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T Sugawara

Publications and source records attributed to T Sugawara.

At least 73 records · Page 4Linked to original sources
PubMed2000

PCR diagnosis of X-linked ichthyosis: identification of a novel mutation (E560P) of the steroid sulfatase gene.

X-linked ichthyosis (XLI) is an inherited skin disorder due to deficiency of steroid sulfatase (STS) activity. XLI has been diagnosed by assaying STS activity in placenta or lymphocytes of patients after birth. Most patients have a large deletion of the STS gene, generated by inaccurate recombination at the STS locus. However, point mutations in the STS gene have been reported in some patients with complete STS deficiency. In a new case of STS deficiency, we identified an STS missense mutation, Glu560Pro or E560P. This new point mutation suggests that the C-terminal region of the STS enzyme is important for STS enzymatic function. Hum Mutat 15:296, 2000.

Amino Acid Substitution↗
PubMed2000

Prediction of recurrence and extratumor spread of hepatocellular carcinoma following resection.

BACKGROUND AND OBJECTIVES: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy depends mostly on tumor recurrence. Portal vein invasion (Vp) and intrahepatic metastasis (IM) might strongly reflect the invasiveness of HCC, but the number of patients in the present series in whom either of these factors were detected was small. In this study, we defined Vp and IM as the extratumor spread, and we focused on the relationship between recurrence in patients after hepatectomy and the extratumor spread and the mitotic activities of cancer cells, in the hope that careful monitoring of recurrence might be possible by simply analyzing histology of the resected specimens. METHODS: Univariate and multivariate analyses were used to determine the factors potentially related to recurrence in 50 patients who underwent hepatectomy for HCC. RESULTS: The cumulative recurrence rate at 5 years was 81.0%. In univariate analysis, absence of the extratumor spread, mitotic index of four or less, and curative resection were significantly correlated with low incidence of recurrence. In multivariate analysis, the extratumor spread was the only significant variable influencing recurrence. The mitotic index in HCCs with the extratumor spread was significantly higher than the mitotic index in HCCs without the extratumor spread. CONCLUSIONS: As a predictive factor for recurrence after resection of HCC, the extratumor spread that reflects the malignant potential of cancer cells was found to be more accurate than is any single invasiveness parameter such as Vp or IM.

Analysis of Variance↗
PubMed2000

Quantitative relationship of the scotopic and photopic ERG to photoreceptor cell loss in light damaged rats.

In order to use the ERG to track the effects of potential photoreceptor rescue treatments, we have compared retinal histology to the ERG in light damage. Male albino CD rats (40) were purchased at 7 weeks of age and reared in 50 lx cyclic light until 8 week old. They were exposed to a range of light intensities using white fluorescent light (1000, 1500, 2000, 2500 or 3000 lx) for 24 or 48 hr (n = 5 per group). Controls remained in dim cyclic light. Seven days after exposure, dark and light adapted ERGs were recorded from threshold up to 200 cd m-2 using 50 ms Ganzfeld white light stimuli. The STR, and scotopic and photopic b-wave thresholds and amplitudes were measured. After recording the ERG, the eyes were removed from the animals in each of the five 48 hr light exposed groups and control group for histological measurements. These included: (1) outer nuclear layer width in rod photoreceptor cell number (cell count) and micrometers, and (2) outer + inner segment layer width along the vertical meridian in the inferior retina. The product of cell count and outer + inner segment length was calculated. All histological measures showed a statistically significant linear relationship to light exposure intensity (P < 0.0001): r2 = 0.94 (cell count), 0.90 (outer nuclear layer width), 0.77 (outer + inner segment length). The log of the scotopic b-wave threshold and log amplitude showed a significant linear correlation to all histological parameters (P < 0.0001) and there was no significant difference between b-wave threshold and amplitude for any one of the histology measures used. However, overall, log b-wave threshold was significantly better correlated to histology P < 0.02. Only log b-wave amplitude showed a significant increase in variability in light damaged retinas (P < 0.02). The b-wave threshold intensity increased 0.33 log cd m-2 and the maximum amplitude decreased 0.23 log microV with each 10% decrease in cell number in the outer nuclear layer. The sensitivity of the scotopic threshold response, which originates from third order neurons, changed much more slowly with cell loss, than did the b-wave (P < 0.0005) and was well fit by a linear relationship to cell loss. The increase in photopic b-wave threshold was not significant for a cell loss of less than 70-80%. Neither the photopic or scotopic b-wave could be reliably recorded with more than 80% cell loss, but the scotopic threshold response remained. Both the scotopic and photopic ERG showed similar waveform changes near the threshold, including loss of the positive going b-wave and the predominance of a negative going response. Outer nuclear layer cell counts in this study showed the same relationship to log b-wave threshold elevation, as has been previously shown for whole retinal rhodopsin content in light damage, indicating that regional histology measurements can be good indicators of overall cell survival. Both the b-wave threshold and amplitude can be reliably used to track photoreceptor cell loss due to the damaging effects of constant light, but the scotopic threshold response may be more useful in severe damage.

Animals↗
PubMed2000

Digestion of plant monogalactosyldiacylglycerol and digalactosyldiacylglycerol in rat alimentary canal.

We investigated digestion of orally fed galactoglycerolipids such as monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) from wheat flour in the rat alimentary canal, especially focusing on the digestive fates of deacylated galactosylglycerol structures. After a single oral administration of MGDG (20 mg/rat), monogalactosylmonoacylglycerol and monogalactosylglycerol (MGG) were found to be major digestion products in the intestinal tract. Similarly, digalactosylmonoacylglycerol and digalactosylglycerol (DGG) were confirmed to be present in the intestinal tract after DGDG ingestion (20 mg/rat). In rats fed wheat flour glycolipids (42 mg MGDG and 81 mg DGDG per rat), completely deacylated galactosylglycerols (MGG and DGG) were not detected in portal plasma. Although the deacylated galactosylglycerols were not significantly decomposed by intestinal mucosa in vitro, they were hydrolyzed by cecal contents. The results demonstrated that orally ingested plant galactoglycerolipids in the rat alimentary canal are rapidly hydrolyzed into constituent fatty acids and that hydrophilic galactosylglycerols and the hydrophilic backbone galactosylglycerols are not absorbed from intestine or degraded into galactose and glycerol in the intestinal tract. Therefore, the presence of deacylated galactosylglycerols may affect the fermentative activity of enterobacteria in the cecum and colon.

Journal Article↗
PubMed2000

Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature.

This report describes two cases of Philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph(+) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. Leukemia(2000) 14, 169-182.

Aged↗
PubMed2000

Impaired cutaneous wound healing in interleukin-6-deficient and immunosuppressed mice.

It has been postulated that an inflammatory response after cutaneous wounding is a prerequisite for healing, and inflammatory cytokines, such as interleukin-6 (IL-6), might be intimately involved in this process. IL-6-deficient transgenic mice (IL-6 KO) displayed significantly delayed cutaneous wound healing compared with wild-type control animals, requiring up to threefold longer to heal. This was characterized by minimal epithelial bridge formation, decreased inflammation, and granulation tissue formation. Using electrophoretic mobility shift assays of wound tissue from IL-6 KO mice, decreased AP-1 transcription factor activation was shown compared with wild-type mice 16 h after wounding. In situ hybridization of wound tissue from wild-type mice revealed IL-6 mRNA expression primarily in the epidermis at the leading edge of the wound. Delayed wound healing in IL-6 KO mice was reversed with a single dose of recombinant murine IL-6 or intradermal injection of an expression plasmid containing the full-length murine IL-6 cDNA. Treatment with rmIL-6 also reconstituted wound healing in dexamethasone-treated immunosuppressed mice. The results of this study may indicate a potential use for IL-6 therapeutically where cutaneous wound healing is impaired.

Animals↗
PubMed2000

Involvement of oxidative stress and caspase-3 in cortical infarction after photothrombotic ischemia in mice.

Apoptosis-related cell death is linked to oxidative stress and caspases in experimental cerebral ischemia. However, the role of oxidative stress in caspase activation and subsequent apoptotic cell death after cerebral ischemia is unknown. The authors evaluated the role of oxidative stress in ischemic cerebral infarction after photothrombosis and the relation between oxidative stress and caspase-related cell death 6 and 24 hours after ischemia with and without U-74389G, a potent free radical scavenger (10 mg/kg, 30 minutes before and after ischemia induction). Reactive oxygen species, detected by hydroethidine oxidation, and cytosolic cytochrome c were detected in early ischemic lesions. Western blot analysis showed the cleaved form and the increased level of the proform of caspase-3 in the ischemic lesion 24 hours after ischemia. Decreased caspase-3 immunoreactivity was detected in the antioxidant-treated group after ischemia. Decreased DNA fragmentation and laddering were detected and the lesion was smaller in the treated group after ischemia compared with the untreated group. Oxidative stress and cytochrome c release occur in the ischemic lesion after photothrombotic ischemia. The free radical scavenger attenuated caspase-3 up-regulation, DNA fragmentation, and the final lesion. The authors concluded that oxidative stress may mediate caspase-related apoptotic cell death and subsequent cortical infarction after photothrombotic ischemia.

Animals↗
PubMed2000

Lithium potassium borate and lithium rubidium borate: new non-linear optical crystals

The title compounds, LiKB(4)O(7) and LiRbB(4)O(7), are newly developed non-linear optical crystals containing two kinds of anionic groups, namely (B(3)O(8))(7-) and (B(5)O(10))(5-). The (B(3)O(8))(7-) groups form infinite spiral chains parallel to the [100] direction, which are interconnected by sharing O atoms with (B(5)O(10))(5-) groups.

Journal Article↗
PubMed2000

Mitotic index is the best predictive factor for survival of patients with resected hepatocellular carcinoma.

BACKGROUND: In patients with hepatocellular carcinoma (HCC), tumor recurrence is not infrequent after resection. It is presumed that characteristics of the tumor such as cellular malignancy might influence the prognosis of the patients in association with tumor stage and radicality of the procedure. METHODS: Univariate and multivariate analyses were used to retrospectively determine the clinicopathologic factors potentially related to survival in 40 patients who underwent hepatectomy for HCC. RESULTS: In univariate analysis, tumor stage I or II, mitotic index of 4 or less/10 random high-power fields, solitary tumor, and curative resection were significantly correlated with better survival. In multivariate analysis, the mitotic index and surgical curability were independently significant variables influencing survival of patients, and the mitotic index was the best predictive factor. A highly significant correlation was found between the mitotic index and Ki-67 labeling index. Compared to tumors with a mitotic index of 4 or less, those with a mitotic index of 5 or more had a higher association with multiple tumors and advanced tumor stage, which preclude curative resection. CONCLUSION: Analysis of the mitotic index is quite simple, and the mitotic index could be a useful factor for predicting the long-term survival of patients with HCC following hepatic resection.

Carcinoma, Hepatocellular↗
PubMed2000

Hepatectomy using an ultrasonically activated scalpel for hepatocellular carcinoma.

BACKGROUND: The first retrospective studies were performed to compare the efficacy of the ultrasonic cavitational aspirator (aspirator group) and the ultrasonically activated scalpel (scalpel group) for hepatic resection in patients with hepatocellular carcinoma. PATIENTS AND METHODS: The aspirator group consisted of 8 patients (6 with liver cirrhosis and 2 with chronic hepatitis in the nontumorous liver), and the scalpel group of 7 patients (6 with liver cirrhosis and 1 with chronic hepatitis). All patients underwent limited hepatic resection, and the intermittent Pringle maneuver was applied during hepatic transection. RESULTS: There were no significant differences in preoperative hepatic function, type of hepatectomy, tumor size and maximum cross-sectional area of the resected specimen between the 2 groups. The amount of intraoperative blood loss was significantly less in the scalpel group than in the aspirator group (684 versus 1,859 ml, p < 0.05). The operation time was significanly shorter in the scalpel group than in the aspirator group (176 versus 262 min, p < 0.05). There were no significant differences in postoperative liver function and morbidity between the 2 groups. CONCLUSIONS: The ultrasonically activated scalpel is effective in reducing blood loss and in shortening the time of operation, and can be employed during limited resection of the liver with cirrhosis or chronic hepatitis.

Aged↗
PubMed2000

Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic acute regulatory protein gene expression.

Steroidogenic acute regulatory (StAR) protein plays a critical role in the movement of cholesterol from the outer to the inner mitochondrial membrane. Steroidogenic factor 1 (SF-1) controls basal and cAMP-stimulated transcription of the StAR gene. The 1.3-kb StAR promoter has three SF-1 binding sites, and two consensus transcription factor Spl binding sequences near the two most distal SF-1 binding sites. Spl mediates cAMP-dependent transcription of steroidogenic P450 enzyme genes, raising the possibility of Sp1 involvement in cAMP regulation of the StAR gene. However, the mechanism of Spl-mediated, cAMP-stimulated responsiveness is not known. In this study, we elucidated the roles of Sp1 and SF-1 in the regulation of the human StAR gene promoter. We found that there was negligible promoter activity in a pGL2 StAR construct (-235 to +39) in which Spl and SF-1 binding sites were mutated in Y-1 adrenal tumor cells. An Sp1 binding site mutation (pGL2Sp1M) did not support promoter activity, suggesting that Spl cooperates with SF-1 in regulating StAR promoter function. In gel shift assays, the SF-1 binding site formed a complex with an SF-1-GST fusion protein and Spl. Coimmunoprecipitation cross-linking experiments indicated that SF-1 physically interacts with Sp1 in vitro. Finally, a mammalian two-hybrid system was employed to demonstrate that Spl and SF-1 associate in vivo. In conclusion, our data indicate that Spl and SF-1 physically interact and cooperate in the regulation of human StAR promoter activity.

Adrenal Cortex Neoplasms↗
PubMed2000

ESR study on the antioxidant activity of TAK-218 in biological model membranes.

TAK-218 has a 2,3-dihydrobenzofuran-5-amine (coumaran) structure which resembles alpha-tocopherol, and is a promising candidate as an agent for central nervous system (CNS) trauma and ischemia. The radical scavenging activity of TAK-218 was studied using electron spin resonance (ESR) spectroscopy. TAK-218 exhibited a more potent scavenging activity towards the hydroxyl radical than did the well-known hydroxyl radical scavengers, mannitol and dimethylsulfoxide. Towards the superoxide radical, TAK-218 showed equal potency to glutathione. TAK-218 reacted rapidly with stable radicals, such as galvinoxyl and 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH), and gave the quinone as a two-electron oxidized product in analogy with alpha-tocopherol. To exhibit an excellent antioxidative activity in living systems, the compounds should not only have the intrinsic radical scavenging activity but also good distribution in the biological lipid-bilayer membrane. To examine the antioxidant activity of TAK-218, the inhibition of lipid peroxidation by alpha-tocopherol and TAK-218 in liposomal membranes was studied using an ESR spin-label technique. Both alpha-tocopherol and TAK-218 completely inhibited lipid peroxidation by radicals generated in an aqueous layer using a water-soluble radical initiator, 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH). At a high incubation temperature (45 degrees C), alpha-tocopherol scavenged radicals more effectively than TAK-218 on the surface of the membrane, while TAK-218 scavenged radicals more effectively in the interior of the membrane. The difference between TAK-218 and alpha-tocopherol for radical scavenging in the membrane system derives from the different distribution pattern of these compounds. TAK-218 can penetrate the membrane freely and can scavenge the radical in the membrane interior. Furthermore, TAK-218 was shown to inhibit lipid peroxidation initiated by a lipid soluble radical initiator, 2,2'-azobis-(2,4-dimethylvaleronitrile) (AMVN), in a membrane more effectively than alpha-tocopherol.

Antioxidants↗
PubMed2000

Thyroid hypertrophic effect of semotiadil fumarate, a new calcium antagonist, in rats.

We studied the effects of semotiadil fumarate (SF), a new calcium antagonist with a unique benzothiazine structure, on the thyroid gland and liver in rats and compared them with those of another calcium antagonist, nicardipine (NCD), a well-known thyroidal hypertrophic agent and microsomal enzyme inducer, phenobarbital (PB), and goitrogen propylthiouracil (PTU). In oral 2-week treatment, SF caused increases in hepatic microsomal protein levels, uridine diphosphate glucuronosyltransferase (UDPGT) activity and an increase in serum thyroid stimulating hormone (TSH) level together with decreases in serum thyroid hormone levels. These results suggest that SF accelerates peripheral disposition of thyroid hormones and subsequently stimulates secretion of TSH from the pituitary gland as a compensatory response. PB and NCD had similar effects on the thyroid gland and the liver. PTU showed obvious thyroid hyperplasia and an increase in relative liver weight. Drastic increase in TSH level was observed in the PTU-treated group together with significant decreases in serum thyroid hormone levels and an increase in hepatic UDPGT activity. Histopathologically, PTU depleted the colloids in follicles, suggesting the inhibition of thyroid hormone synthesis. SF, PB and NCD showed thyroidal hyperplasia, but the extent of the change was far more moderate than that induced by PTU. These results indicate that the effect of SF is similar to those of PB and thyroid hypertrophy seen in the oral 2-week treatment with SF, and may be caused by indirectly elevated TSH levels which resulted from the induction of hepatic UDPGT activity.

Animals↗
PubMed2000

P23H rhodopsin transgenic rat: correlation of retinal function with histopathology.

PURPOSE: To correlate retinal functional changes with structural changes in P23H rhodopsin transgenic rats as a model of autosomal dominant retinitis pigmentosa. METHODS: P23H heterozygote (lines 1 and 3) and Sprague-Dawley control rats were studied at 4 to 29 weeks by retinal histology, electroretinogram (ERG), and a-wave transduction modeling. RESULTS: Both line 1 (faster degeneration) and line 3 (slower degeneration) showed progressive rod outer segment (ROS) shortening and outer nuclear layer (ONL) cell loss with age. ERG b-wave maximum amplitude (Vb(max)) decreased with age, but b-wave threshold remained constant within each line despite progressive ONL thinning and ROS shortening. The only exception was in line 1 at 29 weeks, which showed a slight threshold change relative to earlier ages. Va(max) and a-wave threshold changed more rapidly and were more sensitive than the b-wave in reflecting histologic degeneration. Va(max) was linearly proportional to the product of (ROS x ONL) across a two log unit range of data combined from both lines. The photopic b-wave was normal for both lines until the ONL thinned beyond 50%. Phototransduction sensitivity was normal for both lines, and dark-adaptation recovery after bleaching rhodopsin was normal. CONCLUSIONS: The P23H transgenic rat has a slow rod degeneration with initially normal cone function, consistent with clinical findings of P23H patients. However, the normal bleach recovery and the normal phototransduction sensitivity in this rat model are different from human P23H disease. a-Wave measures were more sensitive than the b-wave for tracking changes. b-Wave threshold was inexplicably poor for tracking degeneration. Although line 1 degenerated faster than line 3, the functional-structural correlates were the same. The tight linear relationship between saturated a-wave amplitude and the product of (ROS x ONL) indicates that the density of cGMP-gated channels per unit ROS plasma membrane area remains constant over a wide range of degenerations.

Animals↗
PubMed2000

[Electrical responses from the inner retina of rats with streptozotocin-induced early diabetes mellitus].

PURPOSE: To evaluate behavior of the scotopic threshold response (STR) and the oscillatory potential (OP) in the electroretinogram (ERG) in streptozotocin (STZ)-induced diabetic rats (DM rats). METHODS: The amplitude of the STR and the OP 3, the implicit time of the STR, and the peak latency of the OP 3 of the DM rats were measured. RESULTS: No significant differences were observed in the mean amplitude or the mean implicit time of the STR between the control and the DM rats. On the other hand, the mean peak latency of OP 3 of the DM rats was significantly prolonged up to 125% of the control rats (p < 0.01), although there were no significant differences between the two groups in the mean OP 3 amplitude. CONCLUSIONS: Although both STR and OP were of inner retinal origin, their behavior was different in DM rats. This result supported some reports describing how dopaminergic amacrine cells generate OP and glycinergic or GABAergic amacrine cells generate STR. In the early stage of diabetic retinopathy, there may be not only minor ischemia but also disorder of neurotransmission of the amacrine cells in the inner retinal layers.

Animals↗
PubMed1999

Immunosuppressants promote adult dorsal root regeneration into the spinal cord.

Immunosuppressants promote neurite extension in culture and facilitate regeneration of peripheral nerves in vivo. However, their neurotrophic effects in the CNS have not been well studied. We utilized a rat dorsal root transaction model to examine the effects of cyclosporine A (CsA) and FK 506 on regeneration of the dorsal root into the spinal cord. After surgery, the rats received daily subcutaneous injections of CsA or FK 506. One month after surgery, dorsal root axons were immunohistochemically labeled to evaluate the extent of regeneration into the spinal cord. Dorsal root axons of CsA/FK 506-treated rats frequently entered into the spinal cord and arborized extensively. Administration of immunosuppressants markedly promoted regeneration of dorsal root axons into the spinal cord.

Animals↗