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Biomedical subjects

S Hatakeyama

Publications and source records attributed to S Hatakeyama.

At least 181 records · Page 10Linked to original sources

A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.

Acute and chronic experimental ulcerative colitis models were produced in mice by providing them with drinking water containing synthetic dextran sulfate sodium. Mice that developed acute colitis showed signs of diarrhea, gross rectal bleeding, and weight loss within 6-10 days after ingesting 3%-10% dextran sulfate sodium. On postmortem examination, multiple erosions and inflammatory changes including crypt abscesses were found on the left side of the large intestine. Mice that developed chronic colitis showed signs of erosions, prominent regenerations of the colonic mucosa including dysplasia, shortening of the large intestine, and frequent formation of lymphoid follicles after 5 administration cycles, where each cycle was composed of 7 days' consumption of drinking water containing 5% dextran sulfate sodium followed by 10 days' consumption of distilled water. The population of intestinal microflora, Bacteroides distasonis and Clostridium spp., increased significantly in mice with acute and chronic ulcerative colitis. Further, morphological studies suggest that the administered dextran sulfate sodium was partially phagocytized by macrophages in the colonic mucosa.

Acute Disease↗

Effects of aerial spraying of insecticides on nontarget macrobenthos in a mountain stream.

The effects of aerial spraying of an insecticide were investigated in a mountain stream using a drift net. The concentration of fenitrothion (organophosphorus insecticide) in the river water increased to ca. 20 micrograms liter-1 3 hr after the spraying and decreased exponentially to half the peak value after 2 hr. A large number of aquatic insects were found drifting after the spraying. The total number of individuals which drifted in the daytime after spraying reached nine times the number found the previous night. The total number of species which drifted during the 24 hr following the spray increased to 43 from 17 on the previous day. Before the insecticide spraying, the drifting benthos were almost entirely made up of three species of Baetis (Ephemeroptera). However, many individuals of several species of Heptageniidae (Ephemeroptera), Apsilochorema sutshanum (Trichoptera), and Chironomidae (Diptera) drifted in addition to Baetis after the spray. A large number of young Baetis, which had not been seen in the natural night drift samples, were found drifting due to the insecticide. Natural night drift almost disappeared from the day following insecticide spraying. At the second insecticide spraying, conducted 20 days after the first, the number of individuals which drifted during the 24 hr following spraying decreased to only 0.85% of that in the first spraying although changes in insecticide concentration showed a similar pattern. Several species of Ephemeroptera were dominant among the fauna in the studied stream, and the causal relationships of this are discussed.

Aerosols↗

S-phase accumulation of human salivary adenocarcinoma cells by cycloheximide.

Cycloheximide (1.0 ug/ml) reversibly induced a 1.7-fold increase in the distribution of cells in S phase and a 0.9-fold decrease in G1 phase in DNA histograms of human salivary adenocarcinoma cells (HSG). At this time, cycloheximide inhibited the synthesis of proteins by HSG cells and secretion of proteins in the media to 28.1% and 9% of the control values, respectively, which resulted in the almost complete arrest of cell reproduction. This indicates that HSG cells can pass through G1 to S phase even under the conditions of the arrest of protein synthesis.

Adenocarcinoma↗

Sequential analysis of the thymocyte differentiation in fully allogeneic bone marrow chimera in mice. I. Relationship between functions and surface characteristics of thymocytes.

Differentiation of thymocytes according to surface phenotype, functional status and cell size was investigated using fully allogeneic bone marrow chimeras. Most of the donor-derived thymocytes obtained from chimeras 9 days after hematopoietic reconstitution were CD4-8- and IL2R+. At day 14, CD4+8+ cells became prominent in the thymus. Eighty-six per cent of thymocytes were CD4+8+ and 9% were CD4-8- at this stage. After day 21, the proportion of CD4+8- or CD4-8+ single positive cells transiently increased and then declined to normal level at day 42. Further, the mean size of CD4+ or CD8+ single positive cells in chimeric thymuses at day 21 after reconstitution was markedly larger than that at day 35. When proliferative responses to various stimuli (PMA + rIL2, anti-CD3 mAb (2C11) and anti-V beta 8 mAb (F23.1] were evaluated, significant responses were generated by thymocytes for the first time at around day 28 and the responses reached their peaks at day 35. These findings demonstrated that the process of thymocyte differentiation in the fully allogeneic chimeras was similar to ontogenic development as observed in fetal mice. However, the tempo at which the differentiation of surface phenotypes and development of functions proceeded was quite different from that seen in normal mice. The relationship among surface phenotypes, cell size and functions of developing thymocytes of bone marrow chimeras is discussed.

Animals↗

Sequential analysis of the thymocyte differentiation in fully allogeneic bone marrow chimera in mice. II. Further characterization of the CD4+ or CD8+ single positive thymocytes.

Differentiation of CD4+8- and CD4-8+ single-positive (SP) thymocytes in fully allogeneic bone marrow chimeras were investigated using multicolor cytometric analysis. The proportion of CD3+ cells in CD4+ SP population derived from donor mice considerably increased between day 12 and 14 after bone marrow transplantation (BMT), and gradually increased thereafter. The proportion of V beta 8+ cells in the CD3+CD4+ population remained constant (around 20%) at each period, suggesting that alpha and beta chains were used as TCR. The proportion of J11d+ cells in the CD4+ SP thymocytes transiently increased from day 12 to 14 and decreased thereafter, even though almost half of CD4+ SP cells were still dull J11d+ at day 35 after BMT. When CD8+ SP populations were analyzed, the proportion of CD3+ cells was very small until day 18. Thereafter, the proportion considerably increased and reached a maximum (83.2%) at day 21. The proportion of V beta 8+ cells in the CD3+ CD8+ SP population fell within range between 20 and 30%. However, before day 18, most of the V beta 8+ cells were dull positive, while after day 21 the majority were bright V beta 8+. Further, CD8+ SP cells at day 12, 14 and 18 were largely bright J11d+. After day 21, however, the proportion of bright J11d+ cells rapidly decreased. Similar results were obtained when the sequence of appearance of CD4+ and CD8+ SP cells was compared among bright CD3+, bright V beta 8+ or J11d- mature populations. The CD4+ SP cells regularly appeared earlier than CD8+ SP cells in the mature populations. These findings indicate that a considerable heterogeneity exists within both CD4+ and CD8+ SP populations and that the differentiation process for CD4+ SP cells precedes that for CD8+ SP cells.

Animals↗

Purification of an active gelatinase from collagen fiber fraction of granulation tissue in rats.

Gelatinase was extracted at 60 degrees C from the collagen fiber-rich fraction of granulation tissue induced by carrageenin in rats. A large part of the extracted gelatinase was unbound to Zn-chelating Sepharose. The unbound gelatinase gave a single band corresponding to a molecular mass of 57 kDa on SDS-substrate PAGE, but showed a much higher molecular mass (greater than 200 kDa) on Sephadex G-150 gel filtration. In addition, that unbound fraction contained gelatin fragments was revealed by SDS-PAGE. When the unbound fraction of Zn-chelating Sepharose was incubated at 37 degrees C, the gelatin fragments disappeared and the apparent molecular mass of gelatinase in gel filtration decreased. This gelatin degradation of the unbound fraction was enhanced by treatment with a 4-aminophenylmercuric acetate (APMA). The results suggest that the gelatinase is bound to gelatin fragments in the unbound fraction. After the treatment with APMA, the gelatinase was purified to to homogeneity; the purified gelatinase gave a single band corresponding to a molecular mass of 57 or 67 kDa on SDS-PAGE under nonreducing or reducing conditions, respectively. The purified gelatinase is a metalloproteinase, and extensively degraded gelatin, but showed no proteolytic activity toward alpha-casein or types I and IV collagens. The results suggest that the 67-kDa active gelatinase is bound to collagen fibers and plays an important role in a rapid degradation of collagen fibers in granulation tissue.

Animals↗

A morphological study of the efferent ducts of the human epididymis.

Efferent ducts of the human epididymis were studied with a light microscope and a computerized three-dimensional image analyser by preparing complete serial sections. The efferent ducts were characterized by a columnar epithelium, which differed both from the cuboidal epithelium of the rete testis and from the tall columnar epithelium of the epididymal duct. Therefore, the junctions of the efferent ducts with the rete testis and epididymal duct could be identified morphologically. Five or six efferent ducts originated from the dilated extra-testicular rete testis, ran in an extremely tortuous manner and transformed into the epididymal ducts in an end-to-end pattern near the border of the epididymal head and corpus. Computerized image analysis confirmed light microscopical findings and demonstrated three-dimensional structures of the junctions of the efferent ducts with both the rete testis and the epididymal ducts.

Aged↗

Sequential analysis of distributions of donor-derived thymocytes bearing T-cell antigen receptor (TCR) and donor-derived Ia+ cells in thymuses of fully allogeneic bone marrow chimera in mice.

Lethally irradiated SJL/J mice were reconstituted with B10 bone marrow cells, and the process of thymic reconstitution by donor-derived cells positive for I-A or V beta 8 molecules was investigated. The donor-derived Ia+ cells appeared in the medulla on day 7 after reconstitution. The Ia+ cells became confluent up to day 14, and the cellularity in the medulla on day 17 was almost the same as that in the normal thymus. Dull V beta 8+ thymocytes were first recognized in the cortex on day 10 and were identifiable in the medulla by day 14. The V beta 8+ cells seemed to be mainly CD4+8+ double-positive. Furthermore, most of the V beta 8+ cells in the medulla of chimeras given cyclosporin A for 3 weeks after reconstitution appeared to be CD4+8+ thymocytes which bear a low concentration of TCR exist in the thymic medulla at a relatively early stage when donor-derived Ia+ cells have already settled there. The coincidental appearance and coexistence of Ia+ cells and TCR+ thymocytes in the medulla suggest that these histological characteristics may be related to the selection of thymocytes in this area.

Animals↗

Carcinosarcoma of the submandibular gland. An autopsy case.

We present a rare case of submandibular gland carcinosarcoma occurring in a 45-year-old male patient. His clinical history revealed that the carcinosarcoma had developed from a carcinoma ex mixed tumor in three years. In spite of repeated resection, intensive chemotherapy and irradiation, the tumor recurred and grew rapidly, and the patient died of hemothorax caused by rupture of a pulmonary metastatic tumor. The fourth recurrent tumor and autopsy specimens showed features of carcinosarcoma consisting of three tumor components, i.e., undifferentiated carcinoma, and chondrosarcomatous and osteosarcomatous growth. The metastatic nodules in both lungs and pulmonary hilar lymph nodes showed the same pattern. Immunohistochemically, the chondrosarcomatous cells were positive for vimentin and S-100 protein, and for epithelial markers such as epithelial membrane antigen (EMA) and cytokeratin (MA-902). Undifferentiated carcinoma cells, on the other hand, were partially positive for muscle actin other than cytokeratin (KL 1). Ultrastructurally, desmosome-like structures were seen in the chondrosarcomatous cells. These findings suggest that the sarcomatous lesions might have originated from epithelial cells.

Actins↗

Immunohistochemical detection of ras p21 in oral papilloma.

Twenty-four oral papillomas were fixed in a 10% formalin solution, and 5 mu paraffin sections were prepared by normal procedure. Using monoclonal antibody NCC-RAS-001 as the primary antibody, the expression of ras p21 in the oral papilloma was searched immunohistochemically by the Histostain SP kit. The ras p21 was detected in 10 (41.7%) of 24 oral papillomas. In the histologic expression, it was less frequently detected in keratinized cell layer and basal cell layer, and it was most often detected in the cytoplasm of the cells in the spinous cell layer. These findings suggested the close relation between the expression of ras p21 and the epithelial proliferation and differentiation in the oral papilloma.

Aged↗

[A myelo dysplastic syndrome (refractory anemia with excess of blasts) occurred in a patient with small cell lung cancer during complete response].

A myelo dysplastic syndrome (MDS), refractory anemia with excess of blasts (RAEB), that occurred in a patient with small cell lung cancer (SCLC) during a period of complete response (CR) was reported. A 66-year-old female patient was diagnosed as SCLC in March, 1985. Induction chemotherapy (CDDP, ADM, VCR, VP-16) achieved CR in May, 1985. She had received maintenance chemotherapy (CDDP, ADM, VCR (or VDS), VP-16) and chest irradiation (48.6 Gy) until May, 1988. The hematologic findings revealed MDS and she was admitted in June, 1989. She died one month after onset of MDS because of pneumonia. An autopsy showed no evidence of recurrence of small cell carcinoma in the primary site and other organs. There is a possibility of the risk of secondary leukemia following long term chemotherapy and irradiation in patients with SCLC, and the role of treatment after the achievement of CR in patients with SCLC remains to be clarified.

Aged↗

[Clinical evaluation of combination assay of tumor markers in primary lung cancer patients].

Recently, the measurement of tumor markers, particularly for combined measurement, have been reported to be useful for the early diagnosis of cancer. In this study, the authors measured the serum levels of SLX, CA19-9, CA153, CA125, NCC-ST-439, CEA, SCC, NSE, TPA and IAP in 155 patients with primary lung cancer before treatment (76 adenocarcinomas, 40 squamous cell carcinomas, 36 small cell cancers, 3 large cell cancers). Seventy three benign lung disease cases were also studied as controls. The serum levels of CA19-9, CA153, CA125, NCC-ST-439, CEA, NSE and TPA were significantly higher in lung cancer patients than in benign lung disease patients. CA125 and CEA levels in adenocarcinoma, SCC levels in squamous cell carcinoma, NSE levels in small cell cancer and NCC-ST-439 in non-small cell cancer were significantly higher than those of other histological types of cancer. The level of each marker became higher, and was related with advance in stage. The probability of lung cancer was 90% when three markers were positive except for IAP, which was frequently false positive in benign lung disease. In conclusion, the simultaneous, combined measurement of at least three markers, including CEA and/or TPA was considered to be useful for the diagnosis of lung cancer.

Adenocarcinoma↗

[A case of renal cell carcinoma associated with rapidly progressive glomerulonephritis].

A 74-year-old man was admitted to our hospital because of a treatment for his right renal tumor. The abdominal CT scanning revealed a mass in the right kidney, and a right selective renal arteriography demonstrated a hypervascular tumor. On admission, urinalysis revealed proteinuria (3-4 g/day) and microscopic hematuria, and serum electrolytes were normal. Serum creatinine and urea nitrogen levels were 1.6 mg/dl and 30 mg/dl, respectively. A percutaneous right renal biopsy specimens showed crescentic glomerulonephritis. Direct immunofluorescence studies showed strong linear staining for IgG and IgA along the glomerular capillary walls. Electron microscopy showed increased mesangial matrix and swollen epithelial cells, but no dense deposits in the para-mesangial area and in the glomerular basement membrane. The patient underwent right radical nephrectomy. Histologic examination of the resected specimen revealed renal cell carcinoma. Postoperatively, he developed rapidly progressive renal failure and the renal function could not be recovered. Using the indirect immunofluorescence technique, we could not confirm the presence of a serum anti-glomerular basement membrane antibody, although the examination could not be carried out until the initiation of hemodialysis therapy. Some cases of glomerulopathies associated with renal cell carcinoma were previously reported, but the case of crescentic glomerulonephritis was very rare.

Aged↗

[Characteristic CT findings in Krabbe's disease].

In 12-month-old girl with Krabbe's disease, serial CT and MRI examinations showed characteristic findings, which were symmetric high densities in globus pallidus and thalami before and during the course of brain atrophy and decreased attenuation in white matter. The low densities in white matter were not so remarkable as other degenerative diseases affecting primarily white matter. The high densities in the globus pallidus changed into low densities with progression of the white matter hypodensities and brain atrophy. These findings on CT in Krabbe's disease may assist neurologists in narrowing the differential diagnosis and requesting appropriate laboratory tests.

Atrophy↗

Long-term tissue distribution and steady state activity ratios of 232Th and its daughters in rats after intravascular injection of Thorotrast.

To estimate the absorbed dose in the critical organs of Thorotrast patients, it is necessary to know not only the distribution and concentration of 232Th but also its daughter nuclides in the body. The present investigation was undertaken in order to clarify the long-term 232Th tissue distribution and steady state activity ratios between subsequent daughters in the critical tissues using about 30 Wister male rats, as a basis for estimating absorbed doses. The tissue distribution of thorium was examined by means of an autoradiography of the whole body and/or the gamma-ray spectrometry at various times during 2 to 24 months following injection. The concentrations of daughter nuclides in tissues were determined by repetitive gamma examination over a period from 1 hr to 35 days after being sacrificed. The data indicate (1) that approximately 90% of injected Thorotrast is retained in the body for a prolonged period, but about 50% of radium and 10% of radon produced from thorium are eliminated from the body, (2) that the mean steady state activity ratios of 224Ra and 212Pb to 228Th for liver are 0.56 and 0.28, and 0.54 and 0.16 for spleen, 0.58 and 0.82 for lungs, respectively, and (3) that the parent 228Th is translocated to the bone.

Animals↗

Long-term observation and effect of age on induction of experimental autoimmune thyroiditis in susceptible and resistant mice.

After induction of experimental autoimmune thyroiditis (EAT) in mice, long-term observation on both the severity of thyroiditis and antibody formation against mouse thyroglobulin (MTg) was carried out over a period of 18 months. In EAT-susceptible strains (CBA, C3H/Anf), both the severity of thyroiditis and MTg antibody production continued for a long term. In EAT-resistant mice (BALB/c), thyroiditis remained minimal, if present, and the low antibody response to MTg became negligible. On the other hand, aging had a prominent effect on the EAT induction in susceptible mice; both MTg antibody response and thyroid infiltration were markedly reduced. These data were well correlated with reduced antibody formation against sheep red blood cells. Young and old mice were further compared as donors or recipients in adoptive transfer of concanavalin A-stimulated cells. Lymph node cells from either young or old MTg-immunized mice transferred appreciable thyroiditis to normal young and old recipient mice. However, similarly treated spleen cells from MTg-immunized old mice responded more poorly to in vitro stimulation with mitogens or MTg and transferred thyroiditis to very few normal young or old mice.

Aging↗

A freshwater shrimp (Paratya compressa improvisa) as a sensitive test organism to pesticides.

The susceptibility of 2-week-old individuals of the freshwater shrimp, Paratya compressa improvisa, to five kinds of insecticide and five kinds of herbicide was examined in comparison with that of two species of Cladocera, Daphnia magna and Moina macrocopa. The shrimp was especially sensitive to two organophosphorus insecticides. The 48-h LC50 values for fenitrothion and fenthion to the shrimp were 1.15 and 1.04 microg litre(-1) (mean value, n=2), in contrast with 37.8 and 35.3 microg litre(-1) in the case of M. macrocopa, and more than 50 microg litre(-1) with D. magna. The shrimp also showed the higher susceptibility to other insecticides, diazinon, carbaryl (NAC) and BPMC, apart from D. magna to diazinon and NAC. The shrimp also showed higher susceptibility to herbicides. The 48-h LC50 values of CNP, benthiocarb, oxadiazon, butachlor, and symetryne to the shrimp were two to eight times lower than those of two species of Cladocera, except for the LC50 value of oxadiazon to M. macrocopa, which was very slightly higher. However, the shrimp showed a somewhat lower susceptibility to heavy metals than the two species of Cladocera, especially to copper, and to cadmium and zinc in comparison with D. magna. A bioassay using the shrimp with river water, collected from the river adjacent to the paddy field, showed clearly the high mortality of the shrimp following the aerial spraying with pesticides.

Journal Article↗