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Biomedical subjects

T Komatsu

Publications and source records attributed to T Komatsu.

At least 19 recordsLinked to original sources

Cytoplasmic elongation and rupture in megakaryoblastic leukemia cells via activation of adhesion and motility by staurosporine on fibronectin-bound substratum.

Human megakaryoblastic leukemia Meg-01 cells were attached to fibronectin (FN)-coated substratum, on which remarkable spreading and cytoplasmic elongation was induced by treatment with a protein kinase inhibitor, staurosporine (stp). This effect was inhibited by RGDS and was also not seen on FN-lacking substratum. The extended cytoplasm had swollen terminals and nodes, which contained GpIIb and beta-thromboglobulin, occasionally included alpha granules, and tended to form particles (2-5 microm) after rupture of the narrowed cytoplasm. Among other protein kinase modulators tested, only K252a promoted the elongation, while calphostin, herbimycin, TPA, and calyculin suppressed it. The cells began to migrate soon after addition of stp, with attachment to the substratum held at some sites during the migration. This tethered movement seemed to cause the cytoplasmic elongation and the rupture into particles. The elongation was retarded by pretreating the cells with cytochalasin A and Clostridium C3 toxin but not with demecolcine. Actin microfilaments in the stp-treated Meg-01 cells accumulated in the filopodia and periphery of the extended cytoplasm, in which vinculin was colocalized as adhesion plaques. The microtubules were longitudinally oriented through the cytoplasmic extension and showed no ring profile in the nodes and particles. Thus, stp in the presence of FN appears to stimulate reorganization of actin-based cytoskeleton and formation of focal contacts in Meg-01 cells. This leads to the activation of cell adhesion and motility, and then cytoplasmic elongation and rupture into particles.

Animals

Complex translocation (6;21;8), a variant of t(8;21), with trisomy 4 in a patient with acute myelogenous leukemia (M2).

The t(8;21)(q22;q22) is the second-most frequently observed nonrandom karyotypic abnormality associated with acute myelogenous leukemia (AML), especially in FAB M2. Trisomy 4 is also a specific chromosomal abnormality for AML FAB M2 or M4. We experienced a 37-year-old woman with a morphologically AML FAB M2 carrying a rare complex translocation (6;21;8)(p21;q22;q22) resulting in AML1 gene rearrangement. A subclone with an additional chromosomal abnormality, trisomy 4, was also revealed. Similarly to the typical t(8;21), a conventional chemotherapy successfully induced into complete remission associated with a recovery of normal karyotype, 46,XX, although AML1/MTG8 (ETO) chimera mRNA was detected by reverse transcriptase polymerase chain reaction.

Adult

Time dependency of the ratio of umbilical vein/maternal artery concentrations of vecuronium in caesarean section.

BACKGROUND: The ratio of umbilical vein (UV) and maternal artery (MA) concentrations of vecuronium may more accurately determine the placental transfer ratio during caesarean section. This ratio potentially correlates with the time from induction of anaesthesia to delivery (I-D time). The aim of this study was to determine the UV/MA ratio of vecuronium and its relationship with the I-D time. METHODS: Eighteen pregnant women at full term undergoing caesarean section were studied. The parturient was given intravenously 0.01 mg/kg vecuronium as a priming dose, followed 180 s later by 0.11 mg/kg vecuronium as an intubation dose and 4 mg/kg thiamylal. The time from the injection of the intubation dose to the clamping of the umbilical cord was regarded as the I-D time. At the time of clamping the umbilical cord, blood samples were collected and the UV and MA of vecuronium were measured. RESULTS: The UV/MA ratio and the I-D time, expressed as the mean (SD), were 0.056 (0.016) and 280 (57) s, respectively. The regression equation indicated y = 0.0083 + 0.00017 x (R2 = 0.381, r = 0.617, P = 0.0063, I-D time (s) = x, UV/MA = y). CONCLUSION: The present study demonstrated that the UV/MA ratio of vecuronium as an index of the placental transfer becomes smaller as the delivery time after injection of this drug becomes shorter during caesarean section.

Adult

Effect of retinoic acid on proliferation and polyamine metabolism in cultured bovine retinal pigment epithelial cells.

Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 microM RA significantly increased both cell number and [3H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N1-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N1-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.

Adenosylmethionine Decarboxylase

Type A aortic dissection involving a right-sided aortic arch.

We report a rare case of a 39-year-old man with type A aortic dissection involving a right-sided aortic arch with the symptom of vascular ring. Computed tomography scanning and angiography were performed to define the extent of the dissection and the anatomy of the branching vessels. The ascending aorta was replaced through a median sternotomy and right thoracotomy using a hypothermic cardiopulmonary bypass associated with selective cerebral perfusion and partial circulatory arrest, and his symptom of vascular ring disappeared postoperatively.

Adult

Viral replication in olfactory receptor neurons and entry into the olfactory bulb and brain.

This communication describes our ongoing studies of the interaction of the mouse host and vesicular stomatitis virus (VSV). When VSV is applied to the nasal neuroepithelium, it initially replicates in olfactory receptor neurons, and is transmitted along the olfactory nerve to the central nervous system (CNS) within 12 hours. In the olfactory bulb, the virus replicates invasively through the layers of the olfactory bulb, reaching the olfactory ventricle by day 4-5 post infection, and the hindbrain by day 8 post infection. In mice, infection may result in a 50% mortality rate. The crucial host innate and specific immune responses responsible for restricting viral propagation and caudal spread of the virus will be discussed. The efficacy of interleukin-12 (IL-12) treatment for enhanced viral clearance and promotion of host recovery are described along with the implications for treatment of human encephalitis. The hosts' response to infection is also regulated by the sex of the host, and the age at infection. The role of specific mucosal humoral immunity and systemic cellular immunity in prevention of infection are described.

Animals

The entropy generation in visual-pigment system by the absorption of light.

We first showed a general theory that reception of information from the outside in a receptor system is accompanied both by an inflow of entropy and by a generation of entropy depending on the reliability of the actual reception mechanism. Then, considering a case for the absorption of light by the visual-pigment system of visual cell, we calculated the time(t)-dependent change in the number N2(t) of excited visual-pigments to obtain the entropy increase. We thus arrived at the following four conclusions: (1) One or two photons can be detected with a reliability of at least 54%; (2) In compensation for this detection, entropy > 1.12 x log2 is generated; (3) An incident photon of frequency v from a ligh source of temperature Ts yields an entropy of hv/Ts; and (4) Depending on the characteristics of the visual-pigment system, another entropy being different from (2) is generated in proportion to N2(t).

Absorption

Circumanal glands of the dog: a new classification and cell degeneration.

BACKGROUND: The circumanal glands of the dog are thought to be a glandular tissue, but there is some controversy as to whether they should be classified as exocrine or endocrine. In this study, we examined the nature of the circumanal glands to determine whether they should be described as exocrine, endocrine, or something else altogether. In addition, we investigated the cell degeneration in lobules of the circumanal glands in relation to the apocrine glands. METHODS: Light microscopic observations were made of paraffin sections stained with hematoxylin and eosin, and after immunohistochemical staining with antibodies against alpha-smooth muscle actin, keratin, filaggrin, and 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD). Samples were also examined by electron microscopy after fixation by aldehyde perfusion. RESULTS: The lobules of circumanal glands could be divided into two types on the basis of the presence or absence of cysts. Four layers (I-IV) were detected in the lobules with cysts. The outermost layer (layer I or the basal layer) consisted of flattened cells that contained bundles of tonofilaments and were stained immunohistochemically with the antibody against keratin. Layer II (the polyhedral or "spinous" layer) consisted of polyhedral cells that contained bundles of tonofilaments. These cells were connected to adjacent cells by desmosomes, interdigitations, and gap junctions, and they were immunopositive for keratin. A small number of polyhedral cells were immunopositive for 3beta-HSD. Layer III (the granular layer) was composed of flattened cells that contained hematoxylin-stainable granules and were moderately immunopositive for filaggrin. The innermost layer (layer IV or the horny layer) consisted of keratin. Lobules without cysts consisted only of layer I (the basal layer) and layer II (the polyhedral layer). Lobules of the circumanal glands were not directly connected to apocrine glands. Polyhedral cells degenerated and were phagocytosed by basal cells at a periphery of lobules. Then, basal cells phagocytosing degenerated polyhedral cells escaped from lobules, moved into the walls of apocrine glands, and, finally, dropped into the lumen of apocrine glands. CONCLUSIONS: Lobules of the circumanal glands have many characteristics of epidermis (a basal layer, a polyhedral or "spinous layer," a granular layer, and a horny layer) and they should not be classified as glandular tissue. The cysts in lobules can be interpreted as "closed hair canals." We suggest that steroid metabolism might occur in the polyhedral cells of the lobules.

Actins

[Left ventricular rupture following mitral valve replacement with preservation of posterior leaflet].

Left ventricular rupture following mitral valve replacement (MVR) with preservation of the posterior leaflet is presented. A 63-year-old man underwent combined AVR, MVR with preservation of the posterior leaflet and TAP under cardiopulmonary bypass with moderate hypothermiat to 28 degrees C and tepid blood cardioplegia. Although a 31-mm valve would fit to the mitral position, a 27 TEKNA was chosen for MVR. Beyond the cardiopulmonary bypass, a left ventricular rupture was found. Cardiopulmonary bypass was re-stated and the aortic clamp was replaced. After removal of the mitral valve prosthesis, an internal tear was detected below the anterolateral commissural area (Type I). The tear was repaired with two 3-0 monofilament buttressed sutures incorporated with felt strips and covered with a bovine pericardial patch by several interrupted pledgeted mattress sutures. Gelatin-resorcin-formaldehyde/Glutaraldehyde glue (GRF) was used to reinforce the ruptured myocardium and to fix a bovine pericardial patch to the affected ventricular wall. Then the prosthesis was re-seated. Although the aortic clamp time was 319 mins., the patient was weaned from the cardiopulmonary bypass easily with the prophylactic use of IABP. The patient was discharged and returned to his previous job.

Aortic Valve

Heterogeneous distribution of K-ras-mutated epithelia in mucinous ovarian tumors with special reference to histopathology.

The carcinogenic process of epithelial ovarian carcinomas is still unknown, and both pathways of de novo carcinogenesis from the surface epithelium and malignant transformation of benign cystadenoma have been suggested. Especially in mucinous ovarian tumors, the transition from benign cystadenomas to tumors of low malignant potential (LMP) or carcinomas has been implicated. To elucidate this possibility, we analyzed the presence or absence of heterogeneity of the K-ras mutation corresponding to the histological heterogeneity in 71 epithelial ovarian tumors, including 31 mucinous tumors. K-ras mutation was identified in nine mucinous tumors (4 of 10 carcinomas, 4 of 14 LMP tumors, and 1 of 7 cystadenomas) and in two nonmucinous carcinomas. Microdissection of multiple sites with reference to their histological appearance showed the heterogeneous distribution of K-ras-mutated epithelia in two of the nine mucinous tumors. One mucinous carcinoma showed K-ras mutation in all of the histologically LMP and malignant portions, but not in benign portions. In another LMP tumor, all of the LMP portions and one of the benign portions showed K-ras mutation, whereas the other two benign portions had no mutation. In the remaining seven mucinous tumors with K-ras mutation, however, there was a homogeneous distribution of K-ras-mutated epithelia irrespective of their histological appearance. These findings suggest that the K-ras mutation occurs during the transformation from benign cystadenomas to LMP or malignant lesions, providing molecular genetic support for the hypothesis of the "adenoma-carcinoma sequence" in some mucinous ovarian tumors, but in other cases an alternative pathway may also be possible.

Adenocarcinoma, Mucinous

Prognostic significance of heat shock proteins HSP70 and HSP90 in endometrial carcinomas.

Heat shock proteins HSP70 and HSP90 are sex steroid receptor-associated proteins, and HSP90 expression has reportedly been correlated with sex steroid receptor status in endometrial carcinomas. HSP70 is also known to associate with several oncogene products such as p53 protein, and expression of HSP70 has been reported to be a prognostic factor in several malignant neoplasms. In endometrial carcinomas, however, little is known about the prognostic significance of these proteins. Therefore, we analyzed the survival of 44 endometrial carcinoma patients treated in our hospital with reference to the immunohistochemical expressions of HSP70 and HSP90, as well as the clinicopathological factors such as age, menstrual status, FIGO stage, histologic grade, p53 protein overexpression, and sex steroid receptor status. The expression of HSP70 was observed in 50% (22 cases), and strong HSP90 expression in 30% (13 cases) of the 44 carcinomas. The patients with HSP70-positive tumors showed significantly poorer survival than the patients with HSP70-negative tumors (p = 0.045), although multivariate analysis did not reveal HSP70 expression to be an independent prognostic factor. In contrast, the strong expression of HSP90 in the tumor was significantly correlated with a favorable prognosis of the patient (p = 0.026). Other prognostic indicators were FIGO stage (p = 0.0086) and the expression of progesterone receptor (p = 0.042). Accordingly, expressions of HSP70 and HSP90 each have different prognostic significance in endometrial carcinoma and may be useful for prediction of patient survival.

Adult

Expression of class I human leukocyte antigen (HLA) and beta2-microglobulin is associated with decidualization of human endometrial stromal cells.

Human leukocyte antigen (HLA) class I molecules play a central role in the immune system through either presentation of endogenous antigen and activation of T lymphocytes or functional emergence of natural killer (NK) cells. Various types of immune cells are present in the human endometrium and are believed to be involved in reproductive function and/or immunological reaction. However, little is known about the expression status and function of HLA class I molecules in the human endometrium. We therefore examined mRNA expression of HLA class I. In addition, we analysed gene expression and localization of beta2-microglobulin (beta2-MG), which is the non-variant chain of all HLA class I molecules. Compared with non-decidualized tissues, mRNA expression of both HLA class I and beta2-MG was significantly higher in decidualized endometria in the late secretory phase, under progestin treatment and during early pregnancy. Immunohistochemical studies revealed that beta2-MG was localized in decidualized endometrial stromal cells, indicating that the distribution of beta2-MG is topologically correlated with that of CD56bright+ NK cells. In-vitro culture of human endometrial stromal cells demonstrated that HLA class I mRNA was induced during the decidualization by progesterone. Accordingly, the expression of HLA class I molecules is transcriptionally activated along with decidualization of human endometrial stromal cells, and may represent an immuno-endocrine function of the endometrium.

Adult

Effect of an endotoxin-removing column containing immobilized polymyxin B fiber in a patient with septic shock from gram-positive infection.

A 67-yr-old patient with septic shock caused by gram-positive infection fell into circulatory collapse. Direct hemoperfusion with an endotoxin-removing column was then carried out for 120 min. As a result, blood pressure and systemic vascular resistance increased significantly during this therapy. Cardiac output changed from hyperdynamic to normodynamic, and plasma endotoxin level decreased. After this treatment, the patient recovered. From this experience, we consider that the endotoxin-removing column may be effective for septic shock patients.

Aged

Immunohistochemical demonstration of cytoskeletal proteins in the testis of the Japanese black bear, Ursus thibetanus japonicus.

The seasonal changes of the cytoskeletal protein expressions were immunohistochemically investigated in the testes of Japanese black bear, Ursus thibetanus japonicus. A strong immunoreaction for alpha-smooth muscle actin is restricted to the vascular smooth muscle cells and the peritubular cells which surround the seminiferous tubules by several layers throughout the year. Weak immunoreactions for B4 antigen and desmin were observed in the vascular smooth muscle cells and in a part of peritubular cells throughout the year. A strong immunoreaction for vimentin was also detected in the fibroblasts and Leydig cells, in addition to the vascular smooth muscle and epithelial cells and the peritubular cells throughout the year. A strong alpha-tubulin immunoreaction was detected in the elongating spermatids during the acrosome phase of spermiogenesis in May and June. The cytoplasm of several Sertoli cells was faintly immunoreacted for vimentin in the basal and lateral region, while an intense alpha-tubulin reaction was seen in the entire cytoplasm in May, April and June. In November, January and March, the immunoreactions for vimentin and alpha-tubulin strongly accumulate in a perinuclear region of Sertoli cells when developmental spermatids are not seen in the seminiferous tubules. These accumulations in the immunoreactions for vimentin and alpha-tubulin seem to be caused by the reduction in size of Sertoli cells cytoplasm with season. However, the seasonal changes of distributions in the cytoskeletal proteins are obscure in the bear testes. These results suggest that the contents of cytoskeletal proteins may not change in relation to the morphological differences with season in the testes of the seasonal breeders.

Actins

Clinical evaluation of a leucocyte-depleting blood cardioplegia filter (BC1B) for elective open-heart surgery.

Activation of leucocytes during extracorporeal circulation has attracted attention in recent years as a cause of reperfusion injury in open-heart surgery patients. In the present study, 40 adult patients undergoing elective open-heart surgery were randomized into two groups: 20 using the Pall BC1B leucocyte-depleting filter for blood cardioplegia (group 1) and the other 20 without the filter (group 2). In order to determine if the filter was effective in protecting the myocardium, CPK-MB and troponin-T (TnT) were measured. In addition, efforts were also made to determine appropriate sites at which the BC1B blood cardioplegia filter should be positioned. There were no significant differences between the two groups in terms of conditions of perfusion. No adverse effects were seen in either group. The total leucocyte reduction rate through the filter was 98.1% with the passage of 2 liters of blood through the filter. A pressure drop of 4.4 +/- 3.2 mmHg was observed through the filter during use. Statistically significant differences were noted between the two groups in CPK-MB (p = 0.031) and TnT (p = 0.004). Findings obtained in previous studies demonstrate that the various advantages of leucocyte reduction, shown in experimental studies, can be translated into clinical advantages. In conclusion, based on the results in this clinical study showing significant difference in CPK-MB and TnT which are known effective indicators for myocardial injury, between leucoreduced and non-leucoreduced group, the Pall BC1B leucocyte-depleting filter for blood cardioplegia has been shown to be effective in alleviating reperfusion injury in open-heart surgery patients.

Adult