Biomedical subjects

Kazutoshi Shibuya

Publications and source records attributed to Kazutoshi Shibuya.

At least 19 recordsLinked to original sources

PubMed2006

Thyroid papillary carcinoma recurring as squamous cell carcinoma: report of a case.

We report a case of local squamous cell carcinoma recurrence of thyroid papillary carcinoma, 4 years after subtotal thyroidectomy, in an 82-year-old woman. The papillary cancer of the right thyroid was histopathologically classified as T2a, N0, M0, Ex1; pT2a, pN1b, pEx1; Stage III. Fine-needle aspiration cytology of the recurrent tumor revealed atypical squamous epithelium-like cells with keratinization. The tumor was judged cytologically to be class III, defined as a suspicious malignancy and, after reoperation, it was diagnosed histopathologically as papillary carcinoma recurrence with extensive squamous metaplasia. The recurrent papillary carcinoma was thought to have changed to a squamous cell carcinoma because most of the tumor was occupied by atypical squamous cells, with a small amount of glandular tissue. The primary tumor was histologically diagnosed as a well-differentiated papillary carcinoma at the initial operation. It contained numerous tall neoplastic cells with eosinophilic granules and pseudostratified nuclei, indicating that it could potentially transform into squamous cell carcinoma. We report this case as an example of how squamous cell carcinoma of the thyroid can develop.

Adenocarcinoma, Follicular↗

PubMed2006

Catalases of Aspergillus fumigatus and inflammation in aspergillosis.

The article describes various features of aspergillosis and a discussed the role of calatases produced by Aspergillus fumigatus during infection. Since a large body of invasive Aspergillus infection occurs as an opportunistic infection in variously impaired defense mechanisms, there is a wide spectrum of histopathological features of lesions demonstrated at the site of infection. Accordingly, histopathology of the lesions can be understood as a phenotypical representation of interaction between differently impaired functions of neutrophils and macrophages and virulence factors of invading Aspergilli. Consideration of previous pathological knowledge regarding infection and inflammation provides much important information to predict the pathophysiology of a patient. Meanwhile, detoxification of hydrogen peroxide by catalases has been proposed as a way to overcome this host response. A. fumigatus produces three active catalases, one from conidia and two from mycelia. CatAp, a spore specific monofunctional catalase, is resistant to heat and metal ions. In spite of their increased sensitivity to H(2)O(2), killing of catA conidia by alveolar macrophages, virulence in animals was similar to wild type conidia. In contrast to mycelial Cat1p, and CatAp catalases, the mycelial Cat2p is a bifunctional catalase-peroxidase enzyme and is also sensitive to heat, metal ions and detergent. Surprisingly, the mycelium of the double cat1 cat2 mutant with no catalase activity has only a slightly increased sensitivity to H(2)O(2) and was as sensitive to the killing of polymorphonuclear neutrophils as the wild type strain. However, it showed a delayed infection in the rat model of aspergillosis compared to the wild type strain. Consequently, it should be emphasized that conidial catalase is not a virulence factor but that mycelial catalases transiently protect the fungus from the host defence reactions.

Aspergillosis↗

PubMed2006

[A case of pleural sarcoidosis in which vats lung biopsy, obtained pleural and pulmonary lesions].

Here we report a case that was diagnosed as sarcoidosis but required differential diagnosis from pneumoconiosis. A 51-year-old asymptomatic man, who showed signs of bilateral hilar lymphadenopathy (BHL) on a chest X-ray taken during a medical check, was given a diagnosis of sarcoidosis, based on the results of mediastinoscopic mediastinal lymph node biopsy. Because of the presence of large and small nodular lesions adjacent to the pleura extending from the bilateral upper lobes into the lung field, and continuous bead-like, small nodular lesions in the right interlobar pleura, pleural sarcoidosis was suspected and thoracoscopy was performed. Macroscopically, multiple grayish-white nodules with distinct margins, up to 1cm in diameter surrounded by a proliferation of capillaries were found in the pleura, particularly in the upper lobes. Lesions were also scattered over the interlobar pleura and diaphragmatic surface. Histopathologically, several non-caseous epithelioid cell granulomas and silicotic nodule-like lesions of hyaline degeneration were found; therefore, pneumoconiosis, or more specifically chronic berylliosis, was suspected. Despite these symptoms, the patient did not have a history of exposure, and the results of the lymphocyte stimulation test using beryllium were negative in blood and bronchoalveolar lavage fluid. The patient was given a diagnosis of pleural sarcoidosis and has been observed without treatment.

Biopsy↗

PubMed2005

Lack of human herpesvirus 8 infection in lungs of Japanese patients with primary pulmonary hypertension.

Samples of lung tissue, taken at autopsy, from 10 Japanese patients with primary pulmonary hypertension (PPH) and samples of lung tissue from 12 Japanese patients with secondary pulmonary hypertension were tested for the presence of human herpesvirus 8 (HHV-8). All samples from patients with PPH contained plexiform lesions around pulmonary arterial vessels, but immunohistochemistry failed to detect the HHV-8-encoded latency-associated nuclear antigen. HHV-8 DNA could not be amplified by polymerase chain reaction for the HHV-8-encoded K1 and KS330(233) genes in any sample. These data suggest that HHV-8 infection is not associated with PPH in Japanese patients.

Adolescent↗

PubMed2005

Granuloma and cryptococcosis.

This review describes the general histopathological features of cryptococcosis in immunocompetent individuals, as well as in patients with acquired immunodeficiency syndrome (AIDS). Details of the histological examination of cryptococcal lesions are described, with the consideration of morphological modifications induced by treatment with highly active antiretroviral therapy (HAART). The essential histological features of cryptococcosis in individuals with impaired T-cell functioning are yeast-cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. Several histological patterns of pulmonary cryptococcal lesions are introduced in this article, some of which could be graded with respect to the degree and type of inflammatory reaction. One pattern was a mild lesion consisting of scattered small foci of intraalveolar cryptococcal proliferation with a histiocytic response. Another pattern involved massive cryptococcal infection, which may have been simply more extensive than that in the mild lesion. Capillary involvement of alveolar septa should be understood as an important common finding in patients with AIDS who had not been treated with HAART. In those patients, the absence of T cells and a decreasing function of antigen-presenting activity in histiocytes were confirmed by immunohistological examination. These findings suggest that the lungs of AIDS patients without HAART offer little resistance to bloodstream dissemination by cryptococci. The unique histological feature demonstrated in patients treated with HAART is characterized by the presence of CD4+ cells, greater response of histiocytes and multinucleated giant-cell formation, and lack of massive capillary involvement.

AIDS-Related Opportunistic Infections↗

PubMed2005

Current status of diagnosis and treatment of invasive fungal infections in Japan: the influence of the new Japanese guidelines.

One year after the release of the Japanese "Guidelines for the Diagnosis and Treatment of Deep-Seated Mycosis" we conducted a survey of clinicians to determine the extent to which the new guidelines had penetrated clinical practice, and compared these results with those of a previous survey. The responses to the current survey regarding the diagnosis and treatment had changed from those of the previous survey to reflect the new recommendations, showing that the guidelines have had an effect on clinical practice. However, the current survey highlights a need to provide more practical information in the guidelines for use in the clinical settings. In particular, physicians expect the guidelines to proactively provide more information about the features of both current and new drugs. In addition, an effective drug against the genus Aspergillus is eagerly awaited. However, because it is difficult to differentiate among filamentous fungi, there is a need for a drug with broad-spectrum coverage against filamentous fungi. Investigation of combination therapy consequently becomes necessary. Definitive diagnoses of invasive fungal infection are too scarce at the national level. The cooperation of clinicians for organizing more definitive diagnoses would be appreciated when the guidelines are revised.

Antifungal Agents↗

PubMed2005

Electron microscopic findings for micafungin-treated experimental pulmonary aspergillosis in mice.

We performed a scanning and transmission electron microscopic study on the efficacy of micafungin (MCFG) to understand what kind of damage MCFG causes to Aspergillus and to confirm its previously reported in vitro killing activity against Aspergillus in a mouse model of pulmonary aspergillosis. Aspergillus hyphae in MCFG-treated mice displayed hyphal burst, evidenced as either flattened or atrophied appearance and leakage of cellular contents after collapse of the cell wall. Thus, MCFG can induce the destruction of Aspergillus hyphae at the focus of infection. The results of the present study indicate that MCFG improves pulmonary aspergillosis due to lethal damage to Aspergillus hyphae. This action can effectively reduce the invasive ability of Aspergillus even though MCFG does not sterilize the fungal burden.

Animals↗

PubMed2005

Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, and is frequently complicated with renal angiomyolipomas. LAM lesions are generated by the proliferation of LAM cells with mutations of one of the tuberous sclerosis complex (TSC) genes. Recent studies indicate that LAM cells can migrate or metastasize to form new lesions in multiple organs, although they show a morphologically benign appearance. In the previous study, we reported LAM-associated lymphangiogenesis and implicated its role in the progression of LAM. In this study, we further focused on the lymphatic abnormalities in LAM: LAM-associated chylous fluid (5 pleural effusion and 2 ascites), surgically resected diaphragm (1 patient), and axial lymphatic system including the thoracic duct, lymph nodes at various regions, and diaphragmatic lymphatic system (5 autopsy cases). We demonstrated that LAM cell clusters enveloped by lymphatic endothelial cells (LCC) in all chylous fluid examined. We identified LAM lesion in the diaphragm (2 of 5 autopy cases and one surgical specimen), thoracic duct (5 of 5), and lymph nodes (retroperitoneal (5 of 5), mediastinal (4 of 5), left venous angle (5 of 5) with total positive rate of 68% to 88% at each region of the lymph node, but less frequent or none at remote lymph nodes located away from the axial lymph trunk (cervical [1 of 5] and axillary [0 of 5]). LCCs were identified in intra-LAM lesional lymphatic channels where LAM cells proliferate along lymphatic system. In in vitro culture system, LCC can fragment into each proliferating LAM cell. These findings suggest that LAM-associated lymphangiogenesis demarcates LAM lesion into bundle- or fascicle-like structure and eventually shed LCC into the lymphatic circulation and that LCCs play a central role in the dissemination of LAM lesion.

Adult↗

PubMed2005

Compensatory response of IL-1 gene knockout mice after pulmonary infection with Klebsiella pneumoniae.

This study was designed to determine the role of interleukin (IL)-1 in the inflammatory response against experimentally induced pneumonia caused by Klebsiella pneumoniae. The host immune responses of IL-1 gene knockout (IL-1 KO) mice and immunocompetent wild-type (WT) mice were compared after pulmonary infection with K. pneumoniae. There were no significant differences between the survival rates and viable bacterial counts in lungs and blood of IL-1 KO and WT mice after pulmonary infections under different conditions. Histopathological analysis showed a similar inflammatory response in both groups of mice. However, in the early stage of infection, the level of tumour necrosis factor alpha (TNF-alpha) in homogenized lungs of IL-1 KO mice was significantly higher than in WT mice. To determine the role of endogenous TNF-alpha in the recovery of the defence mechanism in IL-1 KO mice, mice were treated with an anti-TNF-alpha mAb before infection with K. pneumoniae. The results revealed a significantly lower survival rate of anti-TNF-alpha mAb-treated IL-1 KO mice than BSA-treated IL-1 KO mice. The data suggest that compensatory production of TNF-alpha in IL-1 KO mice contributes to the host defence against K. pneumoniae infection.

Animals↗

PubMed2005

Post-transplant early recurrent proteinuria in patients with focal glomerulosclerosis--angiotensin II immunostaining and treatment outcome.

We reviewed the transplantation data and results of histopathological studies with additional angiotensin II (AII) immunostaining of renal graft biopsies of nine cases (10 grafts) with recurrent proteinuria and three controls without recurrent proteinuria that received renal transplantation for primary focal segmental glomerulosclerosis (FSGS) between 1986 and 2002. Recurrent FSGS was confirmed in six grafts from nine cases by light microscopy. In cases with recurrent proteinuria, loss of graft function was noted in all six renal grafts received between 1986 and early 1992 but in none of four grafts received between late 1992 and 2002. Two of four patients of the late group but none of those of the early group received angiotensin converting enzyme (ACEI) or angiotensin II receptor blocker (ARB) with plasma exchange (PE). In control cases without proteinuria, AII immunostaining was detected in tubules but not in glomeruli in 1-hour biopsies as well as later on. In cases with recurrent proteinuria, AII immunostaining was detected in both tubules and glomeruli, although glomerular AII staining was not observed in 1-hour biopsies. Our results suggest that effective treatment of post-transplantation recurrent FSGS requires ACEI or ARB with PE in the absence of another etiology.

Adolescent↗

PubMed2005

Cellular kinetics and K-ras codon 12 mutations according to histomorphometric type of colorectal polyps with epithelial serrated proliferation.

Recent studies have examined cellular kinetics and genetic abnormalities in colorectal polyps with epithelial serrated proliferation (CP-ESP), including hyperplastic polyps, serrated adenomas, and tubulovillous adenomas. However, difficulty in histologically classifying these lesions and the lack of clear-cut diagnostic criteria have led to inconsistent findings. Some 60 cases of CP-ESP and 6 cases of CP-ESP with malignant transformation were studied. When nuclear size progressively decreased from the bottom and middle layers to the surface layer of the crypts, maturation gradient was considered positive. CP-ESP and CP-ESP adjacent to carcinoma were morphologically classified as being positive or negative for maturation gradient and inferior and lateral glandular branching. Cellular kinetics were evaluated using Ki-67 immunostaining, and polymerase chain reaction (PCR)-dependent preferential homoduplex formation assay was performed to detect the presence or absence of K-ras codon 12-point mutations. CP-ESPs were morphologically classified into five types. In CP-ESP of types 1 to 4, the proliferation zone was confined to the bottom layer of the crypts or extended from the bottom to middle layers. In contrast, the proliferation zone extended throughout the crypts in most type 5 lesions. K-ras codon 12 mutations were detected in only types 3 and 5 CP-ESP. The five histomorphologic types of CP-ESP have distinct patterns of cellular kinetics. Histomorphologically, type 3 CP-ESP is considered an atypical hyperplastic polyp, occasionally associated with an elongated proliferation zone or K-ras mutations. Preliminary evidence indicates some relation between K-ras mutations and structural atypia associated with lateral branching of the crypts.

Cell Proliferation↗

PubMed2004

Pathophysiology of pulmonary aspergillosis.

A description of the pathophysiology of aspergillosis is followed by a review of investigational considerations of animal models. Because a large body of invasive Aspergillus infection occurs as opportunistic infection, there is a large spectrum of the histopathological feature of lesions demonstrated at the site of infection. Histopathology of the lesions can be understood as a phenotypical representation of interaction between lowered defense mechanisms in the host and the virulence of invading fungi. Detailed observations with a consideration of previous pathological knowledge of infection and inflammation provide much important information useful in predicting the pathophysiology of the patient. Moreover, experimental studies can also provide much insight to elucidate pathogenesis of the infection that emerges from the clinical and pathological investigations. The importance of pathophysiology should be emphasized to understand the implications of radiographic images, clinical symptoms, and laboratory dates. By reviewing these, especially computed tomography (CT) images, we can see that they accurately mirror the histological features of the lesion that can be recognized as a phenotypical representation of pathophysiology of Aspergillus infection. This is also confirmed by the reports emphasizing the importance of CT scans to identify hallmark clinical signs and symptoms of the disease.

Animals↗

PubMed2004

Interferon-gamma production and host protective response against Mycobacterium tuberculosis in mice lacking both IL-12p40 and IL-18.

Interferon (IFN)-gamma plays an essential role in host defense against infection with Mycobacterium tuberculosis, and its synthesis is critically regulated by interleukin (IL)-12, IL-18 and the recently identified IL-23. The present study was designed to determine the roles of these cytokines in IFN-gamma-mediated host defenses against M. tuberculosis. For this purpose, we compared host protective responses in IL-12p40 and IL-18 double-knockout (DKO) mice (which lacked both IL-12/IL-18 and also IL-23) and IFN-gamma gene-disrupted (GKO) mice. DKO mice were more resistant to the infection than GKO mice, as indicated by their extended survival and reduced live colony numbers in spleen, liver and lung. IFN-gamma was detected by ELISA in liver and lung homogenates, but not in spleen and serum, and in all organs by RT-PCR in DKO mice at comparable or reduced levels to those in wild-type mice. IFN-gamma production was reduced by depletion of CD4+ T cells, but not of natural killer (NK), NKT, gammadeltaT and dendritic cells. Neutralization of IFN-gamma or TNF-alpha by specific monoclonal antibodies (mAbs) significantly shortened the survival time of the infected DKO mice. Furthermore, anti-TNF-alpha mAb partially attenuated IFN-gamma synthesis in the liver of these mice. Finally, the expression level of inducible nitric oxide synthase (iNOS) mRNA in the spleen, liver and lung was considerable in DKO mice but only marginal or undetected in GKO mice. Our results indicate the presence of IL-12-, IL-18- and IL-23-independent host protective responses against mycobacterial infection mediated by IFN-gamma, which was secreted from helper T cells.

Animals↗

PubMed2004

[A case of allergic fungal sinusitis caused by Bipolaris spicifera].

We describe a case of allergic fungal sinusitis (AFS) caused by Bipolaris spicifera, the first case reported in Japan. A 70-year-old man was admitted to our hospital because of diplopia following bilateral nasal obstruction and discharge. Radiological studies using computed tomographic scan showed a large soft tissue mass occupying the right frontal, bilateral ethmoid and sphenoid sinuses. He underwent drainage surgery and histopathological examination of the contents of the paranasal sinuses revealed scattered fungal hyphae within "allergic mucin". By cytological examination, these hyphae showed septation at irregular intervals, and were swollen to various sizes. Microbiological studies identified the fungus as Bipolaris spicifera. The presence of allergic mucin and scattered fungal hyphae were very important findings in making a diagnosis of AFS histopathologically, so squash cytology of the contents of the paranasal sinuses was quite useful to observe fungal elements and identify the strain in this case.

Aged↗

PubMed2004

[Sigmoid colovesical fistula associated with cancer of the sigmoid colon].

OBJECTIVES: To report one case of colovesical fistula after the diagnosis of unresponsive urinary tract infection. METHODS: The 76-year-old patient underwent a diagnostic work up including cystography, cystoscopy and barium enema. RESULTS: Cystography revealed an image of the sigmoid colon, and cystoscopy showed a granuloma at the bladder dome. A fistula was identified underneath. A colovesical fistula was diagnosed and several intestinal germs grew on urine cultures. Partial cystectomy and end to end anastomosis of the sigmoid colon were carried out. Pathology report showed a well-differentiated adenocarcinoma which invaded down to the bladder mucosa. CONCLUSIONS: Inflammatory diseases are the main the etiology of colovesical fistula, followed by neoplasias. We reviewed around 170 cases reported in our country. It is important to identify the fistula by means of the gastro-intestinal series and the study of the lower urinary tract when treating patients with urinary tract infection difficult to control. We suggest the best radical therapy is surgery in a single procedure.

Adenocarcinoma↗

PubMed2003

Catalases of Aspergillus fumigatus.

Upon infection of a host, the pathogenic fungus Aspergillus fumigatus is attacked by the reactive oxygen species produced by phagocytic cells. Detoxification of hydrogen peroxide by catalases was proposed as a way to overcome this host response. A. fumigatus produces three active catalases; one is produced by conidia, and two are produced by mycelia. The mycelial catalase Cat1p was studied previously. Here we characterized the two other catalases, their genes, and the phenotypes of gene-disrupted mutants. CatAp, a spore-specific monofunctional catalase, is resistant to heat, metal ions, and detergent. This enzyme is a dimeric protein with 84.5-kDa subunits. The 749-amino-acid polypeptide exhibits high levels of similarity to the Aspergillus nidulans CatA catalase and to bacterial catalase HPII of Escherichia coli. In spite of increased sensitivity to H(2)O(2), killing of DeltacatA conidia by alveolar macrophages and virulence in animals were similar to the killing of conidia by alveolar macrophages and virulence in animals observed for the wild type. In contrast to the Cat1p and CatAp catalases, the mycelial Cat2p enzyme is a bifunctional catalase-peroxidase and is sensitive to heat, metal ions, and detergent. This enzyme, an 82-kDa monomer, is homologous to catalase-peroxidases of several fungi and bacteria. Surprisingly, mycelium of the double Deltacat1Deltacat2 mutant with no catalase activity exhibited only slightly increased sensitivity to H(2)O(2) and was as sensitive to killing by polymorphonuclear neutrophils as mycelium of the wild-type strain. However, this mutant exhibited delayed infection in the rat model of aspergillosis compared to infection by the wild-type strain. These results indicate that conidial catalase is not a virulence factor and that mycelial catalases transiently protect the fungus from the host.

Amino Acid Sequence↗

PubMed2002

A case of acute myocardial infarction treated with a new thrombectomy system.

Thrombotic occlusion in the culprit lesion of acute myocardial infarction was successfully recanalized using a 4.5 Fr thrombectomy catheter (RESCUE), which was also used to normalize the coronary blood flow. The retrieved specimens were white thrombi containing red thrombi and cholesterol crystals, indicating plaque rupture.

Adult↗

PubMed2002

Anti-CD11 b monoclonal antibody suppresses brain dissemination of Cryptococcus neoformans in mice.

To elucidate the role of the beta2 integrin family of adhesion molecules in the disseminated infection of Cryptococcus neoformans from the lung to the central nervous system, we examined the effects of monoclonal antibodies (mAbs) against CD11a, CD11b, CD11c and CD18 on the number of live microorganisms in both the lung and brain of mice three weeks after intratracheal infection. Administration of anti-CD11b mAb partially, but reproducibly, reduced the fungal loads in the brain in three independent experiments, while the lung loads were not affected. In addition, the same treatment significantly decreased the number of live microorganisms in the blood. In sharp contrast, the brain loads one week after intravenous injection with C. neoformans were not affected by treatment with anti-CD11b mAb. Finally, administration of mAb against other adhesion molecules (CD11a, CD11c or CD18) failed to affect the fungal loads in the brain as well as in the lung three weeks after intratracheal instillation, except for anti-CD18 mAb which rather increased the brain loads. Our results suggested that CD11b might be involved at least in part in the process of fungal dissemination from lung to brain, although the significance of other beta2 integrin family adhesion molecules remains to be substantiated.

Animals↗