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Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 343 records · Page 19Linked to original sources

Lipogenic enzyme gene expression is quickly suppressed in rats by a small amount of exogenous polyunsaturated fatty acids.

An examination was conducted of the time courses of incorporation of polyunsaturated fatty acids (PUFA) into lipids of plasma, liver and its nuclei, and the time courses of hepatic lipogenic enzyme gene expression after oral administration of perilla oil by a stomach tube to rats fed a fat-free diet. Linolenic acid, 18:3(n-3), and eicosapentaenoic acid, 20:5(n-3), were considered indices of exogenous fatty acids. In total lipids of liver and its nuclei, linolenic acid was detected 1 h after the intubation, continued to increase during the first 4 h, then decreased and almost disappeared by 48 h. Eicosapentaenoic acid also increased within only 1 h of intubation, reached a maximum after 8 h and then gradually decreased. In contrast with the increase of exogenous PUFA, the mRNA concentrations of hepatic lipogenic enzymes began to decrease 2 h after the perilla oil intubation, were at a minimum at 8 h, and then increased. In another experiment to examine the effects of dietary perilla oil concentration on PUFA incorporation and gene expression, rats were given diets containing 0-10% perilla oil (supplemented with hydrogenated fat to 10% fat) for 3 d. Only 1% perilla oil elevated the exogenous PUFA concentrations in liver and its nuclei in comparison with concentrations in rats fed a hydrogenated fat diet. Perilla oil at 2% of the diet was sufficient to suppress lipogenic enzyme gene expressions, which were suppressed to the minimum level by 5% perilla oil in the diet. Thus, lipogenic enzyme gene expression was quickly suppressed by a small amount of exogenous PUFA, in contrast with the increase of PUFA incorporation into liver and its nuclei. Newly incorporated exogenous PUFA appear to be involved in suppression of lipogenic enzyme gene expression.

Animals↗

Induction of long-term remission in advanced hepatocellular carcinoma with percutaneous isolated liver chemoperfusion.

OBJECTIVE: The aim of this study was to report the long-term results of percutaneous isolated liver chemoperfusion with hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) in patients with multiple advanced hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: The results of conventional chemotherapy including regional and systemic chemotherapy in patients with HCC remain dismal, and long-term survivors after treatment are rare among patients with multiple advanced HCC. In an effort to improve this situation, we previously developed a novel system of percutaneous isolated liver chemoperfusion with HVI-CHP. METHODS: Doxorubicin (60 to 150 mg/m2) was administered via the hepatic artery, under conditions of extracorporeal drug elimination by HVI-CHP in 28 consecutive patients with advanced HCC (39 total treatments). Hepatic venous isolation and charcoal hemoperfusion was accomplished mainly by the single catheter technique using a newly developed 4-lumen-balloon catheter, which was used to isolate and capture total hepatic venous outflow and, at the same time, to direct the filtered blood to the right atrium. RESULTS: Complete remission was achieved in five patients, of which four received repeated treatments (two or three times). Although 1 of 5 patients with complete remission died of pulmonary metastases at 8 months, the other 4 remain healthy and free of disease at 20, 24, 27, and 42 months after the first treatment. Partial responses were observed in 12 patients. Duration of response in responders (complete and partial) with repeated treatments was significantly longer than that with a single treatment (p = 0.01). The overall survival rate by the Kaplan-Meier method was 39.7% at 5 years. The treatments were well-tolerated, and the primary side effects were mild to moderate chemical hepatitis and reversible myelosuppression. CONCLUSIONS: The results suggest that percutaneous isolated liver chemoperfusion with HVI-CHP is an effective palliative treatment in the majority of patients and yields long-term complete remission in some patients with multiple advanced HCC.

Adult↗

Role of the transition zone for elevating serum prostate-specific antigen in benign prostatic hyperplasia.

BACKGROUND: Patients with benign prostatic hyperplasia (BPH) have a wide range of concentrations of PSA. However, it is not known what factors influence the concentration of serum PSA other than the prostate volume. BPH is composed of an enlarged transition zone (TZ) and other zones (nonTZ). The TZ is thought to play a more important role than the nonTZ in determining the concentration of serum PSA in BPH patients. METHODS: We investigated the individual glandular zone volume, the amount of PSA produced by each zone and the PSA density in each zone in 23 patients with histologically-confirmed BPH. The PSA density in the TZ was calculated by dividing the difference between the serum PSA before and after surgical resection by the specimen weight. We examined the influence of these parameters on the concentration of serum PSA in BPH patients. RESULTS: The serum PSA concentration correlated with the amount of PSA produced by the TZ (r=0.90, P< 0.0 1), but not the nonTZ (r=0.25, P=0.29). The concentration of serum PSA also showed a significant correlation with the TZ volume (r=0.67, P< 0.01) and the PSA density in the TZ (r=0.51, P< 0.05), but not with the PSA density in the nonTZ (r=-0.06, P=0.81). Also, age was inversely correlated with the PSA density in the TZ (r=-0.69, P< 0.01). CONCLUSION: The hypertrophic prostate cell volume (TZ volume) and activity (PSA density in the TZ) significantly correlated with the concentration of serum PSA in BPH patients, and the TZ cell activity decreased inversely with age in these BPH patients.

Age Factors↗

Primary hepatic lymphoma in a patient with chronic hepatitis B.

Primary hepatic lymphoma is a rare disorder and the clinical behavior remains unknown. We report a patient with primary hepatic lymphoma who had chronic hepatitis B. She was asymptomatic; however, a solitary tumor in the left lobe was incidentally detected. After left hepatic lobectomy was performed, a diagnosis of non-Hodgkin's lymphoma was made. No tumor was found except in the liver. Immunohistochemical stains for hepatitis B surface and core antigens were positive in hepatocytes; however, both were negative in the tumor tissue. The patient received no chemotherapy and the tumor relapsed. After chemotherapy, the tumor disappeared. However, exacerbation of hepatitis occurred after the fourth chemotherapy. The patient was followed up without chemotherapy, and she remains in apparent remission. Chemotherapy is effective against primary hepatic lymphoma and, if possible, patients with this disorder should be treated with chemotherapy postoperatively.

Aged↗

Mouse osteoblastic cell line (MC3T3-E1) expresses extracellular calcium (Ca2+o)-sensing receptor and its agonists stimulate chemotaxis and proliferation of MC3T3-E1 cells.

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+o) homeostasis in parathyroid gland and kidney. Osteoblasts appear at sites of osteoclastic bone resorption during bone remodeling in the "reversal" phase following osteoclastic resorption and preceding bone formation. Bone resorption produces substantial local increases in Ca2+o that could provide a signal for osteoblasts in the vicinity, leading us to determine whether such osteoblasts express the CaR. In this study, we used the mouse osteoblastic, clonal cell line MC3T3-E1. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in MC3T3-E1 cells. We also identified CaR transcripts in MC3T3-E1 cells by Northern analysis using a CaR-specific riboprobe and by reverse transcription-polymerase chain reaction with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of MC3T3-E1 cells to high Ca2+o (up to 4.8 mM) or the polycationic CaR agonists, neomycin and gadolinium (Gd3+), stimulated both chemotaxis and DNA synthesis in MC3T3-E1 cells. Therefore, taken together, our data strongly suggest that the osteoblastic cell line MC3T3-E1 possesses both CaR protein and mRNA very similar, if not identical, to those in parathyroid and kidney. Furthermore, the CaR in these osteoblasts could play a key role in regulating bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local release of Ca2+o.

Animals↗

Estrogen via the estrogen receptor blocks cAMP-mediated parathyroid hormone (PTH)-stimulated osteoclast formation.

Several lines of evidence indicate that estrogen inhibits parathyroid hormone (PTH)-induced bone resorption in vivo and in vitro. However, its precise mechanism remains unknown. The present study was performed to investigate whether osteoclast precursor cells possess the receptors for PTH/PTH-related protein (PTHrP) and/or estrogen and to clarify the mechanism by which estrogen affects PTH-induced osteoclast-like cell (Ocl) formation. The polymerase chain reaction (PCR) product corresponding in size to the mouse PTH/PTHrP receptor cDNA was detected in mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as in osteoblastic MC3T3-E1 cells. The nucleotide sequence of the PTH/PTHrP receptor PCR product of hemopoietic blast cells was found to be 95.4% identical to that of PTH/PTHrP receptor cDNA of rat osteoblastic ROS cells. The PCR product corresponding in size to the mouse estrogen receptor cDNA was detected in mouse hemopoietic blast cells supported by GM-CSF as well as in MC3T3-E1 cells. The nucleotide sequence of the estrogen receptor PCR product of hemopoietic blast cells was completely identical to that of mouse estrogen receptor cDNA. 17Beta-estradiol (17beta-E2) but not 17alpha-E2 dose dependently antagonized Ocl formation stimulated by human (h) PTH(1-34) at a minimal effective concentration of 10(-10) M in the hemopoietic blast cell culture. 17Beta-E2 also significantly inhibited Ocl formation stimulated by 10(-8) M hPTHrP(1-34), while it did not affect 1,25-dihydroxyvitamin D3-induced Ocl formation. However, 10(-8) M 17beta-E2 significantly inhibited Ocl formation stimulated by dibutyryladenosine cAMP (10(-4) M) and Sp-cAMPS (10(-4) M), an activator of cAMP-dependent protein kinase (PKA) as well as forskolin (10(-5) M). In contrast, 17beta-E2 did not affect Ocl formation by either phorbol myristate acetate (10(-7) M), an activator of protein kinase C (PKC), or A23187 (10(-7) M), a calcium ionophore. The pretreatment with 17beta-E2 significantly inhibited Ocl formation induced by the combined treatment with PTH and PKC inhibitors (H7 or staurosporine), while it did not affect Ocl formation stimulated by the combined treatment with PTH and Rp-cAMPS, a PKA inhibitor. The present data indicate that estrogen inhibits PTH-stimulated Ocl formation by directly acting on hemopoietic blast cells, possibly through blocking a PKA pathway but not a calcium/PKC pathway.

Animals↗

Vitamin D receptor genotype is associated with cortical bone loss in Japanese patients with primary hyperparathyroidism.

Vitamin D receptor (VDR) genotype was determined in 66 Japanese patients with primary hyperparathyroidism (pHPT). In contrast to previous report showing an association between VDR genotype bb and the development of pHPT in a Swedish population, we did not find any differences in the frequencies of the VDR genotypes between pHPT and the control. The bone mineral density in the radius was significantly lower (Z score, -1.723 +/- 1.819) in bb genotype than in BB/Bb genotype (+0.255 +/- 2.344) in pHPT patients. Based on the fact that PTH requires vitamin D3 to take effect on calcium mobilization from bone, it is possible that VDR polymorphism may influence the PTH action on bone.

Adult↗

Carboxyl-terminal parathyroid hormone fragments stimulate type-1 procollagen and insulin-like growth factor-binding protein-5 mRNA expression in osteoblastic UMR-106 cells.

The effects of carboxyl-terminal (C-) PTH fragments, (35-84), (53-84) and (69-84), on the proliferation and function of osteoblastic UMR-106 cells were compared with those of amino-terminal (N-) (1-34) and intact (I-) (1-84) PTH. I-PTH as well as N-PTH at 10(-8)M significantly inhibited [3H] thymidine incorporation and stimulated alkaline phosphatase activity in UMR-106 cells. No C-PTH fragments affected them. In contrast, the expression of type-1 procollagen mRNA in these cells was stimulated by all C-PTH fragments, inhibited by N-PTH and not affected by I-PTH. All C-PTH fragments except (69-84) as well as N-PTH and I-PTH stimulated IGFBP-5 mRNA expression. The present study suggests that the C-portion of the PTH molecule exercises biological activities in mRNA expression of type-1 procollagen as well as IGFBP-5 in osteoblasts, and that it might be involved in the anabolic action of PTH on bone in vivo.

Cell Line↗

Familial isolated hyperparathyroidism caused by single adenoma: a distinct entity different from multiple endocrine neoplasia.

Familial hyperparathyroidism (FHPT) is a hereditary disease where hyperparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT). Isolation of the genes responsible for MEN1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT with single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygosity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathyroid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of the affected member of the family, suggesting no relation to MEN2A. Linkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was not overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands remains to be clarified. A search for the gene(s) predisposing to FIHPT is needed.

Adenoma↗

Age-dependent changes in body composition in postmenopausal Japanese women: relationship to growth hormone secretion as well as serum levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3.

The present study was performed to investigate the age-dependent changes in body composition and the possible role of growth hormone (GH), insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) in these changes in postmenopausal Japanese women. A total of 161 Japanese women aged 45-88 years (mean 62) were enrolled in the cross-sectional study. Body composition (bone mineral content (BMC), lean body mass (LBM) and fat) was measured by dual-energy X-ray absorptiometry, and the percentage of BMC, LBM and fat was calculated by dividing each absolute value of body composition by total body mass. Urinary GH concentration divided by creatinine in nocturnal urine samples collected just after waking was used as an index of endogenous GH secretion. Serum levels of IGF-I and IGFBP-3 were measured by RIA. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 declined with age. BMC, %BMC and LBM also declined with age, while fat mass and %fat did not obviously change with age. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 correlated positively with BMC, even if age was taken into account. On the other hand, urinary GH correlated negatively with fat and %fat. In contrast, serum levels of IGF-I and IGFBP-3 correlated positively with fat and %fat. LBM did not correlate with either urinary GH or serum IGFBP-3 levels but exhibited a weakly positive correlation with serum IGF-I level. The present study suggests that the GH-IGF-I-IGFBP-3 axis positively regulates bone mass, and that GH and IGF-I-IGFBP-3 inversely regulate fat mass, i.e. GH negatively and IGF-I-IGFBP-3 positively regulates it.

Aged↗

Prolongation of PT and APTT under excessive anticoagulant in plasma from rats and dogs.

Prothrombin time (PT) and activated partial thromboplastin time (APTT) were studied under excessive sodium citrate using the plasma from rats and beagle dogs. Addition of sodium citrate into the plasma caused a prolongation of PT and APTT. The prolongation was dependent on the concentration of sodium citrate or calculated hematocrit. The degree of prolongation was more severe in rats than in dogs, and in APTT than in PT. These results suggest that an artificial prolongation of PT and APTT occurs under excessive sodium citrate (e.g., elevated hematocrit), and that the degree differs between species and between parameters.

Animals↗

Fatal liver cirrhosis and esophageal variceal hemorrhage in a patient with type IIIa glycogen storage disease.

A 45-year-old woman with type IIIa glycogen storage disease (GSD IIIa) died of variceal hemorrhage secondary to liver cirrhosis. The postmortem examination disclosed increased intracellular glycogen in the liver as well as in the heart and skeletal muscle. Although most liver injuries in GSD IIIa have been considered to be non-progressive in adulthood, liver cirrhosis can be a cause of death in some patients.

Diagnosis, Differential↗

Coxiellosis in domestic and wild birds from Japan.

Serological evidence of infection with Coxiella burnetii was found in 41 (2%) of 1,951 domestic birds and in 167 (19%) of 863 wild birds from 17 and 5 prefectures in Japan, respectively, by microagglutination (MA) test. The bacteriological evidence of the infection was found in 17 (41%) of 41 domestic birds and 37 (22%) of 167 wild birds by the nested polymerase chain reaction (PCR). In addition, C. burnetii was isolated from five each of serum, spleen and fecal specimens from five jungle crows (Corvus macrorhynchos) (whose sera were positive by both the MA test and PCR) by inoculating laboratory mice. Domestic quail (Coturnix coturnix japonica) (3%), domestic muscovy ducks (Cairina moschata) (3%), domestic chickens (2%), domestic mallards (Anas platyrhynchos domesticus) (2%), carrion crows (Corvus corone) (37%), jungle crows (35%), and wild rock doves (Columba livia) (6%) showed serologic evidence of experience with C. burnetii. There was a tendency for a high prevalence among birds living and/or feeding in close proximity to infected livestock. This suggests that these birds are one of the less important links in maintaining the whole cycle of C. burnetii infection.

Agglutination Tests↗

[Basic calponin expressing human neuroblastoma cell line of KP-N-YS].

Recent studies have demonstrated that human neuroblastoma (NB) cell lines have at least two morphological appearance of neuroblastic (N-type) and substrate-adhesive (S-type) cells. Our previous study revealed that S-type cells expressed alpha-smooth muscle actin and/or desmin, suggesting the smooth muscle cell characteristics of S-type cells. In the present study, a new human NB cell line, KP-N-YS, was established from bone marrow metastasis of a four-year-old boy with advanced NB, originating from the left adrenal gland. Subsequently N-type cell clone (YS1n) and S-type cell clone (YS2s) was isolated from the parent cell line. Parent and clones cell lines were identified as NB by surface membrane antigen and cytoskeletal protein analysis, and these cell lines were demonstrated as common progenitors by chromosomal analysis. Furthermore the presence of basic calponin were determined by indirect immunofluorescence, Western blot, as well as by RT-PCR (reverse transcriptase-polymerase chain reaction). Our demonstration of basic calponin not in N-type cells, but in S-type cells supports the plausible smooth muscle cell characteristics of this NB cell line.

Antigens, Surface↗

Results of surgical treatment for thoracoabdominal aneurysm using cardiopulmonary bypass under moderate hypothermia and selective visceral artery perfusion.

From 1994 to 1997, 11 consecutive patients with thoracoabdominal aneurysms underwent surgery using cardiopulmonary bypass under moderate hypothermia (33 degrees C) and selective visceralartery perfusion for spinal cord and visceral organ protection. Distal perfusion pressure was maintained above 60 mmHg (mean) during cardiopulmonary bypass. In the four patients, one or two pairs of large intercostal arteries between Th10 and L2 were reimplanted. In the four patients, visceral and renal arteries were reconstructed. Surgical mortality rate within 1 month was 18.2% (2/11). One patient died of bleeding from old empyema and another of multiple organ failure. No patients had paraplegia. In conclusion, cardiopulmonary bypass with selective visceral artery perfusion under moderate hypothermia may contribute to the prevention of the occurrence of paraplegia and acute renal failure.

Aneurysm↗

[Giant platelet-like cell fragments produced from abnormal promyelocytes in acute myelogenous leukemia].

A 38-year old man was transmitted to our hospital because of his pneumonia and disconsciousness. Laboratory data showed leukocytosis (32,500/microliter), mild anemia, and decreased platelet count (6.7 x 10(4)/microliter). The bone marrow aspiration revealed the presence of 40% blastoid cells and cytogenetic study showed abnormal karyotype, 45, X, -Y, t(8; 21) (q22; q22), indicating acute myeloid leukemia (AML, M2). Furthermore, on the microscopic observation, cell fragments resembling giant platelets were observed which were positive for myeloperoxidase, and several fragments connected with abnormal promyelocytes through thin cytoplasm. These results suggested these cell fragments may be produced from abnormal promyelocytes in this case.

Adult↗