[Allelic loss as prognostic factor in breast cancer].
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Breast Neoplasms↗
Biomedical subjects
S Haga
Publications and source records attributed to S Haga.
[Oral contraceptives and breast cancer].
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Age Factors↗
Comparison between in vivo and in vitro pharmacokinetics of succinylcholine in humans.
PURPOSE: To compare the in vivo and in vitro pharmacokinetics of succinylcholine (SCh) in humans. METHODS: A bolus of SCh 1 mg.kg(-1) (n = 7) or 2 mg.kg(-1) (n = 11) was given to 18 patients anesthetized with thiopental. Arterial blood samples for determination of in vivo SCh concentrations were collected every 30 s for 5 min. Another 20-ml blood sample was obtained before induction of anesthesia for determination of in vitro SCh. Concentrations of SCh were measured by high-performance liquid chromatography. In vivo and in vitro concentrations of SCh vs time data were analyzed by the one-compartment model. RESULTS: The respective in vivo and in vitro pharmacokinetic parameters (SCh 1 mg.kg(-1) vs SCh 2 mg.kg(-1)) were as follows: Plasma clearance was 4.17 +/- 2.37 and 1.85 +/- 0.28 l.min(-1), P < 0.05, vs 2.91 +/- 2.01 and 1.27 +/- 0.43 l.min(-1), P < 0.05. Elimination half-life was 25.4 +/- 10.6 and 47.4 +/- 5.4 s, P < 0.002 vs 26.3 +/- 10.0 and 75.2 +/- 21.8 s, P < 0.00005. CONCLUSION: These results suggest that the rapid disappearance of SCh from the circulation is due to diffusion out of the blood vessels rather than to enzymatic hydrolysis.
Journal Article↗
Correlation of Allelic Loss with Poor Postoperative Survival in Breast Cancer.
BACKGROUND: Allelic losses of tumor suppressor genes or the chromosomal regions harboring them in the DNA of tumor cells may become useful postoperative prognostic indicators. METHODS: To examine whether specific allelic losses correlate with postoperative survival in a five-year prospective follow-up, we tested tumors from a cohort of 504 breast cancer patients for allelic loss of 18 microsatellite markers representing either known tumor suppressor genes or regions where genetic alterations are frequent in breast tumors. RESULTS: Patients with allelic loss at 1p34, 3p25, 8p22, 13q12, 17p13.3, or 17q21.1 had a significantly higher risks of postoperative mortality compared withthose whose tumors retained both alleles at those loci (at 1p34, the 5-year mortality rate was 23% among patients with loss vs 10% with retention, p 0.0100; at 3p25, 22% vs 9%, p =0.0014; at 8p22, 24% vs 7%, p =0.0177; at 13q12, 19%vs 8%, p=0.0093; at 17p13.3, 19% vs 9%, p=0.0078; and at 17q21.1, 17% vs 10%, p =0.0475). CONCLUSION: Allelic losses at these loci can serve as negative prognostic indicators to guide post-operative management, especially in the selection of thosewho will benefit from intensive adjuvant therapies.
Journal Article↗
Maximum Density of Tumor Staining Obtained by Preoperative IV-DSA as a Prognostic Indicator for Node-Negative Breast Cancer.
BACKGROUND: We previously demonstrated that the density of tumor enhancement by intravenous digital subtraction angiography (IV-DSA) is correlated with the number of tumor microvessels and that the incidence of distant metastasis is highin patients with breast cancer who show a high maximum density of tumor enhancement (MAX) on IV-DSA. In the present study, we evaluated the prognostic value ofMAX for node-negative breast cancer patients. Patients and METHODS: A total of 128 node-negative breast cancer patients underwent preoperative IV-DSA, and the region of interest (ROI) was set in the areas enhanced by IV-DSA of the breast. MAX was calculated by the time-density curve. Patients were divided into two subgroups: those with MAX >/= 9 (n=35) and those with MAX < 9 (n=93). RESULTS: Patients with recurrence had a significantly higher MAX value than those without recurrence (11.8 +/- 3.8 vs 7.1 +/- 3.0, p<0.01). The disease-free survival rate was significantly worse in patients with higher MAX values than in those with lower MAX values (p <0.001). Multivariate analysis showed that MAX was the strongest predictor of disease-free survival (p =0.026). CONCLUSIONS: These results suggest that the maximum density obtained by IV-DSA is a strong, independent prognostic indicator for node-negative breast cancer patients.
Journal Article↗
Neuronal localization of a novel mosaic apolipoprotein E receptor, LR11, in rat and human brain.
A new type of mosaic protein was recently discovered as a new member of the low density lipoprotein receptor (LDLR) family, designated as LR11. The predominant expression of LR11 transcripts in brain tissue and the presence of elements found in neural adhesion molecules suggested a function(s) in the central nervous system (CNS). In order to gain insight about this complex receptor in the CNS, we raised a rabbit polyclonal antibody and examined immunohistochemically rat and human brain tissue. A strong LR11 immunoreactivity was found to be localized mainly in neurons throughout the brain in both species. A detailed mapping in the rat brain showed a distribution of LR11 immunoreactivity in a widespread population of neurons, though the intensity varied between different locations. The most prominent immunoreactivity was observed in neurons of the hippocampus, some nuclei of brain stem and Purkinje cells, whereas neurons of the thalamus and the hypothalamus showed weak staining. Uniquely, the single LR11 immunoreactive cytoplasmic puncta were observed in the proximity of apical dendrites, most conspicuously in the pyramidal neurons of hippocampus. In the human brain, one to four immunoreactive puncta were seen within individual neurons. The neuronal localization of LR11 and its unique association of cytoplasmic structure, presumably botrysome, may suggest the roles of LR11 in both the lipoprotein metabolism and intracellular trafficking in certain neuronal population of the CNS.
Adult↗
Pigs with highly prevalent antibodies to human coronavirus and swine haemagglutinating encephalomyelitis virus in the Tohoku District of Japan.
From 1985 to 1988, a total of 2496 swine sera from 60 farms in the Tohoku District of the Honshu Island of Japan were examined for antibodies to swine haemagglutinating encephalomyelitis virus (HEV), human coronavirus (HCV) and bovine coronavirus (BCV) by haemagglutination-inhibition (HI) test. Antibodies to HEV 67N strain and HCV OC43 strain were highly prevalent with positivity rates of 82.1 and 91.4%, respectively, while seropositivity rate to BCV Kakegawa strain was 44.2%. No clinical signs of HEV infection were noticed in any farms including farms with relatively high seropositivity. The results suggested that HCV or antigenitically related virus(es) as well as HEV might be perpetuated in swine in the Tohoku District.
Animals↗
The expression of variant exon v7-v8 CD44 antigen in relation to lymphatic metastasis of human breast cancer.
The purpose of this prospective study was to evaluate the expression of CD44 splice variant epitopes in human breast cancer and their potential as prognostic indicators. Invasive breast cancer tissues obtained from 91 patients were examined for expression of the standard CD44 antigen and variant CD44 antigens (v5, v6, v7, v7-v8, and v8-v10) by immunohistochemical staining to investigate the relations of these antigens to clinicopathological factors and prognosis. The expression of standard CD44 antigen was detected in 54.9% of 91 patients with primary human breast cancer. The variant epitopes of CD44 examined, i.e., v5, v6, v7, v7-v8, and v8-v10, were expressed in 54.9%, 54.9%, 0%, 34.1%, and 0%, respectively. There was a significant difference in tumor size, lymph nodal status, and degree of lymphatic permeation between patients who were positive for exon v7-v8 and those negative for this variant (p < 0.01). Prognosis was also significantly worse in patients positive for CD44 v7-v8 than in those negative for this variant. However, multivariate analysis with the three prognostic indicators tumor size, lymph nodal status, and the degree of lymphatic invasion, has shown that the expression of CD44 v7-v8 antigen in breast carcinoma was not a significant independent prognostic factor and was closely dependent on lymphatic invasion and nodal status. Fourteen of 31 patients who were positive for CD44 v7-v8 experienced recurrences. The mode of recurrence was lymphatic metastasis in 10 out of these 14 patients. Breast cancer cells expressing v7-v8 CD44 antigen have an extremely high affinity for lymph nodes and lymphatic vessels, and are likely to metastasize to distant lymph nodes even at a very early stage in the progression of this disease. This suggests that not only the anatomical factors but also organ affinity plays an important role in the establishment of lymph nodal metastasis of breast cancer.
Adult↗
Prognostic significance of MIB1-determined proliferative activities in intraductal components and invasive foci associated with invasive ductal breast carcinoma.
The prognostic significance of the proliferative activities in intraductal components and invasive foci was investigated using 157 cases of invasive ductal breast carcinoma in which intraductal components predominated. Proliferative activity was expressed as the number of MIB1-positive nuclei per 1000 cancer cells in the most active areas of intraductal components (MLI-DCIS) or invasive foci (MLI-INV). MLI-DCIS correlated closely with MLI-INV (r = 0.710, 95% confidence interval, 0.623-0.780; P < 0.0001). Both MLI-DCIS and MLI-INV were related to oestrogen receptor (ER) (P = 0.0006, P = 0.0028 respectively), grade of invasive tumour (P < 0.0001, P < 0.0001 respectively) and classification of intraductal components (P < 0.0001, P < 0.0001 respectively). In the univariate disease-free survival analysis, both MLI-DCIS and MLI-INV were found to be significant (P < 0.0001, P = 0.0003 respectively). However, in node-negative cases, only MLI-DCIS was significant (P = 0.0416). Multivariate analysis revealed that MLI-DCIS was significant not only in all cases, but also in node-negative cases (P = 0.0223, P = 0.0426 respectively), whereas MLI-INV was not. These findings indicate that MIB1-determined proliferative activity of intraductal components is a significant prognostic determinant of invasive ductal breast carcinoma in which intraductal components predominate.
Adult↗
Short-chain fatty acids suppress cholesterol synthesis in rat liver and intestine.
We previously showed that plasma cholesterol levels decreased following ingestion of a short-chain fatty acid (SCFA) mixture composed of sodium salts of acetic, propionic, and butyric acids simulating cecal fermentation products of sugar-beet fiber (SBF). In the present study, we investigated whether hepatic and small intestinal cholesterol synthesis is involved in the cholesterol-lowering effects of SCFA and SBF. In vitro (expt. 1) and in vivo (expt. 2) cholesterol synthesis rates and the diurnal pattern of SCFA concentrations in portal plasma (expt. 3) were studied in three separate experiments in rats fed diets containing the SCFA mixture, SBF (100 g/kg diet), or the fiber-free control diet. Cholesterol synthesis was measured using 3H2O as a tracer. The in vitro rate of cholesterol synthesis, measured using liver slices, was greater in the SBF group, but not in the SCFA group, than in the fiber-free control group. In contrast, the hepatic cholesterol synthesis rate in vivo was lower in the SCFA group, but not in the SBF group, than in the control group. The mucosal cholesterol synthesis rate for the whole small intestine was <50% of the hepatic rate. The rate in the proximal region was slightly but significantly lower in the SCFA group, and was significantly higher in the SBF group than in the fiber-free group. The rate in the distal small intestines was also significantly greater in the SBF group than in the fiber-free group. Plasma total cholesterol concentrations were lower in the SCFA and SBF groups than in the fiber-free group in both experiments 2 and 3. Diurnal changes in portal SCFA and cholesterol levels were studied in the experiment 3. SCFA concentrations increased rapidly after the start of feeding the SCFA diet, and changes in plasma cholesterol were the reciprocal of those observed in SCFA. These results show that a decrease in hepatic cholesterol synthesis rate mainly contributes to the lowering of plasma cholesterol in rats fed the SCFA mixture diet. Changes in portal SCFA and cholesterol concentrations support this conclusion. In SBF-fed rats, SCFA produced by cecal fermentation are possibly involved in lowering plasma cholesterol levels by negating the counteractive induction of hepatic cholesterol synthesis caused by an increase in bile acid excretion.
Acetic Acid↗
The role of serum imbibition for skin grafts.
Numerous studies of grafted skin suggest that full-thickness skin grafts are nourished by exudate from the recipient bed called a serum imbibition. However, whether serum imbibition by itself is sufficient for nourishment of skin grafts has not been shown definitely and directly. To clarify the role of serum imbibition, we performed a comparative study between 20 skin grafts and 20 musculocutaneous flaps. The nourishment of the cell in the skin graft is by serum imbibition. That in musculocutaneous flaps is mainly derived from blood supply. We evaluated the nourishment by means of the unique characteristics of the cell cycle. Once cells are put into a synthetic phase, they cannot reverse or stop the progress of the cell cycle. To take advantage of this characteristic of the cell cycle, prewounding methods (40 flaps were lifted once and put back to the original sites prior to the evaluation) were intended for the cells in pre-elevated skin to turn into a proliferating phase. Cells were examined by antibody against proliferating cell nuclear antigen immunohistologically, to determine whether they had turned into the proliferating phase or not. After 3 days, all flaps were reelevated; half (20 flaps) had their muscle layer and the neurovascular bundle removed to make a full-thickness skin graft. The rest (20 flaps) were only lifted. They were sutured back to the original sites. Ten skin grafts and musculocutaneous flaps each were harvested at 3 hours (1st day) and at 11 days (11th day) after the second operation. Bromodeoxyuridine, which is a thymidine analog and is taken into the cells in the synthetic phase, was introduced intraperitoneally 2 hours before the harvest. All flaps and grafts were evaluated histologically and immunohistologically. Proliferating cell nuclear antigen analysis showed that the prewounding method induced the cells of skin grafts and musculocutaneous flaps to proliferate before the implantation. Regarding the bromodeoxyuridine uptake, no significant differences could be seen between skin grafts and musculocutaneous flaps irrespective of their different nourishment. No structural changes, such as degenerative or necrotic, could be seen at the hair follicle and other glands even at the 11th day. Almost all of the layers of skin grafts survived as long as they were checked by light microscopy (hematoxylin and eosin stain). No differences could be seen between musculocutaneous flaps and skin grafts or between the 1st and 11th days in this study. We concluded that serum imbibition is sufficient for nourishment of skin grafts, just as blood supply is sufficient for nourishment of musculocutaneous flaps.
Animals↗
Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans.
The effects of exercise and catecholamines on platelet reactivity or coagulation and fibrinolysis appear to be inconsistent. This may be partly due to the methods employed in previous studies. In the present study, we investigated the effects of acute aerobic exercise and catecholamines on the thrombotic status by a novel in vitro method, shear-induced hemostatic plug formation (hemostatometry), using nonanticoagulated (native) blood. Aerobic exercise (60% maximal O2 consumption) was performed by healthy male volunteers for 20 min, and the effect on platelet reactivity and coagulation was assessed by performing hemostatometry before and immediately after exercise. Exercise significantly increased shear-induced platelet reactivity, coagulation, and catecholamine levels. The effect of catecholamines on platelet reactivity and coagulation was assessed in vitro by adding catecholamines to blood collected in the resting state. The main findings of the present study are that elevation of circulating norepinephrine at levels that are attained during exercise causes platelet hyperreactivity and a platelet-mediated enhanced coagulation. This may be a mechanism of an association of aerobic exercise with thrombotic risk.
Adult↗
[A case of esophageal cancer with excellent response to oral UFT treatment].
The patient was an 83-year-old Japanese male with the chief complaint of difficulty in swallowing. On Feb. 24, 1997, he was referred to our hospital under suspicion of esophageal cancer. X-P revealed an image of a protrusion at Im-Iu having a long diameter of 6 cm. Endoscopy revealed that the esophageal lumen was nearly completely obstructed due to the presence of an irregularly-shaped tumor. The pathological finding of biopsized specimen was a squamous cell carcinoma. Thus, this case was diagnosed as esophageal cancer, but surgery was deemed inappropriate due to the patient's advanced age. Accordingly, on March 12, treatment was started with oral administration of UFT-E granules (Tegafur, 450 mg/day). Initially, the patient was unable to ingest even liquids, but beginning around May the blockage of the esophagus disappeared. Endoscopic examination performed in June revealed that the tumor had shrunk to a about 1 cm in diameter. Although tumor tissue remained, the tumor was observed to have undergone further reduction in size at 6 months after the start of chemotherapy. Moreover, the patient gained weight. This is considered to be a very rare case of an excellent response of esophageal cancer to oral administration of only UFT agents.
Administration, Oral↗
X chromosome territories in human female lymphocytes.
We developed an improved bromodeoxyuridine (BrdU)-DNA assay procedure for flow cytometric analysis. Which makes possible cytochemical investigation against cells after BrdU-DNA assay, such as immunochemical staining or in situ hybridization. Using this method, we performed fluorescence in situ hybridization (FISH) technique using DNA probes that recognize whole X chromosome of human lymphocytes in peripheral blood (resting cells) and cultured cells stimulated by phytohemagglutinin (PHA) (proliferative cells). Cultured cells were fractionated precisely into each stage of cell cycle by cell sorter after flow cytometric analysis. Following FISH procedure, the cells were examined for the volumes of two X chromosome territories in the nuclei using the optical section images on a confocal laser scanning microscope (CLSM). And we analyzed the variation in the volume ratio (R) of two X chromosome territories at different stages in cell cycle. Our data indicated that there were no significant difference between the volume of two X chromosome territories in female human lymphocytes at resting (G0) stage. Furthermore, they also showed no significant alternation throughout the cell cycle. These results may challenge the traditional concepts for inactivated chromosome in two points. First, the inactivated X chromosome is more decondensed throughout the cell cycle than previously thought. Second, although the inactivated X chromosome appears more decondensed during its self replication it dose not bring a great change in the volume of its territory.
Cells, Cultured↗
[A case of recurrent colon cancer with complete response to modulation chemotherapy using low-dose leucovorin and 5-fluorouracil].
We experienced a case of lymph node recurrence from colon cancer with complete response to modulation chemotherapy using low-dose leucovorin and 5-FU. The patient was a 68-year-old male. He underwent sigmoid colon resection for sigmoid colon cancer in October 1993. In June 1994, he complained of left lower abdominal pain. Swelling of retroperitoneal lymph node was detected by CT scan and cytology revealed cancer cells in urine. He was diagnosed as having lymph node recurrence. He then was given modulation chemotherapy of 30 mg of leucovorin and 500 mg of 5-FU that were bolus injected intravenously for 5 days. After 2 cycles of this regimen, the recurrent mass disappeared completely for further examination. Until May 1998, he had received 14 cycles. Since this regimen started, his survival period has been 46 months, and his response duration 42 months.
Aged↗
Glial expression of fibroblast growth factor-9 in rat central nervous system.
We examined the expression of fibroblast growth factor (FGF)-9 in the rat central nervous system (CNS) by immunohistochemistry and in situ hybridization studies. FGF-9 immunoreactivity was conspicuous in motor neurons of the spinal cord, Purkinje cells, and neurons in the hippocampus and cerebral cortex. In addition to the neuronal localization of FGF-9 immunoreactivity that we reported previously, the present double-label immunohistochemistry clearly demonstrated that the immunoreactivity was present in glial fibrillary acidic protein (GFAP)-positive astrocytes preferentially present in the white matter of spinal cord and brainstem of adult rats and in CNPase-positive oligodendrocytes that were arranged between the fasciculi of nerve fibers in cerebellar white matter and corpus callosum of both adult and young rats. There was a tendency for FGF-9 immunoreactivity in oligodendrocytes to be more pronounced in young rats than in adult rats. The variation of oligodendrocyte FGF-9 immunoreactivity in adult rats was also more pronounced than that in young rats. With in situ hybridization, FGF-9 mRNA was observed in astrocytes in the white matter of rat spinal cord and oligodendrocytes in the white matter of cerebellum and corpus callosum of adult and young rats. The expression of FGF-9 mRNA in glial cells was lower than in neurons, and not all glial cells expressed FGF-9. In the present study, we demonstrated that FGF-9 was expressed not only in neurons but also in glial cells in the CNS. FGF-9 was considered to have important functions in adult and developing CNS.
2',3'-Cyclic-Nucleotide Phosphodiesterases↗
Effects of acute cold stress on mrna expression and immunoreactivity of three superoxide dismutase isoenzymes in genetically obese mice.
The aim of this study was to investigate the influence of acute cold exposure on the mRNA expression and immunoreactivity of superoxide dismutase (SOD) isoenzymes [Mn-SOD, Cu,Zn-SOD, and extracellular-SOD (EC-SOD)] in different tissues from lean and obese (ob/ob) mice at 10 months of age. The animals were kept at 10 degrees C for 3 h, with the colonic temperature in obese mice declining progressively during the cold stress, but not in lean mice, probably because of a strong tendency to atrophy of the brown adipose tissue (BAT) in obese mice. In the expression of mRNAs for lean mice, acute cold exposure led to a significant increase only in Mn-SOD in testes, but a significant decline in Cu,Zn-SOD in kidney and in Mn-SOD and EC-SOD in white adipose tissue (WAT), as well as in all SOD isoenzymes in lung and BAT. In obese mice, the mRNA level of Mn-SOD in heart and gastrocnemius muscle was significantly decreased following the cold exposure, whereas that of EC-SOD in testes was significantly increased. These changes, however, were not always accompanied by those in the corresponding protein levels; for example, the significant decreases in the expression of mRNAs for the three SOD isoenzymes in lung and BAT from lean mice did not result in any changes in the respective isoenzyme protein levels. These results suggest that, except for testes, a cold-exposure period of 3 h down-regulates SOD isoenzymes at the transcriptional process especially in lean mice, but is not long enough to induce their protein synthesis. It seems likely, thus, that, despite a marked decrease in colonic temperature, acute exposure to cold has less effect on SOD isoenzymes in obese mice as compared with those in normal lean siblings.
Adipose Tissue, Brown↗
Fibroblast growth factor (FGF)-9 immunoreactivity in senile plaques.
We examined fibroblast growth factor (FGF)-9 immunoreactivity in human hippocampal sections of Alzheimer's disease (AD). FGF-9 immunoreactivity was observed in dystrophic neurites of senile plaques in AD and control cases, in addition to the hippocampal and cortical neurons. The amyloid core and neurofibrillary tangles lacked immunoreactivity. FGF-9 immunoreactive astrocytes were conspicuous in AD brains. FGF-9 may be involved in the neuropathology of AD.
Alzheimer Disease↗