Biomedical subjects
Publications and source records attributed to T Shimoyama.
Basaloid squamous cell carcinoma (BSCC), a biologically high-grade variant of squamous cell carcinoma, carries a grave prognosis. In this article, we describe a rare case of BSCC of the esophagus with metastasis to the mandibular gingiva in a 63-year-old man. In addition, we provide a review of the relevant literature along with a discussion of the differential diagnosis.
The aim of this study was to determine what factors correlate with a favorable response to interferon-alpha2a (IFN-alpha2a) treatment in chronic hepatitis C. Fifty patients with chronic hepatitis C who received a 26-week treatment with IFN-alpha2a (474 million units in total) were assessed for pretreatment parameters and biochemical and virologic events during the treatment. According to biochemical and virologic responses to the treatment, 16 patients (32%) were categorized as sustained complete responders (SR), 13 (26%) as initial complete responders (IR), and 21 (42%) as nonresponders (NR). By multivariate analysis, a low viremia level was the only independent predictor of SR among pretreatment parameters (p = 0.0088). The percentage of patients showing hepatitis C virus RNA negativity at 2 and 12 weeks of treatment was significantly higher in SR (94% and 100%, respectively) or IR (69% and 92%, respectively) than in NR (14% and 33%, respectively) (p = 0.001). In contrast, the normalization of serum alanine aminotransferase levels at both time points failed to differentiate among SR, IR, and NR. These results indicate that monitoring of serum hepatitis C virus RNA at an appropriate time during treatment in addition to determination of pretreatment viral load is important in predicting responses to IFN-alpha2a treatment.
The chemical structure of a novel lipid A, which was obtained as a major component from lipopolysaccharide of Helicobacter pylori strain 206-1, was determined to be a glucosamine beta(1-6) disaccharide 1-(2-aminoethyl)phosphate acylated by (R)-3-hydroxyoctadecanoic acid and (R)-3-(octadecanoyloxy)octadecanoic acid at the 2- and 2'-position, respectively. The absence of a phosphoryl group at the 4'-position and fatty acyl groups at the 3- and 3'-position, and the stoichiometric presence of 2-aminoethyl phosphate at the 1-position are unique features, distinguishing it from the lipid A of enterobacteria.
This report describes the morphologic and immunohistochemical features of two cases of glial choristoma arising in the palate. The bulk of the lesions consisted of mature neuroglial tissue admixed with salivary glands, adipose tissue and lymphoid aggregates in case 1 and of cartilage, bone and foci of smooth muscle cells in case 2. In addition, case 2 showed choroid plexus and melanin-containing epithelium. Neuroglial tissue was intensely positive for CD57 as well as for glial fibrillary acidic protein, S-100 protein and vimentin. Neuron-specific enolase and neurofilament were focally or weakly positive. Proliferating cell nuclear antigen was negative in case 1 but sparsely positive in case 2. These features reflect the fact that glial choristoma is a developmental malformation of heterotopic central nervous tissue with limited growth potential.
Leukocytapheresis (LCAP) with a leukocyte removal filter column was administered for 45 patients with ulcerative colitis (UC). We evaluated changes in the leukocyte count and the differential percentages during LCAP. Cytokine production was assessed from each patient's peripheral mononuclear cells or monocytes. Flow cytometry was performed to assess the removal rates of activated cells and adhesion molecule positive cells by LCAP. Clinical improvement was recognized in 35 of 45 patients during intensive LCAP therapy, and it continued throughout maintenance therapy in 32 patients (71.1%). The leukocyte count was decreased to about 40% during the first 30 min, but it increased to approximately 170% at 20 min after the completion of LCAP. The concentration of tumor necrosis factor (TNF)alpha before LCAP in the effective group was higher than it was in either the ineffective group or the control group. Its level decreased to near normal range after LCAP. In the effective group, the concentrations of interleukin (IL)-1beta, IL-2, interferon (IFN)gamma, and IL-8 were near the normal upper limits before LCAP; however, they had decreased after LCAP. The concentration of IL-4 increased after LCAP. In the ineffective group, in contrast, the concentrations had been at or near normal before the initial LCAP treatment. Flow cytometry study revealed that LCAP could remove the activated cells and adhesion molecule positive cells more effectively. The clinical improvement and the changes observed before and after LCAP therapy suggest that LCAP is able to intervene in the causal mechanism(s) of UC.
Atrophic gastritis caused by Helicobacter pylori is the precursor lesion in the development of intestinal-type gastric adenocarcinoma. In animal models, atrophic gastritis induced by Helicobacter felis has been shown to be host dependent, developing in some mouse strains and not in others. The lipopolysaccharide (LPS) of H. pylori has been suggested to play a role in the induction of gastritis. The goal of this study was to compare the inflammation induced by long-term infection of the C3H/He and the C3H/HeJ strains of mice with H. felis. C3H/HeJ mice are unresponsive to LPS. Six months after infection, severe atrophic gastritis had developed in the body mucosae of all infected C3H/He mice, with replacement of parietal and chief cells. Atrophy was associated with a loss of the H. felis from the antral mucosa. In contrast, no atrophy was seen in the infected C3H/HeJ non-LPS responder animals, and heavy colonization of the antrum remained. There were no significant differences between both the quantitative and qualitative serum immunoglobulin G (IgG) and salivary IgA levels in both strains of mice. The main difference between the two strains of long-term-infected mice was a lack of macrophage infiltration in the lamina propria. Immunization induced good protective immunity to challenge with viable H. felis. Helicobacter-induced, host-dependent gastritis is likely to be cell mediated. The C3H/He and C3H/HeJ mouse model provides an excellent opportunity to investigate the cellular basis of atrophic gastritis.
The serum autoantibodies, antinuclear antibody, anti-DNA antibody, anti-smooth muscle antibody, antithyroglobulin antibody, antimicrosomal antibody, antimitochondrial antibody, rheumatoid factor and antibody to deoxyribonucleoprotein were measured at the baseline and on completion of interferon-alpha 2a (IFN-alpha 2a) treatment in chronic hepatitis C (CHC) patients who did not present with any autoimmune disease prior to treatment. Of the 57 patients examined, 27 spontaneously manifested at least one autoantibody. Only the prevalence of rheumatoid factor (26%) was significantly higher in the CHC patients than in the control subjects. There were no differences in the prevalence of the 8 autoantibodies examined between hepatitis C virus (HCV) genotypes 1b and 2a/2b. Twenty-six patients responded to IFN-alpha 2a. Subclinical hypothyroidism developed in two patients with elevated antithyroid antibody titres during treatment. No relationship was observed between changes in the status of autoantibodies and either response to IFN-alpha 2a or HCV genotype. Irrespective of the HCV genotype, autoantibodies might be present in CHC patients before and during the IFN-alpha 2a treatment. The presence of such antibodies does not represent a contraindication to the use of IFN-alpha 2a in CHC patients not complicated by autoimmune diseases. Careful observations are necessary for CHC patients positive for antithyroid antibodies during the IFN-alpha 2a treatment. Preexisting or newly developed autoantibodies do not necessarily predict a poor response to IFN-alpha 2a.
A 40-year-old male was admitted to our hospital on August 30, 1994 to receive a new ulcerative colitis (UC) therapy, leukocytapheresis (LCAP). On the admission day, he had bloody stool 5 to 6 times/day, abdominal pain, slight fever, and hypoproteinemia. His UC type was moderately severe left-sided colitis with pseudopolyposis. Prior to admission to our hospital, his condition had not improved for about 9 months, despite drug therapies such as salicylazosulphapyridine, intravenous high dose prednisolone, protease inhibitor, intraarterial hydrocortisone sodium succinate, 4 series of pulse therapies with metylpredonisolone, enema of corticosteroid, azathioprine (Imuran), and cyclosporine at another hospital. Thus he was introduced to our college hospital and treated by LCAP since September 1. After 10 LCAP sessions, remission was observed and the patient discharged on December 23. Until he was later operated on for heavy bleeding after he had discontinued treatment and had drunk heavily, he had maintained remission for 13 months with LCAP only once a month even after we gradually decreased the other medical supports and stopped all of them. After LCAP, the normalization of high percentage of leukocytes presented HLADR+ and lymphocytes presented CD 11 a+ CD 8+ was also observed. This suggests LCAP intercepts the excess immune reaction in UC by removing leukocytes.
BACKGROUND: Several studies have shown that infection of Helicobacter pylori strains possessing cagA is associated with atrophic gastritis and gastric cancers. METHOD: In 58 pairs of early gastric cancer patients and sex- and age-matched controls, isolated H. pylori strains were tested for possession of cagA. The presence of atrophic gastritis was also examined. RESULTS: Proportions of cagA-positive strains were 100% in cancer patients and 92.3% in controls. Atrophic gastritis was seen in 96.7% and 95.8% of cancer and control patients in whom cagA-positive strains (NS) were detected. However, it was seen in only 20% of H. pylori-negative control patients (P < 0.01). CONCLUSIONS: The present results do not suggest any specific association between cagA-positive strains and gastric cancer. However, frequent prevalence of cagA-positive strains might be associated with the high incidence of atrophic gastritis in Japanese populations.
Helicobacter pylori has been defined as a "definite carcinogen" at the WHO/IARC meeting in 1994. H. pylori causes histological gastritis. Long-lasting infection may induce atrophic gastritis, which is considered to be the first step in the gastritis-metaplasia-carcinoma sequence of the stomach. In a pooled analysis of the three prospective epidemiological studies, the relative risk for developing gastric cancer with H. pylori infection was 3.8, which was statistically significant. Thus, it was concluded that there was sufficient evidence in humans for the carcinogenicity of infection with H. pylori. However, there was no evidence experimentally for the carcinogenicity of infection with H. pylori. Further study is necessary to elucidate the role of H. pylori in gastric carcinogenesis.
Major inclusion criteria for leukocytapheresis (LCAP) therapy were mainly insufficient response to conventional drugs therapy. LCAP was administered once a week for 5 weeks of intensive therapy and once approximately a month for maintenance therapy, for 38 patients with UC. LCAP could remove approximately 1 x 10(10) white blood cells in each session. In the evaluation, we classified the response to the LCAP as: 1) excellent, 2) moderately improved, 3) no change, and 4) deterioration. Clinical improvement was recognized in 29 of 38 patients (76%) including 8 with dramatic response during the intensive therapy, and continued throughout the maintenance therapy in 26 patients (68.4%). Even though their symptoms were mild, the patients with more than 5 years UC history seemed to be not effective. The patients with moderately improvement and with excellent response have kept remission for about 20 months and about 2.5 years on an average, respectively. Clinical and blood examinations showed no side effects in any cases. It suggests that LCAP is able to be a UC treatment between drug therapies and an operation.
Chemokines are a family of low-molecular-weight proinflammatory cytokines that have leukocyte chemotactic and activating properties. Chemokine protein and mRNA are increased in the gastric mucosa of Helicobacter pylori infection and they are considered to regulate migration of leukocyte populations. The increase of C-X-C chemokines (e.g. IL-8, GRO-alpha) which effect primarily neutrophils is significantly associated with gastric polymorphonuclear cell activity suggesting that these chemokines play a primary role in active gastritis induced by H. pylori infection. In vitro enhanced epithelial chemokine responses are induced by cagA positive strains which have been clinically associated with more severe clinical outcome. Infection with cagA-positive H. pylori strains associates in vivo specifically with a C-X-C profile and enhanced polymorphonuclear infiltration in the gastric mucosa. Whilst infection with H. pylori, especially cag positive strains, is associated with more severe disease, genetic variability in host chemokine responses may also contribute to disease outcome.
We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).
We developed a solid-phase inhibition assay for the binding of biotinylated von Willebrand factor (vWF) to platelet glycoprotein (GP)Ib based on an enzyme-linked immunosorbent assay (ELISA) with platelet-bound microtiter wells. Washed platelets were immobilized onto the microplates via the anti-GPIIb/IIIa monoclonal antibody (mAb) VNR-5. In the presence of an antibiotic ristocetin (1 mg/ml, final) or the snake venom botrocetin (2 micrograms/ml, final), biotinylated vWF bound to the affixed platelets with half-maximal binding occurring at a vWF concentration of approximately 2 micrograms/ml. Several specific inhibitors of the binding of vWF to GPIb abolished the interaction of biotinylated vWF with GPIb in a dose-dependent fashion, with comparable protein concentrations to those seen in the liquid-phase inhibition assay using 125I-vWF. These inhibitors included mAb against vWF (NMC-4), mAb against GPIb (AP-1), and two vWF fragments containing vWF's putative GPIb-binding domain, namely a 39/34-kDa dispase-digested vWF fragment and a recombinant vWF fragment. Thus, this new assay is a convenient alternative to the conventional inhibition assay using 125I-vWF.
Many diagnostic methods have been developed and used for detecting Helicobacter pylori to evaluate the success of treatment of H. pylori infection. We investigated and compared the suitability of the rapid urease test (RUT), polymerase chain reaction (PCR), 13C-urea breath test (13C-UBT), and serology with culture for evaluating cure of H. pylori infection. Forty-seven H. pylori-positive gastric ulcer patients received dual therapy of lansoprazole (30 mg u.i.d.) and clarithromycin (200 mg b.i.d.). Four weeks after the completion of treatment, RUT, PCR, 13C-UBT, and culture were performed and the negative rates of these tests were compared. Anti-H. pylori IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA) before and 4 weeks after completion of the treatment to evaluate changes of titers during the treatment. The negative rate of RUT (55%) was significantly greater than that of culture (27%). Significant declines in titers were seen in the patients who had negative culture results, while the decline in the titer was not significant in the patients who had positive results. PCR assay and 13C-UBT were suitable for the evaluation of H. pylori eradication, but RUT was not suitable, because of its sensitivity. By monitoring anti-H. pylori IgG antibody titers, therapeutic failure can be detected early after completion of treatment.
Hepatitis C virus (HCV) RNA was tested for, and HCV genotypes determined, in 96 patients with haemophilia A in Japan. Of 88 patients aged > or = 10 years, 74 (84%) were positive for HCV RNA at a frequency higher than that in patients aged less than 10 years (one of eight, 13%, P < 0.001). Genotype I/1a was detected in 30(40%), II/1b in 12 (16%), III/2a in eight (11%), IV/2b in five (7%) and V/3a in 12 (16%); mixed infection with HCV of two different genotypes was identified in the remaining nine (12%). This distribution was markedly different from that in 767 Japanese HCV carriers without haemophilia, in whom II/1b accounted for the majority (68.7%), I/1a was rare (0.5%), V/3a was absent, and mixed infection was observed rarely (1.3%). Mixed infection was transient in all of the seven haemophilic patients who were followed for 1 to 7 years. One of them was infected with genotype II/1b and an unclassifiable genotype, which showed nucleotide sequence similarity to genotype 4c from Zaire (82% homology in the E1 gene) and to 4a from Egypt (91% homology in a part of the NS5b region). In this patient, HCV of genotype II/1b disappeared while that of group 4 survived during a 4-year observation period. These results indicate different epidemiology of HCV genotypes in Japanese haemophiliacs, attributable to HCV contaminating factor VIII imported in the past, and an increased opportunity in haemophiliacs for mixed infection with HCV of different genotypes.
An unusual case of polypoid carcinoma in a 72-year-old woman is reported. The tumor showed a pedunculated growth on the lateral border of the tongue and was composed of a malignant basaloid component in intimate association with definable foci of epithelial dysplasia of the surface mucosa. It was considered that histologic features of the present case corresponded with those of basaloid squamous carcinoma.
We present an unusual case of glandular odontogenic cyst (GOC) enclosing the crown of an impacted canine that developed in the anterior mandible in a 54-year-old woman. Microscopically, it contained numerous glandular structures and hyaline bodies in the epithelial lining. The present rare case is sufficiently distinctive to be considered a dentigerous variant of GOC.