Trichilemmal carcinoma in situ.
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Biomedical subjects
Publications and source records attributed to T Nishikawa.
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MOTIVATION: In cDNA sequencing projects, it is vital to know whether the protein coding region of a sequence is complete, or whether errors have occurred during library construction. Here we present a linear discriminant approach that predicts this completeness by estimating the probability of each ATG being the initiation codon. RESULTS: Because of the current shortage of full-length cDNA data on which to base this work, tests were performed on a non-redundant set of 660 initiation codon-containing DNA sequences that had been conceptually spliced into mRNA/cDNA. We also used an edited set of the same sequences that only contained the region following the initiation codon as a negative control. Using the criterion that only a single prediction is allowed for each sequence, a cut-off was selected at which discrimination of both positive and negative sets was equal. At this cut-off, 67% of each set could be correctly distinguished, with the correct ATG codon also being identified in the positive set. Reliability could be increased further by raising the cut-off or including homologues, the relative merits of which are discussed. AVAILABILITY: The prediction program, called ATGpr, and other data are available at http://www.hri.co.jp/atgpr CONTACT: swintech@hri.co.jp
Accelerated changes in the DNA ploidy associated with in vitro aging were examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short-lived) mice, and were compared to changes observed in cell lines from SAMR1 (accelerated senescence-resistant, long-lived) mice. Flow cytometric analysis of the DNA content in confluent cells and chromosome analysis in mitoses revealed that the diploid cells were being replaced with tetraploid cells until a growth crisis; thereafter, hypotetraploid cells became predominant, accompanied by immortalization. The number of mitoses decreased as the crisis ensued, then increased. Although these changes were observed in the cell lines from both strains of mice, the changes occurred more rapidly and at earlier population doublings in the cell lines from the SAMP11 mice. These results suggest that the cell lines from SAMP11 mice might have higher susceptibility to factors that cause polyploidization, including oxidative stress.
UNLABELLED: Because clonidine has analgesic and sedative properties, it may influence the awakening concentration or dose of an anesthetic. To investigate the effects of oral clonidine premedication on emergence from isoflurane anesthesia, we studied 61 ASA physical status I or II patients undergoing superficial operations. They were randomly allocated to one of three groups according to the dose of clonidine they received: the clonidine-2.5 group (n = 21), clonidine-5 group (n = 20), and control group (n = 20) received approximately 2.5, 5, or 0 microg/kg oral clonidine, respectively, in addition to 20 mg of famotidine 90 min before general anesthesia induction. Anesthesia was induced by thiamylal 5 mg/kg, and tracheal intubation was facilitated with succinylcholine 1.5 mg/kg I.V. Anesthesia was maintained with a 1.1% end-tidal isoflurane concentration and 67% N2O in oxygen, while ventilation was controlled to maintain end-tidal CO2 tension between 33 and 38 mm Hg. After surgery, N2O was discontinued while the end-tidal isoflurane concentration was maintained at 1.1%. After confirming the end-tidal N2O concentration of 0%, isoflurane was discontinued. The end-tidal isoflurane concentration at the time when patients responded to a standardized verbal command to open their eyes was recorded as MAC-Awake. The MAC-Awake values in the clonidine-5 group (0.22% +/- 0.09% [mean +/- SD]) was significantly less than those in the clonidine-2.5 and control groups (0.28% +/- 0.07% and 0.30% +/- 0.07%, respectively, P < 0.05). The wake-up time, from discontinuance of isoflurane until arousal, was longer in the clonidine-2.5 and clonidine-5 groups than in the control group (17.3 +/- 8.0, 16.9 +/- 7.0, and 10.6 +/- 5.3 min, respectively; P < 0.05). In conclusion, oral clonidine premedication 5 microg/kg decreases the awakening concentration of isoflurane, and arousal from isoflurane anesthesia is prolonged with oral clonidine in a dose of 2.5-5 microg/kg. IMPLICATIONS: Preanesthetic medication with oral clonidine, 2.5-5 microg/kg, is associated with prolonged recovery from isoflurane anesthesia in adults.
UNLABELLED: An epidural test dose containing small doses of epinephrine does not produce a reliable increase in heart rate (HR) in children under halothane anesthesia. Because sevoflurane is increasingly used in clinical practice, we designed the present study to determine the hemodynamic responses to, and efficacy of, a simulated IV test dose containing a small dose of epinephrine in sevoflurane-anesthetized children. Sixty ASA physical status I infants and children (4.1 +/- 2.5 yr) undergoing elective minor surgeries were studied during 1.0 minimum alveolar anesthetic concentration of sevoflurane and 60% nitrous oxide in oxygen. The patients were randomly assigned to receive either saline (n = 15), a test dose consisting of 1% lidocaine (0.1 mL/kg) with 1:200,000 epinephrine (0.5 microg/kg, n = 15), atropine 0.01 mg/kg followed 5 min later by saline (n = 15), or atropine followed by the test dose (n = 15) via a peripheral vein to simulate intravascular injection of the epidural test dose. HR and systolic blood pressure were recorded every 15 and 30 s, respectively. The test dose increased the HR from 15 to 60 s and from 15 to 90 s without and with atropine, respectively. Mean maximum increases in HR were similar with and without atropine (21 +/- 8 and 22 +/- 6 bpm, respectively). Of 15 children, 7 and 5 developed HR changes < 20 bpm after the test dose with and without atropine, respectively, whereas all children who received saline had an increase in HR < 20 bpm. No dysrhythmia occurred during the study. Our results indicate that an epidural test dose containing epinephrine is unreliable based on the conventional HR criterion (positive if > or = 20 bpm increase), but reliable on the modified HR criterion (positive if > or = 10 bpm increase) in children anesthetized with sevoflurane. I.v. atropine before the test dose injection did not improve the efficacy based on the conventional HR criterion. Because test doses of epinephrine-containing solution are used to determine whether an epidural catheter is intravascular, it is important to define the optimal test dose under sevoflurane anesthesia. IMPLICATIONS: We found that during sevoflurane anesthesia in children, a heart rate increase > or = 10 bpm and a systolic blood pressure increase > or = 15 mm Hg, when preceded by atropine, may be reliable indicators for detecting intravascular injection.
UNLABELLED: During isoflurane anesthesia, an epinephrine-containing test dose produces unreliable heart rate (HR) responses with a high incidence of hypertension, whereas an isoproterenol-containing test dose results in a high incidence of hypotension. We designed this study to determine whether different combination doses of epinephrine and isoproterenol produce reliable HR changes without overt fluctuations of systolic blood pressure (SBP). Seventy-five healthy patients were anesthetized with 1% end-tidal isoflurane after endotracheal intubation and randomized to one of five groups (n = 15 each) according to the combination dose given i.v.: epinephrine 15 microg, epinephrine 15 microg + isoproterenol 1.5 microg, epinephrine 7.5 microg + isoproterenol 3 microg, isoproterenol 3 microg, and saline. HR and SBP were measured at 20-s intervals for 4 min after injection. Based on the conventional HR criterion (positive if > or = 20 bpm increase), the epinephrine 15 microg + isoproterenol 1.5 microg, the epinephrine 7.5 microg + isoproterenol 3 microg, and the isoproterenol 3 microg groups yielded 100% sensitivities, specificities, and positive and negative predictive values, whereas all groups yielded 100% efficacy according to the modified HR criterion (positive if > or = 10 bpm increase). Four (27%) and three patients (20%) in the epinephrine 15 microg and the epinephrine 15 microg + isoproterenol 1.5 microg groups, respectively, developed systolic hypertension (SBP > or = 180 mm Hg), whereas four (27%) patients in the isoproterenol 3 microg group developed systolic hypotension (SBP < or = 80% of the preinjection value). We conclude that epinephrine 7.5 microg + isoproterenol 3 microg provides the most reliable HR changes with the least SBP fluctuations. IMPLICATIONS: To test whether an epidural catheter may be in a blood vessel, various vasoactive drugs are administered during general anesthesia. The authors found that the combination of epinephrine 7.5 microg and isoproterenol 3 microg produced the most reliable heart rate changes with minimal blood pressure fluctuations.
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UNLABELLED: Clonidine premedication enhances the pressor effects of ephedrine in awake and anesthetized patients. To test the hypothesis that clonidine augments the pressor response to ephedrine during spinal anesthesia, 48 ASA physical status I or II patients were randomly assigned to either the clonidine group (n = 23), receiving oral clonidine approximately 5 microg/kg 90 min before spinal anesthesia, or the control group (n = 25), receiving no clonidine. Spinal anesthesia was performed at either the L2-3 or the L3-4 interspace using 0.5% hyperbaric tetracaine solution 1.4-3.0 mL. Blood pressure (BP), heart rate, and the upper dermatomal level of analgesia were determined at 1-min intervals with the patient in the supine position after tetracaine injections. When systolic BP decreased to <80% of the prespinal value or <100 mm Hg, IV ephedrine 0.2 mg/kg was administered as a bolus. There were no differences in the duration until the first dose of ephedrine after tetracaine injections, and the upper level of analgesia between groups (control group 8.5+/-3.7 min, T5; clonidine group 7.7+/-2.7 min, T6). Although prespinal and preephedrine BP values were higher in the control group, the magnitude of increases in mean BP after ephedrine was significantly greater in the clonidine group (P < 0.05). We conclude that oral clonidine premedication augments the pressor response to IV ephedrine during spinal anesthesia. IMPLICATIONS: The pressor effect of ephedrine is enhanced in patients given oral clonidine premedication during spinal anesthesia.
BACKGROUND: The present study was designed to determine whether augmentation of cardiac performance by milrinone is affected by acidosis in in vivo canine and in vitro guinea pig preparations, and to elucidate a mechanism in relation to the cyclic adenosine monophosphate (cAMP) formation. METHODS: Halothane-anesthetized, ventilated dogs were randomly assigned to a control group (arterial pH [pHa] approximately 7.4, base excess [BE] > -2 mM; n = 7), mild acidosis group (pHa approximately 7.2, BE < -9 mM; n = 7); or severe acidosis group (pHa < 7, BE < -20 mM; n = 6). Arterial blood pressure, left ventricular pressure (including maximum rate of increase, LV dP/dtmax), and pulmonary blood flow (PBF) were measured. Acidosis was induced by transient hypoxia and maintained with hydrogen chloride infusion. Hemodynamic responses to milrinone infusions at 2 and 5 microg x kg(-1) x min(-1) were then studied. In addition, left atria and right ventricular strips were dissected from guinea pig hearts and suspended in HEPES-Tyrode solution, with pH values adjusted to 7.4, 7, or 6.6. The concentration-response relation of isometric contractions for milrinone (10(-7) to 10(-4) M) and 8-bromo-cAMP (10(-4) to 10(-3) M) were determined. RESULTS: In the control group of dogs, significant increases in LV dP/dtmax (2,674 +/- 822 to 3,999 +/- 1,016 mmHg/s [means +/- SD]) and PBF (2.04 +/- 0.98 to 2.44 +/- 0.96 l/min [means +/- SD]) were seen with a milrinone infusion of 5 microg x kg(-1) x min(-1). In the mild acidosis group, 5 microg x kg(-1) x min(-1) milrinone also increased LV dP/dtmax and PBF. However, neither LV dP/dtmax nor PBF changed in the severe acidosis group. In in vitro experiments, milrinone exerted a positive inotropic effect in a concentration-dependent manner on the right ventricular preparations at pH 7.4, but not at pH 7 and 6.6, whereas no significant difference was observed in inotropic responses to 8-bromo-cAMP at pH values of 6.6, 7, and 7.4 on the right ventricular strips. In the right ventricular in vitro preparation, 10(-4) M milrinone was accompanied by a significant increase in intracellular cAMP content at apH of 7.4 but not 7. CONCLUSIONS: These results indicate that the inotropic effect of milrinone is attenuated by acidosis due, at least in part, to decreased cAMP formation in acidotic muscle.
BACKGROUND: Clonidine reduces heart rate (HR) responses to atropine, whereas neostigmine causes bradycardia. This study was designed to determine whether clonidine premedication would reduce tachycardia after neostigmine-atropine administration. METHODS: Fifty adult patients without cardiovascular disorders who were scheduled for elective surgeries were randomly assigned to receive approximately 5 microg/kg (oral clonidine clonidine group, n=25) or no clonidine (control group, n=25) 90 min before induction of general anesthesia. After tracheal intubation, anesthesia was maintained with N2O and 12% isoflurane in oxygen while patients were paralyzed with vecuronium and mechanically ventilated. When surgeries were completed, adequate spontaneous respiration, responses to verbal commands, and sustained tetanus by stimulating the ulnar nerve were confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s under stable hemodynamic condition (systolic blood pressure and HR within +/-5% of preceding values), and blood pressure and HR were measured noninvasively at 1-min intervals for 10 min. RESULTS: Increases in HR in the clonidine group were significantly less 1-4 min after neostigmine--atropine injections compared with HR values in the control group. A maximum increase in HR of the clonidine group was also significantly less than the control group (15+/-7 vs. 23+/-10 beats/min; means+/-SD), whereas absolute values of mean blood pressure were similar. Severe bradycardia (HR < 50 beats/min) developed in no patients in either group. CONCLUSIONS: Premedication with 5 microg/kg oral clonidine attenuates the initial increases in HR without subsequent decreases in HR.
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We examined the effect of Japanese green tea extract (JGTE) on enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection in a gnotobiotic mouse model. Gnotobiotic mice inoculated with an EHEC strain developed neurologic and systemic symptoms, usually culminating in death. In contrast, none of mice receiving dietary JGTE showed clinical signs or death. This report describes the effect of JGTE, which includes the inhibition of bacterial growth in vivo. The Shiga-like toxin (SLT) level in the feces of the JGTE diet group was significantly lower than that of the control group.
Microtubule-associated protein tau has been reported to be significantly increased in cerebrospinal fluid (CSF) of the patients with Alzheimer's disease (AD), which suggests that it is possibly a biological marker for the diagnosis of AD. The underlying mechanism of the increased tau level in CSF, however, is not known. In this study, the tau levels were compared between antemortem and postmortem CSF. The postmortem tau levels in CSF were significantly increased in all groups including AD, neurological control, and nondemented control. A striking elevation of CSF tau was observed during the postmortem change with the nondemented subjects. These findings may offer some insight into the understanding of the mechanism of the increased tau level in CSF with AD and other related disorders.
BACKGROUND: Several reports in the 1970s suggested that etidronate disodium might be clinically useful to prevent calcium stones, but the use of etidronate in the urolithiasis field was discontinued due to adverse effects of this drug on skeletal turnover and mineralization. Because the drug might affect not only crystallization, but also crystal-tubular interactions, we investigated the minimum dose of etidronate necessary to effectively prevent stone recurrence without adverse side effects. METHODS: We examined the effect of etidronate on the crystallization of calcium oxalate, calcium phosphate and magnesium ammonium phosphate using synthetic urine and measured by an aggregometer. We also studied its effect on the adhesion of calcium oxalate monohydrate crystals to Madin-Darby canine kidney (MDCK) cells in vitro. RESULTS: Etidronate affected the crystallization+ of not only calcium phosphate and calcium oxalate, but also magnesium ammonium phosphate in synthetic urine. The inhibitory activities on these crystallizations were detected at extremely low drug concentrations. Etidronate also had a strong inhibitory activity against the adhesion of calcium oxalate crystals to MDCK cells. CONCLUSION: Although further studies are necessary regarding the effects of etidronate on crystallization and crystal adhesion both in vivo and in vitro, and the appropriate schedule of dosing to prevent side effects, it is possible that etidronate may be useful in the treatment of urinary stones.
We examined fecal specimens of Japanese residents in developing countries in order to know the prevalence of intestinal parasites in the group. One fecal specimen was collected from each 981 (in 1995) and 1275 (in 1996) Japanese living in Asia, the Middle East, Europe, Africa and Latin America. The specimens were fixed with 10% formalin in each area, and were examined in Japan by concentration method (formalin-ether sedimentation) to find protozoan cysts or helminth eggs. The infection rate of intestinal parasites was 3.0% in 1995 and 2.4% in 1996. The rate was high in Africa (1995: 5.7%, 1996: 4.7%) and Asia (1995: 3.8%, 1996: 3.0%). Regarding to the species of the parasites, Giardia lamblia (17 cases), Trichuris trichiura (14) and Ascaris lumbricoides (11) were detected frequently. Additionally, 7 cases of Heterophyes heterophyes infection were found in Asia and the Middle East. The infection rate was higher in adults than that in children, and a positive relationship between the infection rate and duration of stay was observed. Among the Japanese infected with intestinal parasites, abdominal symptoms such as diarrhea or abdominal pain were common (36.8%). It is also noteworthy that 28.1% of the Japanese infected had a history of gastric diseases such as gastric ulcer. Although the infection rate of intestinal parasites among Japanese residents in developing countries was low, compared to that of the natives in the countries, the rate is still higher than that in Japanese living in the home country. It is necessary to continue preventive measures such as health education in order to eradicate intestinal parasitic infections from this group.
BACKGROUND: Several autoimmune subepidermal blistering diseases with autoantibodies against the epidermal basement membrane zone (BMZ) have been identified. Each shows distinct immunological findings. OBJECTIVES: Our patient showed clinical features which were indicative of bullous pemphigoid or linear IgA bullous dermatosis. In his serum, circulating IgG antibodies binding to the dermal side of skin split with 1 M NaCl were detected. To clarify the immunological character of the patient, we performed further studies. METHODS: Western immunoblot analysis using normal human skin extracts and indirect immunofluorescence (IF) with affinity-purified IgG antibodies to the detected dermal protein were done. RESULTS: Western immunoblot analysis demonstrated IgG antibodies reacting with a dermal 200-kD protein. Affinity-purified IgG antibodies to the 200-kD protein reacted to the dermal side of the split by indirect IF. Therefore, this dermal 200-kD protein is believed to be the epidermal BMZ antigen. CONCLUSION: Our patient showed an immunologically unique subepidermal blistering disease.
BACKGROUND: Among matrix metalloproteinases (MMPs), MMP-2 and MMP-9 are considered to play important roles in the tissue metabolism. OBJECTIVE: To study the production of MMP-2 and MMP-9 in cultured keratinocytes. METHODS: We examined the effect of cell passage number and cell differentiation on these enzymes by zymography and immunocytochemistry. RESULTS: Both MMP-2 and MMP-9 gelatinases were detected in keratinocyte-conditioned media using zymography. The level of MMP-2 in the medium decreased after sequential passage, whereas MMP-9 was detected at a constant level. Treatment of keratinocytes with Ca2+, a potent stimulator for cell differentiation. induced secretion of MMP-9, which was confirmed immunocytochemically. Inversely, treatment with retinoic acid, which inhibits cell differentiation, increased the level of MMP-2. CONCLUSION: These results suggest that keratinocytes regulate their secretion of MMP-2 and MMP-9 gelatinase in distinct and independent patterns during differentiation.
Cryoultramicrotomy was originally established to provide ultrathin cryosections as substrates for on-section immunolabeling in immunoelectron microscopy. Recently, we recognized that ultrathin cryosections of skin (0.2 micrometer thick) could serve as substrates for immunofluorescence (IF) with excellent resolution. To assess the advantages and the limitations of IF on ultrathin cryosections, we compared the labeling of IF on 0.2-micrometer ultrathin cryosections of skin with those of routine IF on 6-micrometer cryostat sections, confocal laser scanning microscopy (LSM), and immunogold electron microscopy using several markers of keratinocyte cell surface and basement membrane zone molecules. IF on ultrathin cryosections clearly demonstrated a lack of bullous pemphigoid antigens beneath the melanocytes, desmosomal antigens as discontinuous dot-like labeling, and nondesmosomal plasma membrane antigen as a ladder-like pattern. IF on ultrathin cryosections provided convincing images with higher resolution than confocal LSM, which corresponded well to those of immunogold electron microscopy. IF on ultrathin cryosections had superior resolution compared to routine IF or confocal LSM and should serve as a powerful tool in future studies for the analysis of skin antigens. (J Histochem Cytochem 46:1455-1460, 1998)