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Biomedical subjects

K Miki

Publications and source records attributed to K Miki.

At least 145 records · Page 8Linked to original sources

Differentially expressed MHC class II-associated invariant chain in rat stomach pyloric mucosa with N-methyl-N-nitro-nitrosoguanidine exposure.

Administration of N-methyl-N'-nitro-N-nitrosoguanidine, a glandular stomach carcinogen, at the concentration of 100 microg/ml in drinking water for 8 days induced the appearance of a MHC class II-associated invariant chain in the target organ of stomach pyloric mucosa of male Lewis rats. The up-regulation of the MHC class II-associated invariant chain was revealed by fluorescent differential display analysis, reverse transcription-PCR, Northern blot, and histochemical staining. The appearance of MHC class II and MHC class I was also demonstrated by reverse transcription-PCR and Northern blot. The results suggest the involvement of MHC-controlled immune reactions in chemically-induced stomach carcinogenesis.

Animals↗

Expression of three membrane-type matrix metalloproteinases (MT-MMPs) in rat vascular smooth muscle cells and characterization of MT3-MMPs with and without transmembrane domain.

Matrix metalloproteinases (MMPs) produced by rat smooth muscle cells (SMCs) were investigated. SMCs expressed three kinds of membrane-type MMP, MT1-MMP, MT2-MMP, and MT3-MMP, and the MT-MMP expression was stimulated by the presence of serum. MT3-MMP was characterized further by cloning its cDNA. A rat MT3-MMP cDNA encoding 607 amino acids and a cDNA for its transmembrane domainless variant MT3-MMP-del were cloned from a rat SMC cDNA library; a human MT3-MMP cDNA was cloned from a fetal brain cDNA library. Human brain MT3-MMP was similar but not identical to the previously reported human placenta MT3-MMP (94.4% homology). When the MT3-MMP cDNA was expressed in COS-7 cells, endogenous progelatinase A was processed to the mature form. The transfection of rat MT3-MMP-del efficiently converted progelatinase A to the intermediate form but not to the mature one, indicating that the transmembrane domain is important for the complete processing of progelatinase A to maturation. Both MT3-MMP-del and MT3-MMP hydrolyzed gelatin and casein, indicating their broad substrate specificity. Results of experiments with a synthetic MMP inhibitor suggested that MT3-MMP-del and MT3-MMP are rapidly degraded immediately after maturation. The present study suggests that multiple forms of MMPs including MT3-MMP are involved in the matrix remodeling of blood vessels.

Amino Acid Sequence↗

Substratum-dependent and region-specific control of attachment and proliferation of gastrointestinal epithelial cells in primary serum-free culture.

A system for the primary serum-free culture of fetal rat gastrointestinal epithelial cells was used to examine the role of the extracellular matrix (ECM) in the attachment and proliferation of these epithelial cells. Forestomach epithelial cells (FSEC) were able to attach to and proliferate on plastic dishes without a substratum, while glandular stomach epithelial cells (GSEC) and duodenal epithelial cells (DEC) were unable to do so. The presence of a substratum promoted the attachment and proliferation of these epithelial cells. The effects of various components of the ECM differed depending on the type of cell. FSEC attached most efficiently to a substratum of fibronectin, while GSEC did so to laminin. DEC attached more efficiently to type I collagen and fibronectin than to any other substratum. FSEC proliferated most rapidly on laminin, while GSEC and DEC did so on collagen gels. These substrata induced the most efficient attachment and proliferation of FSEC, and they were effective in promoting the attachment and proliferation of GSEC and DEC in decreasing order of efficiency, indicating the existence of a head-to-tail gradient in the response of epithelial cells to substrata. The expression of c-myc mRNA in these cells differed depending upon the substratum on which they were cultured and the mRNA level was well correlated with the extent of the cell proliferation, indicating that the cell proliferation is mediated by c-myc gene expression, which is regulated by cell-ECM interactions. The results of the present study demonstrate that proliferation of gastrointestinal epithelial cells is regulated region-specifically not only by soluble factors but also by insoluble components of the ECM.

Animals↗

Cowden's disease with a defined genetic alteration--chromosomal duplication at 15q11-q13.

Cowden's disease, multiple hamartoma syndrome, is a dominantly inherited disorder characterized by multiple hamartomas of ectodermal, endodermal, and mesodermal origin and also by a high incidence of malignant tumors. Despite many efforts to identify the genetic alterations responsible for the syndrome, the molecular mechanism remains unclear. We report a case of Cowden's disease in which karyotype analysis revealed a small duplication (about 1 Mb) at 15q11-q13. This part of the genome is a region that is deleted in the Prader-Willi/Angelman syndrome and is a "hot spot" of chromosomal duplication.

Chromosome Aberrations↗

Intestinalization of gastric signet ring cell carcinomas with progression.

Recent developments in mucin histochemistry and immunohistochemistry have made reliable determination of the gastric and intestinal phenotypes of gastric carcinoma cells possible. Phenotypic expression changes from gastric epithelial cell type to intestinal epithelial cell type with the growth of gastric tumours in experimental animals. We studied cell differentiation in gastric signet ring cell carcinomas with progression in 203 surgically obtained specimens. The results showed that the proportion of gastric phenotype carcinomas, in which over 90% of the tissue consists of gastric epithelial cell type cells, decreases with the depth of invasion. The proportion of mixed phenotype carcinomas (between 10% and 90% of the tissue made up of gastric and/or intestinal epithelial cell type cells) increases. The intestinal phenotype (over 90% intestinal epithelial cell type carcinoma cells) was found in four carcinomas (about 2%) involving the serosa. No clear relationship was evident between phenotypic expression of carcinoma cells and the degree of intestinal metaplasia of the surrounding mucosa. Progression of gastric signet ring cell carcinomas is associated with a phenotypic shift from gastric to intestinal type expression.

Carcinoma, Signet Ring Cell↗

Evaluation of mean skin temperature formulas by infrared thermography.

To study the reliability of formulas for calculating mean skin temperature (Tsk), values were computed by 18 different techniques and were compared with the mean of 10,841 skin temperatures measured by infrared thermography. One hundred whole-body infrared thermograms were scanned in ten resting males while changing the air temperature from 40 degrees C to 4 degrees C. Local, regional average and mean skin temperatures were obtained using an image processing system. The agreement frequency, defined as the percentage of the calculated Tsk values which agreed with the corresponding infrared thermographic Tsk within +/- 0.2 degree C, ranged for with the various formulas from 7% to 80%. In many sites, the local skin temperature did not coincide with the regional average skin temperature. When the local skin temperatures which showed the highest percentage similarity to the regional average skin temperature within +/- 0.4 degree C were applied to the formula, the agreement frequency was markedly improved for all formulas. However, the agreement frequency was not affected by changing the weighting factors from specific constants to individually measured values of regional surface area. By applying the physiologically reliable accuracy range of +/- 0.2 degree C in the moderate and +/- 0.4 degree C in the cool condition, agreement frequencies of at least 95% were observed in formulas involving seven or more skin temperature measurement sites, including the hand and foot. We conclude that calculation of a reliable mean skin temperature must involve more than seven skin temperature measurement sites regardless of ambient temperature. Optimal sites for skin temperature measurement are proposed for various formulas.

Adult↗

Helicobacter pylori infection and gastric cancer. A nested case-control study in a rural area of Japan.

We conducted a seroepidemiological nested case-control study to determine the association of gastric cancer with Helicobacter pylori infection and atrophic gastritis. A cohort of 2858 participants in an annual multiphasic health check-up were followed for eight years. Data for 45 gastric cancer cases and 225 sex-, age-, and address-matched control subjects were analyzed. Helicobacter pylori infection was determined by IgG antibodies, and atrophic gastritis was diagnosed by both serum pepsinogen I level (< or = 70 ng/ml) and the pepsinogen I/II ratio (< or = 3.0). Univariate analysis showed that Helicobacter pylori and atrophic gastritis were significantly associated with gastric cancer. In a multivariate analysis, atrophic gastritis was associated with significantly increased risk of cancer (odds ratio, 3.38; 95% confidence interval, 1.54-7.42); however, Helicobacter pylori was not associated with cancer (odds ratio, 1.84; 95% confidence interval, 0.59-5.72). These results suggest that Helicobacter pylori infection alone is not directly associated with gastric carcinogenesis but has an indirect relation to gastric cancer through the development of atrophic gastritis.

Adult↗

Crystal structure of DNA photolyase from Anacystis nidulans.

The crystal structure at 1.8 A resolution of 8-HDF type photolyase from A. nidulans shows a backbone structure similar to that of MTHF type E. coli photolyase but reveals a completely different binding site for the light-harvesting cofactor.

Amino Acid Sequence↗

Proliferation, differentiation and morphogenesis of fetal rat glandular stomach transplanted under the kidney capsule of syngeneic hosts.

Undifferentiated glandular stomach tissue fragments from 16.5-day fetal rats were transplanted under the kidney capsule of syngeneic adult rats, and the proliferation, differentiation and morphogenesis of the transplanted tissues were investigated. Gastric epithelial cells began to invaginate 3-4 days after the transplantation and immature glands were formed after 1 week. During the period, there was a gradual increase in the expression of pepsinogen and cathepsin E, markers of cytodifferentiation of the stomach epithelia, both at protein and mRNA levels. Cathepsin E was weakly expressed in undifferentiated gastric epithelial cells at 16.5 days of gestation, and a higher level of the expression was observed in differentiated epithelia of the transplants. In contrast, the pepsinogen-producing cells first appeared around days 3-4 after transplantation and gradually increased in number to about 30% of the epithelial cells and became localized at the bottom of the gland. During the period of the experiment up to 1 month, the pepsinogen-producing cells were all positive for class III mucin and cathepsin E, indicating the immature character of these cells. In addition, no parietal cells were observed. When the tissue fragments were transplanted into adrenalectomized animals, the epithelial differentiation and morphogenesis was suppressed, but its proliferation was enhanced. The observed changes were reversed by hydrocortisone replacement. These results suggest that the development of the 16.5-day fetal stomach is regulated intrinsically to a certain extent by the genetic program of the cells involved and various gastric functions develop in the absence of luminal stimulation, stage-specific systemic hormonal change, neuronal regulation or other systemic influences, and that glucocorticoids modulate the developmental program of the fetal stomach tissues.

Adrenalectomy↗

Measurement of liver volume and hepatic functional reserve as a guide to decision-making in resectional surgery for hepatic tumors.

The respective volumes of hepatic tumors and nontumorous parenchyma of 50 patients requiring hepatectomy of more than one segment of Healey for tumor removal were measured using computed tomography (Vol-CT). The volume estimated by Vol-CT was found to correlate with the real weight resected (P < .0001) with a mean absolute error of 64.9 mL. The ratio of the nontumorous parenchymal volume of the resected liver to that of the whole liver (R2) in 15 patients who underwent right or extended right hepatic lobectomy was 43% +/- 15%. Eight of 15 patients with R2s < 60% underwent the procedures without right portal vein embolization (PE). The other seven with R2s exceeding 60% or an indocyanine green retention rate after 15 minutes (ICG15) of 10% to 20% underwent PE: in six of seven, the nontumorous parenchyma of the right hepatic lobe became atrophic and in all seven, the volume of the remaining left hepatic lobe increased with a decrease in the mean R2 from 62% +/- 14% to 55% +/- 8% (P = .0006). In the remaining 35 who underwent other hepatectomy procedures, R2s also remained <60%. Overall, at surgery, in 27 with normal liver function (ICG15 < 10%), R2s exceeded 60% in one, remained at 50% to 60% in five, and <50% in 21, whereas 23 patients except for one with an ICG15 exceeding 10%, had R2s of <50%. The postoperative serum total bilirubin levels in 84% of the patients remained within the normal range and there was no surgery-related mortality. In conclusion, 1) Vol-CT can accurately assess the extent of liver resection, 2) individuals with normal liver function can undergo resection of up to 60% of the nontumorous parenchyma without the need for PE, and 3) PE can be used to reduce the size of the resected tissue and increase the volume of the remnant liver to approximate the target limits in individuals with large tumors or minimally abnormal liver function.

Aged↗

Expression of the long arm sequence of mouse laminin alpha1, beta1, or gamma1 chain in COS1 cells and assembly of monkey-mouse hybrid laminin.

Mouse laminin alpha1, beta1, or gamma1 sequence covering truncated regions of the long arm was transiently expressed in monkey COS1 cells. Unlike natural laminins, in which only alpha beta gamma trimers are selectively assembled and disulfide-bonded at the long arm, a large fraction of mouse chains formed disulfide-bonded homopolymers. However, a small fraction of mouse beta1 (or gamma1) formed hybrid beta1gamma1 dimers with endogenous monkey gamma1 (or beta1). These hybrid beta1gamma1 dimers formed alpha1 beta1 gamma1 trimer with monkey alpha1. Mouse alpha1 also formed disulfide bonds with monkey beta1gamma1 dimer. Thus, a common mechanism is shared by laminin chains of different animal origins. Sequences in the E8 region at the C-terminal end of the long arm were crucial for this chain-selective assembly. When the C-terminal sequence of mouse beta1 long arm was extended beyond the alpha-loop, the hybrid trimer formation was diminished. This supported the model of altered chain arrangement around the alpha-loop.

Animals↗

Crystallization and preliminary X-ray diffraction studies of expressed Pseudomonas putida catechol 2,3-dioxygenase.

Crystals of recombinant Pseudomonas putida catechol 2,3-dioxygenase, metapyrocate-chase, composed of four identical subunits, each with a molecular mass of 35 kDa and one nonheme ferrous iron, have been grown by the vapor diffusion method using sodium citrate as the precipitant. Repeated macroseeding and the addition of ethanol to protein solutions were together effective for obtaining crystals suitable for further crystallographic characterization. The crystals belong to the tetragonal space group P4(2)2(1)2 with unit-cell dimensions of a = b = 266 A, c = 60 A. They diffracted beyond 2.5 A resolution with synchrotron radiation. Assuming that one tetramer (alpha-Fe2+)4 is contained in an asymmetric unit, the crystal volume per unit molecular mass, Vm, is calculated to be 3.8 A3/Da, which corresponds to the solvent content of 67.6%.

Catechol 2,3-Dioxygenase↗

Helicobacter pylori infection and atrophic gastritis. A case-control study in a rural town of Japan.

We enrolled five hundred twenty-one patients with atrophic gastritis and 769 controls in a case-control study of atrophic gastritis and Helicobacter pylori infection and lifestyle factors. The participants had no history of upper gastrointestinal surgery. They were selected from 1,395 adult (35 years or older) residents of a rural town in Kyoto prefecture who participated in an annual health examination in 1987. Atrophic gastritis was diagnosed on the basis of serum pepsinogen levels: pepsinogen I levels (< or = 70 ng/ml) and pepsinogen I/pepsinogen II ratios (< or = 3.0). The presence of immunoglobulin G antibodies to H. pylori indicated H. pylori infection. At the time of the health examination, participants were interviewed about daily lifestyle habits such as use of cigarettes and alcoholic beverages and consumption of green-yellow vegetables. Unconditional logistic regression analysis indicated that H. pylori infection was associated with a significantly increased risk for atrophic gastritis for all participants (odds ratio, 8.17; 95% confidence interval, 5.63-11.84); for men (odds ratio, 10.91; 95% CI, 5.25-22.67); and for women (odds ratio, 7.28; 95% CI, 4.72-11.22). We found no statistically significant relations between lifestyle factors and atrophic gastritis.

Adult↗

Gastric and intestinal mixed and solely intestinal types of intestinal metaplasia in the human stomach.

To generate a novel understanding of intestinal metaplasia (IM) on the basis of cellular differentiation status, a total of 132 gastric surgical specimens were studied using gastric and small intestinal cell markers by mucin histochemical and immunohistochemical techniques. The cases were divided into two types: (i) gastric and intestinal (GI) mixed type; and (ii) solely intestinal (I) type, with the reference to the presence of gastric and/or intestinal cell markers. The GI mixed type was subdivided into six subtypes: (I) a subtype consisting of surface mucous (Su), pyloric gland (Py), intestinal absorptive (Ab), and goblet (Go) cells, but lacking Paneth (Pa) cells, GI(Pa-); (ii) a GI(Pa-) subtype without Py cells, GI(Py-, Pa-); (iii) a GI(Pa-) subtype without Su cells, GI(Su-, Pa-); (iv) a GI(Su-, Pa-) subtype with Pa cells, GI(Su-, Pa+); (v) a GI(Pa-) subtype with Pa cells, GI(Pa+); and (vi) a GI(Pa+) subtype without Py cells, GI(Py-, Pa+). The I type was subdivided into: (i) a subtype consisting of cells with Ab and Go cells, I(Pa-); and (ii) a I(Pa-) subtype with Paneth cells, I(Pa+). The GI mixed subtypes, except for the GI(Py-, Pa-) and GI(Py-, Pa+), were characterized by intestinalized gastric pits connected with underlying pyloric glands. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) revealed a common proliferative cell zone between the two. The GI mixed type, especially the GI(Pa-) subtype, predominated in the pyloric mucosa, while the I type was most frequent in the fundic region, suggesting that the pathogenesis of IM differs between these two locations. The results of the study confirm that IM is an abnormal and unstable differentiation status between the stomach and small intestine.

Adult↗

[Usefulness of Helicobacter pylori detection from feces specimens of the patients with peptic ulcer by polymerase chain reaction].

Detection of Helicobacter pylori was studied on the feces and biopsy specimens of 91 patients with gastric ulcer by using cultured and polymerase chain reaction methods. Number of samples from feces and biopsy specimens were 1 (1.1%) and 56 (61.5%) by culture method, on the other hands 49 (53.8%) and 70 (76.9%) in polymerase chain reaction method, respectively. Sensitivity of polymerase chain reaction applied to feces and biopsy specimens were 68.1 and 97.2, respectively. Noninvasive diagnosis such as detection of organisms from feces is effective for patients who have difficulty in collecting the gastric biopsy specimens. Infection route was not clarified, however, fecal-to-oral transmission was strongly suggested by the fact that the organisms were detected from feces samples in this study.

Biopsy↗

Characterisation of relaxation of the lower oesophageal sphincter in healthy premature infants.

BACKGROUND: Gastro-oesophageal reflux disease causes significant morbidity in premature infants, but the role of dysfunction of the lower oesophageal sphincter (LOS) in this condition is unclear. METHODS: Oesophageal manometry was performed after gavage feeding in 13 healthy preterm neonates (postmenstrual age > or = 33 weeks) with a perfused sleeve with side hole assembly. Swallow related (both single and multiple) and transient LOS relaxations (TLOSRs) were identified and the characteristics of these events defined. Reflux was identified with manometric criteria (common cavity episodes). RESULTS: Five hundred and eleven relaxation of the LOS were observed, 55% related to single swallows, 23% related to multiple swallows, and 22% TLOSRs. The time to maximal LOS relaxation was longer for TLOSRs than for single or multiple swallows (mean (SEM) 5.0 (0.3) s v 3.0 (0.1) s and 3.3 (0.1) s, p < 0.0001 and p < 0.005). The durations of multiple swallows and TLOSRs were longer than single swallows (12.2 (0.5) s and 11.2 (0.4) s v 5.3 (0.2) s, p < 0.0001). Most of the oesophageal body common cavity episodes (94%) occurred during TLOSRs. CONCLUSIONS: In healthy preterm infants (postmenstrual age > or = 33 weeks) the motor events associated with LOS relaxation were similar to those seen in healthy adults. TLOSRs may be an important mechanism of reflux in premature infants.

Deglutition↗

An increase in noradrenaline excretion during prolonged mental task load.

To investigate the effects of prolonged mental work, urinary excretion of catecholamines and cortisol was measured in 18 human subjects from 9:30 to 17:00. On the "task day,' the subjects performed mental tasks during the morning (10:20-11:45) and afternoon sessions (13:00-17:00), otherwise taking chair rest. On the "control day,' the subjects took chair rest in the afternoon after performing mental tasks in the morning. In the morning session, urinary excretion of adrenaline during mental work increased greatly compared to that before the mental work. Mental work in the afternoon session also caused a marked increase in adrenaline excretion compared to the rest level in the afternoon on the control day. Cortisol levels in the first hour of the afternoon mental work were significantly higher than those during the corresponding time on the control day. Urinary excretion of noradrenaline during mental work in the morning session only increased slightly compared to that before the mental work. In the afternoon session, however, noradrenaline excretion during mental work on the task day was markedly elevated compared to that during the rest condition at the corresponding time on the control day. These findings suggest that prolonged exposure to mental work, but not short-term mental work, produces a marked increase in noradrenaline excretion in human subjects.

Adult↗