Search

Photosensitizers have attracted considerable attention in various fields such as organic synthesis and medical care. For the development of high-performance photosensitizers, highly efficient and p...

Toshida H, Funaki T, Ono K, et al. Drug Des Devel Ther. 2017;11:1871– 1879 The authors have advised there are some mistakes in themean changes and standard errors of the paper: 1. The standard errors of groups Placebo and VApal wereall the same value for staining and symptom scores inFigure 1 (on page 1875) and Figure 3 (on page 1876),and Table 3 (on page 1877). 2. There were slight discrepancies in the Mean changes ofPlacebo group at 1, 2 and 4 weeks in Figure 3D. 3. There was a slight discrepancy in the Mean change offoreign body sensation in Placebo group at 1 week inTable 3. The authors have advised the errors were due to: 1. The standard error listed in a different table on thestatistical analysis software was adopted. 2. There were typing errors when transferring numericalvalues from statistical analysis software to graph creationsoftware. 3. There was a mistake when rounding numerical value. Since the statistical analysis had been performed using theoriginal mean values (correct values), all results do notchange. The authors apologize for these errors and advise they donot affect the results of the paper. Read the original article

A nonporous molecular crystal (NMC) has been developed for use as a host material. The NMC comprises a platinum dibromide complex with coordinating 9-phenyl-9-arsafluorene ligands. The NMC also contains chlorobenzene (PhCl) molecules, which quench emissions from the platinum complex. On exposure to the vapors of several volatile organic compounds (VOC), the encapsulated PhCl was released. With the loss of PhCl, the crystal once again showed the intrinsic luminescence of the platinum complex. Furthermore, the NMC can recognize the molecular shape of VOCs; consequently, VOCs having small minimum diameters turn on emission, but large VOCs do not cause the release of the included PhCl quencher, and emission remains switched off. Interestingly, a wide range of VOCs (e.g., alcohol, ether, haloalkane, and alkane) could be used, implying that the shape recognition ability of the present NMC system is polarity independent. This is the first example of NMCs having widespread molecular shape recognition properties.

Platinum dihalide (chloride, bromide, and iodide) complexes with 9-phenyl-9-arsafluorene, which can be safely prepared and are air stable, were synthesized. The dibromide and diiodide complexes showed highly efficient phosphorescence even at 298 K in the solid state, and their quantum yields were up to a value of 0.52. The structures of the complexes were analyzed by X-ray crystallography. Time-dependent density functional calculations support our understanding of the initial electron transition processes. The rigid and bulky structure of the arsafluorene backbone effectively induced solid-state phosphorescence unlike that of a triphenylarsine analogue, which has three unbridged phenyl groups.

Nucleophilic arsenic reagents were prepared in situ from a nonvolatile cyclooligoarsine. As-As bond cleavage of the cyclooligoarsine readily proceeded with anion sources. Various kinds of organoarsenic compounds were easily constructed in high yields by selecting anion sources and electrophiles. In comparison with conventional methods of As-C bond formation, a wide variety of organoarsenic compounds were safely and easily synthesized by using this method.

Organoarsenic ligands were synthesized via a safe and easy procedure, superior to the conventional synthetic methodologies. Diiodophenylarsine was prepared in situ, and was readily converted to diarylphenylarsines. Pd-catalyzed Mizoroki–Heck reaction was investigated using the obtained arsenic ligands. It was found that bulky and electron-donating ligands were effective for the reaction, meaning that the success in the screening of arsenic ligand structures was based on the present facile strategy.

Dimethyl acetylenedicarboxylate and one equivalent of aryl amines lead to dimethyl arylaminofumarates, and subsequent addition of alkyl amines readily gave arylaminomaleimide derivatives. Unsymmetrical structures were easily constructed without troublesome purification process. The obtained compounds showed aggregation induced emission (AIE) properties. The luminescence maximum wavelength at the obtained arylaminomaleimide derivatives in solid state were observed from 492 nm to 535 nm, and the quantum yields were up to 0.51. They also exhibited intense luminescence in a polymer matrix.

The mononuclear diiodoplatinum(II) complex (trans-PtI2(cis-DHDAMe)2), where cis-DHDAMe = cis-1,4-dihydro-1,4-dimethyl-2,3,5,6-tetrakis(methoxycarbonyl)-1,4-diarsinine, forms three different crystalline polymorphs that can be either concomitantly or separately obtained on varying the recrystallization conditions. Cubic red crystals (α-phase) and red-orange needles (β-phase) exhibit solid-state red emissions at room temperature. Cubic red crystals of the γ-phase show no solid-state emission at room temperature. All crystalline structures were confirmed by X-ray crystallography. Room-temperature strongly luminescent crystals (α-phase) (λem = 657 nm, Φ = 0.52) have a triclinic P1 (No. 2) structure and no voids in the crystal structure. Red-orange needle-shaped crystals of the β-phase exhibit moderate red luminescence (λem = 695 nm, Φ = 0.09) at room temperature and have a trigonal, R3 (No. 148), structure. In the needlelike crystals of the β-phase, stable hexagonal arrays of nanoporous channels, 5.0 Å in diameter, are formed. Room-temperature nonluminescent crystals (γ-phase) have an orthorhombic, Pbca (No. 61), structure with a void volume that is 4.9% of the total crystal volume. After heating the α-phase crystals at 150 °C for 2 min, a powder XRD pattern different from the original crystal is obtained, and its solid-state emission at room temperature decreased. After heating the β-phase crystals at 150 °C for 2 min, the emission wavelength and the quantum yield of the solid-state emission at room temperature and the powder XRD pattern are the same as those of the α-phase after heating at 150 °C. A crystal-to-crystal transition triggered by the thermal stimulus produces a different stable polymorph of the mononuclear diiodoplatinum(II) complex. The one-dimensional nanoporous crystals encapsulated iodine without distorting the crystal packing.

We developed an in-situ iodination of organoarsenic homocycles for facile and general As–C bond formation. Quantitative in-situ generations of arsenic diiodides from organoarsenic homocycles and io...

Dithieno[3,2-b:2′,3′-d]arsoles have been synthesized via a safe and easy synthetic procedure, in which volatile arsenic intermediates are excluded. The obtained dithienoarsole derivatives were stable in the ambient atmosphere, unlike their phosphorus analogues, dithienophospholes. The Suzuki–Miyaura coupling reaction is applicable for structural modification and expansion of the π-conjugated system, and carried out the polymerization of the compounds. Dithienoarsoles showed an intense emission not only in solution but also in the solid state, and their molecular packing was analyzed by X-ray crystallography. The main-chain type dithienoarsole polymer formed a luminescent film. This work has demonstrated that dithienoarsole is a promising building block for luminescent materials.

We developed an in-situ iodination of organoarsenic homocycles for facile and general As–C bond formation. Quantitative in-situ generations of arsenic diiodides from organoarsenic homocycles and io...

Background and Aim: The relationship between Helicobacter pylori infection and body mass index (BMI) and dyspeptic symptoms is controversial. We investigated the changes in BMI and dyspeptic symptoms after H. pylori eradication among stages of atrophic gastritis classified according to the serum pepsinogen (PG) I/II ratio. Methods: One hundred and sixty-three H. pylori-positive patients underwent eradication therapy for H. pylori. Serum PG I and II concentrations were measured before treatment, and the PG I/II ratio was classified into three groups: PG I/II ratio Results: The mean BMI changes 1 year after treatment in the low PG I/II ratio group were significantly higher than those in other groups. Most abdominal symptoms in the high PG I/II ratio group were most severe before eradication but improved significantly after eradication. Conclusions: The effects of H. pylori eradication on BMI and dyspeptic symptoms may be different according to the serum PG I/II ratio before eradication.

Helicobacter pylori infection is causally related to chronic type-B gastritis, and may also be associated with an increased risk of gastric carcinoma. Vacuolating cytotoxin, which is an 87-kDa protein secreted by H. pylori, induces eukaryotic cell vacuolation in vitro. To determine whether there is an association between H. pylori vacuolating cytotoxin and gastric carcinoma, we investigated several characteristics of H. pylori infection, i.e., isolation of H. pylori from gastric biopsies, antibodies specific for H. pylori, detection of neutralizing activity to vacuolating cytotoxin in serum and immunological detection of cytotoxin by serum. Out of 6 sera from gastric-carcinoma patients, all showed the neutralizing activity to vacuolating cytotoxin, in contrast to 3 of 5 sera from peptic-ulcer patients. Normal individuals showed no neutralizing activity. All sera possessing the neutralizing activity recognized an 87-kDa protein band by Western blot analysis. Our results confirmed that cytotoxin-neutralizing activity in human sera was associated with immunodetection of an 87-kDa protein. To further evaluate neutralizing activity in serum from gastric-carcinoma patients, we retrospectively analyzed frozen-stocked serum samples from 22 gastric-carcinoma patients. Sera from 21 of these 22 patients exhibited neutralizing activity. These sera were also checked for antibodies to H. pylori, using an ELISA; 16 sera showed positive results. Our results indicate that detection of cytotoxin-neutralizing activity in sera is strongly associated with H. pylori infection, and probably with gastric carcinoma, and is also of interest in the diagnosis of H. pylori infection. © 1994 Wiley-Liss, Inc.

2,5-Diarylarsoles were easily synthesized from nonvolatile arsenic precursors. Diiodoarsine was generated in situ and reacted with titanacyclopentadienes to give 2,5-diarylarsoles. The structures and optical properties were studied in comparison with those of 2,5-diarylphosphole. It was found that the arsoles were much more stable in the air than the phosphole. Single crystal X-ray diffraction revealed the arsenic atoms adopted a trigonal pyramidal structure, reflecting on the s-character of the lone pair. The obtained 2,5-diarylarsoles and 2,5-diarylphosphole showed intense emission in solutions and solid state. In addition, the optical properties were controlled by transition-metal coordination.

To investigate the expression of extracellular matrix collagens and their relationship to corneal opacities after implantation of epithelial cells in the flap–stroma corneal interface. A corneal flap was made on rabbit eyes, and epithelial cells, mechanically scraped from tissue surrounding the flap, were implanted beneath the flap. The corneas were harvested 1, 3, 7, and 30 days following surgery. Histological and immunohistochemical examinations were performed. The expression and localization of types I, III, and IV collagens and gelatinase A were determined. Slit-lamp examination showed corneal opacity in the area where the epithelial cells were implanted. Histological study revealed clusters of epithelial cells between the flap and stromal interface. One week and 1 month after the implantation, intense immunoreactivity for collagen type IV was detected at the perimeters of the intrastromal epithelial islands, but not in the interface outside the implanted epithelial cells. Weak positive staining for gelatinase A was detected in the implanted epithelial cells and surrounding keratocytes. The heavy deposition of collagen type IV surrounding the implanted epithelial cells indicated that it might be an essential component of the interface haze observed in patients following laser in situ Keratomileusis. Gelatinase A may also play a role in the regulation of stromal remodeling after epithelial ingrowth.

Background: Helicobacter pylori infection is generally acquired in childhood and persists as an asymptomatic infection for decades in most infected individuals. Only a minority develops a clinical outcome even in childhood, such as peptic ulcer. It has been reported that H. pylori infection with the type I strain, which expresses the VacA and CagA antigen, is associated with peptic ulcer. Aim: We examined the diversity of vacA and cagA genes in isolates obtained from Japanese paediatric patients with peptic ulcer or chronic gastritis to investigate the relationship between genetic diversity and clinical outcome. Methods: The diversity of vacA and cagA genes was investigated by PCR and sequence analysis in 30 isolates obtained from Japanese paediatric patients with peptic ulcer (eight strains) or chronic gastritis (22 strains). Results: All isolates from Japanese children were cagA-positive strains. Twenty-six strains (86.7%) had East Asian type CagA, and 4 (13.3%) had Western type CagA. The predominant vacA genotype was s1c/m1b (22/30, 73.3%). There was no significant association between the diversity of cagA and vacA genes and clinical outcome. All four children infected with Western CagA strain had a history of overseas travel or residence. Conclusion: The predominant genotype of H. pylori in Japanese children is East Asian CagA and vacA s1c/m1b genotype, regardless of clinical outcome. Japanese H. pylori strains are homogeneously of the East Asian type; however, Western strains can be introduced into Japan concomitant with host movement from foreign countries in childhood.

Heating 1,4-dihydro-1,4-diarsininetetracarboxylic acid dianhydride with excess amounts of aniline and toluidine provided 3-anilino-N-phenylmaleimide and 3-p-toluidino-N-p-tolylmaleimide, respective...

Background: The relationship between H. pylori infection and body mass indices is controversial. Aim: To investigate the relationship between H. pylori infection and body indices, and to examine the effect of H. pylori eradication therapy on body indices. Methods: Nine-hundred and thirty-two employees of an industrial corporation were examined for H. pylori infection and body mass indices. Three hundred and two H. pylori-positive cases diagnosed with chronic gastritis by upper gastrointestinal endoscopy or radiography underwent eradication therapy. Body mass indices, serum total cholesterol levels and symptom scores were obtained before and at 12 months after eradication therapy. Results: There was no significant difference in body weight, body mass index (BMI) or serum total cholesterol level between the H. pylori-positive and H. pylori-negative groups. However, body weight and BMI increased significantly 12 months after eradication of H. pylori infection. In contrast, there was no significant difference in body weight and BMI 12 months after eradication therapy in the non-eradication group. Serum total cholesterol levels did not change after eradication therapy in either the eradication or non-eradication groups. Conclusion: Eradication of H. pylori infection induced an increase in BMI in industrial workers with chronic gastritis in Japan.

BACKGROUND—Leptin regulates feeding behaviour and therefore may be a mediator of anorexia associated with acute and chronic inflammation. Recently, leptin mRNA and leptin protein were found in the gastric epithelium. AIM—The aim of the present study was to examine the effect of Helicobacter pylori infection on gastric leptin expression to investigate the pathophysiological role of gastric leptin. METHODS—Surgically resected human stomach tissues were subjected to immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) to check for the presence of leptin in the human gastric epithelium. A total of 201 H pylori positive patients with chronic gastritis underwent eradication therapy for H pylori and were examined for the effect of infection cure in terms of body mass index (BMI) and serum leptin levels. Biopsy specimens from the gastric fundic mucosa were obtained from 40 of the 201 patients before and three months after eradication therapy. These samples were subjected to quantitative RT-PCR to examine the effect of eradication therapy on leptin expression in the gastric fundic mucosa. RESULTS—Leptin immunoreactive cells were detected in the lower half of the gastric fundic glands and a leptin PCR product was also found in the gastric fundic mucosa. H pylori infection significantly increased gastric leptin expression. In addition, cure of H pylori infection significantly reduced gastric leptin expression, with a concomitant increase in BMI. In contrast, serum leptin levels did not change significantly after cure of H pylori infection. CONCLUSION—Leptin is present in the human gastric mucosa. Gastric leptin may play a role in weight gain after eradication of H pylori infection. Gastric leptin may have a local rather than systemic action. Keywords: Helicobacter pylori; leptin; gastric mucosa; body mass index; gastritis

Laser epithelial keratomileusis (LASEK) is a surgical technique that may be performed in patients with low myopia who are considering conventional photorefractive keratectomy (PRK), in patients with thin corneas, and in patients with professions or lifestyles that predispose them to trauma. Ethanol (18%) is applied for 25 seconds and a hinged epithelial flap is created. After laser ablation, the flap is repositioned over the ablated stroma. Our data showed that epithelial defects occurred in 63% eyes on Day 1. Postoperative pain was absent in 47%. Uncorrected visual acuity of 20/40 or better was achieved in all patients at 1 week. Data from several studies suggest that LASEK may reduce postoperative pain and corneal haze associated with PRK. LASEK offers the potential advantage of avoiding flap-related complications associated with laser in situ keratomileusis and decreasing postoperative pain and corneal scarring associated with PRK. Long-term studies are needed to confirm these potential advantages and to determine the safety, efficacy, and predictability of this surgical technique.

Background: The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is still controversial. The potential benefits and risks of the treatment could depend on local conditions, such as the prevalence of the infection and the local rates of gastric cancer. Aim: To evaluate the effects of H. pylori eradication therapy on non-ulcer dyspepsia symptoms in industrial workers in Japan. Methods: A total of 615 employees of an industrial corporation were examined for H. pylori infection and symptom scores; 215 H. pylori-positive non-ulcer dyspepsia cases underwent eradication therapy. Symptom scores were also analysed 12 months after the eradication therapy. Serum pepsinogen A and pepsinogen C levels were analysed and chronic atrophic gastritis was serologically diagnosed on the basis of the criteria of a pepsinogen A

Purpose To investigate mutations of the human transforming growth factor beta-induced gene (TGFBI), transforming growth factor-beta-induced gene product (betaig-h3, keratoepithelin), in Japanese patients with Avellino corneal dystrophy (ACD), lattice corneal dystrophy (LCD), granular corneal dystrophy (GCD), and Reis-Bucklers corneal dystrophy (RBCD). Methods Genomic DNA was extracted from the peripheral blood of 75 patients and 7 unaffected relatives from 60 families with ACD, 34 patients and 8 unaffected relatives from 21 families with LCD, 4 patients and 4 unaffected relatives from 4 families with GCD, and 4 patients and an unaffected relative from 3 families with RBCD. Fifty normal volunteers served as controls. Exons 4, 11, and 12 of the TGFBI gene were amplified by polymerase chain reaction and were directly sequenced. Results Six different heterozygous missense mutations were detected in codons R124, L518, L527, and R555 of the TGFBI gene in the 117 patients from 88 families. A R124H mutation was detected in the patients with ACD. A R124C mutation was detected in the patients with LCD type 1 (LCD1), L518P was in atypical LCDI, and L527R in LCD with opacities deep in stroma. A R555W mutation was detected in the patients with GCD. A R555Q mutation was detected in the patients with RBCD. Conclusions We conclude that codons R124 and R555 of the TGFBI gene are also hot spots in Japanese patients with ACD, LCD, GCD, and RBCD. Many Japanese patients with CD had ACD with R124H mutation. GCD with R555W mutation was rare.

This paper is concerned with the development of a palpation probe for assessment of prostatic cancer and hypertrophy. The sensor is constructed by layering two polivinylidene fluoride (PVDF) films into soft material layers such as vulcanized rubber and sponge rubber sheets. Since the contact condition between the sensor and soft objects influences the sensor output significantly, the improvement of its sensitivity is investigated by design of an attachment covered over the sensor surface. In this report, the theoretical model of the sensor and the design of the attachment are presented and the attachment is validated for soft substances due to experimental investigation. Finally, a compact probe developed for clinical testing is presented and the data obtained from the patients are treated by the wavelet transform for de-noising. Some representative clinical data show that the sensor could be a useful tool for group medical checkup on prostatic cancer and hypertrophy.

AIMS—To investigate the histopathological changes of rabbit corneas after laser in situ keratomileusis (LASIK) and to evaluate the corneal wound healing process. METHODS—A LASIK was performed on white rabbit eyes. Postoperatively, rabbits were killed on days 1 and 7, and at 1, 3, and 9 months. RESULTS—Periodic acid Schiff (PAS) positive material and disorganised collagen fibre were seen along the interface of the corneal flap even 9 months after operation. CONCLUSIONS—The wound healing process still continued at 9 months after LASIK indicating that a much longer time than expected was required for corneal wound healing following LASIK.

BACKGROUND/AIMS The biochemical basis for the development of subepithelial opacity of the cornea after excimer laser keratectomy has yet to be fully defined. The aim of this study was to evaluate the alterations of glycosaminoglycans (GAGs) after excimer laser keratectomy. METHODS Rabbit corneas were harvested on days 5, 10, 20, and 30 after excimer laser photoablation. The amount of main disaccharide units was determined by high performance liquid chromatography (HPLC). In addition, immunohistochemical studies were performed on corneal sections 20 days after the ablation. RESULTS The concentrations of ΔDi-0S at 5 and 10 days were significantly lower than before the ablation. ΔDi-6S showed a significant increase 5 days after the ablation but ΔDi-4S did not show any significant change. There was a significant increase in ΔDi-HA at 20 and 30 days after ablation. In immunohistochemistry, the positive staining for ΔDi-6S and hyaluronic acid was observed in the subepithelial region. These immunohistochemical results were well correlated with the HPLC findings. CONCLUSIONS The increase in chondroitin-6 sulphate and hyaluronic acid may be related to corneal subepithelial opacity after excimer laser keratectomy.

c-Kit is a receptor tyrosine kinase, and it isencoded by the mouse W locus. Mutant W/Wvmice develop spontaneous gastric antral ulcers. The aimof the present study was to investigate the pathogenesis of these gastric ulcers and to examine theeffects of two antiulcer drugs; a proton pump inhibitor(2{[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl-sulfinyl}-1H-benzimidazole sodium salt, rabeprazole) and a mucosal protective drug(geranylgeranylacetone, GGA), on the gastric ulcers. Theinhibition of the gastric acid secretion by rabeprazole(30 mg/kg body weight, subcutaneous injection once a dayfor six weeks) significantly increased the gastriculcer formation compared to the controls. In contrast,the GGA treatment (100 mg/kg body weight, oraladministration for six weeks) significantly inhibited the ulcer formation. Bile reflux was seen inthese mutant mice, and they showed no cyclic intensecontractions in the gastric antrum. These resultssuggest that bile reflux due to the disturbance ofgastric antral movement is a cause of the spontaneousgastric ulcers in W/Wv mice.

Electron transfer reactions between donor and acceptor centers immersed in acetonitrile clusters are studied theoretically by using the dielectric continuum model and molecular dynamics simulations. The distribution of the electrostatic potential energy difference eΔV , between donor and acceptor sites, the solvent reorganization energy and the first-order electron transfer rate constants are estimated as functions of the cluster size. The results of both models for the clusters are compared with the corresponding results obtained for the bulk system.

This paper is concerned with the development of a palpation sensor for detecting the prostatic cancer and hypertrophy. The sensor is a layered medium with two polyvinylidene fluoride (PVDF) films embedded in the matrix rubber block. The temporal mean values, I1 and I2, of absolute voltage signals from the polymer films are calculated and their ratio I1/I2 is used as the sensor output. First, the fundamental characteristics of sensor are examined on a rectangular sensor with a plane surface. Then, the surface geometry of sensor is designed so that the sensor output clearly extracts the features on the stiffness of the materials. Finally, a compact cylindrical sensor which is inset in the doctor's forefinger is presented and its characteristics as a palpation sensor are studied experimentally. Some representative clinical data on the hardened and normal prostate glands are also presented.

This paper is concerned with the development of a soft palpation sensor for detection of prostatic cancer and hypertrophy. The sensor is a layered medium with two polyvinylidene fluoride (PVDF) films embedded in the matrix sponge rubber. It is pressed against the prostates and the output voltage signals from the polymer films are measured. The temporal mean values, I1 and I2, of absolute voltage signals from the films are calculated and their ratioI1=I2 is used as the sensor output. First, the fundamental characteristics of a rectangular sensor with a plane surface are examined. Then, the surface geometry of the sensor was designed so that it clearly indicates the nature on the stiffness of the soft material. Finally, a compact cylindrical sensor attached to the doctor's forefinger is described and experimental studies of its performance as a palpation sensor are presented. Some representative clinical data on the normal and hardened prostate glands are also presented.

Background: Primary and acquired resistance to antibiotics is an important factor in determining the reason for treatment failure in Helicobacter pylori infection. We examined the relationship between the susceptibility of H. pylori isolates and the efficacy of chemotherapy. Methods: The minimal inhibitory concentrations (MICs) of metronidazole (MNZ), clarithromycin (CLAR) and amoxycillin (AMOX) of 320 H. pylori pre-treatment isolates were determined by the agar dilution method. In 290 patients with peptic ulcers, H. pylori infection was treated by dual or triple combination therapies for 2 weeks: one proton pump inhibitor (30 mg/day lansoprazole or 20 mg/day omeprazole) and one or two antibiotics (500 mg AMOX, 200 mg CLAR or 250 mg MNZ twice a day). MICs were also determined after the treatment failure. Results: Among the drugs tested, for MNZ and CLAR, 8.1% and 9.1% of the isolates, respectively, were resistant, while no isolate was resistant to AMOX. After unsuccessful treatment using MNZ and CLAR, 66.7% and 70.6% of the isolates changed from sensitive to resistant, respectively. All isolates were sensitive to AMOX after treatment failure. Conclusions: The failure of the H. pylori treatment results in the induction of resistance to CLAR and/or MNZ. Regimens with a high cure rate should be used in order to prevent the generation of acquired resistance to antibiotics.

Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.

The vacuolating cytotoxin and urease secreted by Helicobacter pylori are thought to be virulent factors. Because vacuolation is potentiated by the presence of ammonium ion, which is produced by urease in vitro, it is of interest to examine whether cytotoxin and urease work reciprocally in the development of atrophic gastritis or duodenal ulcer. In the present study, patients (all H. pylori-positive) were divided into four groups: mild atrophic gastritis (group 1; nine patients), severe atrophic gastritis (group 2; 36 patients), duodenal ulcer with mild atrophic gastritis (group 3; 19 patients) and duodenal ulcer with severe atrophic gastritis (group 4; 12 patients). Cytotoxin production and urease activity of H. pylori isolated from these patients were analysed. Cytotoxin production was observed in four of nine (44.4%), 28 of 36 (77.8%), 11 of 19 (57.9%) and eight of 12 (66.7%) isolates from groups 1, 2, 3 and 4, respectively. Cytotoxin-producing H. pylori isolates were found significantly more in patients with severe atrophy than in patients with mild atrophy (P = 0.048). The mean of relative activity of cytotoxin in H. pylori isolate was 1.6 +/- 2.3, 7.9 +/- 7.4, 5.8 +/- 6.0 and 9.0 +/- 9.1 in groups 1, 2, 3 and 4, respectively. Helicobacter pylori isolates from severe atrophy or duodenal ulcer patients in groups 2 or 4 possessed significantly higher activity than those from non-ulcer patients in group 1 (P = 0.017 and 0.030, respectively). The mean of urease activity was 8.6 +/- 4.6, 10.0 +/- 5.9, 10.0 +/- 8.5 and 11.2 +/- 7.7 IU/mg in groups 1, 2, 3 and 4, respectively. These differences indicated no statistical significance. In each H. pylori isolate, the production of cytotoxin and urease were independent, which indicated that there was no reciprocal effect between them in vivo. Thus, cytotoxin-producing H. pylori isolates were more prevalent in patients with severe atrophic gastritis and the cytotoxin activities of H. pylori isolates from the patients with severe atrophic gastritis or duodenal ulcer were much higher than those from the patients with mild atrophic gastritis, which suggested that vacuolating cytotoxin may be a disease-inducing factor.

Electron transfer reactions between a disk-shaped donor and acceptor are theoretically studied. The reorganization energy and the first-order and the second-order rate constants are calculated and compared with those for the case of a spherical donor and acceptor. The energy gap dependence of the second-order rate constant obtained for the disk-shaped donor and acceptor is compared with the experimental result of Rehm and Weller. The reorganization energy and the first-order rate constant are also calculated for the case where a donor and an acceptor are connected through a spacer.

We treated a married couple who developed Mycoplasma pneumonia at the same time, and whose clinical courses and serum soluble interleukin-2 receptor (sIL-2R) levels were markedly different. The 30-year-old wife developed acute respiratory failure and her sIL-2R levels were extremely increased. After pulse therapy, her clinical state was improved, with a marked decrease in sIL-2R. In contrast, the 36-year-old husband, also suffered from the pneumonia with a moderate increase of sIL-2R, and recovered without any complications. The difference in their clinical states may be reflected in their serum sIL-2R levels, a marker of T cell activation in vivo.

A rapid diagnostic system for Helicobacter pylori (H. pylori) was developed based on an urease analyser using a pH-sensitive field effect transistor (pH-FET). The system is composed of a solid-phase capillary-tube and a pH-measuring cell. The solid-phase tube, with an inner diameter 0.55 mm and coated with a monoclonal antibody against H. pylori's urease, was used to selectively capture the urease in endoscopically collected gastric mucus. The urease activity on the inner surface of the solid-phase tube was measured by coupling it with ph-FET in a pH measuring cell containing urea solution. Before immuno reaction in the solid-phase, gastric mucus was diluted with a phosphate buffered saline containing 1% n-octylglucoside, which was effective for accelerating the release of active urease from H. pylori's cells suspended in the sample solution. As a result of preliminary evaluations, it was found that the clinical sensitivity and specificity were 100 and 86%, respectively, using a bacteriological test as a reference.

Objective: To clarify the effect of ammonia produced by Helicobacter pylori, which has strong urease activity, on the blood ammonia level. Design: (1) The quantification of ammonia production by live H. pylori in vitro. (2) The measurement of venous and portal ammonia levels following the instillation of H. pylori into the stomachs of normal or cirrhotic rats. Methods: (1) The urease reaction was carried out at 37°C with bacteria suspended in phosphate-buffered saline and 400 mmol/l urea solution in acetate buffer, pH 5.0. (2) Bacterial suspensions with or without urea solution were instilled into the stomachs of male normal Wistar rats or into rats in which cirrhosis had been induced by injection of carbon tetrachloride; venous and portal ammonia levels were then measured

Since the first successful isolation of Helicobacter pylori (H. pylori) from human gastric mucosa, this Organism has been demonstrated to be closely related to chronic, active gastritis and peptic ulcerations. It also promotes glandular atrophy of the gastric mucosa, and adversely affects healing and or relapse of peptic ulcers in man. However, the source of H. pylori infection has remained controversial. In our clinic, AGML developed in 2–3% of patients endoscoped. In some of these patients, phenol red dye spraying endoscopy was performed before and after the test, and H. pylori infection after the preceding endoscopy wm ascertained with the phenol red reaction and in culture. To prevent H. pylori infection from contaminating endoscopic instruments, several sterilization methods using running water, 70% ethanol, 0.2% benzalkonium chloride and 2% glutaraldehyde were compared. The results obtained showed that sterilization of endoscopic instruments with running water or 70% ethanol was insufficient to eliminate the risk of H. pylori infection, whereas sterilization with 0.2% benzalkonium chloride or 2% glutaraldehyde was sufficient. It was especially important that the biopsy channel was washed with these latter solutions.

Experimental studies have suggested that the continuous administration of 0.02% NH, solution, induced by Helicobacter pylori (H, Pylori), leads to a glandular atrophy of the gastric mucosa, and adversely affects healing of acetic acid ulcers in rats, because of the suppression of cell kinetics of the regenerative epithelial cells and connective tissues at ulcer margins. To visualize the distribution of H. pylori in human gastric mucosa, a phenol red dye spraying endoscopy was performed in 45 patients with gastric ulcers, and 43 patients with duodenal ulcers, who were medicated with a full dose of H2-blocker until ulcer healing, and with half doses thereafter. In the H. pylori negative cases, 8 (88.9%) of 9 gastric ulcers healed within 3 months after medication, with no relapse discernible up to 6 months after healing of the preceding ulcer. The relapse rate was 25% up to 12 months after ulcer healing. In contrast, only 22 (66.1%) of 36 gastric ulcers healed within 3 months after medication in the H. pylori positive cases. The relapse rate was 12.5% up to 3 months, 30.4% UP to 6 months and 63.6% up to 12 months after ulcer healing. In addition, all 6 duodenal ulcers healed within 2 months after medication in the H. pylori negative cases, with no relapse discernible up to 12 months after healing of the preceding ulcer. In contrast, in the H. pylon positive cases, 20 (53.1%) of 37 duodenal ulcers healed within 2 months, and the relapse rate was 14.3%, 33.3%, and 66.7% up to 3, 6 and 12 months respectively after healing of the preceding ulcer. These data suggest that H. pylori is likely to interfer with ulcer healing, and promotes peptic ulcer relapse.

In animals a continuous administration of 0.02% NH3 induced by Helicobacter pylori is well known to lead to glandular atrophy of the gastric mucosa and to induce active, chronic gastritis. In addition, this organism has been demonstrated to be closely related to chronic, active gastritis in man. In the present study, a phenol red dye spraying endoscopy was re-formed in 54 patients with chronic, atrophic gastritis to elucidate the distribution of this organism in the human gastric mucosa, and to clarify the relationship between its presence and chronic, atrophic gastritis. No red color reaction was found in 12 (92.3%) of 13 patients who had no glandular atrophy of the stomach. A diffuse and/or regional red color reaction was most prominent in those with slight degrees of glandular atrophy of the stomach, and was less striking in those with severe atrophy of the gastric mucosa associated with intestinal metaplasia. In addition, no red color reaction was visible in 14 (87.5%) of 16 patients showing a C0 pattern in the fundic-pyloric border classification, whereas a diffuse and/or regional red color reaction was observed in over 75% of patients showing C1 -O2 patterns and less frequently in those with an O3 Pattern. These data suggest a positive relationship between the presence of this organism and chronic, atrophic gastritis in man.

This paper describes a patient with duodenal carcinoma showing the features of a submucosal tumor, leading to difficulty in making an accurate preoperative diagnosis. A 63-year-old woman was admitted for investigation of a duodenal mass. An examination of the upper gastrointestinal tract revealed a semicircular compression of the stomach and the duodenum. Endoscopy of the stomach and duodenum disclosed a hemispherical tumor with a deep ulcer in the apex. Computer tomography revealed a tumor of about 5 cm in diameter at the same site. Laparotomy was performed under the tentative diagnosis of a submucosal tumor. A tumor was found occupying the duodenum, which compressed the gastric antrum exteriorly, and was also adherent to the head of the pancreas by direct invasion. A curative resection was performed by combining a pancreatoduodenectomy with a transverse colectomy along with regional lymph node clearance. A microscopic examination showed that the tumor contained neoplastic cells growing in a tubular pattern, particularly in its peripheral regions. Thus, this lesion was finally diagnosed as primary adenocarcinoma of the duodenum.

The relationship between Helicobacter pylori infection and body mass index (BMI) and dyspeptic symptoms is controversial. We investigated the changes in BMI and dyspeptic symptoms after H. pylori eradication among stages of atrophic gastritis classified according to the serum pepsinogen (PG) I/II ratio.One hundred and sixty-three H. pylori-positive patients underwent eradication therapy for H. pylori. Serum PG I and II concentrations were measured before treatment, and the PG I/II ratio was classified into three groups: PG I/II ratio2.0, PG I/II ratioor=2.0 and4.0, and PG I/II ratioor=4.0 were considered to be low, middle, and high, respectively. Their BMI and abdominal symptoms were checked before, 1 and 5 years after treatment, and these changes were investigated among the three groups.The mean BMI changes 1 year after treatment in the low PG I/II ratio group were significantly higher than those in other groups. Most abdominal symptoms in the high PG I/II ratio group were most severe before eradication but improved significantly after eradication.The effects of H. pylori eradication on BMI and dyspeptic symptoms may be different according to the serum PG I/II ratio before eradication.

To estimate the distribution of Helicobacter pylori in human gastric mucosa in vivo, the phenol red dye spraying endoscopy lias been successfully developed and is performed after an oral and/or intravenous premedication of famotidine 20mg. This technique was conducted on 25 patients with chronic, atrophic gastritis, on 21 patients with a gastric ulcer and on 14 patients with duodenal ulcers. The red color changes which occurred on the gastric mucosa were classified into three types; the diffuse staining type, the regional staining type and the patchy staining type. In the chronic gastritis group, the diffuse staining type, the regional staining type and the patchy staining type occurred in 11 patients (44%), 7 patients (28%) and 2 patients (8%), respectively. The remainder of the patients' mucosa was unstained. In addition, the regional staining type occurred most frequently in the gastric ulcer group, while the diffuse staining type was dominant in the duodenal ulcer group. Notably, a recurrent and intractable ulcer was surrounded by regional staining fields in the stomach, and showed a diffuse staining at the antrum of the duodenum. These facts suggest that Helicobacter pylori prevented ulcer healing. This concurs with the results of our previous experimental study which found that the low concentration NH3 solution, produced by Helicobacter pylori, prevented an acetic acid ulcer healing in rats and resulted from the suppression of the cell kinetics of the regenerative epithelial cells and the fibroblasts in the connective tissues at the ulcer margins.

Monoclonal gammopathy is a group of disorders characterized by proliferation of a single clone of plasma cells that produce monoclonal protein. Sometimes benign monoclonal gammopathy that is a symptomatic can turn into a malignancy like multiple myeloma. We present a case of monoclonal gammopathy with corneal deposits which was treated with deep lamellar keratoplasty (DLKP). The corneal button obtained at the time of DLKP was studied with both light and electron microscopy.Fine corneal deposits developed bilaterally in a 69-year-old man. There was no family history of ocular diease.We diagnosed monoclonal gammopathy in a blood test that showed elevation of serum immunoglobulin G and the Kappa chain. The corneal button obtained during DLKP was analyzed histologically and ultrastructurally. Electron microscopy showed electron-dense deposits composed of fine parallel filaments in the corneal epithelium and stroma.Corneal deposits of unknown origin might turn into monoclonal gammopathy that could be a life-threatening disease. It is important for ophthalmologists to check the whole body of a patient when finding corneal deposits.

The purpose of this study is to determine whether angiostatin is involved in maintaining corneal avascularity after wounding. We generated polyclonal rabbit anti-mouse angiostatin antibodies directed against each of the five kringle domains, (K1-5) and anti-mouse plasmin B chain antibodies. Mouse corneas were immunostained with anti-K1 angiostatin antibody after excimer laser keratectomy. Corneal epithelial cell lysate was harvested and angiostatin was isolated using lysine sepharose. Purified plasminogen was incubated with lysate of mouse corneal epithelial cells from wild type mice in the presence or absence of MMP inhibitors. Angiostatin activity was determined using calf pulmonary artery endothelial (CPAE) cell proliferation assay with and without angiostatin immunoprecipitation; and corneal neovascularization was assayed by intrastromal injection of anti-plasminogen, anti-K1-3 or anti-B chain antibodies after corneal wounding. Using the anti-mouse angiostatin antibodies that we generated, we confirmed that angiostatin-like molecules were expressed in the corneal epithelium and in cultured corneal epithelial cells. Western blotting after incubation of scraped corneal epithelial cell lysate with purified plasminogen showed reduction of the plasminogen bands at 6, 12, and 24 hr, respectively. Complete cleavage of plasminogen occurred by 48 hr. Functional assays in which corneal epithelial cell extracts were incubated with CPAE cells resulted in inhibition of vascular endothelial cell proliferation. Depletion experiments using anti-angiostatin (K1) antibodies resulted in a 25 +/- 1.2% increase in vascular endothelial cell proliferation as compared to 12 +/- 1.8% using the protein A control (p0.05). Corneal neovascularization was observed after excimer laser keratectomy when anti-angiostatin antibodies were injected into the cornea (65 +/- 13%) which was significantly higher than when plasmin B chain antibodies were injected (10 +/- 2.6%; p0.05). Plasminogen and angiostatin are produced in the cornea. They may play a role in preventing vascularization and may contribute to the maintenance of corneal avascularity after excimer laser keratectomy.