RELATIONSHIP OF DELIVERY DATE TO PREDICTED DATE

Gastroduodenostomy after gastric resection is a procedure which can be readily performed if the short gastric vessels are first divided. It makes for a more physiological restoration of the gastrointestinal tract than is accomplished with gastrojejunostomy and permits proper admixture of the food with the bile and pancreatic enzymes. It avoids several potential dangers such as leakage from the duodenal stump, the possibility of a gastrocolic fistula, and malfunction of the anastomosis due to distortion of a jejunal loop. Apparently the "dumping syndrome" does not occur after gastroduodenostomy as it sometimes does after gastrojejunostomy.     

Vagotomy without Diarrhoea

The incidence of diarrhoea after three types of vagotomy was assessed “blind” at a gastric follow-up clinic one year after operation. Diarrhoea was recorded in 24% of patients after truncal vagotomy and pyloroplasty, in 18% after selective vagotomy and pyloroplasty, but in only 2% of patients after highly selective vagotomy without a drainage procedure. The incidence of diarrhoea was significantly less (P < 0·01) after highly selective vagotomy than after either of the other procedures.Hypertonic glucose solution given by mouth to 15 representative patients from each group and to 15 patients before operation provoked the onset of diarrhoea in 67% of the patients who had undergone truncal vagotomy and pyloroplasty, in 60% of those who had undergone selective vagotomy and pyloroplasty, in 13% of those who had undergone highly selective vagotomy without a drainage procedure, and in none of the preoperative patients. Again the difference between the “highly selective” group and the other two groups of vagotomized patients was statistically significant.It is suggested that postvagotomy diarrhoea is attributable both to unregulated gastric emptying after truncal or selective vagotomy with a drainage procedure and to the extragastric denervation produced by truncal vagotomy. “Postvagotomy” diarrhoea can be virtually eliminated by using highly selective vagotomy without a drainage procedure.     

Changes in gastric mucosa after vagotomy and gastrojejunostomy for duodenal ulcer.

Gastric mucosa was studied histologically in 141 patients. Eighty two had undergone vagotomy and gastrojejunostomy between 15 and 25 years previously for duodenal ulcer, and 59 control patients had a long history (minimum 15 years) of duodenal ulcer treated medically. No carcinoma was found in either group. Two patients with severe dysplasia and 13 patients with moderate dysplasia were found in the study group, compared with none in the control group (p less than 0.01). Intestinal metaplasia was seen in 44 (53%) of the study group and 16 (27%) of the control group (p less than 0.01). Atrophy and gastritis were more severe (p less than 0.01 for atrophy; p = 0.05 for gastritis) in the study group. Gastric mucosal changes were more severe after surgical treatment for duodenal ulcer than after medical treatment, and possibly a high incidence of gastric carcinoma may occur 25 years after vagotomy and gastrojejunostomy.     

Recent Advances in the Physiology of Gastric Acid Secretion

The classic scheme of gastric acid secretion which divided the digestive period into cephalic, gastric and antral phases has become obsolete in the last 10 years. These “phases” are now seen as concurrently acting mechanisms which depend upon one another to be fully efficient. About half of all gastrin released during a meal is dependent upon vagal stimulation of the antrum. Also, vagotomy desensitizes the acid-secreting parietal cells to the effect of all other types of stimuli.The number of parietal cells (parietal cell mass) varies greatly according to the gastric secretory activity of each individual. It is highest with duodenal ulcer and lowest with gastric ulcer.Parietal cell hyperplasia or atrophy can be induced experimentally, but the factors controlling the size of the parietal cell mass in man have not been studied.A scheme of acid secretion which incorporates recent advances is presented.     

THE CYTOLOGICAL DIAGNOSIS OF GASTRIC CANCER

Established centers find that cytological study of gastric washings with saline or chymotrypsin, adequately performed, is a valuable diagnostic tool in the detection of early and curable gastric carcinoma.Our experience with a small series of 150 patients, studied by saline gastric washing, has emphasized the difficulties of collection and the particular importance of obtaining, by repeated washings if necessary, an adequate specimen of gastric epithelial cells for diagnosis, before an opinion is given.It seems likely that the cytological method will be of future value in study of the natural history of gastric malignant disease and in detection of its surface lesions in their earliest form in asymptomatic, known-susceptible persons. Further, it should become a complementary part of the “stomach profile” in gastric diagnostic problems, where roentgenologic and gastroscopic studies may be expected to reveal the older, necrotic, or infiltrative lesions; cytological study, the earlier and more superficial stages of disease.     

Vagotomy and Pyloroplasty for Gastric Ulcer

In a series of 68 patients with gastric ulcer who were treated by vagotomy and pyloroplasty there were no operative deaths, though one patient who received massive transfusions died 14 weeks later from hepatic necrosis probably associated with serum hepatitis. Four patients developed recurrent peptic ulceration requiring further surgical treatment. The clinical condition of all but three of the remainder was satisfactory after an average follow-up period of three years and two months. Of the 14 patients who presented with an acutely bleeding gastric ulcer, one subsequently required gastrectomy for continued bleeding; in all the others the immediate and long-term results were satisfactory. Of 21 patients with a “high” ulcer and 29 with combined gastric and duodenal ulceration one (4·8%) and three (10%) respectively suffered recurrences. We conclude that vagotomy and pyloroplasty is a satisfactory form of treatment for a high or bleeding gastric ulcer, but that for all other gastric ulcers some form of gastric resection is preferable.     

Proximal gastric vagotomy: interim results of a randomized controlled trial.

In a randomized controlled trial 50 patients with duodenal ulcer treated by proximal gastric vagotomy (P.G.V.) without drainage were compared with 50 who underwent selective vagotomy and gastrojejunostomy. The clinical results were assessed in 99 patients one to four years after operation. Patients who had undergone P.G.V. had significantly less dumping, nausea, and bile vomiting and fared better in their overall clinical grading. The postoperative Visick grading of the 50 patients with P.G.V. was similar to that of 56 controls with no known gastrointestinal disease who had not undergone operation. The results obtained in the patients who had had P.G.V. without drainage were compared with those of a further group of 24 patients subjected of P.G.V. with gastrojejunostomy, and the better results obtained in the former group were thought to be due to elimination of the drainage procedure. The average follow-up period of the trial was just over two years, but there were no indications that the recurrent ulceration rate after P.G.V. would be any higher than after other types of vagotomy and drainage.     

EXTERNAL BARREL TEMPERATURE OF A SMALL BORE OLYMPIC RIFLE AND SHOOTING PRECISION

Investigations on changes in a rifle''s barrel temperature during shooting in a rhythm typical for practitioners of Olympic shooting sports are presented. Walther KK300 (cal. 5.6 mm), a typical rifle often used in Olympic competitions, R50 RWS ammunition and a high speed thermographic camera were used in the study. Altair version 5 software was used to process thermal images and a stationary wavelet transform was applied to denoise signals for all the studied points. It was found that the temperature of the rifle barrel does not exceed 0.3°C after one shot whereas the total temperature increase does not exceed 5°C after taking 40 shots and does not affect the position of the hitting point on a target. In fact, contrary to popular belief, the so-called “warming shots” are not done for barrel heating but for cleaning of remnants in the barrel.     

Immunoenzymological Evidence Suggesting a Change in Conformation of Adenylic Acid Deaminase and Creatine Kinase during Substrate Combination

The kinetics of inhibition of 5′-adenylic acid deaminase and creatine-ATP transphosphorylase by their respective antibodies are studied and rate constants of combination are ascertained. It is shown that the single substrate 5′-adenylic acid (AMP) of deaminase “protects” the enzyme against antibody inhibition. However, phosphate, a competitive inhibitor of the highly specific deaminase, enhances combination with antibody. With creatine kinase, however, addition of either of the substrates, alone or in combination with the required magnesium, each of which separately bind to the enzyme, does not prevent inhibition of the enzyme by its antibody. However, the “working” enzyme combined with all substrates is “protected” against antibody inhibition.     

Tokyo-Yokohama Asthma—A Review and Some Current Concepts

Soon after the occupation of Japan, military physicians began recording an unusually large number of patients with asthma. Subsequent reports labeled the condition “Yokohama asthma” and called it a new environmental respiratory disease. It occurred in the Tokyo-Yokohama area, in previously healthy persons, from October to May during the time of the heaviest concentration of air pollution.The disease begins with cough at night, wheezing and shortness of breath, and apparently does not respond to the usual forms of treatment for asthma. It was reported that the symptoms subsided upon removal of the patient from the Tokyo-Yokohama area but abruptly recurred upon return to the area. It has been implied that the disease is a hypersensitivity phenomenon due to some unknown contaminant in the atmosphere. More recent studies indicate that Tokyo-Yokohama asthma is not a disease but a syndrome seen in people with bronchial infections and asthma. The high level of air pollution is thought to have an aggravating rather than a sensitizing effect.     

An Imputation Approach for Oligonucleotide Microarrays

Oligonucleotide microarrays are commonly adopted for detecting and qualifying the abundance of molecules in biological samples. Analysis of microarray data starts with recording and interpreting hybridization signals from CEL images. However, many CEL images may be blemished by noises from various sources, observed as “bright spots”, “dark clouds”, and “shadowy circles”, etc. It is crucial that these image defects are correctly identified and properly processed. Existing approaches mainly focus on detecting defect areas and removing affected intensities. In this article, we propose to use a mixed effect model for imputing the affected intensities. The proposed imputation procedure is a single-array-based approach which does not require any biological replicate or between-array normalization. We further examine its performance by using Affymetrix high-density SNP arrays. The results show that this imputation procedure significantly reduces genotyping error rates. We also discuss the necessary adjustments for its potential extension to other oligonucleotide microarrays, such as gene expression profiling. The R source code for the implementation of approach is freely available upon request.     

Prognostic Implication of M2 Macrophages Are Determined by the Proportional Balance of Tumor Associated Macrophages and Tumor Infiltrating Lymphocytes in Microsatellite-Unstable Gastric Carcinoma

Tumor associated macrophages are major inflammatory cells that play an important role in the tumor microenvironment. In this study, we investigated the prognostic significance of tumor associated macrophages (TAMs) in MSI-high gastric cancers using immunohistochemistry. CD68 and CD163 were used as markers for total infiltrating macrophages and M2-polarized macrophages, respectively. The density of CD68+ or CD163+ TAMs in four different areas (epithelial and stromal compartments of both the tumor center and invasive front) were analyzed in 143 cases of MSI-high advanced gastric cancers using a computerized image analysis system. Gastric cancers were scored as “0” or “1” in each area when the density of CD68+ and CD163+ TAMs was below or above the median value. Low density of CD68+ or CD163+ macrophages in four combined areas was closely associated with more frequent low-grade histology and the intestinal type tumor of the Lauren classification. In survival analysis, the low density of CD163+ TAMs was significantly associated with poor disease-free survival. In multivariate survival analysis, CD163+ TAMs in four combined areas, stromal and epithelial compartments of both tumor center and invasive front were independent prognostic indicator in MSI-high gastric cancers. In addition, the density of CD163+ TAMs correlated with tumor infiltrating lymphocytes (TILs). Our results indicate that the high density of CD163+ TAMs is an independent prognostic marker heralding prolonged disease-free survival and that the prognostic implication of CD163+ TAMs might be determined by the proportional balance of TAMs and TILs in MSI-high gastric cancers.     

IGFBP3, a Transcriptional Target of Homeobox D10, Is Correlated with the Prognosis of Gastric Cancer

Homeobox D10 (HoxD10) plays important roles in the differentiation of embryonic cells and progression of breast cancer. Our previous report revealed that insulin-like growth factor binding protein-3 (IGFBP3) was regulated by HoxD10 in gastric cancer cells; however, the functional roles and underlying mechanisms of IGFBP3 in gastric cancer remain unclear. Here, we found that the expression of IGFBP3 were upregulated after ectopic expression of HoxD10 in gastric cancer cells. Chromatin immunoprecipitation assay showed that HoxD10 bound to three potential regions of IGFBP3 promoter. Exogenous HoxD10 significantly enhanced the activity of luciferase reporter containing these binding regions in gastric cancer cells. Further data showed that all of these binding sites had Hox binding element “TTAT”. Immunohistochemical staining results revealed that IGFBP3 expression was significantly downregulated in 86 gastric adenocarcinomas tissues relative to their adjacent non-cancerous tissues (p<0.001). Moreover, IGFBP3 expression was significantly lower in gastric tumor with lymph node metastasis compared with that without lymph node metastasis (p=0.045). Patients with high expression level of IGFBP3 showed favorable 5 year overall survival (p=0.011). Knockdown of IGFBP3 accelerated gastric cancer cell migration and invasion and induced the expression of invasive factors including MMP14, uPA and uPAR. Thus, our data suggest that HoxD10-targeted gene IGFBP3 may suppress gastric cancer cell invasion and favors the survival of gastric cancer patients.     

Identification of miRNAs Expression Profile in Gastric Cancer Using Self-Organizing Maps (SOM)

In this paper, an unsupervised artificial neural network was implemented to identify the patters of specific signatures. The network was based on the differential expression of miRNAs (under or over expression) found in healthy or cancerous gastric tissues. Among the tissues analyzes, the neural network evaluated 514 miRNAs of gastric tissue that exhibited significant differential expression. The result suggested a specific expression signature nine miRNAs (hsa-mir-21, hsa-mir-29a, hsa-mir-29c, hsa-mir-148a, hsa-mir-141, hsa-let-7b, hsa-mir-31, hsa-mir-451, and hsa-mir-192), all with significant values (p-value < 0.01 and fold change > 5) that clustered the samples into two groups: healthy tissue and gastric cancer tissue. The results obtained “in silico” must be validated in a molecular biology laboratory; if confirmed, this method may be used in the future as a risk marker for gastric cancer development.     

Effect of Several Drugs on Gastric Potential Difference in Man

Measurement of gastric mucosal potential difference was used to study the effect on the gastric mucosal barrier in six volunteer subjects of several drugs known to provoke ulcers. Potential differences were also recorded in nine patients with rheumatoid arthritis being treated with long-term aspirin and five patients on long-term prednisone. Unbuffered aspirin and ethanol “broke” the barrier as shown by a rapid fall in potential difference. The effects of aspirin were dose related, with 600 mg causing a greater reduction than 300 mg. The effects of aspirin and ethanol given together were additive and caused the greatest fall in potential difference. Sodium acetylsalicylate did not alter the normal potential difference. Indomethacin, phenylbutazone, and prednisone all failed to cause any change in potential difference. The patients on long-term aspirin and prednisone had readings within the normal range and responded the same as normal subjects to an acute challenge. These studies show that aspirin and ethanol will damage the gastric mucosal barrier but that indomethacin, phenylbutazone, and prednisone do not.     

Immobilisation stress-induced anorexia is not due to gastric ulceration

The relationship between the anorexia following immobilisation and the associated gastric pathology in male and female rats was investigated. Male rats were injected with saline or the histamine-H2. antagonist, ranitidine, which inhibits gastric acid secretion but does not readily enter the brain. Thirty minutes later, the animals were immobilised for 2 hours. Ranitidine pretreatment reduced the number of gastric lesions but had no effect on the degree of stress-induced anorexia. The number of gastric lesions did not correlate significantly with the degree of anorexia or weight loss. Previous studies have reported that female rats (unlike males) exhibit anorexia after repeated daily immobilisations and have greater gastric pathology following stress. Therefore, in a second experiment, female rats were pretreated with saline or ranitidine and immobilised for 2 hours/day for 4 days. The drug did not decrease the number of lesions observed after this treatment. However, as in the first experiment, the number of lesions did not correlate significantly with anorexia or weight loss. It is therefore unlikely that immobilisation stress-induced anorexia in either male or female rats is merely a consequence of gastric ulceration.     

Role of gastrin in duodenal mechanisms of inhibition of gastric secretion in the dog and man

Gastrin serum levels after acidification of the second portion of the duodenum were studied, in dogs and humans, while simultaneously measuring secretin levels and gastric acid secretion. After duodenal acidification in dogs, a 50% inhibition of gastric acid secretion with parallel 100% increases in the serum secretin levels was noted whereas gastrin serum levels did not change (after duodenal acidification). In humans, a 25% inhibition of gastric acid secretion with parallel 50% (not significative) increases in the secretin serum levels was noted. In the entire group gastrin levels did not change, but in 35.2% of the subjects a little increment without statistical significance was noted. It is concluded that the inhibition mechanism of gastric acid secretion after duodenal acidification is more important in dog than in man, and that, probably, gastrin does not play an important role in this mechanism.     

Calpain 8/nCL-2 and Calpain 9/nCL-4 Constitute an Active Protease Complex,G-Calpain,Involved in Gastric Mucosal Defense

Calpains constitute a superfamily of Ca²⁺-dependent cysteine proteases, indispensable for various cellular processes. Among the 15 mammalian calpains, calpain 8/nCL-2 and calpain 9/nCL-4 are predominantly expressed in the gastrointestinal tract and are restricted to the gastric surface mucus (pit) cells in the stomach. Possible functions reported for calpain 8 are in vesicle trafficking between ER and Golgi, and calpain 9 are implicated in suppressing tumorigenesis. These highlight that calpains 8 and 9 are regulated differently from each other and from conventional calpains and, thus, have potentially important, specific functions in the gastrointestinal tract. However, there is no direct evidence implicating calpain 8 or 9 in human disease, and their properties and physiological functions are currently unknown. To address their physiological roles, we analyzed mice with mutations in the genes for these calpains, Capn8 and Capn9. Capn8^−/− and Capn9^−/− mice were fertile, and their gastric mucosae appeared normal. However, both mice were susceptible to gastric mucosal injury induced by ethanol administration. Moreover, the Capn8^−/− stomach showed significant decreases in both calpains 9 and 8, and the same was true for Capn9^−/−. Consistent with this finding, in the wild-type stomach, calpains 8 and 9 formed a complex we termed “G-calpain,” in which both were essential for activity. This is the first example of a “hybrid” calpain complex. To address the physiological relevance of the calpain 8 proteolytic activity, we generated calpain 8:C105S “knock-in” (Capn8^CS/CS) mice, which expressed a proteolytically inactive, but structurally intact, calpain 8. Although, unlike the Capn8^−/− stomach, that of the Capn8^CS/CS mice expressed a stable and active calpain 9, the mice were susceptible to ethanol-induced gastric injury. These results provide the first evidence that both of the gastrointestinal-tract-specific calpains are essential for gastric mucosal defense, and they point to G-calpain as a potential target for gastropathies caused by external stresses.     

Autocatalysis in a reconstituted chloroplast system

In whole plants and intact chloroplasts, photosynthesis does not reach its full rate immediately upon illumination but only after a lag which is believed to reflect an autocatalytic increase in the concentration of carbon cycle intermediates. Autocatalysis has now been observed in a reconstituted system containing envelope-free chloroplasts augmented with ferredoxin and other stromal proteins but only catalytic amounts of ATP and NADP. With ribose 5-phosphate as substrate, the CO₂ dependent O₂ evolution recorded for such mixtures implies rates of “endogenous” or ferredoxin-dependent photophosphorylation as high as 360 μmoles of orthophosphate esterified mg⁻¹ chlorophyll hr⁻¹.     

Distribution of cell surface saccharides on pancreatic cells

We describe here a simple, general procedure for the purification of a variety of lectins, and for the preparation of lectin-ferritin conjugates of defined molar composition and binding properties to be used as probes for cell surface saccharides. The technique uses a “universal” affinity column for lectins and their conjugates, which consists of hog sulfated gastric mucin glycopeptides covalently coupled to agarose. The procedure involes: (a) purification of lectins by chromatography of aqueous extracts of seeds or other lectin-containing fluids over the affinity column, followed by desorption of the desired lectin with its hapten suge; (b) iodination of the lectin to serve as a marker during subsequent steps; (c) conjugation of lectin to ferritin with glutaraldehyde; (d) collection of active lectin-ferritin conjugates by affinity chromatography; and (e) separation of monomeric lectin-ferritin conjugates from larger aggregates and unconjugated lectin by gel chromatography. Based on radioactivity and absorbancy at 310 nm for lectin and ferritin, respectively, the conjugates consist of one to two molecules of lectin per ferrritin molecule. Binding studies of native lectins and their ferritin conjugates to dispersed pancreatic acinar cells showed that the conjugation procedure does not significantly alter either the affinity constant of the lectin for its receptor on the cell surface or the number of sites detected.