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Biomedical subjects

I Sato

Publications and source records attributed to I Sato.

At least 73 records · Page 4Linked to original sources

Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary.

OBJECTIVES: Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined use of two serum tumor markers, macrophage colony-stimulating factor (M-CSF) and squamous cell carcinoma antigen (SCC), is effective in preoperatively diagnosing squamous cell carcinoma arising in mature cystic teratoma of the ovary, distinguishing it from mature cystic teratoma without malignant transformation. METHODS: Serum levels of M-CSF and SCC were assayed using blood samples collected preoperatively from 31 patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary and 133 patients with mature cystic teratoma of the ovary without malignant transformation. RESULTS: In 22 of the 31 (71.0%) patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary, the serum M-CSF levels exceeded the upper limit of the normal level (1056 U/ml). This positive incidence of the elevated serum M-CSF levels was significantly higher compared with that (13.5%, 18/133) observed in patients with benign cystic teratoma of the ovary (P < 0.0001). Regarding the serum levels of SCC, 13 of 31 (41.9%) patients with malignant tumors showed positive values exceeding the cutoff value of 2.0 ng/ml. Again, this incidence of positive cases was significantly higher compared with that (15.0%, 20/133) observed in patients with benign tumors (P < 0.01). There was no correlation between the serum levels of M-CSF and SCC among patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary. Patients with malignant tumors testing positive for elevated M-CSF did not necessarily test positive for SCC. Patients with positive values for excess M-CSF and/or SCC constituted 87.1% of the total (27/31). Even when patients were restricted to those with stage I tumors, a value as high as 83.3% (15/18) was still obtained for those testing positive for elevated M-CSF and/or SCC. CONCLUSION: Serum M-CSF was proven to be useful as a tumor marker for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. Combined use of serum M-CSF and SCC as a marker seemed to be useful in the selective diagnosis of mature cystic teratoma of the ovary harboring malignant squamous carcinoma, discriminating it from that without malignant carcinoma.

Adolescent↗

Assessment of proliferation index with MIB-1 as a prognostic factor in radiation therapy for cervical cancer.

OBJECTIVES: The relationship between the expression of murine monoclonal antibody MIB-1, which reacts with Ki-67 nuclear antigen, a marker for proliferating cells, and the prognosis of stage IIIb cervical cancer after radiation therapy was analyzed. METHODS: A total of 67 patients with stage IIIb cervical cancer who had received radiation therapy were included in the retrospective study. The labeled streptavidin-biotin method was used for immunohistochemical staining of the MIB-1 protein. RESULTS: In 32 patients showing a high MIB-1 index (percentage of cells labeled with MIB-1 >/=26.4%), the cumulative 5- and 8-year survival rates were 75.8 and 61.5%, respectively, significantly better (P < 0.05) than those in 35 patients with a low MIB-1 index (<26.4%) (59.6 and 41.1%, respectively). Serum squamous cell carcinoma antigen levels, an index of the response to radiation therapy, decreased to </=2.0 ng/mL in 100 and 68% of patients in the high and low MIB-1 index groups, respectively (P < 0.05). CONCLUSION: These results indicate that MIB-1 antigen may be effective in predicting the sensitivity of cervical cancer to radiation therapy and stage IIIb cervical cancer prognosis.

Adult↗

Lymph node metastasis in stage I epithelial ovarian cancer.

OBJECTIVES: A relatively high incidence of para-aortic and pelvic lymph node metastasis is found in epithelial ovarian cancer. This paper investigates the clinicomorphological features of intra-abdominal stage I epithelial ovarian cancer that may predict the occurrence of lymph node metastasis and the prognosis of patients in whom lymph node metastases are identified. METHODS: From November 1988 to December 1997 we performed systematic para-aortic and pelvic lymphadenectomy as primary surgery in 47 patients with intra-abdominal stage I epithelial ovarian cancer. The incidence of lymph node metastasis in these patients and the clinicomorphological features of the patients with lymph node involvement were examined. RESULTS: Five patients (10.6%) were metastasis positive (IC: four; IA: one), of whom four had serous adenocarcinoma. Serous adenocarcinoma was associated with a significantly higher incidence of metastases than other histological types (P < 0.05). The number of positive lymph nodes was one in four patients and two in one patient, and the metastatic sites ranged from the para-aortic to the suprainguinal lymph nodes. All five metastasis-positive patients were alive and disease free at the time of this report (survival 28-85 months: median 59 months). CONCLUSION: This clinical study suggests that serous adenocarcinoma carries a high risk of lymph node metastasis, requiring systematic lymphadenectomy for accurate staging in intra-abdominal stage I epithelial ovarian cancer.

Adenocarcinoma↗

Enzyme histochemistry on human placental trophoblasts: the effect of fixation delay on enzyme activity.

We examined the effect of time delay in tissue fixation on enzyme histochemically detectable enzyme activity and its localization in term human placental trophoblasts. Four placental enzymes, alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, and cytochrome c oxidase, were studied. A fixation delay of 15 min did not markedly alter the activity or distribution pattern of the four enzymes, excepted for a slight reduction in cytochrome c oxidase activity and the appearance of dilated endoplasmic reticula positive for glucose-6-phosphatase. A fixation delay of 60 min abolished cytochrome c oxidase activity, but the activities of the other three enzymes remained positive. When the placental tissue was stored at 4 degrees C without cutting for 24 h before fixation, cell degeneration occurred. However, alkaline phosphatase activity was still clearly demonstrable. In enzyme histochemistry, ,,immediate" fixation is superior, but even if this cannot be performed, the placentas, especially when they are from patients with rare disorders, should not be discarded. Observations made here will be useful for clinician's attempting enzyme histochemistry in organs other than the placenta.

Acid Phosphatase↗

Enzyme-histochemically detectable glucose-6-phosphatase is present in chorion laeve trophoblasts of human fetal membranes.

The purpose of the present study was to demonstrate the presence of glucose-6-phosphatase (G6Pase) in fetal membranes from various gestational ages (20-40 weeks of gestation). Ultrastructural enzyme-histochemical analysis of G6Pase was performed using cerium and lead as capturing agents. Precipitates indicating G6Pase activity were present mainly in the endoplasmic reticulum and partly in the nuclear envelope of chorion laeve trophoblasts, but absent in amniotic epithelial cells. Stringent histochemical control experiments performed ensured specific detection of G6Pase activity. The results indicate that histochemically detectable G6Pase is present in the chorion laeve trophoblasts of human fetal membranes. This enzyme may have some physiological significance in carbohydrate metabolism in human fetal membranes and regulation of amniotic fluid glucose concentration.

Amnion↗

The effect of atorvastatin on serum lipids and lipoproteins in patients with homozyous familial hypercholesterolemia undergoing LDL-apheresis therapy.

The efficacy of atorvastatin, a new hydroxymethylglutaryl (HMG)-CoA reductase inhibitor, in reducing serum lipid levels, modifying lipoprotein composition, and suppressing cholesterol synthesis was evaluated in patients with homozygous familial hypercholesterolemia (homozygous FH) undergoing LDL-apheresis therapy. Atorvastatin was given in escalating doses (10, 20, and 40 mg/day) to nine patients with homozygous FH. Five of nine patients responded well to atorvastatin; four of these patients were receptor-defective and the remaining one was receptor-negative. The change in LDL-cholesterol in the receptor-defective patients averaged -20.6% compared to the baseline level at the highest dose of atorvastatin. Of five receptor-negative type patients, only one showed good response to atorvastatin therapy with a LDL-cholesterol reduction of 14.9%. Although the other four receptor-negative patients did not show a change in LDL-cholesterol, all of them exhibited a considerable increase in HDL-cholesterol. All patients showed reduced urinary excretion of mevalonic acid, suggesting that atorvastatin decreases LDL-cholesterol by inhibiting cholesterol biosynthesis even where LDL-receptor activity is not present. Atorvastatin also decreased serum triglycerides in both receptor-negative and defective patients, especially in the latter. As cholesterol level rebounds quickly after each apheresis procedure, a combination therapy using atorvastatin and apheresis may increase the efficacy of the apheresis treatment, improving cost-benefit effectiveness by reducing the frequency of the apheresis treatment.

Adolescent↗

Meconium-stained amniotic fluid exhibits chemotactic activity for polymorphonuclear leukocytes in vitro.

We have studied whether meconium-stained, turbid amniotic fluid (turbid AF) obtained during term pregnancy possesses chemotactic activity for polymorphonuclear leukocytes (PMNs) in the absence of clinically apparent infection. Eight samples of turbid AF were obtained from eight women who underwent a cesarean section (four emergency and four elective cesarean sections) in the absence of signs of clinical infection or fetal distress. Samples of clear AF obtained from nine women during an elective cesarean section served as a control. We used also a negative control (medium only) and a positive control containing 10 nM N-formyl-methionyl-leucyl-phenylalanine. The control or turbid AF specimen was placed in the lower compartment of a blind well chamber, and the PMN suspension was placed in the upper compartment. Following incubation, the number of PMNs that had migrated and passed through the filter to the AF was counted. The number of control PMNs that migrated to the turbid AF (200+/-59) was comparable to that of the positive (162+/-24) but significantly exceeded that of the clear AF (17+/-11; P < 0.0001) and of the negative control (25+/-9; P < 0.0001). Checkerboard assay indicated that the turbid AF exhibited a dose-dependent chemotactic activity for PMNs. The turbid AF contained higher levels of TNFalpha, IL-1beta and IL-8 than the clear AF. The concentration of IL-8 in the AF was correlated positively with the chemotactic activity of the AF (r = 0.733, P = 0.0005). Anti-human IL-8 antibody added in the turbid AF dose-dependently abolished the chemotactic activity of the turbid AF. It is concluded that meconium-stained AF is a chemoattractant for PMNs and that cytokines such as an IL-8 may be involved in this phenomenon.

Adult↗

DNA replication errors are frequent in mucinous cystadenocarcinoma of the ovary.

To elucidate the genetic etiology of sporadic epithelial ovarian carcinoma, we examined replication errors (RER) in its two common types, serous cystadenocarcinoma (SAC) and mucinous cystadenocarcinoma (MAC). The subjects were 63 patients with sporadic epithelial ovarian carcinoma, consisting of 34 patients with SAC and 29 with MAC. The specimens were formalin-fixed and paraffin-embedded tissues from the ovary. The presence of RER was examined by polymerase chain reaction using 5 microsatellite markers. Of the 61 informative patients with ovarian carcinoma, RERs were observed at greater than or equal to 1 locus in 15 patients (25%). Four of the 32 SAC patients (13%) were RER-positive, and 11 of the 29 MAC patients (38%) were RER-positive, the incidence being significantly higher in the latter than in the former (P < 0.05). The incidence of RER was not related to the patients' age, stage, histologic grade, or prognosis. The MAC patients in stages I and II showed a relatively high incidence of RER (30%). These results suggest that RER are involved in the development and/or progression of MAC among sporadic epithelial ovarian carcinoma in its relatively early stage.

Base Sequence↗

Onapristone (ZK299) blocks the suppressive effect of progesterone, but not that of dexamethasone, on inducible nitric oxide synthase gene expression and nitric oxide production in murine macrophages.

Suppressive effects of progesterone on inducible nitric oxide synthase (iNOS) protein expression and nitric oxide (NO) production in murine peritoneal macrophages in response to bacterial lipopolysaccharide (LPS) and the inhibition of the suppressive activity of progesterone by onapristone (ZK299), a synthetic progesterone inhibitor, were studied. Progesterone suppressed dose-dependently LPS-induced NO production by macrophages, and scarcely detectable expression of iNOS was seen in the macrophages. ZK299 liberated the macrophages from the inhibitory effect of progesterone. Although dexamethasone, a synthetic glucocorticoid, can potently suppress LPS-induced NO production by macrophages, ZK299 did not liberate the suppression by dexamethasone, suggesting that these two corticosteroids induce suppression through independent mechanisms. RT-PCR analysis showed that murine macrophages expressed no progesterone-receptor. These findings indicate that the inhibitory effect of progesterone occurs at least on the level of iNOS protein expression in the signaling pathway after the LPS-stimulus. Furthermore, our present data may suggest the existence of a yet unknown type of progesterone-receptor in murine macrophages, the binding to which is responsible for the inhibitory effect of progesterone, or that progesterone may act non-specifically on the macrophages without involvement of any receptor.

Animals↗

Antihyperalgesic effects of intrathecally administered magnesium sulfate in rats.

Intrathecal administration of MgSO(4) is reported to cause paralysis. However, the characteristic sensory disturbances have not been thoroughly investigated. We examined the effect of intrathecally administered MgSO(4) on the nociceptive threshold, using three different nociceptive measures, formalin test, hot plate test and paw pressure test in rats. The dose of MgSO(4) was 30, 100 or 300 microg. In acute nociceptive tests, intrathecal MgSO(4) did not cause any significant changes in the pain threshold. However, phase 2 of the formalin test was suppressed dose-dependently. It is known that spinal NMDA receptors are involved in the changes seen during the second (tonic) phase of the formalin test and in vitro studies showed that Mg(2+) can cause voltage-dependent blockade of NMDA receptor channel in the neurons of spinal dorsal horn. Thus, the suppressive effect of intrathecally administered MgSO(4) on the tonic inflammation-evoked behavior is mediated by the spinal NMDA receptors. Our results suggest that intrathecal administration of MgSO(4) may be therapeutically beneficial for patients with tonic pain involving the spinal NMDA receptors.

Animals↗

Enantioselective automultiplication of chiral molecules by asymmetric autocatalysis.

Asymmetric autocatalysis is a process of automultiplication of a chiral compound in which chiral product acts as a chiral catalyst for its own production. The discovery and the development of asymmetric autocatalysis of pyrimidyl-, quinolyl-, and pyridylalkanols are described in the enantioselective additions of diisopropylzinc to the corresponding nitrogen-containing aldehydes. (Alkynylpyrimidyl)alkanols automultiply with a yield of over 99% and over 99.5% ee. Asymmetric autocatalysts with extremely low ee's automultiply with significant amplification of ee's without the need for any other chiral auxiliaries. Small enantiomeric imbalances of chiral molecules induced by physical factors can be amplified by the present asymmetric autocatalysis.

Alcohols↗

Effects of ketamine on formalin-induced activity in the spinal dorsal horn of spinal cord-transected cats: differences in response to intravenous ketamine administered before and after formalin.

BACKGROUND: Although formalin has been widely used as an algesic substance in rodent studies, the unique biphasic effect seen in rats is not present in humans. Humans, like cats, have a monophasic behavioral response to formalin injection. Electrophysiologically, spinal dorsal horn neurons in cats also have what could be considered a monophasic response after the initial burst of activity following formalin injection. Although several studies of the effects of ketamine on formalin responses have been carried out in rodents, we are unaware of similar studies in cats. We hypothesize that such species differences may explain observed differences in preemptive analgesic effects. Therefore, we examined the effects of ketamine on activity of spinal wide dynamic range (WDR) neurons evoked by formalin injection in cats. METHODS: We investigated in cats the effect of ketamine on the activity of WDR neurons in the spinal dorsal horn that was evoked by formalin. In addition, we studied the effects of pre- and post-administration of ketamine on the maintained phase of the formalin response. Each dose was a subanesthetic, anesthetic or high anesthetic dose (3.0 mg x kg(-1), 10 mg x kg(-1), and 30 mg x kg(-1)). RESULTS: Intravenously administered ketamine produced a dose-dependent depression of evoked activity that was significantly greater when the drug was administered before formalin. CONCLUSION: In spite of the species differences in responses to formalin, there still appears to be a clear preemptive effect of ketamine in the cat. Species differences may not explain apparent differences between human and animal preemptive analgesia.

Anesthetics, Dissociative↗

High-performance affinity beads for identifying drug receptors.

We have developed a method using novel latex beads for rapid identification of drug receptors using affinity purification. Composed of a glycidylmethacrylate (GMA) and styrene copolymer core with a GMA polymer surface, the beads minimize nonspecific protein binding and maximize purification efficiency. We demonstrated their performance by efficiently purifying FK506-binding protein using FK506-conjugated beads, and found that the amount of material needed was significantly reduced compared with previous methods. Using the latex beads, we identified a redox-related factor, Ref-1, as a target protein of an anti-NF-kappaB drug, E3330, demonstrating the existence of a new class of receptors of anti-NF-kappaB drugs. Our results suggest that the latex beads could provide a tool for the identification and analysis of drug receptors and should therefore be useful in drug development.

Amino Acid Sequence↗

Ultracytochemical localization of 5'-nucleotidase activity in human ejaculated spermatozoa.

5'-nucleotidase, an adenosine producing enzyme with a glycosylphosphatidylinositol-anchored structure, was localized in human ejaculated spermatozoa. The poly-L-lysine-coated dish method was used to prepare the specimens, and the cerium method was employed for electron-microscopic enzyme localization. Precipitates indicating enzyme activity were detected on the outer side of the external plasma membrane of the acrosomal region. This enzyme may play a role in sperm motility and male infertility.

5'-Nucleotidase↗

Predicting the risk of pre-eclampsia and a small-for-gestational-age infant by quantitative assessment of the diastolic notch in uterine artery flow velocity waveforms in unselected women.

OBJECTIVES: To develop a new quantitative index, the notch depth index (NDI), to evaluate its association with the risk of pre-eclampsia and a small-for-gestational-age (SGA) infant and to compare its clinical usefulness with that of the uterine artery resistance index (RI) and the peak systolic to early diastolic velocity (A/C) ratio. METHODS: Uterine artery color Doppler ultrasound was performed in 288 consecutive healthy pregnant women at 20.2 +/- 2.0 (range 16.0-23.9) weeks of gestation. The NDI represents the depth of the early diastolic notch divided by the maximal diastolic velocity. RESULTS: Nine (3.1%) of the 288 women developed pre-eclampsia and 18 women (6.3%) delivered an SGA infant. The NDI was associated with subsequent onset of pre-eclampsia. The optimal cutoff value for the NDI in predicting pre-eclampsia was 0.14, giving a sensitivity, specificity and a positive predictive value (PPV) of 67, 92, and 22%, respectively. The PPV of the NDI was the largest of the three indices evaluated (12% for the RI and 16% for the A/C ratio). The relative risk for pre-eclampsia in women with values equal to or greater than the optimal cutoff values of the RI, A/C ratio and the NDI was 9.7 (95% confidence interval, 2.5-3.7), 19.2 (4.2-91), and 19.2 (5.1-71), respectively. The NDI of 0.14 improved the PPV of 18% determined by the presence of notches in bilateral uterine arteries. The optimal cutoff value of 0.14 for the NDI in predicting an SGA infant yielded a higher PPV (22%) than those for the RI (9%) and A/C ratio (12%). CONCLUSIONS: The NDI value in the second trimester is associated with the later onset of pre-eclampsia, and is clinically more useful in predicting pre-eclampsia than the two conventional indices.

Adult↗

An interobserver and intraobserver study of buccal mucosal bleeding time in Greyhounds.

Two observers experienced with the buccal mucosal bleeding-time technique using a standardised device (Surgicutt) performed the test on 20 Greyhounds, to evaluate interobserver and intraobserver repeatability. The interobserver and intraobserver repeatability were both about 2 minutes. The results indicated that, for any two readings within a dog, the buccal mucosal bleeding time may differ by up to +/- 2 minutes. A single reading was accurate to within +/- 80 seconds. Sixty-one Greyhounds were used to establish a reference interval for the buccal mucosal bleeding time, and to assess the relationship between the buccal mucosal bleeding time and plasma von Willebrand factor concentration. The mean was 129.5 (SD 44.2) seconds. The reference interval was 53 to 235 seconds, which was slightly lower than non-greyhounds. No significant correlation (r=-0. 18, P=0.17) between the buccal mucosal bleeding time and plasma von Willebrand factor concentration was found in the 61 Greyhounds, where plasma von Willebrand factor concentration was in the range 29 to 160 Canine Units dL(-1).

Animals↗

Recurrent ovarian clear cell carcinoma: complete remission after radiation in combination with hyperthermia; a case study and in vitro study.

Since clear cell carcinoma of the ovary does not respond to conventional platinum-based chemotherapy, the prognosis of recurrent tumors is especially poor. In a 51-year old female who underwent surgery for clear cell carcinoma of the ovary, a solitary metastatic carcinoma developed in the pelvic cavity seven months after the initial surgery. The patient underwent a whole pelvic irradiation at a total dose of 65 Gy combined with hyperthermia. Complete remission was achieved 46 months after treatment. A study using gynecologic carcinoma cell lines showed that the mean 50% growth inhibitory dose of radiation was 1.2 +/- 0.4 Gy in several clear cell carcinoma cell lines. The value did not significantly differ from those for serous carcinoma cell lines (2.3 +/- 1.2 Gy) and uterine cervical carcinoma cell lines (1.6 +/- 0.4 Gy). Currently, no anticancer agents are effective for clear cell carcinoma. Radiotherapy combined with hyperthermia may be effective for localized tumors.

Adenocarcinoma, Clear Cell↗