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The analgesic effect of 156-S on postoperative pain after removal of impacted lower wisdom teeth was clinically elvaluated. After the appropriate dose of 156-S was preliminarily studied among 50 mg, 100 mg, 200 mg, 300 mg, and 400 mg groups, 300 mg of 156-S was compared with 500 mg of mefenamic acid by the double blind test.The result were as follows:1) Of the total 520 cases, 408 cases (78. 5%) needed analgesics after the extraction.2) The analgesic effect of 156-S increased dosedependently among 50 mg, 100 mg, and 200 mg groups in the first preliminary test.3) 200 mg, 300 mg, and 400 mg of 156-S were clinically effective and useful to control the postoperative pain in the second preliminary test.4) Although both 300 mg of 156-S and 500 mg of mefenamic acid showed the almost same analgesic effect clinically, postoperative pain was statistically better controlled by 156-S than by mefenamic acid at 30 and 60 minutes after administration of the analgesics.However, the analgesic effect of mefenamic acid is statistically superior to that of 156-S at 4 hours after the administration. These results suggest that 156-S has quick analgesic action and mefenamic acid has a long one.5) Side effects of 156-S slight gastrointestinal disorder, were found in only 6 of 322 cases (1.8%).6) Therefore, 156-S is good for controlling the postoperative pain after extraction of impacted lower wisdom teeth.

Proliferative activity of cardiomyocytes in ICR mice aged from 1 to 200 days old was studied by 3H-thymidine autoradiography. To determine the outcome of cardiomyocytic DNA synthesis, the DNA content of the cardiomyocytic nuclei in different age groups was also examined by a cytofluorometric method. Flash labelling experiments with 3H-thymidine showed that the cardiomyocytes synthesised DNA most actively in the first 14 days after birth; the label was equally distributed in various parts of the heart and seen in about 8.8% of the cardiomyocytic nuclei on the tenth day. Cumulative labelling experiments for seven and 14 days showed that about 90% of the cardiomyocytic nuclei became labelled, indicating that most cardiomyocytic nuclei of young growing mice developed in this period. Twenty days after birth DNA synthesis of the cardiomyocytes rapidly decreased, the label being evident in less than 0.2%. From 100 to 200 days DNA synthesising cardiomyocytes were seen occasionally in the subendocardial region of the left ventricle (labelling index 0.04%). The cytofluorometric study showed that under normal conditions cardiomyocytes in mice contained mostly diploid nuclei, with a few double diploid nuclei considered to be premitotic nuclei. DNA synthesised cardiomyocytes in adult mice hearts usually became binucleated cells.

The absorption bands due to the infrared-active localized modes of Li and Na substitutional impurity in AgBr and of Li in AgCl are studied at 2 K. The isotope effects of the localized modes are observed in AgBr: Li and AgCl: Li systems. The high frequency sidebands of the Li6 localized mode in AgBr are also measured.

Photoluminescence excitation spectra of donor-acceptor pairs have been observed in phosphorus doped ZnTe. Binding energies of the donor and the acceptor is estimated from the spectra. Emission spectra measured under below-band-gap excitation showed sharp bands superimposed with a broad emission band. The result indicates the existence of two decay processes under the below-band-gap excitation: (1) recombination of an electron and a hole trapped on a given D-A pair, and (2) recombination of D-A pairs with various distances for which bound electrons are formed via conduction band.

Three spin-flip transitions in ZnTe:P are interpreted in terms of the shallow acceptor Hamiltonian of Bir, Butikov, and Pikus.

Cell proliferation was studied in the developing epididymal adipose tissue of mice by means of 3H-thymidine autoradiography. 4 mice in each age group were killed 30 min after a single injection of 3H-thymidine given at the 6th, 10th, 16th, 21st, 28th, 35th, 42nd, 49th or 56th postnatal day. The labeling index of the adipose tissue was high for several postnatal days but it was highest on the 6th day. The labeling index decreased thereafter, and cell proliferation appeared to almost cease after 56 days. Another 16 mice were given a single injection of 3H-thymidine at 6 days old; pairs of animals were killed at 30 min, 2, 4, 6, 8, 10, 14 and 18 days later. From the 2nd to 6th days of pulse labeling, the number of labeled fat cells increased significantly, whereas the number of labeled poorly differentiated mesenchymal cells decreased reciprocally. The labeling index of fat cells remained unchanged from the 6th to the 18th day. These results suggest that there is a population of fat cell-precursor cells in the mesenchymal tissue of the new born mouse, and that it takes 2-6 days for the precursor cells to become mature fat cells in the epididymal fatty tissue.

A case of granular cell tumor of the esophagus in a 50-year-old man is reported. Gastrointestinal endoscopy revealed a round, sessile, non-ulcerated white-yellow elevated tumor at the lower third of the esophagus. Biopsy revealed a granular cell tumor. Immunohistochemical staining demonstrated that granules in the cytoplasm of tumor cells were positive for S-100 protein and negative for carcinoembryonic antigen. An electron microscopic study revealed that tumor cells were closely packed in clusters, surrounded by basal lamina and collagen fibers. Most cells contained dark cytoplasm filled with electron-dense granules. These granules resembled lysosomes and phagosomes. In a few cells with clear cytoplasm, some mitochondria and poorly developed endoplasmic reticulums were seen. Fibrillar internal materials, myelin-like figures and a premature angulate body were observed in the clear cytoplasm. The lesion has remained unchanged in gross appearance and in size for twenty-three months without any treatment.

Cell number and proliferation of reactive astrocytes were studied quantitatively in the stabbed cerebral cortex of adult mice, using immunohistochemistry for glial fibrillary acidic protein (GFAP) and [3H]thymidine autoradiography. GFAP-positive astrocytes increased in cell number gradually from 24 to 96 h after stabbing, and their immunoreactivity became intense. The maximum number of GFAP-positive cells was about 4.5 times normal in the layers II–VI of the cortex, whereas it was only 1.5 times normal in the layer I (molecular layer). In contrast to the gradual increase in cell number, no GFAP-positive astrocytes were labeled with [3H]thymidine prior to 48 h after stabbing, in either the layer I or the layers II–VI. Then 3–5% of them were labeled at 72 and 96 h, but very few again after 6 days. By injecting [3H]thymidine successively for 6 days after stabbing, only 17% of GFAP-positive astrocytes of the layer I or the layers II–VI were labeled. These results reveal that, in the cortical layers II–VI, many GFAP-negative source cells initially express much more GFAP-antigen without proliferation and change into GFAP-positive reactive astrocytes. Proliferation of reactive astrocytes is not the major factor for the marked increase in number of them. The cortical layer I would have few GFAP-negative source cells for reactive astrocytes. These source cells may be protoplasmic astrocytes.

Ploidy patterns of gastric carcinomas of 54 Japanese patients, ranging in age from 28 to 82 years, were determined by cytofluorometry. The gastric cancers were divided into four basic ploidy patterns; the first pattern was a diploid mode, the second was a heteroploid mode, the third was a mosaic pattern of a diploid and a heteroploid mode, and the fourth was a mosaic of two or more different heteroploid modes. The incidence was 68.4%, 14.8%, 12.9%, and 3.7% in the first, second, third, and fourth patterns, respectively. All the cancers contained polyploid populations, whereas the early cancers tended to contain a lesser amount of polyploid cells than the advanced ones. Diffuse-type cancers and well-differentiated, intestinal-type adenocarcinomas were mostly unimodal cancers of the diploidy or heteroploidy, whereas poorly differentiated adenocarcinomas were often mosaic cancers of several different ploidies. There was no correlation between ploidy patterns and ages and sexes of patients. For 11 cases, labeling indices with 3H-thymidine were determined. Labeling indices of the intestinal-type and diffuse-type cancers were 12% to 27% and 7% to 19%, respectively.

To elucidate the histogenesis of gastric adenocarcinomas, the author looked for smaller carcinomas, and studied their histologic features and the histologic characteristics of the neighboring gastric mucosa. In 325 resected stomachs, 27 microcarcinomas, including initial lesions, were detected. Most of them were typical adenocarcinomas, whose histologic features were different from those of dysplasias. The gastric mucosa around the microcarcinomas was mostly intestinalized. However, the smaller the carcinomas, the less complete was the form of intestinal metaplasia, and the metaplasia was under progression in many gastric tubules. The smallest carcinomas consisted of a few, newly formed glandular complexes, confined to the neck region of the tubules, whereas the upper and the lower part of the tubules were still lined by normal gastric cells. The smallest dysplasia was an in situ lesion, also confined to the neck region of the tubules. These findings indicate that a starting point of adenocarcinomas and dysplasias is in the proliferative cell zone at the neck region. Intestinal metaplasia, dysplasia, and adenocarcinoma arise coincidentally. This implies that no precursor is present for each of them. It appears that most adenocarcinomas arise in gastric tubules when an abnormal differentiation is induced in stem cells after intestinal metaplasia. They are not a consequence of dysplasia, but share a common origin with it.

An immunoperoxidase method was used to compare the distribution of fibronectin and laminin between superficially spreading and deeply infiltrating parts of signet-ring-cell carcinoma of the stomach. In both parts, laminin-containing basement membranes were generally scarce, but they were observed on some of the cancer cells which had differentiated to glandular cells. Intramucosal invasion fronts of superficially spreading cancers often showed a layered structure, consisting of a middle zone of small cancer cells together with a superficial and a deep zone of signet-ring cells. In this structure, linear fibronectin and laminin deposits were common on the cancer cells in the deep zone, but rare in the superficial zone. However, fibrillar fibronectin deposits in the stroma were not considerably larger in either zone. At extramucosal invasion fronts of deeply infiltrating (advanced) cancers, a stromal remodelling with an increased amount of fibrillar fibronectin deposits was often observed around the cancer cells, whose cell surface fibronectin was largely lost even from some basement membranes. These findings suggest that invasive activity of signet-ring-cell carcinoma may not be related to the mere presence or absence of cell-surface fibronectin and laminin but to the amount of stromal fibronectin, which could reflect a cell-stroma interaction. Signet-ring-cell carcinomas have a stage of intramucosal growth in which cancer cells may live in dependence upon the pre-existing stroma and form the layered structure, while in advanced stages cancer cells seemed to have acquired an ability to elicit their own "tumor stroma".

The origin and renewal of the argentaffin cells in the pyloric glands of hamsters were studied by flash, cumulative and pulse labelling autoradiography with 3H-thymidine. The argentaffin cells were identified by the Diazo Method using Fast Red B Salt. By flash labelling autoradiography, it was shown that the argentaffin cells located from the middle to the lower level of the pyloric mucosa were not labelled with 3H-thymidine, indicating that this cell type has no proliferative activity. On the 10th and the 20th day of cumulative labelling, 31% and 63% of the argentaffin cells in the gland were found to be labelled, respectively. The labelled argentaffin cells were concentrated in the upper part of the gland (around the region of the isthmus), and no label was found over nuclei of the cells at the lowermost level of the gland. These labelled cells were shown to undergo a downward migration in the days following pulse labelling. They were replaced by unlabelled (and weakly or very weakly labelled) cells which arose at the region of the isthmus. The argentaffin cells in the pyloric gland are thought to arise from epithelial precursor cells at the region of the isthmus. The labelled argentaffin cells in the gland were found to decrease in number almost exponentially after pulse labelling. This indicates that the life span of argentaffin cells is not fixed, but their renewal conforms to the "random loss system". The half time of turnover of this cell population was 15 days on average.

The origin and renewal of secretin cells in the duodenum were investigated using the unlabeled antibody peroxidase-antiperoxidase technique and radioautography in rats killed at various times after single or multiple injections of [3H]thymidine. Secretin cells were spatially distributed from the upper crypt to the villus tip, being particularly numerous in the upper two-thirds of the duodenal villi. After a single injection of [3H]thymidine, there were no labeled secretin cells, indicating a lack of self-replicating activity. After repeated injections of the isotope, labeled secretin cells appeared and increased in number. They first occurred at the upper part of the crypt and the lower part of the villus, and later at the villus tip. All these cells were found to be labeled after continuous labeling for 120 h, which is considered to be the renewal time for this cell population.

Ten hamsters received repeated injections of 3H-thymidine for 4 days and were allowed to survive for 7, 28, 42 and 100 days. Changes in spatial distribution of the labelled cells and in labelling indices of each cell line in the gastric glands were studied at various days after 3H-thymidine, the labelled parietal cells and the mucous neck cells were concentrated at the neck area. Starting from the neck area, they migrated an average of 3 micra downwards per day. By 42 days, they reached the middle level of the glands, where the labelled mucous neck cells decreased but the labelled chief cells increased in number. The differentiation of the chief cell then appears to take place at the middle level of the glands through transformation of the migratory mucous neck cells. After 4 days of the labelling, about 1.8% of the chief cells located in the lower part of the glands was found to undergo in situ replication. This indicates that the renewal of this cell type is partly assured by its own mitotic activity. The foveolar cell--the future surface epithelium--seems to migrate upwards along the long axis of the glandular tubule in the pipe line system, which means "first produced, first migrates". After migrating out from the neck area, the parietal cell and the mucous neck cell (the future chief cell) take an average of 200 days to reach the lower end of the glands. In the process of migration, however, the cells produced contemporaneously at the neck area became scatteringly spread from the neck towards the bottom of the gland. The time required for the newly-formed cells to reach the lower end of the gland varied between 100 and 300 days. In the gastric glands the cells first produced at the neck area do not first reach the lower end of the glands. This mode of random migration is referred to as the "stochastic flow system". As one of the probable factors which disturb the pipe line flow of downward cell migration, cellular movements perpendicular to the long axis of the glandular tubule were suggested to occur at random at any level of the gastric glands.

Reactions of glial cells after stab wounding of mouse cerebral cortex were studied by [3H]thymidine autoradiography combined with immunohistochemistry for S-100 protein. S-100-positive cells in the stabbed cortex had the light and electron microscopic characteristics of astrocytes, and they showed remarkable hypertrophic changes 4 to 5 days after stabbing. There were many cells labeled with [3H]thymidine in the stabbed cortex from 24 h to 8 days after stabbing, and the number of labeled cells was maximum at 48 h. A few of the labeled cells were S-100-positive, and the labeled S-100-positive cells were seen 24 h to 6 days after stabbing, mostly after 72–96 h. By successive injections of [3H]thymidine for 6 days after stabbing, about 90% of labeled cells were S-100-negative, and about 90% of S-100-positive cells were unlabeled with [3H]thymidine. The increase in number of S-100-positive cells by day 6 after stabbing was not statistically significant (P > 0.05). These results suggest that reactive proliferation of astrocytes is a minor phenomenon in gliosis of injured cerebral cortex, in contrast with their remarkable reactive hypertrophy.

A fractographic study combined with light and transmission electron microscopy and3H-thymidine autoradiography was carried out to examine cell proliferation and differentiation of the fundic mucosa. The following results were obtained. 1. A gastric gland and a gastric pit into which the gland opens constitute an inseparable structural unit. This unit is called glandular tubule. The glandular tubule consists of an upper, smooth tubular portion and a lower, knobby gastric gland. The tubular portion corresponds to the gastric pit viewed from outside. The so-called isthmus of the gland in which generative cells are confined corresponds to the part of the tubular portion immediately above the constriction. 2. Each glandular tubule of the mucosa is supported by connective tissue only around the tubular portion. The generative cell zone in it appears to be tightly enclosed in a stromal sheath. 3. Surface epithelial cells as well as parietal, mucous neck and chief cells lie outside the stromal sheath and these cell types do not incorporate 3H-thymidine. Mucous neck cells that lie between parietal cells in the upper part of the gastric gland are morphologically similar to the undifferentiated cells of the constriction. 4. From these results, it is suggested that undifferentiated proliferative cells confined to the stromal sheath, when free of the latter, grow and mature as they migrate. The parietal cell arises directly from the undifferentiated cell at the constriction, and it is suggested that the mucous neck cell is an immature form of the chief cell migrating from the generative cell zone.

A fractographic study employing scanning electron microscopy combined with light microscopy, was carried out to examine how gastric pits and glands increase in number in the developing gastric mucosa of young hamsters. The results led us to the hypothesis that the continuing increase in the number of pits and glands of young animals takes place via a gland division cycle, an essential feature of which is the periodic dichotomous division of the generative cell tubule after thickening, followed by budding of a new gland and fission of a new pit.

THE conjugal transfer of episomal elements in bacteria is assumed to take place through specific pili, which are formed on the surface of donor bacteria carrying these elements1. Recipient ability seems to be influenced by the surface structure of the cell wall2. We previously isolated rough mutants of Salmonella typhimurium LT-2 which had increased recipient abilities for the conjugal transfer of foreign deoxyribonucleic acids. B. A. D. Stocker (Stanford University) has shown that there are several types of these mutants by using rough-specific phages (personal communication).

Background It is suspected that early gastric carcinoma (GC) is a dormant variant that rarely progresses to advanced GC. We demonstrated that the dormant and aggressive variants of tubular adenocarcinomas (TUBs) of the stomach are characterized by loss of MYC and gain of TP53 and gain of MYC and/or loss of TP53, respectively. The aim of this study is to determine whether this is also the case in undifferentiated-type GCs (UGCs) of different genetic lineages: one with a layered structure (LS+), derived from early signet ring cell carcinomas (SIGs), and the other, mostly poorly differentiated adenocarcinomas, without LS but with a minor tubular component (TC), dedifferentiated from TUBs (LS−/TC+). Methods Using 29 surgically resected stomachs with 9 intramucosal and 20 invasive UGCs (11 LS+ and 9 LS−/TC+), 63 genomic DNA samples of mucosal and invasive parts and corresponding reference DNAs were prepared from formalin-fixed, paraffin-embedded tissues with laser microdissection, and were subjected to array-based comparative genomic hybridization (aCGH), using 60K microarrays, and subsequent unsupervised, hierarchical clustering. Of 979 cancer-related genes assessed, we selected genes with mean copy numbers significantly different between the two major clusters. Results Based on similarity in genomic copy-number profile, the 63 samples were classified into two major clusters. Clusters A and B, which were rich in LS+ UGC and LS−/TC+ UGC, respectively, were discriminated on the basis of 40 genes. The aggressive pattern was more frequently detected in LS−/TC+ UGCs, (20/26; 77%), than in LS+UGCs (17/37; 46%; P = 0.0195), whereas no dormant pattern was detected in any of the UGC samples. Conclusions In contrast to TUBs, copy number alterations of MYC and TP53 exhibited an aggressive pattern in LS+ SIG at early and advanced stages, indicating that early LS+ UGCs inevitably progress to an advanced GC. Cluster B (enriched in LS−/TC+) exhibited more frequent gain of driver genes and a more frequent aggressive pattern than cluster A, suggesting potentially worse prognosis in UGCs of cluster B.

Background Eradication of early gastric carcinoma (GC) is thought to contribute to reduction in the mortality of GC, given that most of the early GCs progress to the advanced GCs. However, early GC is alternatively considered a dormant variant of GC, and it infrequently progresses to advanced GC. The aim of this study was to clarify the extent of overlap of genetic lineages between early and advanced tubular adenocarcinomas (TUBs) of the stomach. Methods Immunohistochemical staining for p53 was performed using 28 surgically resected stomachs with 13 intramucosal and 15 invasive TUBs. By chromosome- and array-based comparative genomic hybridization (CGH), genomic copy number constitution was compared between the mucosal and invasive parts of the invasive TUBs and between the mucosal parts of the invasive and intramucosal TUBs, using 25 and 22 TUBs, respectively. TP53 mutation in exons 5-8 was examined in 20 TUBs. Results Chromosomal CGH revealed that 4q+ and 11q+ were more common in advanced and early TUBs, respectively, whereas copy number changes in 8q and 17p showed no significant differences between early and advanced TUBs. However, array CGH revealed that, of the 13 intramucosal TUBs examined, loss of MYC (MYC-) and gain of TP53 (TP53+) was detected in 9 TUBs and MYC+ and/or TP53- was detected in 3 TUBs. Of the mucosal samples of 9 invasive TUBs, 7 showed MYC-/TP53+ and none showed MYC+ and/or TP53-. Of the 9 samples from the invasive parts, 1 (from submucosal cancers) showed MYC-/TP53+ and 6 (1 from submucosal and 5 from advanced cancers) showed MYC+ and/or TP53-. The latter 6 tumours commonly showed a mutant pattern (diffuse or null) in p53 immunohistochemistry, and 4 of the 6 tumours assessable for TP53 sequence analysis revealed mutations. The overall array CGH pattern indicated that, between the mucosal and invasive parts, genetic lineage was found discontinuous in 5 advanced cancers and continuous in 3 submucosal cancers. Conclusions Genetic lineages often differed between early and advanced TUBs. MYC-/TP53+ and MYC + and/or TP53- may be the signatures of dormant and aggressive TUBs, respectively, in the stomach.

Background Early detection and treatment of non-invasive neoplasms can effectively reduce the incidence of advanced gastric carcinoma (GC), but only when the lineage is continuous between non-invasive and advanced tumours. Although a fraction of non-invasive neoplasms progress to invasive GC, it is difficult to identify individual progression-prone non-invasive neoplasms. To classify non-invasive gland-forming gastric neoplasms into clusters of different levels of progression risk, we applied mucin phenotyping and genomic DNA microarray analyses to intramucosal gland-forming gastric neoplasms. Methods Formalin-fixed, paraffin-embedded tissues from 19 non-invasive and 24 invasive gland-forming neoplasms were obtained via endoscopic submucosal dissection or surgical excision. According to the Vienna classification, intramucosal neoplasms were classified as low-grade or high-grade non-invasive neoplasms (LGNs [category 3] and HGNs [category 4], respectively) or invasive carcinomas (intramucosal GCs and mucosal parts of submucosal or deeper GCs [category 5]). Neoplastic lesions were characterized by mucin phenotypes determined using monoclonal antibodies against MUC2, MUC5AC, MUC6, and CD10. Genomic DNA samples from mucosal neoplasms were subjected to array-based comparative genomic hybridization and subsequent unsupervised, hierarchical clustering with selected large-sized genes. Results There was no significant difference in mucin phenotype between HGNs/LGNs and invasive carcinomas. The clustering classified samples into stable, unstable, and intermediate. The histological tumour grade or mucin phenotype of non-invasive neoplasms did not correlate with the clustering results. Each cluster may represent an independent lineage of different outcome because the size distribution of non-invasive tumours among the 3 clusters almost overlapped. In contrast, the unstable cluster alone included invasive carcinomas. Conclusions These findings suggest that the outcome of individual tumours is not stochastically determined but can be predicted from the genomic copy-number profile even at the non-invasive stage. Non-invasive neoplasms of the unstable clusters, which accounted for 21% of non-invasive neoplasms, may progress to invasive carcinomas, whereas those of stable cluster may not. Electronic supplementary material The online version of this article (doi:10.1186/s12920-015-0080-6) contains supplementary material, which is available to authorized users.