[Log-term administration of clarithromycin as a possible adjuvant therapy of HIV infections].
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AIDS-Related Complex↗
Biomedical subjects
M Sakamoto
Publications and source records attributed to M Sakamoto.
Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors.
Ten human colorectal cancer (CRC) cell lines were implanted orthotopically into the ceca and also into the livers, muscles and peritoneal cavities of SCID mice in order to analyze the characteristics regulating metastatic behaviors of CRCs. All the CRC cell lines formed tumors in the muscle and cecum, but they could be classified into two groups: (1) six cell lines with high tumorigenicity in the liver (HTLs) forming differentiated tumors, and (2) four with no tumorigenicity in the liver (NTLs) forming poorly differentiated tumors in SCID mice. After orthotopic implantation, NTLs never metastasized to the liver, whereas HTLs did. Therefore, intrahepatic tumorigenicity and differential status were closely associated with liver metastasis whereas differentiation was not associated with lung metastasis. The 6 HTLs demonstrated an inverse correlation between liver metastases and peritoneal dissemination, and immunohistochemistry indicated expression of sLeX, CA19-9 and carcinoembryonic antigen in tumors which correlated well with the liver metastatic rate. We found a strong correlation between liver metastasis and intrahepatic tumorigenicity and could reproduce the clinical correlations between the pattern of the metastatic spread and the differentiation phenotype of CRC in vivo. We consider further examination using this model will be useful for analyzing the complex mechanisms involved in clinically metastasizing CRCs.
Adenocarcinoma↗
Sensitive response of cultured vascular smooth-muscle cells to cadmium cytotoxicity: comparison with cultured vascular endothelial cells and kidney epithelial LLC-PK1 cells.
Response to cadmium cytotoxicity of cultured bovine aortic smooth-muscle cells was compared with that of cultured bovine aortic endothelial cells and porcine kidney epithelial LLC-PK1 cells. The cell damage was evaluated by morphology and the lactate dehydrogenase leakage assay. It was found that vascular smooth-muscle cells are markedly sensitive to cadmium cytotoxicity. The accumulation of intracellular cadmium was much higher but that of metallothionein was much less in vascular smooth-muscle cells than in LLC-PK1 cells; vascular endothelial cells were in between vascular smooth-muscle cells and LLC-PK1 cells. The content of reduced glutathione was slightly increased by cadmium in all three cell types. The present data suggest that a much lower inducibility of metallothionein with a high accumulation of intracellular cadmium in vascular smooth-muscle cells resulted in a marked sensitivity of the cells to cadmium cytotoxicity. Vascular smooth-muscle cells may be one of the critical target of cadmium toxicity.
Animals↗
[Coping with intractable femur head necrosis in patients with collagen diseases].
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Adolescent↗
Cancer cell morphology at the invasive front and expression of cell adhesion-related carbohydrate in the primary lesion of patients with colorectal carcinoma with liver metastasis.
BACKGROUND: Liver metastasis from colorectal carcinoma is an important problem in surgical treatment and profoundly affects the prognosis of patients. If it were possible to identify characteristic features in the primary lesion strongly related to liver metastasis, these could be used as prognostic markers for liver metastasis. To search for such features, the primary lesions of patients with colorectal carcinoma with liver metastasis were investigated. METHODS: Three groups of colorectal carcinoma were examined: Group A with synchronous liver metastases; Group B with only lymph node metastases without recurrence for 5 years; and Group C with recurrence of liver metastases. Groups A and B included 24 cases and Group C, 20. We focused on cancer cell morphology at the invasive front and expression of sialyl Lewis X (sialyl Lex) in the primary cancer. RESULTS: At the invasive front in Group A it was frequently found that polygonal, not columnar, cancer cells with a single or solitary trabecular form with indistinct polarity, showed an infiltrative growth pattern. This type of morphology was termed "focal dedifferentiation" and graded four levels. Eleven of 24 cases (46%) had severe focal dedifferentiation in Group A, 1 of 24 (4%) in Group B, and 6 of 20 (30%) in Group C. Sialyl Lex staining was positive in 12 of 24 cases (50%) in Group A, in 3 of 24 cases (13%) in Group B, and in 7 of 20 cases (35%) in Group C in the primary carcinoma. In respect to the staining of (sialyl Lex) at focal dedifferentiation, it was positive in 17 of 24 cases (71%) in Group A, in 4 of 24 cases (17%) in Group B and in 11 of 20 cases (55%) in Group C. Focal dedifferentiation and sialyl Lex staining in the primary cancer showed a significant difference between Groups A and B. Sialyl Lex staining at focal dedifferentiation showed a significant difference between Groups A and B and Groups B and C. Other adhesion related molecules, sialyl LeA and CEA, showed no difference among Groups A, B, and C. CONCLUSIONS: Both focal dedifferentiation and expression of sialyl Lex antigen in the primary lesion are considered good markers for assessing the metastatic proclivity of colorectal cancer.
Adult↗
Strong coupling quantum gravity and physics beyond the Planck scale.
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Journal Article↗
Cerebral adenosine triphosphate-sensitive K+ channels may be impaired during acute cerebral ischemia in spontaneously hypertensive rats.
To elucidate the role of cerebral adenosine triphosphate (ATP)-sensitive K+ channels (KATP) on arterial pressure regulation during acute cerebral ischemia in spontaneously hypertensive rats (SHR), intracerebroventricular (i.c.v.) injections of either glibenclamide, a specific blocker of KATP, or pinacidil, a KATP opener, were performed in SHR and Wistar-Kyoto rats (WKY). Intracerebroventricular injections of glibenclamide elicited a vasopressor response in WKY with bilateral ligation of the carotid arteries, whereas the response was smaller in SHR. It increased plasma AVP, but decreased pituitary AVP in WKY with ligation, but not in SHR. Systemic administration of an AVP V1 receptor antagonist, OPC-21268, abolished the vasopressor responses to i.c.v. injections of glibenclamide in WKY. Bilateral ligation of the carotid arteries augmented the vasodepressor responses to i.c.v. injections of pinacidil in WKY, but not in SHR. Cerebral KATP may play a role in buffering a rise in arterial pressure by inhibiting the release of AVP from the pituitary glands during acute cerebral ischemia in WKY, but this mechanism might be deranged in SHR, probably due to impaired responsiveness of cerebral KATP to ischemia.
Adenosine Triphosphate↗
Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection.
BACKGROUND: Percutaneous ethanol injection (PEI) therapy is now widely used for small hepatocellular carcinomas (HCC). However, only limited information is available regarding local tumor recurrence after PEI treatment. METHODS: We investigated the relationship of pretreatment clinicopathologic variables (tumor size, tumor cell differentiation and tumor staining) to local recurrence in 170 PEI-treated HCC nodules (measuring 5-39 mm in greatest dimension) in 84 patients. RESULTS: Local recurrence was observed in 17 of 170 PEI-treated nodules. Among these, 13 local recurrences were observed as the first event of progression after PEI. Local recurrence rates at 1, 2, and 4 years were 6.6%, 14.2%, and 14.2%, respectively, and all recurrences were observed within 2 years after PEI. Of the 3 variables investigated, large tumor size (31 mm or larger in greatest dimension) was significantly associated with a higher local recurrence rate. CONCLUSIONS: This study demonstrated that tumor size influences the local efficacy of PEI for small HCC. Therefore, we recommend that a reasonable indication for PEI therapy is HCC lesions measuring less than 30 mm in greatest dimension.
Antineoplastic Agents↗
Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease.
Pathologic water loss from sickle erythrocytes concentrates the abnormal hemoglobin and promotes sickling. The Ca2+-activated K+ channel (Gardos channel) contributes to this deleterious dehydration in vitro, and blockade of K+ and water loss via this channel could be a potential therapy in vivo. We treated five subjects who have sickle cell anemia with oral clotrimazole, a specific Gardos channel inhibitor. Patients were started on a dose of 10 mg clotrimazole/kg/d for one week. Protocol design allowed the daily dose to be escalated by 10 mg/kg each week until significant changes in erythrocyte density and K+ transport were achieved. Blood was sampled three times a week for hematological and chemical assays, erythrocyte density, cation content, and K+ transport. At dosages of 20 mg clotrimazole/kg/d, all subjects showed Gardos channel inhibition, reduced erythrocyte dehydration, increased cell K+ content, and somewhat increased hemoglobin levels. Adverse effects were limited to mild/moderate dysuria in all subjects, and a reversible increase in plasma alanine transaminase and aspartic transaminase levels in two subjects treated with 30 mg clotrimazole/kg/d. This is the first in vivo evidence that the Gardos channel causes dehydration of sickle erythrocytes, and that its pharmacologic inhibition provides a realistic antisickling strategy.
Administration, Oral↗
Interaction between cadmium and zinc in the production and sulfation of glycosaminoglycans in cultured bovine vascular endothelial cells.
Previously, we showed that cadmium stimulates the production of glycosaminoglycans (GAGs) but inhibits their sulfation in cultured bovine aortic endothelial cells. The effect of zinc on such alterations of GAGs induced by cadmium was investigated in the present study. The incorporation of [3H]glucosamine and [35S]sulfate into GAGs was determined by the cetylpyridinium chloride precipitation method as a marker of GAG production and GAG sulfation, respectively. The incorporation of both [3H]glucosamine and [35S]sulfate was not changed in GAGs accumulated in the endothelial cell layer and the conditioned medium after exposure to zinc at 20 micrometers or less alone. A simultaneous exposure of the endothelial cell layer to zinc at 20 micrometers or less and cadmium at 2 micrometers resulted in prevention of the cadmium-induced decrease in [35S]sulfate incorporation; however, the cadmium-induced increase in [3H]glucosamine incorporation was not affected by zinc. Characterization of GAGs in the cell layer revealed that such an interaction between zinc and cadmium occurred in both heparan sulfate and the other GAGs. Zinc significantly prevented the inhibition of either [3H]thymidine or [3H]leucine incorporation caused by cadmium with less accumulation of intracellular cadmium suggesting that zinc decreased intracellular cadmium and protected endothelial cells from cadmium-induced inhibition of DNA and protein synthesis. The present data showed that a simultaneous exposure to cadmium and zinc resulted in an increase in heparan sulfate without a reduction of sulfation in the endothelial cell layer. The alteration may potentiate the antihrombogenic property of vascular endothelium.
Animals↗
Effects of cadmium on the release of tissue plasminogen activator and plasminogen activator inhibitor type 1 from cultured human vascular smooth muscle cells and fibroblasts.
To evaluate the toxicity of cadmium on the blood fibrinolytic system during hemostasis, human vascular smooth muscle cells and human fibroblasts were cultured in the presence of cadmium chloride. It was found that cadmium markedly decreased the release of both tissue plasminogen activator antigen (t-PA:Ag) and plasminogen activator inhibitor type-1 antigen (PAI-1:Ag) from vascular smooth muscle cells. Other heavy metals including lead, manganese, mercury and nickel also decreased the t-PA:Ag and PAI-1:Ag release, however, cadmium was the most potent inhibitor. On the other hand, the release of t-PA:Ag was significantly increased whereas that of PAI-1:Ag was unaffected in fibroblasts after exposure to cadmium. Of the tested heavy metals, only cadmium increased the t-PA:Ag release from the cells. Electrophoretic enzymography revealed that cadmium reduced the activity of plasminogen activators in the conditioned medium of both vascular smooth muscle cells and fibroblasts. Cadmium markedly decreased the incorporation of [3H]leucine accompanied with a significant increase in the leakage of lactate dehydrogenase in vascular smooth muscle cells; however, the metal did not change these markers in fibroblasts. These results suggest that the regulation of fibrinolysis mediated by vascular smooth muscle cells and fibroblasts during hemostasis may be disturbed by cadmium.
Cadmium↗
Inactivation of p16INK4 in hepatocellular carcinoma.
We analyzed the p16INK4 status of 6 hepatocellular carcinoma (HCC) cell lines and 32 primary HCC tumors, including 9 early-stage tumors, to determine whether p16INK4 tumor-suppressor gene inactivation participates in hepatocarcinogenesis. p16INK4 was studied at its protein level through Western blotting, at its messenger RNA (mRNA) level through reverse-transcriptase polymerase chain reaction analysis (RT-PCR) and Northern blotting, and at its genomic level through Southern blotting and PCR-single-strand conformation polymorphism analysis. The p16 protein was absent from 3 of 6 cell lines (50%) and 11 of 32 primary tumors (34%), but present in noncancerous tissues, indicating that p16INK4 is involved in hepatocarcinogenesis. Furthermore, we suggest that the p16 protein loss may contribute to the following: (1) early-stage hepatocarcinogenesis, because it was observed in 22% of early stage tumors; and (2) tumor progression, because it occurred approximately twice as often in advanced rather than in early stage tumors (40%). It was striking that neither p16INK4 homozygous deletion and mutation nor loss of p16INK4 mRNA expression were observed in HCC cell lines and primary tumors, including those specimens from which the p16 protein was absent except the Li7HM cell line, in which p16INK4 mRNA was not detected. These results suggest that p16INK4 in HCC is inactivated predominantly by posttranscriptional regulation rather than by genomic aberrations and lack of transcription.
Base Sequence↗
Aqueous flare in eyes with senile disciform macular degeneration: correlation with clinical stage and area of neovascular membrane.
BACKGROUND: The aim of the present study was to investigate the aqueous flare in eyes with senile disciform macular degeneration (SDMD), divided into different clinical stages, and the correlation between the aqueous flare and the area of the neovascular membrane. METHODS: Eighty-six eyes of 44 patients with SDMD were examined using a laser flare meter. The area of the neovascular membrane was measured by means of a digitizer in images obtained using indocyanine green videoangiography. RESULTS: The mean value of the aqueous flare was 5.91 +/- 2.51 (photon count/ms) in 7 predisposing stage eyes, 5.68 +/- 1.64 in 15 initial stage eyes, 9.09 +/- 7.65 in 24 advanced form eyes, 5.40 +/- 1.42 in 11 disciform scar eyes, and 5.36 +/- 1.72 in 29 fellow eyes. The aqueous flare value was significantly (P < 0.01) higher in eyes with the advanced form of SDMD than in the fellow eyes. There were no significant differences in aqueous flare values between eyes with predisposing stage, initial stage, and disciform scar and fellow eyes. The aqueous flare value increased significantly with increasing area of neovascular membrane (R = 0.68, P < 0.01). CONCLUSION: The present results suggest that the aqueous flare increases with increasing neovascular membrane area in eyes with SDMD, and decreases with scarization of the neovascular membrane.
Aged↗
Laparoscopic varicocele ligation.
Varicocele, an abnormal dilatation of the pampiniform plexus, frequently contributes to male factor infertility. We performed laparoscopic varicocelectomy in 20 patients with varicoceles and abnormal seminal findings. The spermatic artery was identified and preserved in 13 patients and was clipped along with the veins in 7 patients including 1 patient with bilateral varicocele. The time required for the artery-ligating surgery ranged from 90 to 120 minutes with an average of 113.2 minutes, while the time needed for the artery-preserving technique ranged from 90 to 250 minutes with an average of 158.0 minutes. Some analgesics were administered to 11 patients, while the other 9 patients needed no analgesics. All patients were able to walk within 24 hours of the operation. The mean hospitalization period after the operation was 5.9 days. Sperm concentrations significantly improved postoperatively (p < 0.05). No difference in postoperative improvement of seminal findings was observed between artery-ligating and artery-preserving groups. A slight scrotal emphysema developed during the operation in 1 patient. Abdominal pain was experienced in 1 patient, but subsided within a few days. No serious complications were observed. The laparoscopic technique may replace routine open high ligation as the surgical treatment of choice, especially in patients with bilateral varicocele.
Adult↗
Bismuth induces metallothionein but does not protect against cadmium cytotoxicity in cultured vascular endothelial cells.
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Adenine↗
A new method for theoretical analysis of static indentation test.
A new mathematical method was developed to study the indentation problem of an infinite elastic layer overlaid on a rigid foundation. Rigid, flat-ended cylindrical or spherical indenters are pressed onto the upper surface of the elastic layer causing a small deformation mode. Shear stresses between the indenter and the layer are assumed negligible and the layer is assumed to be either bonded or unbonded to the rigid foundation. The problem is equivalent to a mixed boundary-value problem of the theory of elasticity. Instead of using the Fredholm integral equation reported in the literature, the new approach obtained closed-form solutions through an infinite series. Convergence can be achieved using less than 10 terms of the series.
Algorithms↗
Histologic findings and prognosis of uveal malignant melanoma in japanese patients.
PURPOSE: To determine factors of uveal malignant melanoma that would help to predict prognosis in Japanese patients. METHODS: From 1969 to 1994, 23 eyes with uveal malignant melanoma were enucleated from 23 Japanese patients, and 16 of these patients were studied. In the 16 patients, enucleated eyes were evaluated for tumor characteristics, including cell type and microvascular architecture. Patient records were reviewed for follow-up therapy and outcome. Mortality rate was evaluated four years after enucleation. RESULTS: In Japanese patients with uveal malignant melanoma, the average tumor size was larger (average largest diameter, 11.36 mm; average increase, 6.25 mm) and the average patient age was younger (55.2 years old) than previously reported for white populations. Patients with spindle cell type melanoma tended to have a better prognosis than those with epithelioid cell type (four-year mortality rates: spindle cell type, 0%; mixed cell type, 43%; epithelioid cell type, 66%). Microvascular architecture patterns interpreted as either network or closed loop patterns were associated with a poorer prognosis (network pattern, P = .03; closed loop pattern, P = .005). CONCLUSIONS: The prognosis for Japanese patients with uveal malignant melanoma is poorer, and epithelioid cell-type melanoma is more common, than has been reported in white populations. Mitotic figures are well correlated with poor prognosis, as are two microvascular patterns, the network pattern and the closed loop pattern.
Adult↗
Side effects of high-dose interferon therapy for chronic hepatitis C.
BACKGROUND/AIMS: Various side effects have been reported in patients treated with alpha interferon, but their incidence and prognosis remain unknown. METHODS: Nine hundred and eighty-seven patients with chronic active hepatitis C received 6 to 10 MU of alpha interferon per day for 2 weeks and 3 times per week for 22 weeks. Autoantibodies, thyroid function tests, and fasting plasma glucose concentrations were evaluated prior to alpha interferon therapy. RESULTS: Of the 987 patients, 310 were required reduction in the dose of alpha interferon to 3 MU/day or cessation of alpha interferon therapy because of adverse reactions such as flu-like symptoms, leukopenia, and thrombocytopenia. Of the remaining 677, five developed diabetes mellitus, 12 had hyperthyroidism, and six acquired hypothyroidism. Of the 18 with thyroid disorders, five demonstrated antimicrosomal antibodies before therapy. Forty-four patients revealed high or low concentrations of thyroid stimulating hormone at the end of alpha interferon therapy. Three patients developed interstitial pneumonia, one acquired systemic lupus erythematosus-like syndrome, two had autoimmune hepatitis, two developed rheumatoid arthritis, and one developed autoimmune thrombocytopenic purpura. No patients had a history of an autoimmune disorder. One patient experienced sudden hearing impairment and one had retinal detachment. Melena was seen in three patients; two of these cases were compatible with ischemic colitis. Symptoms of depression were seen in 23 patients, and one patient manifested memory loss. CONCLUSION: High-dose alpha interferon therapy induces various adverse effects. Most of the side effects cannot be predicted, but are reversible.
Adult↗