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Biomedical subjects

T Goto

Publications and source records attributed to T Goto.

1,058 records · Page 59Linked to original sources
PubMedDate not supplied

Effect of lipoprotein lipase activators bezafibrate and NO-1886, on B16 melanoma-induced cachexia in mice.

Our recent study has demonstrated that B16 melanoma-induced cachexia in mice is inhibited by ponalrestat, an aldose reductase inhibitor, which has the ability to activate lipoprotein lipase (LPL) activity both in vitro and in vivo. In this study, the effect of bezafibrate and NO-1886, LPL activators, on B16 melanoma-induced cachectic symptoms was investigated in mice. Treatment with bezafibrate resulted in an attenuation of the decrease in the weight of epididymal fat and whole body lipid observed in mice following intraperitoneal inoculation of B16. The increase in the levels of triglyceride and non-esterified fatty acid, and a decrease in the level of glucose in the blood, which was induced by the presence of tumor, were also restored to that of normal mice after treatment with bezafibrate. The reduction in the weight of epididymal fat and whole body lipid induced by B16 was also ameliorated by NO-1886. Overall, this study demonstrated that cachexia induced by B16 melanoma in mice was alleviated by the LPL activators bezafibrate and NO-1886, suggesting the involvement of the impaired LPL activity in the establishment of cachexia syndrome in mice bearing B16 melanoma.

Adipose Tissue↗
PubMedDate not supplied

Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome induced by colon26 adenocarcinoma in mice.

Our recent study has demonstrated that ponalrestat, an aldose reductase inhibitor, activates lipoprotein lipase activity and alleviates B16 melanoma-induced cachexia in mice. In this study, the effect of ponalrestat on murine adenocarcinoma colon26-induced cachexia was investigated in mice. Mice bearing colon26 subcutaneously lost weight and became cachectic, associated with the tumor growth. Although tumor growth was slightly stimulated when tumor bearing mice were treated with ponalrestat: nevertheless, the drug attenuated the reduction in the weight of body mass, epididymal fat, gastrocnemius muscle and carcass induced by colon26, as well as significantly prolonged the survival of the colon26 bearing mice. Ponalrestat inhibited the production of interleukin-1 (IL-1) from human monocytes stimulated by Lipopolysaccharide (LPS) in vitro, and also suppressed LPS-induced increase of IL-1 in the blood in mice. Overall, this study showed that ponalrestat suppresses IL-1 production both in vitro and in vivo, and inhibits the cachectic symptoms induced by colon26 adenocarcinoma in mice, suggesting that ponalrestat has a therapeutic potential for the treatment of cancer cachexia.

Adenocarcinoma↗
PubMedDate not supplied

Interferon gamma and tumor necrosis factor alpha induce Fas expression and anti-Fas mediated apoptosis in a salivary ductal cell line.

BACKGROUND: We previously reported that Fas antigen was strongly expressed on salivary duct epithelial cells and that some salivary infiltrating cells showed the Fas ligand in patients with severe sialoadenitis due to Sjögren's syndrome (SS). Apoptotic changes were observed in ductal epithelial cells and some infiltrating cells by DNA nick end labeling methods. These findings suggest that the Fas-Fas ligand system may play a role in the pathogenesis of sialoadenitis in SS. OBJECTIVE: To elucidate the mechanism of the de novo expression of ductal Fas antigen in sialoadenitis associated with SS, we investigated the induction of Fas antigen and apoptosis by cytokines in a human salivary duct cell line. METHODS: Human salivary duct cell line (HSG) was cultured with interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin 4 (IL-4), and granulocyte monocyte colony stimulating factor (GM-CSF). The expression of Fas antigen in HSG was examined by immunoperoxidase cell ELISA. The appearance of DNA strand breaks during apoptosis induced by anti-Fas antibody was detected by DNA nick end labeling methods. RESULTS: Unstimulated HSG cells constitutively expressed low levels of Fas antigen. IFN-gamma and TNF-alpha consistently upregulated constitutive levels of Fas. In contrast, IL-1 beta, IL-2, IL-4, and GM-CSF had no effect on Fas levels. HSG cells expressing Fas antigen in response to IFN-gamma or TNF-alpha were susceptible to apoptosis by anti-Fas antibody. CONCLUSION: Our findings suggest that IFN-gamma or TNF-alpha secreted by infiltrating lymphocytes induces ductal Fas expression and ductal apoptosis in sialoadenitis associated with SS.

Antineoplastic Agents↗
PubMedDate not supplied

Cachexia induction by EL-4 lymphoma in mice and possible involvement of impaired lipoprotein lipase activity.

Several lines of evidence have postulated that reduction in the activity of lipoprotein lipase (LPL) is involved in cachexia induction in cancer patients. Recently we have demonstrated that murine melanoma B16 has the ability to reduce the LPL activity and thereby induce cachexia symptoms in mice following intraperitoneal inoculation. In order to further investigate the relationship between LPL activity and cachectic syndrome, cachexia models other than melanoma B16 are required. However, there are few animal cachexia models in which LPL activity is involved in the induction of cachectic symptoms. In this study, cachectic symptoms and plasma LPL activity were investigated in mice bearing EL-4 mouse lymphoma. In EL-4 bearing mice the body weight including tumor weight in the abdominal cavity was rather higher than that of normal mice without tumor, whereas weights of carcass wet and gastrocnemius muscle were significantly decreased in EL-4 bearing mice. Elevated blood levels of triglyceride and non-esterified fatty acid were observed in mice bearing EL-4, associated with the impaired plasma LPL activity. Overall, this study indicated that EL-4 lymphoma in mice results in a severe cachexia which is possibly related to impaired LPL activity and also provided a useful cachexia model for understanding the role of LPL in the development of cancer cachexia.

Animals↗
PubMedDate not supplied

Induction of bone loss by bile duct ligation in rats.

Metabolic bone loss is the most common complication of chronic liver disease. However, there is little information available about bone loss in rats with a ligated bile duct, a biliary-type of experimental cirrhosis model. Therefore, in this study, the effect of bile duct ligation (BDL) on bone mineral density (BMD) and plasma insulin-like growth factor-I (IGF-I) levels was examined in rats. Two weeks after BDL operation, the rats with a ligated bile duct showed a pronounced and significant decrease in both trabecular and cortical BMD of the femur. In these rats, decreases in food intake and plasma IGF-I levels plus elevated levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin were also observed. When the effect of dietary restriction (30% or 50%) over 2 weeks was then investigated in normal rats, 50% food restriction resulted in a significant decrease in femoral trabecular bone density although BMD was unchanged by 30% dietary restriction. The plasma levels of IGF-I were also decreased in food-restricted rats. Thus, the decrease in femoral bone density in 50% food-restricted rats was less potent compared with BDL rats; nevertheless, the decrease in plasma levels of IGF-I was almost equally potent in both BDL and food-restricted rats. Overall, this study showed that BDL operation resulted in a pronounced bone loss in rats, but also that this bone loss might not be merely due to the decreases in food intake and plasma IGF-I levels. These results suggest that BDL in rats is a useful experimental cirrhosis model for evaluating the bone loss associated with chronic liver disease.

Animals↗
PubMedDate not supplied

A hypothesis of epiarachnoidal growth of vestibular schwannoma at the cerebello-pontine angle: surgical importance.

AIMS: The purpose of this study is to clarify the rearrangement of the arachnoid membrane on the vestibular schwannoma during its growth in relation to adjacent neurovascular structures for a better understanding of dissecting plane of arachnoid during surgery. METHODS: Arachnoid membrane over the tumour was investigated during surgery with suboccipital transmeatal approach in twenty-six tumours. All microsurgical procedures were recorded with a video and reviewed. The tumour growth was classified into five stages depending upon the tumour diameter in the cerebello-pontine (CP) angle: Stage 1; purely intracanalicular (2 cases), Stage 2; less than 5 mm (2 cases), Stage 3; > or = 5 and <15 mm (8 cases), Stage 4; > or = 15 and <25 mm (9 cases) and Stage 5; > or = 25 mm (5 cases). Rearrangement of the arachnoid on the tumour was conceptualised throughout all stages. RESULTS: All tumours of Stage 1 and 2 were entirely located in the subarachnoid space of the cerebello-pontine cistern without arachnoidal rearrangement, while all tumours of Stages 3 to 5 were enveloped, in the CP angle, with invaginated arachnoid membrane consisting of cerebello-pontine cistern except two surfaces; the medial pole and the tumour surface under the facial and cochlear nerves near the porus. CONCLUSION: The tumour originates subarachnoidally within the internal auditory meatus (IAM) and grows epiarachnoidally in the CP angle. Rearrangement of the arachnoid begins with its adhesion on the medial pole of the tumour along the porus, resulting in the arachnoidal invagination into the cerebello-pontine cistern with further growing of the tumour.

Adult↗
PubMedDate not supplied

Mycotoxin analysis by fast atom bombardment tandem mass spectrometry.

Positive fast atom bombardment tandem mass spectrometry is demonstrated to be an effective technique for determination of crude aflatoxins and sterigmatocystin-related compounds. The molecular ion was selected by the first system and bombarded to produce characteristic daughter ions that could be used to identify mycotoxins in mixtures and with the same molecular weight.

Aflatoxins↗
PubMedDate not supplied

Fractionation of radioactivity in the milk of goats administered 14C-aflatoxin B1.

A detailed fractionation of radioactivity in the milk of goats administered 14C-aflatoxin B1 at low doses was performed. The milk collected in the first 24 h following dosing contained radioactivity equivalent to 0.45-1.1% of the dose given. The radioactivity in each sample was partitioned into 4 fractions: ether, protein, dichloromethane, and water-alcohol. Over 80% of the radioactivity was detected in the dichloromethane fraction, of which over 95% was attributable to aflatoxin M1. No aflatoxin B1 or other known aflatoxin metabolites were detected in any fraction. The results indicate that the major metabolite of aflatoxin B1 in goat milk is aflatoxin M1 and that other metabolites, including conjugates, are of minor significance.

Aflatoxin B1↗
PubMedDate not supplied

Antihypertensive effect of MK-421 in rats. Role of the renal kallikrein-kinin system.

To study the hypotensive mechanism of the new oral converting-enzyme inhibitor, MK-421, we evaluated the antihypertensive effect of MK-421 in rats with hypertension induced by chronic administration of norepinephrine (NE) or vasopressin and measured urinary kallikrein and kinin excretions as indices of the renal kallikrein-kinin system. When 6 mg/kg/day of MK-421 was administered simultaneously with 1.8 mg/kg/day of NE, the systolic blood pressure of conscious rats rose on Day 1 to only 122.6 +/- 3.4 mm Hg compared with the rise to 146.3 +/- 1.6 mm Hg when NE alone was infused (p less than 0.001). Similarly, when the same dose of MK-421 was administered simultaneously with 7.2 U/kg/day of vasopressin, the systolic blood pressure of conscious rats rose on Day 1 to only 117.4 +/- 3.8 mm Hg compared with the rise to 141.6 +/- 3.4 mm Hg when vasopressin alone was infused (p less than 0.01). The antihypertensive effect of MK-421 was sustained for 6 days in rats infused with NE or vasopressin. Infusion of NE alone resulted in a small but significant increase in urinary kallikrein excretion and no change in urinary kinin excretion. The combined administration of NE with MK-421 induced additional increases in urinary kallikrein and kinin excretions. Vasopressin alone resulted in marked decreases in urinary kallikrein and kinin excretions. The combined administration of vasopressin with MK-421 induced no additional changes in urinary kallikrein and kinin excretion. These results indicate that the hypotensive effect of MK-421 may depend on a reduced sensitivity of the peripheral arteries to vasoconstrictor substances.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Ten-year follow-up study of conical crown-retained dentures.

This study reports the results of a long-term evaluation of conical crown-retained dentures. One hundred fifty-two restorations that had been in place for over 10 years were analyzed. Restorations were divided according to the Kennedy classification. Abutment and periodontal health, occlusion, retention, and frequency of relining and repair were among the factors evaluated. Good prognoses of removable partial dentures were shown in Kennedy Classes I, II, and III arches. However, some of the restorations placed on only a few remaining abutments showed rather unfavorable situations with almost all of the factors evaluated.

Crowns↗
PubMedDate not supplied

Intensive preoperative chemotherapy for osteosarcoma in the lower extremity.

BACKGROUND: The aims of this study were to investigate the effect, if any, of preoperative chemotherapy and to investigate the adaptation and the limits for achieving a more functional limb in our limb-salvaging procedure. MATERIALS AND METHODS: Since 1983 to 1997 we have treated 53 cases of osteosarcoma in an upper or lower limb at our Institute. According to surgical staging by Enneking, there were 37 cases at stage II B, and 16 cases at stage III. Neoadjuvant chemotherapy was performed according to one or other of our four protocols. RESULTS: The 5-year-survival rate was 68% for those cases at stage II B, and was 13% for those at stage III. In particular, we adopted the protocol involving hyperthermic isolated regional perfusion (HIRP) for those cases in which the lesion affected the knee joint. CONCLUSION: The various protocols of chemotherapy including HIRP were effective to permit reduction in the surgical margin and were also effective to achieve an increase in the limb-salvaging rate and especially effective for increasing the salvaged limb-functionality.

Adolescent↗