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Biomedical subjects

J Kumagai

Publications and source records attributed to J Kumagai.

At least 19 recordsLinked to original sources

The role of leptin during the development of mouse preimplantation embryos.

Leptin is known to regulate diverse reproductive functions, and recent studies have implicated involvement of leptin in the early mouse embryo development. The aim of the present study was to investigate the expression of leptin and its functional receptor (OB-Rb) in mouse oocyte and preimplantation embryo, and to examine whether leptin influenced the early embryo development. Leptin mRNA was detected in blastocyst and hatched blastocyst, and OB-Rb mRNA was detected in oocytes, 1-cell, 2-cell, morula, blastocyst and hatched blastocyst. As for the origin of leptin, leptin mRNA was identified in both the oviduct and uterus of the pregnant mouse. Furthermore, in the pregnant mouse, the levels of leptin in uterine fluid were higher than those in the non-pregnant mouse. Supplementation of culture medium with leptin promotes the development of preimplantation embryos from 2-cell stage to the blastocysts, fully expanded blastocysts and hatched blastocysts. Leptin significantly increased the total cell number of blastocysts, and the effect was preferentially observed in the trophectoderm. These findings raise the possibility that leptin regulates the development of mouse preimplantation embryo through a paracrine pathway.

Animals↗

Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.

p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a Delta N-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues. In cultured cells, Delta Np63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

Base Sequence↗

Invasive subglottal aspergillosis in a patient with severe aplastic anemia: a case report.

A 19-year-old female with aplastic anemia who developed subglottal aspergillosis is reported. She presented with fever, cough and stridor. Inspiratory dyspnea progressed rapidly and emergent tracheostomy was performed, which confirmed the diagnosis. In spite of intensive anti-fungal treatment combined with adoptive immunotherapy, Aspergillus infection expanded and she died of pulmonary aspergillosis. Autopsy revealed the fungal mass obstructing the trachea and disseminated pulmonary aspergillosis. Difficulties in diagnosis and management of subglottal Aspergillus infection are discussed.

Adult↗

Histopathological diagnosis of biopsy samples from early esophageal carcinoma.

Carcinoma of the esophagus is frequently diagnosed in advanced clinical stages. When an esophagic carcinoma has infiltrated the submucosa or the muscular or serosa, metastases are a common finding. Thus, early diagnosis and opportune treatment are vital for patients with this type of neoplasm. Timely diagnosis can be done through endoscopic or X-ray studies and confirmed through a histopathological study by directed biopsy. We presently report the case of a 65 year old man with precedents of achalasia who underwent an endoscopic study using the Lugol staining technique for suspected malignant lesion classified as 0-IIc. After two biopsies it was diagnosed as early carcinoma of the esophagus and was subjected to mucosectomy. Histopathological findings are reviewed at architectural and cellular level and are essential to establish the diagnosis of early neoplastic lesions of the esophagus epithelium. These cellular changes are corroborated by immunohistochemical studies with nuclear expression of p53. The relevant literature was reviewed and experiences by Japanese and North American pathologists compared with emphasis on the need for multidisciplinary management to make an early diagnosis by endoscopic studies, Lugol staining, X-rays, biopsy and conservative treatment based on mucosectomy.

Aged↗

Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated.

BACKGROUND: Glandular atrophy and intestinal metaplasia are precancerous lesions; whether Helicobacter pylori eradication affects these lesions is controversial. OBJECTIVE: To determine whether H. pylori eradication is associated with improvement in glandular atrophy and intestinal metaplasia after at least 1 year. DESIGN: Single-blind, uncontrolled prospective trial. SETTING: Academic gastroenterology clinic in Japan. PATIENTS: 163 consecutive patients with dyspepsia and H. pylori infection. INTERVENTION: One-week course of a proton-pump inhibitor and antibiotic therapy. MEASUREMENTS: Endoscopic examination with antral and corporal biopsy was done before treatment and at 1 to 3 and 12 to 15 months after treatment. Gastritis, atrophy, and metaplasia were graded according to the updated Sydney System. RESULTS: In the 115 patients in whom H. pylori was eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3 months, and both glandular atrophy in the corpus and intestinal metaplasia in the antrum had decreased by 12 to 15 months. Glandular atrophy in the corpus improved in 34 (89%) of 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of 46 patients who had metaplasia at baseline. In the 48 patients in whom eradication was unsuccessful, no significant histologic changes were observed. CONCLUSION: In the year after successful H. pylori eradication, precancerous lesions improved in most patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Fibrous dysplasia with cystic appearance in maxillary sinus.

Fibrous dysplasia (FD) in the paranasal sinuses is uncommon, and its management may be difficult. We report the case of a 25-year-old female with FD exhibiting a cystic appearance in the maxillary sinus. The patient had been complaining of facial swelling for few years. Imagery study showed a cystic lesion and dense bone changes in the maxillary bone. Inferior meatal antrostomy with a nasal endoscope failed to confirm a histological diagnosis. After a 3-year follow-up, the degree of facial swelling was unchanged, and the patient underwent middle meatal antrostomy and was diagnosed with FD.

Adult↗

Expression of Fas and Fas ligand mRNA in rat and human preimplantation embryos.

The Fas-Fas ligand (L) system is one of the major signalling pathways to induce apoptosis in various cells and tissues. The aim of this study was to investigate the expression of the Fas-Fas L system in rat and human oocytes and preimplantation embryos. We determined the expression of Fas and Fas L mRNA of rat oocytes and embryos up to the blastocyst stage, and of human embryos at the 2- or 4-cell stage, using reverse transcription polymerase chain reaction (PCR) and nested PCR techniques. Moreover, we investigated the expression of Fas mRNA in human fragmented embryos. In rat embryos, Fas mRNA was expressed at the 2-cell stage only, whereas Fas L mRNA was expressed in oocytes, and at the pronuclear (1-cell) and 2-cell stages. In human embryos, Fas mRNA was expressed at the 4-cell stage only, whereas Fas L mRNA was expressed at both 2- and 4-cell stages. Human fragmented embryos expressed both Fas and Fas L mRNA. Because simultaneous expression of Fas and Fas L mRNA occurred in 2-cell rat embryos and in 4-cell human embryos, the Fas-Fas L system might be involved in the apoptotic pathway in the early embryos of these species.

Animals↗

Early gastric carcinoma: evaluation with high-spatial-resolution MR imaging in vitro.

PURPOSE: To determine signal intensity characteristics of the gastric wall layers and to assess the accuracy of the evaluation of early gastric carcinomas in vitro by using resected specimens studied with high-spatial-resolution magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifteen gastric specimens obtained from patients suspected of having early gastric carcinoma were studied with a 1.5-T MR system with a 4-cm-diameter loop coil. High-spatial-resolution spin-echo MR images were obtained with a field of view of 50 mm, a matrix of 256 x 256, and a section thickness of 2 mm, resulting in a voxel size of 0.08 mm(3). Findings from MR images were compared with histopathologic findings. RESULTS: T1- and T2-weighted MR images clearly depicted the normal gastric wall as consisting of four and six layers, respectively, which corresponded well to the histologic layers. In 14 (93%) of 15 gastric carcinomas, the depth of mural invasion visualized with MR imaging correlated well with the histopathologic stage. The stage determined with MR imaging, however, was lower in one instance (7%) than the histopathologic stage. MR imaging also depicted the gross features of the tumor, presence of ulceration, and adjacent lymph node swelling. CONCLUSION: High-spatial-resolution MR imaging has a high diagnostic accuracy in the evaluation of the mural invasion of early gastric carcinoma in vitro and thus potentially enables preoperative histopathologic staging.

Adenocarcinoma↗

Electron spin echo study of long-lived radicals which cause mutation in gamma-ray irradiated mammalian cells.

Long-lived radicals, produced by gamma-ray irradiation of mammalian cells at room temperature, cause mutation and morphological transformation in the cells. The local environment near the long-lived radicals in irradiated cells was investigated here by the analysis of electron spin echo envelope modulation (ESEEM) spectra. The number of hydrogen (deuterium) atoms surrounding the long-lived radical, which may correspond to the number of water molecules, was estimated roughly as one or two. It is postulated that the long-lived radicals are generated in the interior of biopolymers. The radicals are not produced by the reaction of OH radicals, but mainly by the decomposition of biopolymer which absorbed directly the energy of the ionizing radiation.

Albumins↗

Germ cell-specific heat shock protein 105 binds to p53 in a temperature-sensitive manner in rat testis.

Heat shock protein (HSP)105 is a testis-specific and HSP90-related protein. The aim of this study was to explore the functions of HSP105 in the rat testis. Signals of HSP105 were detected immunohistochemically in the germ cells and translocated from the cytoplasm to the nucleus at 2 days after experimental induction of cryptorchidism. In cultured testicular germ cells, a significant increase in the expression of HSP105 in response to heat stress (37 degrees C) was detected in the insoluble protein fractions. Several binding proteins were isolated from rat testis using a HSP105 antibody immunoaffinity column, and p53, the tumor suppressor gene product, was copurified with these. Furthermore, immunoprecipitation using antibodies to p53 led to coprecipitation of HSP105 together with p53 after culturing germ cells at 32.5 degrees C, but not at 37 or 42 degrees C. In conclusion, HSP105 is specifically localized in the germ cells and may translocate into the nucleus after heat shock. HSP105 is suggested to form a complex with p53 at the scrotal temperature, and dissociate from it at suprascrotal temperatures. At scrotal temperature, HSP105 may thus contribute to the stabilization of p53 proteins in the cytoplasm of the germ cells, preventing the potential induction of apoptosis by p53.

Animals↗

Endoscopic and histological comparison of nonulcer dyspepsia with and without Helicobacter pylori infection evaluated by the modified Sydney system.

OBJECTIVE: Our aim was to identify endoscopic features associated with Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia. METHODS: A total of 50 infected patients with nonulcer dyspepsia who underwent endoscopy with antral and corporal biopsies and 50 patients matched for age and sex but with nonulcer dyspepsia without H. pylori were reviewed retrospectively by three endoscopists blinded to the H. pylori status and the patient's history. The endoscopic findings of gastritis, classified by a modification of the Sydney system as present or absent, were evaluated, and the histological severity was graded by the updated Sydney system. RESULTS: For endoscopic features, the odds ratio was 53.1 (95% confidence interval, 6.8-414.9) for edema, 18.8 (5.8-60.5) for erythema with reddish streaks excluded, 0.0275 (0.0002-0.477) for reddish streaks, 17.4 (0.97-313.7) for friability, 14.2 (5.1-40.0) for exudate, 17.2 (2.2-137.6) for flat erosions, 2.54 (0.81-7.94) for raised erosions, 40.1 (2.3-694.5) for rugal hypertrophy, 19.1 (2.4-151.6) for rugal atrophy, 96.2 (23.4-395.9) for a vascular pattern, 0.125 (0.010-1.06) for bleeding spots, and 21.0 (2.6-166.5) for nodularity. The histological severity of inflammation, neutrophil activity, and atrophy in the antrum and corpus and of metaplasia in the antrum was greater in the infected patients than in the noninfected patients. CONCLUSIONS: Endoscopic features associated with H. pylori were a vascular pattern, edema, rugal hypertrophy, nodularity, rugal atrophy, erythema with reddish streaks excluded, flat erosions, and exudate. These endoscopic features were associated with the histological findings of inflammation, neutrophil activity, atrophy, and metaplasia.

Atrophy↗

Chaperonin 10 in the rat oocytes and early embryos: its expression and activity for early pregnancy factor.

PROBLEM: The aim of this study was to investigate the expression of chaperonin (cpn) 10 and cpn 60 mRNA in oocytes or embryos, and to further explore the possibility that early pregnancy factor (EPF) is identical with cpn 10. METHOD OF STUDY: The expressions of cpn 10 and cpn 60 mRNA in oocytes and embryos at the different stages (1-cell, 2-cell, 8-cell, and morula) were examined by polymerase chain reaction techniques. The EPF activity of native rat cpn 10 isolated from rat livers was evaluated by the rosette inhibition test. RESULTS: Similar levels of mRNA of cpn 10 and cpn 60 were detected in oocytes and embryos at every stage. There were no detectable EPF activities in the native cpn 10. Immunoprecipitation using polyclonal antibodies against cpn 10 did not affect the activity of EPF in the pregnant rat serum. CONCLUSION: Our results do not support the hypothesis that cpn 10 is identical with EPF.

Animals↗

Postmortem study of ataxia with retinitis pigmentosa by mutation of the alpha-tocopherol transfer protein gene.

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of alpha-tocopherol transfer protein (alpha-TTP) gene was recently proposed. After studying the first postmortem case with this mutation pathologically and biochemically, whether the symptoms can be treated by supplementation of vitamin E or not is discussed. The major pathological findings were retinal atrophy; severe dying back-type degeneration of the posterior column; and massive accumulation of lipofuscin in neurons including dorsal root ganglion (DRG) cells, which were almost identical to those in vitamin E deficient animals and patients with fat malabsorption. Also, mild loss of Purkinje cells was noted. Because robust expression of alpha-TTP was detected in the cerebellum as well as in the liver and the tissue concentration of vitamin E in the cerebellum was still low even after oral supplementation, the mild Purkinje cell loss might be related to the mutant alpha-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of alpha-TTP was detected, and the tissue concentration of vitamin E increased to normal after supplementation. It is therefore considered that oral supplementation of vitamin E should effectively counteract the progression of ataxia.

Aged↗

Direct infusion of ascites into the blood circuit during hemodiafiltration in uremic patients with cirrhosis.

Two chronic dialysis patients with massive ascites caused by cirrhosis were treated by infusion of their ascites directly into the blood circuit. This stabilized their hemodynamics during dialysis, facilitating the control of weight gain and ascites, and thus markedly improving their general condition. Long-term use of this therapy was able to prevent the accumulation of ascitic fluid. Interestingly, fever occurred when this therapy was performed with hemodialysis, but not with hemofiltration or hemodiafiltration, suggesting that a pyrogen in the ascites was removed by filtration.

Aged↗

Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice.

Intestines of mice with colitis caused by dextran sulfate sodium (DSS) contain more Bacteroidaceae cells than untreated controls. We investigated the roles of intestinal bacteria and succinic acid, a by-product of Bacteroidaceae metabolism, in this model of colitis. CBA/J mice were given 3% DSS in water for 14 days. After mice were anesthetized and killed, concentrations of organic acids in stools from the cecum and colon were measured. The resected rectum and colon were washed with sterile saline; some specimens were incubated with imipenem in saline for 1 h to kill bacteria on the surfaces and others were not. Their homogenates were cultured anaerobically and aerobically. Separately, 1 mL of 20 mM succinic acid was infused into the rectum of mice, whose anal verge was glued. Animals were anesthetized and killed the next day. The rectum and colon were examined histologically. Concentrations of succinate were higher everywhere in the colon of mice with colitis than in controls. Mice with colitis had more Bacteroidaceae cells, especially B. caccae, than controls. Mice given succinate enemas had focal erosions of the mucosa and edema of the submucosa. Succinic acid, produced abundantly by members of the family Bacteroidaceae, especially B. caccae, may be the ulcerogenic agent in DSS colitis.

Acetates↗

Spontaneous conception after the birth of infants conceived through in vitro fertilization treatment.

OBJECTIVE: To investigate the incidence of spontaneous conception after the birth of infants conceived through IVF in couples with subfertility caused by endometriosis, a mild male factor, or unexplained factors, and to identify clinical conditions related to the occurrence of spontaneous conception. DESIGN: Retrospective analysis. SETTING: Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita, Japan. PATIENT(S): One hundred forty-two women who conceived through IVF and 25 of the 142 women who subsequently conceived spontaneously. INTERVENTION(S): Patient characteristics and IVF data were obtained from hospital records, and follow-up data were collected through telephone interviews. MAIN OUTCOME MEASURE(S): Cumulative conception rate. RESULT(S): The cumulative conception rate at 60 months after the delivery of infants conceived through IVF was 18%, with most conceptions occurring within 2 years of delivery. Proportional hazard analysis indicated that patient age was the most important clinical variable related to the occurrence of spontaneous conception. CONCLUSION(S): This study provides information that will be useful in counseling subfertile couples who have conceived through the use of IVF.

Adult↗