were significantly lower in wheat bran-fed 3MC-treated rats than in control diet-fed 3MC-treated rats. Immunohistochemical analysis showed much weaker immunofluorescence for cytochrome P450IA1 in the surface epithelium of the colonic mucosa of the wheat bran-fed 3MC-treated rats. These observations suggested that dietary fiber can affect the induction of cytochrome P450IA1 in colonic mucosa by dietary inducers or carcinogens.
BACKGROUND AND RATIONALE: The authors report the quantitation of myocardial enhancement using iodinated contrast medium in patients with ischemic heart disease. Twenty-eight patients with chronic ischemic heart disease and 11 controls were examined by ultrafast computed tomography (CT) using 100-msecond scans. METHODS: The authors analyzed M/L (ratio of post-contrast incremental increases in the left ventricular myocardial and luminal CT number) in early and late phases after contrast injection. RESULTS: In controls, mean values of early and late M/L were 30% and 51%, respectively. In infarcted or severely ischemic segments, early M/Ls (19%, 16%) were significantly small (P less than .001), whereas late M/Ls (90%, 63%) were higher (P less than .001, .01) than controls. Segments with infarction or severe ischemia were differentiated from mild or nonsignificant ischemia by using this parameter (sensitivity, 99%; specificity, 88%). CONCLUSIONS: M/L is useful for detection of the ischemic myocardium.
The effect of prolonged administration of an antiulcer drug, sofalcone, on the physicochemical properties of gastric mucus was investigated. The experiments were conducted with two groups of rats in which one group received a dose of 100 mg/kg of sofalcone twice daily for three consecutive days, and the control group received daily doses of vehicle. The rats were killed 16 h after the last dose, their stomachs dissected, and the mucosa subjected to physicochemical measurements. The results revealed that sofalcone evoked a 23% increase in mucus gel thickness, and its content of sulfo- and sialomucins increased by 54 and 25%, respectively. These changes in mucus with sofalcone were accompanied by a 16% increase in H+ retardation capacity, twofold increase in viscosity, and a 39% increase in the gel hydrophobicity. The mucus elaborated in the presence of sofalcone exhibited a 10% lower content of protein, 30% higher content of carbohydrate, and 18% higher content of total lipids, which were particularly enriched (20%) in phospholipids and contained 67% more covalently bound fatty acids. Furthermore, the high molecular weight mucus glycoprotein form accounted for about 30% of gel mucin in the control group, whereas its content in mucus gel of animals receiving sofalcone reached 50%. The results indicate that sofalcone enhances the protective qualities of the mucus component of the gastric mucosal barrier and hence strengthens the gastric mucosal integrity.
The prevalence of two types of Epstein-Barr virus (EBV) in Japan was studied by using the polymerase chain reaction (PCR). The U2 region encoding EBV nuclear antigen 2 (EBNA-2) was chosen as the target of amplification. Consensus primers were synthesized from sequences common to the two types but encompassing a large stretch of deletion in the sequence of type 1 EBV. The primers were capable of amplifying both types at the same time but allowed differentiation of each type by the size of the amplification products. Thus we could carry out detection and typing of EBV in a one-step PCR. EBV was detected in mouth washings of 21 (23%) of 91 seropositive healthy adults. Twenty samples (22%) contained type 1 and only one (1%) type 2. Seventy-nine patients suffering from various types of tonsillitis were also studied. EBV was detected in mouth washings of 37 patients (47%). Thirty-four (43%) contained type 1 and three (4%) type 2. Double infection was not seen in either healthy donors or patients. These results indicate that type 1 EBV is highly dominant and the type 2 variant is quite rare in Japan.