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Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 487 records · Page 27Linked to original sources

Studies on antiallergy agents. III. Synthesis of 2-anilino-1,6-dihydro-6-oxo-5-pyrimidinecarboxylic acids and related compounds.

A series of 2-anilino-1,6-dihydro-6-oxo-5-pyrimidinecarboxylic acids with various substituents was synthesized and evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. High activity by intraperitoneal and oral administrations was observed for the 3-trifluoromethyl and 2-alkoxyanilino derivatives (64, 79, 81, 82 and 85). Structure-activity relationships are discussed.

Aniline Compounds↗

Binding of glycyrrhizin to human serum and human serum albumin.

The binding of glycyrrhizin (GLZ) to human serum and human serum albumin (HSA) was examined by an ultrafiltration technique. Specific and nonspecific bindings were observed in both human serum and HSA. The association constants (K) for the specific bindings were very similar: 1.31 x 10(5) M-1 in human serum and 3.87 x 10(5) M-1 in HSA. The number of binding sites (n) and the linear binding coefficient (phi) in HSA were 1.95 and 3.09 x 10(3) M-1, respectively. When the human serum protein concentration was assumed to be 4.2% (equal to the measured serum albumin concentration), n in human serum was 3.09, which is similar to the n value in HSA, and phi in human serum was 0.71 x 10(3) M-1, which is reasonably close to that for HSA. The binding pattern of GLZ with human serum protein on Sephadex G-200 column chromatography showed that GLZ binds to only the albumin fraction. It was concluded that the GLZ-binding sites in human serum exist mainly on albumin and GLZ binds to specific and nonspecific binding sites at lower and higher concentrations than approximately 2 mM, respectively.

Glycyrrhetinic Acid↗

Pharmacokinetics of glycyrrhetic acid, a major metabolite of glycyrrhizin, in rats.

The pharmacokinetics of glycyrrhetic acid (GLA) was examined in rats after bolus i.v. injection at a dose of 2, 5, or 12 mg/kg. The decline in plasma concentration was generally biexponential at each dose, but the terminal disposition became much slower with increase of dose. A greater than proportional increase in plasma GLA concentration was observed with increase of dose, suggesting a dose-dependency of GLA disposition. Apparent total body clearance decreased significantly with increase of dose. On the other hand, the apparent steady-state distribution volume after i.v. administration was unaffected by dose. The plasma disposition at each dose fitted well to a two-compartment pharmacokinetic model with Michaelis-Menten elimination. It was concluded that the pharmacokinetics of GLA in the rat is dose-dependent owing to a saturable elimination rate. The plasma level of GLA after glycyrrhizin (GLZ) i.v. dosing (100 mg/kg) in the control rats (without biliary fistulization) sustained the concentration range of 1.5-3 micrograms/ml during 1-48 h, but that in the rats with biliary fistulization declined with time. It was suggested that the sustained plasma level of GLA is accounted for by the intestinal reabsorption of GLA produced from GLZ and GLA-conjugates during the enterohepatic recycling of both.

Animals↗

Relation between mixed venous blood oxygen saturation and cardiac pumping function at the acute phase of myocardial infarction.

In this study, we monitored changes in the mixed venous blood oxygen saturation (Sv-O2) level of 45 patients with acute myocardial infarction and compared these results to the traditional parameters. The Sv-O2 level was found to correlate well with the clinical course of patients and their hemodynamic conditions. The mean Sv-O2 level of the group having congestive heart failure (53.3 +/- 8.4%) was found to be statistically lower than those without (69.8 +/- 5.6). Furthermore, patients whose Sv-O2 level was lower than 60% were found to be at greater risk for heart failure and a very high mortality rate. Patients were classified into four subsets according to Forrester's hemodynamic classification; their Sv-O2 levels were 70.7 +/- 4.1% (I: 23 cases), 54.7 +/- 6.9% (II: 8 cases), 55.8 +/- 9.4% (III: 10 cases), and 47.0 +/- 8.0 (IV: 4 cases), respectively. A severe relationship between pulmonary capillary wedge pressure and Sv-O2 having a correlation coefficient of r = -0.64 was observed, and a logarithmic curvilinear relation between cardiac index approximately Sv-O2, stroke volume index approximately Sv-O2 and left ventricular stroke work index approximately Sv-O2 was also evident. When the decrease in the Sv-O2 level was more than 5%, it always showed a significant decrease in the cardiac index. This study suggested tht continuous monitoring of the Sv-O2 level revealed simultaneous changes in the hemodynamic state, which lead to the assistance and aid for treating patients with critical conditions of acute myocardial infarction. In such circumstances, it was noted that the Sv-O2 level should be maintained above 60% in order to stabilize the hemodynamic state.

Aged↗

[Development and application of an optical system to measure the movements of organs with soft tissue].

We proposed a new optical system to measure the movements of less accessible organs with soft tissue. The sensor unit is composed of a phototransistor and two LEDs. Two LEDs of light sources are driven by two phase signals with phase shift of 90 degrees. The distance between the sensor and the measuring object can be obtained as the function of the phase angle of reflex light signal detected by the phototransistor. The system can be easily constructed and provides simultaneous recordings of multiple points with the fast response in real time. The Relative precision is 0.5 mm and the resolution is 0.05 mm. Output characteristic of the system was less affected by the reflection factor of the object. We conducted to observe the tongue movements in speech production.

Humans↗

Effects of cholesterol feeding on the distribution, metabolism, and accumulation of pentachlorobenzene in rats.

To investigate the influence of cholesterol content in tissue on the distribution, metabolism, and accumulation of pentachlorobenzene (PECB), rats were fed on a cholesterol-enriched (CHE) diet or a basal diet for 4 weeks. At two weeks, a single dose or a 6-day dosage of PECB was orally administered. The serum cholesterol concentration in the CHE diet group was 2.1-2.9 times higher than that in the basal diet group, while the serum triglyceride concentration decreased. The serum lipid levels were similar to the levels at two weeks. The blood PECB concentration was not different between the two groups. Increases in the contents of PECB and lipid in tissue due to the CHE diet feeding were observed only in liver (PECB, 2.6-3.0 times; triglyceride, 2-3 times; cholesterol, 10-15 times). Content of pentachlorophenol, a main metabolite of PECB, and the level of drug-metabolizing enzymes in liver of the CHE diet group tended to be higher than those of the basal diet group. These results suggested that the increase in PECB accumulation in the liver of the CHE diet group was not due to the decrease of PECB metabolism but due to the increase in the content of cholesterol and triglyceride.

Animals↗

[Evaluation of exercise thallium-201 myocardial single photon emission computed tomography in silent myocardial ischemia].

To evaluate the diagnostic significance of exercise Tl-201 myocardial SPECT in silent myocardial ischemia, 41 patients with angiographically-proven coronary artery disease (27 effort angina, 14 post-infarction angina) were tested using this method. Double product (blood pressure x heart rate) during exercise was used as a hemodynamic parameter. Thirty-two projections were obtained throughout 180 degrees by a rotating gamma camera, immediately, and four hours after exercise. Myocardial Tl-201 washout rate of the entire left ventricle was presented in two-dimensional polar function maps. Normal lower limit of myocardial Tl-201 washout rate was defined as mean-2SD of normals, and the region with a washout rate lower than normal was defined as an ischemic region. The location of myocardial ischemia was visually determined using a Bull's eye polar map. The ischemic size was quantified by the defect volume ratio (ratio of the ischemic myocardium to total myocardium). Coronary lesions were quantitatively assessed by the Pujadas score using coronary angiography. Results were as follows: There was no significant difference between painful myocardial ischemia and silent myocardial ischemia according to double product and the Pujadas scores. In most silent ischemia, the region of the reduced washout rate was in the inferior or lateral area of the Bull's eye polar map, whereas it was in the anterior area in painful ischemia. The defect volume ratio indicating the extent of ischemia was smaller in silent ischemia than in painful ischemia. In conclusion, the ischemic location and size may be contributing factors in silent myocardial ischemia.

Exercise Test↗

[Intraocular fluid antibody quotients following inoculation with two different antigens in experimental herpes simplex virus retinochoroiditis].

Viral retinochoroiditis was induced experimentally by inoculation of herpes simplex virus into the vitreous body in rabbits. The animals were sensitized systemically using 2 pathogens as antigens (herpes simplex virus and toxoplasma gondii) 3 weeks prior to intraocular inoculation. Serum and intraocular fluid were collected 2 weeks after inoculation. The intraocular fluid antibody titers and quotients for these 2 pathogens were then measured to determine the effects of serum antibodies, which are thought to enter the eyes as a result of destruction of the blood-ocular barrier. Experimental criteria for antibody quotients were also determined. Antibody quotients for the etiological virus (herpes simplex virus) ranged from 2 to 20, with an average of 9.7. Those for toxoplasma gondii, the antibody of which is thought to enter the eye from the blood, were all less than 5 with average of 1.9. From these results, it would seem that when the antibody quotient of a pathogen in more than 6 in the intraocular fluid, it is likely to be an etiological organism, while the possibility of infection is very low when the quotient is under 2. More precise studies are required to identify an etiological pathogen when the quotient is 2-6.

Animals↗

[Malignant lymphoma presenting with bilateral orbital apex syndrome].

This is the first report of bilateral orbital apex syndrome caused by malignant lymphoma. A 73-year-old man suffered from right forehead pain, diplopia and right numb cheek. Thereafter progressed bilateral visual disturbance rapidly, and soon he became blind. Cavernous sinus thrombosis was suspected clinically, but histological study of the biopsied specimen from the nasopharynx revealed malignant lymphoma (non-Hodgkin, diffuse, large cell type) (LSG). The patient died 5 months after the onset of his illness. Autopsy revealed lymphoma cell invasion and necrosis in parasellar region, bilateral optic nerves, nasopharynx, and left posterior root of L3. There was no lymphoma cell in the liver, spleen, or gastrointestinal tract. The nasopharynx was suspected to be the primary site of the tumor. In bilateral orbital apex syndrome, malignant lymphoma should be taken into consideration. Remission can be expected if treatment is started in early stage.

Aged↗

[Pharmacokinetic and clinical studies on cefmenoxime in neonates and infants].

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and infants were conducted. 1. CMX 20 mg/kg was administered by intravenous bolus injection to 6 neonates (with ages 2 to 20 days) and 5 infants (with ages 36 to 107 days) and its serum concentration and urinary excretion rates were determined. In the neonates, serum concentrations of CMX after intravenous administration reached peak levels of 48.2 to 90.7 micrograms/ml (mean 70.4 +/- 14.3 micrograms/ml) in 1/4 hour, then declined with half-lives of 1.27 to 5.19 hours (mean 2.28 +/- 1.56 hours), and were 3.6 to 16.9 micrograms/ml (mean 8.3 +/- 6.0 micrograms/ml) at 6 hours. In the infants, serum concentrations at 1/4 hour were 67.5 to 111.0 micrograms/ml (mean 95.5 +/- 18.0 micrograms/ml); half-lives were 0.64 to 0.94 hour (mean 0.81 +/- 0.13 hour); and the serum concentrations at 6 hours were 0.2 to 1.1 micrograms/ml (mean 0.7 +/- 0.4 micrograms/ml). Mean peak serum concentrations in the neonates tended to be lower than those in the infants, but higher than those in children. Regarding the age differences of serum concentrations due to age in the neonates, their peak levels tended to be lower in younger ones. Half-lives were shorter in older subjects and, in early infancy, approached values observed in children. Urinary recovery rates in the first 6 hours after intravenous administration ranged from 43.6 to 87.5% (mean 61.6 +/- 14.6%) in the neonates and from 52.1 to 90.8% (mean 78.0 +/- 15.1%) in the infants. Thus, recovery rates were high even in younger subjects and tended to be higher in older subjects. 2. CMX was administered to 27 neonates and 4 infants to investigate its clinical effect, bacteriological effect and side effects. Clinical efficacy ratings of the drug in 19 neonate cases that could be evaluated (1 with purulent meningitis, 2 with suspected septicemia, 1 with acute bronchitis, 12 with acute pneumonia, 1 with impetigo, 1 with periumbilical abscess and 1 with acute pyelonephritis) were "excellent" in 14 cases, "good" in 4, and "poor" in 1. The efficacy rate covering "excellent" and "good" was 94.7%. In 4 infants (2 with acute pneumonia, 1 with periumbilical abscess and 1 with acute pyelonephritis), "excellent" was obtained in 2 cases and "good" in 2 cases. Thus, all the cases showed "good" or higher ratings. Bacteriologically, 1 strain of Staphylococcus aureus and 3 strains of Escherichia coli in neonates were eradicated while, in infants, 1 strain of S. aureus persisted but 1 of E. coli was eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine Transaminase↗

[A study on hemolysis in hemodialysis patients].

In order to investigate the pathogenesis of hemolysis in chronic renal failure, red cell life span and hemolysis starting point (HSP) by coil planet centrifuge method were studied in 32 hemodialysis (HD) patients and 16 healthy subjects. Mean red cell life span was 22.0 days before recombinant human erythropoietin (r-HuEPO) therapy, and prolonged up to 28.1 days after r-HuEPO therapy. Mean HSP in HD patients was significantly elevated than healthy subjects. Mean HSP was 106.7 mOsm before r-HuEPO therapy, and improved to 101.0 mOsm after r-HuEPO therapy. HSP improved from 106.8 mOsm to 100.8 following the correction of bicarbonate level with HD. HSP was negatively correlated to bicarbonate level pre- and post-r-HuEPO therapy, but HSP was not correlated to BUN, serum creatinine, hydrogen ion, anion gap and amount of body water removal during HD. When blood PH in 18 HD patients was adjusted by 7% NaHCO3 from 7.21 to 7.40, HSP improved to normal range in all. These data suggested that osmotic fragility was normal in younger erythrocyte in HD patients, and a decrease of plasma bicarbonate level resulted in an increase of hemolysis.

Adult↗

Imaging diagnosis of bile duct cystadenocarcinoma.

Two patients with surgically resected biliary cystadenocarcinoma are presented. Both were asymptomatic and the cancer was incidentally found by ultrasonography (US). In the first case, a huge multilocular tumor (21 X 15 cm in diameter) having many papillary projections and septa within it and small daughter lesions occupied both the right anterior and left medial areas of the liver. They were clearly demonstrated on US and computed tomography (CT). Angiography disclosed tumor vessels in some area of the lesion, these features strongly suggested cystadenocarcinoma. The second case had a solid mass (7 X 7 cm) in the left hepatic lobe, in which many septal structures within the lesion were seen on enhanced CT and light dot like stains were recognized on angiography. The former findings coincided with the internal gross feature of the resected specimen. Both patients are doing well 8 months and 1 year and 6 months after operation, respectively.

Aged↗

Properties and localization of the anterior semicircular canal-activated vestibulocollic neurons in the cat.

Unit activities of secondary vestibular neurons that selectively responded to stimulation of the anterior semicircular canal nerve (ACN) were recorded extracellularly in the anesthetized cat. Axonal pathways and projections in the spinal cord of the ACN-activated neurons were examined by recording their antidromic responses to stimulation of the lateral and medial vestibulospinal tracts (LVST and MVST), and the bilateral neck extensor motoneuron pools in the C1 segment (C1 dorsal rami [DR] motoneuron pools). In order to determine whether the neurons had ascending axon collaterals to the extraocular motoneurons, the contralateral (c-) inferior oblique (IO) motoneuron pool was also stimulated. Twenty-seven neurons sent their axons to the ipsilateral (i-) C1DR motoneuron pool via the LVST without any projection to the extraocular motoneuron pool. All the cells except one were located in the ventral part of the lateral vestibular nucleus. This pathway produced monosynaptic EPSPs with short time-to-peak and short half-width in C1DR motoneurons (16/16 motoneurons). Eight neurons sent axons to the i-C1DR motoneuron pool via the MVST without any to the extraocular motoneuron pool. Cell somata were located in the descending nucleus or in the ventral part of the lateral nucleus. These neurons did not produce postsynaptic potentials (PSPs) in any C1DR motoneurons. All thirty-five neurons sending axons to the c-C1DR motoneuron pool have ascending axon collaterals to the c-IO motoneuron pool.

Action Potentials↗

Axonal trajectories of posterior canal-activated secondary vestibular neurons and their coactivation of extraocular and neck flexor motoneurons in the cat.

Unit activities of 148 secondary vestibular neurons related to the posterior semicircular canal were recorded extracellularly in anesthetized cats. Axonal projections of these neurons were examined by their antidromic responses to stimulation of the excitatory target motoneurons of the contralateral (c-) inferior rectus muscle (IR) and bilateral (bi-) motoneuron pools of longus capitis muscles, neck flexors, in the C1 segment (C1LC). The neurons were classified into 4 groups according to their axonal projections. The first group of neurons, termed vestibulo-oculo-collic (VOC) neurons, sent axon collaterals both to the c-IR motoneuron pool and to the c-C1LC motoneuron pool. The majority of them (72%) were located in the descending nucleus. The second group of neurons were termed vestibuloocular (VO) neurons and sent their axons to the c-IR motoneuron pool but not to the cervical cord. Most of them (86%) were located in the medial nucleus. The third group of neurons, termed vestibulo-collic (contralateral) (VCc) neurons, sent axons to the c-C1LC motoneuron pool via the contralateral ventral funiculus but not to the oculomotor nuclei. They were mostly (75%) found in the descending nucleus. The last group of neurons were vestibulo-collic (ipsilateral) (VCi) neurons, which gave off axons to the ipsilateral (i-) C1LC motoneuron pool via the ipsilateral ventral funiculus but not to the oculomotor nuclei. One of them also sent an axon collateral to the c-C1LC motoneuron pool. The majority of them (74%) were located in the ventral part of the lateral nucleus. It was also observed in some of the VOC and VCi neurons that they produced unitary EPSPs in the c-C1LC and i-C1LC motoneurons, respectively. Their synaptic sites were estimated to be on the cell somata and/or proximal dendrites of the motoneurons.

Animals↗