Reg I-knockout mice reveal its role in regulation of cell growth that is required in generation and maintenance of the villous structure of small intestine.

Reg I (regenerating gene product I) is a growth factor that plays a central role in the generation and regeneration of the gastric mucosal architecture. On the other hand, mouse Reg I mRNA is expressed at the highest levels in the small intestine among the gastrointestinal tissues. In the current study, with the aim to clarify the role of Reg I protein in the small intestine, the temporal and spatial pattern of Reg I expression and the phenotype of Reg I-knockout mice in the tissue were examined. In the wild-type mice, immunohistochemistry localized Reg I protein expression in absorptive cells located in the lower half of the intestinal villi. Reg I expression was undetectable until embryonic day 13 (E13), when the fetal intestine still lacks villous structure; however, it dramatically increased at E17 along with the formation and maturation of the fetal intestinal villi. In the small intestine of the adult Reg I-knockout mice, less densely packed, round-shaped aberrant morphology of the absorptive cells was observed light microscopically, and electron microscopical examination revealed a strikingly loose connection of these cells to the basement membrane. Antiproliferating cell nuclear antigen staining and anti-Ki67 staining demonstrated the marked decrease in the number of proliferating cells in the small intestinal mucosa of the knockout mice. The cell migration speed visualized by one shot labeling of 5-bromodeoxyuridine was significantly slower in the knockout mice. These phenotypes of Reg I-knockout mice emerged, in accordance with the temporal pattern of Reg I expression described above, from E17. Reg I was considered to be a regulator of cell growth that is required to generate and maintain the villous structure of the small intestine.

Interobserver agreement on classifying endoscopic diagnoses of nonerosive esophagitis.

BACKGROUND AND STUDY AIMS: The majority of patients with gastroesophageal reflux disease in Japan have low-grade esophagitis, including minimal changes. A modified Los Angeles classification of esophagitis, consisting of erosive esophagitis (grades A - D) and nonerosive esophagitis (grades M and N) has been proposed and is in clinical use in Japan. However, it is unclear whether nonerosive esophagitis with only undemarcated mucosal discoloration (grade M) is clinically significant, since interobserver variations in classification have not been investigated. The aim of the present study was therefore to evaluate interobserver variance and diagnostic agreement in the diagnosis of nonerosive esophagitis (grades M and N). MATERIALS AND METHODS: A total of 84 endoscopists were enrolled to assess the grade of esophagitis in 30 patients by viewing endoscopic images of the gastroesophageal junction. The images were projected onto a screen, and all of the endoscopists reviewed them concurrently. The diagnosis was selected from the following three categories in the modified Los Angeles classification: grades N, M, or A. The endoscopists were grouped according to their experience, whether they had a board license, and whether they had received specialist training in esophagitis. The kappa coefficient of reliability was calculated. RESULTS: The kappa coefficient of reliability for all the endoscopists in the diagnosis of cases of grade M and N nonerosive esophagitis was unacceptably low at 0.22 (95 % CI, 0.21 - 0.24). Endoscopists with a board license and those who had completed a special esophagitis diagnostic course had slightly higher kappa values (0.26; 95 % CI, 0.23 - 0.30 and 0.29; 95 % CI, 0.26 - 0.32), respectively. CONCLUSIONS: Interobserver agreement on the endoscopic diagnosis of nonerosive esophagitis (grades M and N) is too low to be of clinical value.

Evaluation of modified crystal violet chromoendoscopy procedure using new mucosal pit pattern classification for detection of Barrett's dysplastic lesions.

BACKGROUND: Pit pattern diagnosis is important for endoscopic detection of dysplastic Barrett's lesions, though using magnification endoscopy can be difficult and laborious. We investigated the usefulness of a modified crystal violet chromoendoscopy procedure and utilised a new pit pattern classification for diagnosis of dysplastic Barrett's lesions. METHODS: A total of 1,030 patients suspected of having a columnar lined oesophagus were examined, of whom 816 demonstrated a crystal violet-stained columnar lined oesophagus. The early group of patients underwent 0.05% crystal violet chromoendoscopy, while the later group was examined using 0.03% crystal violet with 3.0% acetate. A targeted biopsy of the columnar lined oesophagus was performed using crystal violet staining after making a diagnosis of closed or open type pit pattern with a newly proposed system of classification. The relationship between type of pit pattern and histologically identified dysplastic Barrett's lesions was evaluated. RESULTS: Dysplastic Barrett's lesions were identified in biopsy samples with an open type pit pattern with a sensitivity of 96.0%. Further, Barrett's mucosa with the intestinal predominant mucin phenotype was closely associated with the open type pit pattern (sensitivity 81.9%, specificity 95.6%). CONCLUSIONS: The new pit pattern classification for diagnosis of Barrett's mucosa was found to be useful for identification of cases with dysplastic lesions and possible malignant potential using a crystal violet chromoendoscopic procedure.

A prospective randomized comparative study on the safety and tolerability of transnasal esophagogastroduodenoscopy.

BACKGROUND AND STUDY AIM: Transnasal esophagogastroduodenoscopy (EGD) with a small-caliber endoscope is well tolerated by patients. However, the effect of this procedure on cardiopulmonary function has not been fully investigated. The aim of this prospective, randomized study was to investigate the effect of transnasal EGD in comparison with transoral EGD on cardiopulmonary function. PATIENTS AND METHODS: The study involved 450 patients referred for diagnostic EGD. Patients were randomly assigned to one of three types of unsedated EGD (150 patients per group): transnasal EGD using a small-caliber endoscope (the "XP-N" group), transoral EGD using the same small-caliber endoscope ("XP-O" group), and transoral EGD using a conventional endoscope ("XQ" group). Systolic and diastolic blood pressure, pulse rate, and arterial oxygen saturation were monitored before, and 2, 4 and 6 minutes after intubation, and just after endoscope extubation. Gagging episodes were also counted, to determine tolerance. RESULTS: It was not possible to perform transnasal EGD in 12 patients (8.0%). A small amount of epistaxis was observed in eight (5.8%) of 138 patients who were examined successfully by transnasal EGD. Systolic and diastolic blood pressure, pulse rate, rate-pressure product (pulse rate x systolic blood pressure/100), and the drop in arterial oxygen saturation in the XQ group were significantly greater than in the XP-N and XP-O groups at each time point. In the XP-N group, these parameters were significantly lower than those in the XP-O group at 2 minutes after intubation. Of the tree groups the number of gagging episodes was significantly lower in the XP-N group. CONCLUSION: Transnasal EGD is safer than transoral EGD as it is associated with fewer adverse effects on cardiopulmonary function and is better tolerated by patients.

Crystal structure of 1-aminocyclopropane-1-carboxylate deaminase from Hansenula saturnus.

The pyridoxal 5'-phosphate (PLP)-dependent enzyme 1-aminocyclopropane-1-carboxylate deaminase (ACCD) catalyzes a reaction that involves a ring opening of cyclopropanoid amino acid, yielding alpha-ketobutyrate and ammonia. Unlike other PLP-dependent enzymes, this enzyme has no alpha-hydrogen atom in the substrate. Thus, a unique mechanism for the bond cleavage is expected. The crystal structure of ACCD from Hansenula saturnus has been determined at 2.0 A resolution by the multiple wavelength anomalous diffraction method using mercury atoms as anomalous scatterers. The model was built on the electron density map, which was obtained by the density averaging of multiple crystal forms. The final model was refined to an R-factor of 22.5% and an R(free)-factor of 26.8%. The ACCD folds into two domains, each of which has an open twisted alpha/beta structure similar to the beta-subunit of tryptophan synthase. However, in ACCD, unlike in other members of the beta family of PLP-dependent enzymes, PLP is buried deep in the molecule. The structure provides the first view of the catalytic center of the cyclopropane ring opening.

Inhibition of the acid lipase activity by apolipoprotein A-I in the presence of lysosomal proteases.

It was found that the inhibition of the lysosomal acid lipase activity by rat apolipoprotein A-I (apo A-I) was increased with the degradation of apo A-I by the lysosomal proteases. We demonstrated that apo A-I could effectively inhibit the acid lipase activity even in the presence of the lysosomal proteases using the hepatic lysosomal fraction.

[The importance of nutrition for cancer patients]. / Kostholdets betydning for kreftpasienter.

Good nutrition and nutritional therapy are important for cancer patients before, during and after treatment. The goal for the dietary advices and the nutritional therapy is to maintain or improve the nutritional status of the cancer patients. This seems to have beneficial effects on the oncological therapy. To achieve good results by using nutritional therapy in cancer treatment, a close collaboration between nutritionists, doctors and nurses will be important. The National Nutrition Council initiated in 1996 a working group in order to provide recommendations for diet and nutritional therapy in cancer patients. The group performed a literature review and studied the practice of nutritional therapy in Norwegian hospitals using a mailed questionnaire answered by 33 (72%) hospital departments. This paper gives a summary of this work.

[Dietary information after radiotherapy of head and neck cancer]. / Kostveiledning etter strålebehandling for kreft i hode- og halsregionen.

After completed radiotherapy, 24 in-patients and 25 out-patients enrolled at the Department of Otolaryngology, National Hospital, were randomised to either tailored dietary information and instruction by a clinical nutritionist or regular dietary information from a nurse. At the six weeks follow-up examination the incidence of malnutrition, as evaluated by anthropometry and routine blood analyses, was lower among the patients who had been given intensive information than those who had received regular information (p < 0.05). Out-patients lost more weight than in-patients did (p < 0.05). The in-patients randomised to intensive dietary information were the only ones who did not lose weight. This study indicates a beneficial effect of intensive dietary advice in order to improve nutritional status after radiation treatment.

Quality of life during pelvic radiotherapy.

BACKGROUND: A randomized clinical trial was carried out to evaluate the effect of a diet low in fat and lactose to prevent acute radiation-induced diarrhea. The effect of the diet treatment on the patients' health related quality of life was studied. METHODS: 143 women with gynecological malignancies were included. The daily number and consistency of stools, use of antidiarrheal agents and quality of life measured by using the EORTC Core Quality of life Questionnaire 36 item version, were recorded before therapy, in the last week of treatment, six weeks after end of radiotherapy and every eight weeks during one year's follow up. RESULTS: Fourteen patients (23%) in the intervention group reported diarrhea during radiotherapy, compared to 32 (48%) in the control group (p < 0.01). This difference was not seen with the EORTC questionnaire. The diet intervention did not interfere with emotional and social well-being. Within the control group diarrhea was associated with higher scores on the physical functioning scale (p < 0.01), and fatigue and malaise scale (p < 0.01) indicating more pronounced dysfunction of symptoms. CONCLUSION: When measuring specific phenomena such as diarrhea in a clinical trial, the EORTC questionnaire does not seem to be as sensitive as specific trial-related instruments. Diet intervention during radiotherapy might influence the patients' ability to cope with diarrhea by giving them more control over their own situation.

The effect of a low fat, low lactose diet on nutritional status during pelvic radiotherapy.

The food intake and nutritional status were assessed before, during and after radiotherapy in 143 women with gynaecological malignancies randomized to either a low fat, low lactose diet or a normal diet during treatment. The patients on the low fat, low lactose diet had an intake of fat of 34 g per day during radiotherapy, 41 g per day 6 weeks after radiotherapy and 52 g per day 1 year after radiotherapy, when they were no longer on the diet. The intake in the control group was 57 g per day, 67 g per day and 66 g per day respectively. The total energy intake was reduced in both groups during radiotherapy. The reduced intake of energy resulted in weight loss, greatest in the intervention group. 1 year after radiotherapy both groups had almost regained their initial weight. No marked changes were observed in nutritional status as a result of decreased nutritional intake during radiotherapy.

The influence of low fat, low lactose diet on diarrhoea during pelvic radiotherapy.

In a prospective clinical trial 143 women undergoing pelvic radiotherapy for gynaecological malignancies, were randomized to receive either a low-fat, low-lactose diet (intervention group) or a regular diet (control group) in order to evaluate the possible impact of diet therapy on radiation induced diarrhoea, nausea and vomiting. The daily number and consistency of stools, use of antidiarrhoeal agents, nausea and vomiting were recorded before radiotherapy was begun (week 0), in the last week of therapy (week 6) and 6 weeks after the end of therapy (week 12). The intervention group used half the amount of antidiarrhoeal agents in week 6, than used by the control group (mean 0.6 tablets per day versus 1.1, p < 0.01). 14 patients (23%) in the intervention group reported diarrhoea, versus 32 (48%) in the control group (p < 0.01). In week 12 there were no differences in the use of antidiarrhoeal agents and the prevalence of diarrhoea between the groups.

Separate measurements of surface shapes and refractive index inhomogeneity of an optical element using tunable-source phase shifting interferometry.

A phase shifting interferometer using a tunable laser as a light source is proposed for measuring shapes of both surfaces of a glass plate and the distribution of refractive index. To separate the superimposed interferograms generated with many wavefronts reflected from the plate, the phase shift associated with the wavelength shift is applied in the phase shifting interferometer with unequal optical paths in testing and reference beams. A laser diode is used for the tunable light source, and the data processing for obtaining phase distribution is based on the least-squares fitting in interferograms. The rms errors of the measurements are <1/50 wavelength for the surface shape, and 10(-5) of the refractive index for a 5-mm thick optical glass plate.

Acute subjective morbidity after cisplatin-based combination chemotherapy in patients with testicular cancer: a prospective study.

In a randomized trial, 22 patients with metastatic testicular cancer used low-fibre diet during and after their first cycle of cisplatin and vinblastine containing combination chemotherapy, in order to reduce the acute gastrointestinal post-treatment morbidity (Group 1). Their subjective morbidity, including aspects of general well-being, was compared to 23 comparable patients having no diet restrictions (Group 2). A third similarly composed group consisted of 10 testicular cancer patients without diet restrictions, who received etoposide (VP-16) instead of vinblastine. Low-fibre diet did not reduce the frequency or severity of the acute post-treatment gastrointestinal morbidity. Severe constipation and/or paralytic ileus was observed in 23 patients in Groups 1 and 2 and necessitated short-term hospitalization in 14. The substitution of vinblastine by etoposide resulted in a significant reduction of the acute gastrointestinal morbidity and in a considerable improvement of the patients' general well-being. It is concluded that VP-16 should be given instead of vinblastine to patients receiving cisplatin-based combination chemotherapy in order to maintain an optimal quality of life during cytostatic treatment. This study also indicates that the frequency and severity of subjective treatment-related morbidity often is underestimated by retrospective routine clinical assessment, and should preferably be assessed prospectively by frequently applied patients' questionnaires.

Remote interferometer using an optical fiber.

A simple and stable fiber-optic remote interferometer is constructed by using polarization-maintaining fiber for the transmission of the optical signals and a conventional two-beam interferometer as the sensor. The remote interferometer is sensitive and fringe countable using the two-channel properties of the fiber.