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Biomedical subjects

Keiji Takahashi

Publications and source records attributed to Keiji Takahashi.

10 recordsLinked to original sources

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↗

Expression and characterization of Rab38, a new member of the Rab small G protein family.

Rab38 is a new member of the Rab small G protein family that regulates intracellular vesicle trafficking. Rab38 is expressed in melanocytes and it has been clarified that a point mutation in the postulated GTP-binding domain of Rab38 is the gene responsible for oculocutaneous albinism in chocolate mice. However, basic information regarding recombinant protein production, intracellular location, and tissue-specific expression pattern has not yet been reported. We produced recombinant Rab38 using a baculovirus/insect cell-protein expression system. A combination of Triton X-114 phase separation and nickel-affinity chromatography yielded exclusively prenylated Rab38 that bound [alpha-32P]-GTP. The mRNA and the native protein were expressed in a tissue-specific manner, e.g., in the lung, skin, stomach, liver, and kidney. Freshly isolated rat alveolar type II cells were highly positive for the mRNA signal, but the signal was rapidly lost over time. Immunofluorescence staining demonstrated that expressed GST-tagged Rab38 was mainly co-localized with endoplasmic reticulum-resident protein and also partly with intermittent vesicles between the endoplasmic reticulum and the Golgi complex. These results indicate that Rab38 is expressed non-ubiquitously in specific tissues and regulates early vesicle transport relating to the endoplasmic reticulum, and hence suggest that Rab38 abnormality may cause multiple organ diseases as well as oculocutaneous albinism.

Animals↗

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↗

COPD in Japan: the Nippon COPD Epidemiology study.

OBJECTIVES: Despite high smoking rates, few prevalence studies of COPD have been performed in Asia. The Nippon COPD Epidemiology (NICE) Study used spirometry to measure prevalence of airflow limitation in Japanese adults. METHODOLOGY: Clinical, spirometric, and risk factor exposure data were collected on 2343 subjects aged > or = 40 years who were demographically similar to the Japanese population. Airflow limitation was defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC < 70%). RESULTS: Prevalence of airflow limitation was 10.9%. Based upon GOLD severity criteria, 56% of these cases were found to be mild, 38% moderate, 5% severe, and 1% very severe. Airflow limitation was significantly more prevalent in males than females (16.4% vs. 5.0%; P < 0.001), in male ever-smokers than female ever-smokers (17.1% vs. 7.5%; P < 0.001), and in older subjects (3.5% in 40-49 years olds vs. 24.4% in those > 70 years; P < 0.001). Of note, airflow limitation was also found in 5.8% of non-smokers and 4.6% of those younger than age 60 years. Only 9.4% of cases with airflow limitation reported a previous diagnosis of COPD. CONCLUSIONS: Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.

Adult↗

Improved survival of vitrified in vivo-derived porcine embryos.

An efficient cryopreservation protocol for porcine morulae was investigated with three types of vitrification having different cooling rates (Exp. 1). Survival of embryos vitrified after removal of cytoplasmic lipid droplets was also examined by means of the minimum volume cooling (MVC) method (Exp. 2). In Exp. 1, the morula stage embryos were vitrified with a 0.25 ml plastic straw (ST-method), gel loading tip (GLT-method) and the MVC-method, respectively, and stored in liquid nitrogen after which they were warmed in sucrose solutions with cryoprotectants being subsequently removed in a stepwise manner. In Exp. 2, morulae were centrifuged with 7.5 microg/ml cytocharasin B at 12000 x g for 20 min to polarize the cytoplasmic lipid droplets that were then removed from the embryos by micromanipulation (delipation). Both those delipated at the morula stage and the intact embryos at the morula to blastocyst stages were vitrified by the MVC-method. In vitro survival of the vitrified embryos was assessed in both experiments by culturing in NCSU-23 + 10% FCS for 48 h. In vitro developments of vitrified embryos after warming to blastocysts were 20% (6/30) for the ST-method, 39% (18/46) for the GLT-method, and 60% (26/43) for the MVC-method. Embryo survival was further improved by vitrification after delipation (95%, 35/37) compared to intact vitrified morulae (24/42, 57%, P<0.001) and blastocysts (23/31, 74%, P<0.05). Moreover, the number of cells in blastocysts (92 +/- 25) derived from the delipated-vitrified morulae was comparable to those derived from intact control non-vitrified embryos (103 +/- 31). Our results demonstrate that vitrified porcine morulae have the highest survival when using the MVC-method in conjunction with delipation.

Animals↗

[A case of atypical pulmonary carcinoid accompanying skin metastasis].

A 73-year-old woman underwent cranial surgery in 1999 after receiving a diagnosis of suspected malignant meningioma. She began complaining of headache 2 years postoperatively, and around the same time, she noticed a painful skin tumor. She was then transferred to our hospital for further evaluation. The skin tumor was diagnosed by skin biopsy as an atypical metastatic carcinoid tumor. Systemic examination demonstrated a primary lesion in the left lung. Pulmonary, skin and bone biopsy samples exhibited the same pathological findings as those of the atypical pulmonary carcinoid tumor. She did not show any carcinoid symptoms. EP therapy (etoposide + carboplatin) and CAV therapy (cyclophosphamide + doxorubicin + vincristin) were administered, but there was no clinical response. The patient is currently doing well without chemotherapy and is being followed by the Outpatient Department.

Aged↗

Time-dependent effect of pneumonectomy on alveolar epithelial fluid clearance in rat lungs.

OBJECTIVE: Because pneumonectomy initiates compensatory growth of the remaining lung, we determined the time-dependent effects of pneumonectomy on alveolar fluid clearance capacity. METHODS: Alveolar fluid clearance capacity with the Evans blue-labeled albumin concentration was measured in rats 3 hours, 2 days, 7 days, 14 days, and 28 days after left pneumonectomy. The mechanisms responsible for the increase in alveolar fluid clearance were explored. RESULTS: Alveolar fluid clearance in the remaining lung was normal through 7 days and then increased 14 and 28 days after pneumonectomy. The increase in alveolar fluid clearance at 28 days after pneumonectomy was accounted primarily by an increase in amiloride-sensitive transport. The expression of epithelial sodium channel messenger RNA was increased in the remaining lung and in type II alveolar epithelial cells isolated from rats 28 days after pneumonectomy. The number of isolated type II cells was larger in pneumonectomized rats than in control rats. Also, beta-adrenergic agonist therapy increased the rate of alveolar fluid clearance at the 3-hour and 28-day time points. CONCLUSIONS: The capacity to remove alveolar fluid in the remaining lung is maintained at a normal level for up to 7 days after pneumonectomy in a rat, and then there is a marked increase in amiloride-sensitive alveolar fluid transport capacity that might depend, at least in part, on increased expression of epithelial sodium channels in type II cells and in part on the increased number of type II cells.

Adrenergic beta-Agonists↗

[An intra-pulmonary lymphnode resembling typical pulmonary primary adenocarcinoma on high-resolution computed tomographic (HR-CT) chest images].

A 40-year-old man was admitted to our hospital for further evaluation of a pulmonary nodule in chest radiographs. The 8-mm nodular lesion was located in the right anterior basal lobe on a plain chest radiograph, and showed 1) spiculation, 2) pleural indentation and 3) a converging vessel formation in high-resolution computed tomography of the chest. The radiographic findings were highly suggestive of primary pulmonary adenocarcinoma and the patient underwent video-assisted thoracoscopic surgery (VATS) to obtain a precise diagnosis. The nodule was diagnosed histopathologically as an intrapulmonary lymph node. In cases with such radiographic findings, careful attention should be paid in the differential diagnosis to distinguish intrapulmonary lymph nodes from primary pulmonary adenocarcinoma.

Adenocarcinoma↗