Unusual spiral wave dynamics in the Kessler-Levine model of an excitable medium.

The Kessler-Levine model is a two-component reaction-diffusion system that describes spatiotemporal dynamics of the messenger molecules in a cell-to-cell signaling process during the aggregation of social amoeba cells. An excitation wave arising in the model has a phase wave at the wave back, which simply follows the wave front after a fixed time interval with the same propagation velocity. Generally speaking, the medium excitability and the refractoriness are two important factors which determine the spiral wave dynamics in any excitable media. The model allows us to separate these two factors relatively easily since the medium refractoriness can be changed independently of the medium excitability. For rigidly rotating waves, the universal relationship has been established by using a modified free-boundary approach, which assumes that the front and the back of a propagating wave are thin in comparison to the wave plateau. By taking a finite thickness of the domain boundary into consideration, the validity of the proposed excitability measure has been essentially improved. A novel method of numerical simulation to suppress the spiral wave instabilities is introduced. The trajectories of the spiral tip observed for a long refractory period have been investigated under a systematic variation of the medium refractoriness.

Selection of spiral waves in excitable media with a phase wave at the wave back.

Universal relationships between the medium excitability and the angular velocity and the core radius of rigidly rotating spiral waves in excitable media are derived for situations where the wave front is a trigger wave and the wave back is a phase wave. Two universal limits restricting the region of existence of spiral waves in the parameter space are demonstrated. The predictions of the free-boundary approach are in good quantitative agreement with results from numerical reaction-diffusion simulations performed on the Kessler-Levine model.

Autonomic nervous system activity in idiopathic dilated cardiomyopathy and in hypertrophic cardiomyopathy.

To assess autonomic nervous activity in patients with cardiomyopathies, analysis of heart rate variability was performed using 24-hour ambulatory electrocardiograms in 14 patients with idiopathic dilated cardiomyopathy (IDC), 15 with hypertrophic cardiomyopathy (HC) and 18 healthy subjects. Heart rate variability during the night and daytime was calculated using fast-Fourier transform, and power spectra were quantified in 2 frequency bandwidths: 0.00 to 0.15 Hz (low-frequency power [LF]) and 0.15 to 0.50 Hz (high-frequency power [HF]). Log(HF) was used as an index of parasympathetic nervous activity, and log(LF/HF), of sympathetic nervous activity. Log(HF) was significantly lower and log(LF/HF) was significantly higher in IDC. These changes were related to ejection fraction. In HC, lower log(HF) and higher log(LF/HF) were recognized only during the night, and these changes were independent of the degree of myocardial hypertrophy. Our results indicated attenuation of parasympathetic activity and enhanced sympathetic activity in HC during the night, and also in IDC. Assessment of autonomic imbalance by analysis of heart rate variability may be useful for understanding the pathophysiology of cardiomyopathies.

Discrimination between cardiac para- and sympathetic damage in diabetics.

To analyze the autonomic mechanism on heart rate (HR) variations, pharmacological studies were performed on 8 healthy subjects and 6 diabetic patients. Three HR variations--in supine resting position, during deep breathing in supine position (respiratory HR variations), and on standing (orthostatic tachycardia; delta HR)--were examined. The results in healthy subjects and diabetics were similar. After administration of parasympathetic blockade with atropine, respiratory HR variations were almost abolished. However, no significant difference in delta HR was found. With the addition of beta-adrenergic blockade with propranolol, delta HR was remarkably reduced. Propranolol alone did not affect the respiratory HR variations, but after propranolol administration delta HR was significantly reduced compared with that of the control. The present studies show that respiratory HR variations are predominantly mediated by parasympathicus, whereas orthostatic tachycardia is mediated by both sympathicus and parasympathicus, particularly by sumpathicus. This result suggests the possibility of discriminating the impairment of the 2 cardiac autonomic nervous systems by these simple and non-invasive tests.

Activity of ecdysone analogs in enhancing N-acetylglucosamine incorporation into the cultured integument of Chilo suppressalis.

Ecdysone analogs with various side chains at the 17-position of the steroid structure enhanced the incorporation of N-acetylglucosamine as 20-hydroxyecdysone into the cultured integument prepared from Chilo suppressalis. Their activity in terms of the concentration required to give 50% of the maximum response varied with the structure. Piperonyl butoxide, an inhibitor of oxidation metabolism, did not enhance the in vitro effect of the compounds. The order of potency was ponasterone A > 20-hydroxyecdysone > cyasterone > inokosterone > makisterone A >> ecdysone.

An endo-(1 lead to 6) -beta-D-glucanase from Mucor hiemalis.

An endo-(1 lead to 6)-beta-D-glucanase (EC 3.2.1), isolated from the culture filtrate of Mucor hiemalis, was purified by ammonium sulphate fractionation and gel filtration. The homogeneity of the enzyme was confirmed by disc electrophoresis. The enzyme had a wide range of temperature and pH stability, high substrate specificity, and an action pattern of the endo-type.

Structural examination of antitumour, water-soluble glucans from Grifora umbellata by use of four types of glucanase.

Antitumour glucans (GU) from the fungus Grifora umbellata have been subjected to periodate oxidation, Smith degradation, methylation analysis, and treatment with endo-(1 leads to 6)-beta-D-, endo-(1 leads to 3)-beta-D-, and exo-(1 leads to 3)-beta-D-glucanases, and alpha-amylase; the following structural features were revealed. GU-2 contains a backbone involving (1 leads to 6)-beta- and () leads to 3)-beta linkages, and two kinds of branches involving (1 leads to 6)-beta and (1 leads to 4)-alpha linkages. GU-3 has a (1 leads to 3)-beta-linked backbone and branches involving (1 leads to 6)-beta linkages or (1 leads to 4)-alpha and (1 leads to 6)-beta linkages. GU-4 also contains a (1 leads to 3) beta-D-glucan backbone and a small number of (1 leads to 6)-beta-linked branches. Probable structural units of these glucans are proposed.

An endo-(1 leads to 3)-beta-D-glucanase from Mucor hiemalis.

An endo-(1 leads to 3)-beta-D-glucanase (EC 3.2.1.6), isolated from the culture filtrate of the fungus Mucor hiemalis, was purified by ammonium sulfate fractionation, gel filtration, and column chromatography on O-(carboxymethyl)cellulose. The optimum pH, optimum temperature, and Km value of the enzyme were pH 5.0, 50 degrees, and 0.048%, respectively. The enzyme was strongly inactivated by Pb2+, Cu2+, and Hg2+ ions and also inhibited by Zn2+ and Fe3+ ions. The enzyme was specific for laminaran and the action pattern of the enzyme was of the endo-type. The molecular weight of the enzyme, as determined by gel filtration, was 30,000.

Relationship between the chemical structure and anti-tumour activity of glucans prepared from Grifora umbellata.

Glucans from Grifora umbellata and their enzyme-treated fractions have been tested for antitumour activity against subcutaneously implanted Sarcoma 180 (solid type). The results indicate that the basic common unit of the glucans is of primary importance for the antitumour activity, which is also influenced by the type of sugar linkage, length of branch, branching frequency, molecular size, and molecular conformation.

[Cefpiramide: antibacterial activity, pharmacokinetics, and clinical evaluation].

We determined MIC values of cefpiramide (CPM) against clinical isolates from 100 patients who were subjected to total hysterectomy between April 1986 and March 1988. We also investigated the concentrations of CPM in uterine tissue and assessed the clinical efficacy of postoperative prophylaxis. 1. Against bacteria isolated from clinical materials the MIC80 values of CPM were as follows: Staphylococcus epidermidis 1.56 micrograms/ml, Enterococcus faecalis 25 micrograms/ml, and Escherichia coli 6.25 micrograms/ml. 2. Peak concentrations of CPM in various tissues and tissue/serum ratios of AUC were as follows: cervix uteri 35 micrograms/g (39.5%), perimetrium 43 micrograms/g (44.9%), endometrium 39 micrograms/g (51.6%), myometrium 28 micrograms/g (26.8%), oviduct 67 micrograms/g (41.9%), and ovary 27 micrograms/g (45.8%). In all tissues examined CPM concentrations were above 4 micrograms/g after 600 minutes. 3. Serum half-lives were T 1/2(alpha) = 13.2 minutes and T 1/2(beta) = 260.2 minutes. 4. The efficacy rate in postoperative prophylaxis was 97.9%. 5. No serious side effects were observed.

[Pharmacokinetic and clinical studies on latamoxef in the field of obstetrics and gynecology].

Latamoxef (LMOX) 1 g was administered twice daily for 5 days to patients undergoing operation for myoma uteri and the time course of tissue concentrations of the drug and the prophylactic effect of the treatment on postoperative infection were studied. 1. Area under concentration-time curve (AUC) of LMOX was the highest in the perimetrium (45.3%), followed by the cervix uteri (39.2%), endometrium (35.9%), oviduct (35.1%), myometrium (29.5%), and ovary (24.4%). 2. Cmax was the highest in oviduct (46.9 micrograms/g), followed by Cmax's in perimetrium (44.2 micrograms/g), cervix uteri (35.8 micrograms/g), myometrium (26.9 micrograms/g), endometrium (25.6 micrograms/g), and ovary (24.3 micrograms/g). 3. Serum half-lives were T1/2(alpha) = 0.27 hour and T1/2(beta) = 1.81 hours. 4. Prophylactic efficacy against postoperative infections was 94.3%, and febrile morbidity was 5.7%. The preoperative and postoperative laboratory tests did not show appreciable changes, no adverse reaction was observed. In the present study, LMOX showed good transfer into gynecological tissues, suggesting its very high usefulness in the treatment of infection and in the postoperative management.

[Intraperitoneal versus intravenous infusion of cis-platinum in advanced ovarian cancer--examination of pharmacokinetics].

The pharmacokinetics of i.p.- and i.v.-infused cis-platinum (55 mg/m2) was studied in five patients with advanced ovarian cancer. The area under the concentration time (AUC) of non-protein-binding platinum in ascites had on anti-tumor activity 44 times larger with i.p. infusion than that with i.v. infusion. Comparing with the concentration curve of non-protein-binding platinum in plasma, there was little difference between i.p. and i.v. infusion, and the AUC of non-protein-binding platinum was almost equal between i.p. and i.v. infusion. In cases of low renal function, cisplatin was infused at 70 mg/m2 with sodium thiosulfate (STS). The AUC of ultrafiltrable platinum in plasma was 3 times larger in STS combination therapy. Therefore, STS was confirmed to be a powerful antidote against cis-platinum in plasma. Amounts of total platinum in 24-h urinary secretion were slightly less for i.p. than for i.v. infusion. Consequently, i.p. infusion of cis-platinum was shown to be highly effective on the local site and as effective as i.v. infusion on the whole body. Moreover, this route is effective for reducing ascites production and is expected to be effective against metastatic sites other than the abdominal cavity.

Quantitative evaluation of diabetic autonomic neuropathy by using heart rate variations--determination of the normal range for the diagnosis of autonomic neuropathy.

Heart rate (HR) variations--in supine resting position, during deep breathing and on standing--were measured in 162 healthy subjects and 168 diabetics by use of an instantaneous-HR-change continuous recorder. As indices of HR variations, the standard deviation of the HR at rest (SD of HR), the mean difference between maximal and minimal HR during deep breathing (delta I-E) and the HR increase on standing (delta HR) were determined. In healthy subjects, the values for each test declined with age and the log-transformed data fitted the linear regression. The 90% confidence limits were calculated for the normal range and the values below normal range were defined as abnormal. In diabetics, the incidence of abnormal response were 19% in the SD of HR, 38% in the delta I-E and 22% in the delta HR. The delta I-E was the most sensitive index for the autonomic neuropathy. The delta HR was considered to be able to detect the different mechanisms of neural reflexes because of the poor correlation between the delta HR and the respiratory HR variations. The present studies suggested that delta I-E and delta HR should be measured at the same time to evaluate the autonomic neuropathy.

Quantitative evaluation of diabetic autonomic neuropathy by using heart rate variations: relationship between cardiac parasympathetic or sympathetic damage and clinical conditions.

It was previously suggested that respiratory heart rate (HR) variations were predominantly affected by the parasympathetic nerve and HR increase to standing was predominantly affected by the sympathetic nerve. To compare parasympathetic and sympathetic nerve function in diabetics, these two tests were performed in 95 diabetics and 38 controls by use of an instantaneous-HR-change continuous recorder. All subjects were between 40 and 59 years-old. As indices of autonomic nerve function, the mean difference between maximal and minimal HR during deep breathing (delta I-E) and the HR increase on standing (delta HR) were determined. The mean delta I-E and delta HR in the diabetics were 9.4 beats/min and 15.1 beats/min, respectively. These values were significantly lower than those in the controls (delta I-E 14.4, delta HR 20.5 beats/min). delta I-E correlated negatively to duration of diabetes and mean fasting blood glucose during the last 6 months in the diabetics, but delta HR did not correlate to them at all. Diminished delta I-E was found in the patients with insulin treatment, retinopathy or persistent proteinuria. Diminished delta HR, however, was found only in the patients with long-standing complicated diabetes. Thus, both cardiac parasympathetic and sympathetic nerve function were significantly impaired in the diabetics as compared with the controls and that parasympathetic nerve damage occurred early whereas sympathetic innervation was preserved.

Three-dimensional observations on intermediate filaments of the squamous epithelium of the uterine cervix.

The following conclusions have been drawn from electron-microscopic three-dimentional observations on the intermediate filaments (IFs) of the squamous epithelium from the uterine cervix. (1) IFs form a three-dimensional reticular network and wrap around the intracellular periphery of cells extending from the basal to the superficial layers. (2) In basal and parabasal cells, the IFs are distributed in a pattern radiating from the perinuclear location toward the cellular periphery. (3) The use of PEG-embedding method after detergent-extraction with Triton X-100 and saponin is suitable for the three-dimensional observations on IFs of stratified squamous epithelium from the uterine cervix.

Immunohistochemical localization of carcinoembryonic antigen in adenocarcinoma of the endocervix and the endometrium.

Immunoperoxidase localization of carcinoembryonic antigen (CEA) was performed on tissue sections of adenocarcinoma of endocervical and endometrial origin to clarify the criteria for their differentiation. Twenty-two (96%) of 23 endocervical and 32 (70%) of 46 endometrial adenocarcinomas revealed positive CEA immunostain. The extent of staining did not seem to correlate with the degree of differentiation in either kind of cancer. Among the positive cases, CEA staining was located over whole cytoplasm in 18 (80%) of 22 positive endocervical adenocarcinomas and on apical surface in 24 (75%) of 32 positive endometrial adenocarcinomas. The pattern of CEA distribution in endocervical adenocarcinoma of endometrioid type was not similar to that observed for primary endometrial adenocarcinoma.

Immunohistochemical demonstration of papillomavirus antigen in cervical dysplasia and vulvar condyloma.

Biopsies from 30 cases of vulvar condyloma, 460 cases of cervical dysplasia, 30 cases of carcinoma in situ and 75 cases of invasive carcinoma of the cervix were screened for the presence of human papillomavirus (HPV) antigen by means of the peroxidase-antiperoxidase method. Positive reaction for HPV was detected in 14 cases of condyloma and 80 cases of dysplasia as a brown intranuclear precipitate in the superficial layer of the epithelium. None of the cases of carcinoma in situ and invasive cancer were positive for HPV. The mean age of the women with HPV-positive dysplasia was significantly lower than that of the women with HPV-negative dysplasia. Condylomatous dysplasia showed a significantly higher positive rate than did noncondylomatous dysplasia. Cases of condylomatous dysplasia with severe stromal inflammation were negative for HPV more frequently than those with mild stromal inflammation.

Immunohistochemical and electron microscopic demonstration of human papillomavirus in dysplasia of the uterine cervix.

Twenty-five cases of dysplasia of the uterine cervix were studied for the presence of human papillomavirus (HPV) by means of immunohistochemical and electron microscopic techniques. Serial sections of the same histological specimen were examined in each case. HPV was detected in 14 cases by both immunohistochemistry and electron microscopy, while 10 cases were negative with both methods. In only one case, there was a discrepancy in the results derived from these two methods. It was concluded that the relation between HPV infection and cervical dysplasia was confirmed and that immunohistochemical and electron microscopic methods led almost to the same result in detecting HPV in cervical dysplasia.

Flow cytometric DNA analysis of human endometrial carcinoma.

Analysis of endometrial carcinoma of 15 cases and the normal endometrium from 12 control cases was made using flow cytometry. The proliferative activity and the ploidy level of the tumors were determined and a comparative study of the tumors classified by the nuclear grade of the tumor was made. In comparison with normal endometrium, endometrial carcinoma tissue had a significantly larger S-phase fraction of the cell cycle. Moreover, among the endometrial carcinoma cases, the percentage of S-phase cells was found to increase with increases in abnormalities of nuclear morphology. Endometrial carcinoma cases had higher levels of G2+M phase fractions than normal endometrium, but not significantly so. The proliferation index of endometrial carcinomas was significantly higher than that in normal endometrium, and it was found that proliferative activity became more robust the more irregular the nuclear morphology. With regard to the ploidy level, all of the normal endometria and Nuclear Grade 1 or 2 endometrial carcinoma cases showed a DNA distribution between diploid and tetraploid. In contrast, Nuclear Grade 3 cases could be subdivided into two groups, one which had a DNA distribution between diploid and tetraploid with an extremely high proliferation index and the other which had an aneuploid DNA stem line.

Parasympathetic activity is a major modulator of the circadian variability of heart rate in healthy subjects and in patients with coronary artery disease or diabetes mellitus.

Autonomic heart rate control was assessed by power spectral analysis of heart rate variability in 24-hour ambulatory electrocardiographic recordings from 23 healthy subjects, 14 patients with coronary artery disease without cardiac dysfunction, and 14 patients with diabetes mellitus. The log value of the ratio of the low-frequency component (LF = 0.04 to 0.15 Hz) to the high-frequency component (HF = 0.15 to 0.5 Hz) and logHF were employed as indexes of sympathetic and parasympathetic activity, respectively. Diurnal and nocturnal logLF, logHF, and log(LF/HF) values were calculated for heart rates of 60, 70, and 80 beats/min. Intergroup differences among these three variables were not significant at any heart rate. Although a heart rate-related decrease in logHF was generally observed, the relationship between log(LF/HF) and heart rate was not consistent. The correlation between diurnal and nocturnal logHF values was significant at all three heart rates (r = 0.63, 0.87, and 0.59), whereas the diurnal log(LF/HF) was correlated with the nocturnal value only at 70 beats/min (r = 0.77). These results suggest that the heart rate during normal daily activities is a reliable indicator of parasympathetic tone, if not sympathetic tone, in healthy subjects and patients with coronary artery disease or diabetes mellitus.