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Biomedical subjects

Y Kikuchi

Publications and source records attributed to Y Kikuchi.

At least 883 records · Page 49Linked to original sources

Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals.

The pharmacokinetics of YM09330, a new semisynthetic cephamycin, were determined after intravenous and intramuscular administration to experimental animals. Mean plasma levels of YM09330 at 30 min after intravenous administration of 20 mg/kg were 5.5 micrograms/ml for mice, 17 micrograms/ml for rats, 24 micrograms/ml for rabbits, 42 micrograms/ml for dogs, and 76 micrograms/ml for monkeys; plasma half-lives were 13.0, 15.9, 30.5, 55.5, and 75.6 min, respectively. The half-lives of YM09330 were longer than those of cefmetazole in all species tested. In monkeys, plasma levels of YM09330 were higher and more prolonged than those of cefazolin. In rats and dogs, the concentrations of YM09330 were highest in the kidneys, followed by the liver, plasma, lung, spleen, and heart in that order; they were similar to those of cefazolin in rats. Urinary excretion of YM09330 within 48 h of intravenous administrations was 67% of the dose in mice, 52% in rats, 74% in rabbits, 53% in dogs, and 60% in monkeys. In rats, 48% of the dose of YM09330 was detected in the plasma, urine, or bile. However, small amounts of an antibacterially active tautomer of YM09330 were recovered in the urine of mice, rats, and dogs, whereas large amounts of the tautomer were recovered in the urine of rabbits and monkeys. Serum protein binding of YM09330 was 30% of rats, 51% for rabbits, 39% for dogs, 87% for monkeys, and 91% for humans.

Animals↗

Continuous measurement of coronary artery diameter in situ.

The diameter of the coronary artery was measured in dogs in situ by an ultrasonic dimension gauge using 10-MHz piezoelectric crystals. Underestimation in measurements due to crystal rotation was limited to < 1% by adding a convex lens to the crystal. A pair of small 10- and 5-MHz crystals were sutured to the adventitia of the left circumflex coronary artery (LCX) and the descending aorta (Ao), respectively. Using cuff occluders for vessel constriction of the inferior vena cava (IVC) or the Ao, curvilinear relationships between pressure and diameters were obtained. Phasic changes of the aortic as well as coronary diameter were grossly similar to changes in the pressure wave. After intravenous administration of dipyridamole, aortic pressure (AP) decreased by 17% along with 3% decline of the Ao and LCX diameter, however, after nitroglycerin given by the same route, LCX diameter increased by 5% (P < 0.05) despite 16% and 2.3% reductions in AP and Ao diameter, respectively. This ultrasonic technique, which allows continuous measurement of the diameter of small vessels, should provide a new tool for the study of coronary circulation.

Animals↗

Reelevation of ST segment on precordial mapping in natural time course following acute anterior myocardial infarction.

Serial recordings of ST segment mapping were performed in 15 patients with acute anterior myocardial infarction. Reelevation of ST segment was observed in all cases between 12 hours and one week after infarction without clinical evidence of reinfarction. There was significant correlation between the magnitude of the sum of ST reelevation (sigma ST) and time to the peak of ST reelevation. The higher was sigma ST at the peak, the later was the appearance of the peak of ST reelevation. sigma ST recorded between 24 and 72 hours after infarction correlated with the extent of abnormal Q (NQ) in the precordial mapping as well as the percent of abnormally contracting segment (%ACS) on left ventricular angiography examined after 4 weeks following infarction. However, there was no correlation between sigma ST recorded at 12 hours after infarction and NQ studied at 4 weeks after infarction. The results indicate that the magnitude of sigma ST changes in time during the course after infarction and that the time of recording is important when sigma ST is used for the estimation of infant size. Reelevation of ST segment should be considered in the study of therapeutic intervention in acute myocardial infarction.

Adult↗

Transvascular osmotic flow reflected by changes in plasma oncotic pressure of anesthetized dog.

To assess overall bodily transvascular fluid flow due to osmotic imbalance between blood and interstitial fluid during or after addition of hypertonic saline, sugar-, albumin- and dextran solutions or CO2 mixture to blood, arterial blood colloid osmotic pressure (COP) of anesthetized dogs was continuously measured with a needle-type colloid osmometer. Plasma volume change (delta Vp) was estimated from the changes in either the equivalent albumin concentration (C) or the albumin concentration equivalent to plasma COP, which was well confirmed in inanimate model experiments. Carbon dioxide inhalation caused RBC swelling (1.5% volume increase/10 mmHg of PCO2). Intravenous injection of hypertonic solutions resulted in transient osmotic flow (8.5 +/- 2.2 ml/g of solute per kg of animal weight by NaCl, and 1.7 +/- 0.4 by glucose), and albumin and dextran also induced fluid flow (1.3 +/- 0.4 by albumin and 2.2 +/- 0.7 by dextran), which depended on van't Hoff's law and reflection coefficient of solutes.

Animals↗

Role of protein adsorption in micropore passability of red blood cells.

Micropore passability of fresh human blood was measured by means of an improved Nuclepore membrane filter method under varying concentrations of electrolytes and proteins in the plasma. The method gives an average pore passage time required for single red blood cells to flow through 5 micrometers pores of the filter membrane. Micropore passability is reduced with increasing ionic osmolarity above 320 mOsM when the protein concentration is normal However, it remains constant up to 370 and 430 mOsM when the protein concentration is lowered to 1/3 and 1/6 of normal, respectively. Furthermore, when red blood cells are added to an hyperosmotic plasma, the protein concentration detectable in the plasma is reduced to a level lower than expected from a simple osmotic water shift. The excess reduction in the protein concentration is nearly proportional to the amount of added red blood cells. The following succession of events was assumed in order to interpret these results. An electric repulsive force between red blood cells and plasma proteins is weakened by an increased ion concentration. This reduction in this repulsive force will increase the adsorption of proteins on the surfaces of the red blood cells. The adsorbed proteins will restrict cell membrane flexibility, causing a reduced micropore passability of red blood cells.

Blood Proteins↗

Cerebral atherosclerosis in Japanese part 6: the interaction of plasma lipoproteins with glycosaminoglycans isolated from the cerebral arteries and aortas.

The binding to plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) of chondroitin sulfate (CS) and heparin sulfate (HS), isolated from cerebral arteries and aortas, was studied. The binding of CS to LDL was higher than that of HS and neither bound to HDL. CS from cerebral arteries contained a higher percentage of iduronic residues (IDUA-Ga1NAc 4S) and a lower percentage of G1cUA-Ga1NAc 4S, and bound more strongly to LDL than CS from aortas. Our results suggest a strong dermatan sulfate (DS) activity on binding to LDL.

Aorta↗

Effects of 2-nicotinamidethyl nitrate (SG-75) and/or nitroglycerin on systemic hemodynamics and coronary blood flow in conscious dogs.

The effect of 2-nicotinamidethyl nitrate (SG-75), a newly synthesized nitroester, on hemodynamics and coronary circulation was studied in conscious dogs, comparing it with nitroglycerin (NG). Dogs were previously instrumented with catheters in the aorta and left atrium and a Doppler flow probe on the left circumflex coronary artery. Percent increases in coronary flow rate were 11 (10 micrograms/kg), 20 (50 micrograms/kg), 71 (100 micrograms/kg) and 169% (200 micrograms/kg) in SG-75 and 3 (1 microgram/kg), 28 (5 microgram/kg), 65 (10 micrograms kg) and 99% (20 micrograms/kg) in NG, thus the dose ratio for an equivalent increase in mean coronary flow is about 10:1 between SG-75 and NG. The duration of coronary flow increase was also dose dependent and 2.1 min in 200 micrograms/kg SG-75 and 1.3 min in 20 micrograms/kg NG. Comparable changes in heart rate increase and pressure reduction were noted both in SG-75 and NG. The peculiar difference between two drugs was their time course of coronary flow increase: SG-75 showed monophasic increase while NG showed bipeaked increase in flow. The results suggest that the reflex increase in heart rate elicited by pressure drop after SG-75 did not influence the envelope of coronary flow increase such as observed upon NG administration.

Animals↗

Effects of dilazep on regional myocardial blood flow during selective coronary hypotension.

Effects of 1,4-bis-[3-(3,4,5-trimethoxybenzoyloxy)-propyl]-perhydro-1,4-diazepine (dilazep), a powerful coronary dilator via adenosine potentiation, on regional blood flow during acute selective coronary hypotension were studied in the canine heart under anesthesia and thoracotomy. The proximal left circumflex coronary artery (LCX) was partially obstructed and mean LCX pressure distal to obstruction was reduced to 40-45 mmHg and two different doses of dilazep were given i.v. The left ventricular free wall and interventricular septum were divided into normally perfused, borderline ischemic, moderately ischemic and severely ischemic area according to the level of regional myocardial blood flow measured by tracer microspheres. 50 microgram dilazep/kg b.w. increased myocardial flow in the normally perfused and borderline ischemic areas without a significant alteration of blood flow to the moderately and severely ischemic areas. The fall of aortic pressure was more striking in dogs receiving 100 microgram dilazep/kg b.w. than in animals with 50 microgram dilazep. 100 microgram dilazep increased flow in the normally perfused area, but increased the number of segments in the moderately and severely ischemic area. These results indicate that an appropriate dose of dilazep causing a slight reduction of aortic pressure increased flow to the borderline ischemic as well as normally perfused myocardium in selective coronary hypotension.

Animals↗

[Study on uterine peroxidase as a specific marker of estrogen-dependence in rat (author's transl)].

Uterine Peroxidase (UP) can be induced by the administration of estradiol (E2) in the rat. We studied whether this biochemical parameter can be a specific marker of estrogen-dependence of rat uterus. 1. UP content in both immature castrated mature rat uteri was negligible. Whereas UP could be detected after vaginal openning of intact rats. 2. UP induction by E2 administration was first detected at 15-day-old rat uteri. 3. UP induction by E2 or mare serum gonadotropin was detected in both immature and castrated mature rats with the increase of uterine weight. 4. UP induction by E2 was observed only in estrogen-dependent tissues, such as uterus and vagina. 5. UP induction by E2 was prominently suppressed by the treatment with actinomycin-D, cycloheximide and tamoxifen. These results suggest that UP induction by E2 is an useful specific marker when hormone-dependence of rat uterus is investigated.

Aging↗

[A case report of a primary pure squamous cell carcinoma of the stomach associated with dermatomyositis (author's transl)].

A 54-yr-old man was admitted to Hokkaido University Hospital, complaining of fever, multiple arthralgia, edematous erythema and face and muscular weakness of extremities during the last 2 months. He was diagnosed as dermatomyositis by acceleration of ESR, elevation of GOT, GPT, CPK, aldolase, moderate increases of collagen fibers in biopsy specimen of skin and his clinical signs. Although stools were positive for occult blood, the routine radiographic examination failed to detect the bleeding site in the upper GI. tract. However, in the double contrast picture of the stomach, a very fine abnormal linear shadow was observed at the upper corpus of the lesser curvature. This linear shadow was a margin of the tumor, retrospectively. About 4 months later, abnormal pain occurred and a mass was palpable in the left lumbar region, suggesting a pancreatic tumor. He was operated on excising the tumor, but was performed only exploratory laparotomy because of the presence of intra-abdominal metastases. Death occurred 40 days after the operation and necropsy was done. The gross anatomical findings of the abdomen showed a stomach tumor as large as an infant's head and its metastases to pancreas, lymph nodes, and greater and lesser omentum. Esophageal mucosa including esophagocardiac junction was intact. Histological examination of the intragastric tumor revealed a typical squamous cell carcinoma with keratinization. According to the absence of the components of adenocarcinoma and squamous metaplastic gastric mucosa of non-cancerous areas in the stomach, it seemed likely to be a heterotopic squamous cell carcinoma. It was unknown about the precedence between the stomach cancer and dermatomyositis. There have been 11 cases of primary pure squamous cell carcinoma in the world literature since 1968, but this is the first case report of coexistence of these two diseases.

Carcinoma, Squamous Cell↗

Histogenesis of yolk sac carcinoma induced by fetectomy in the rat.

Pregnant rats whose fetuses were removed on the 12th day of gestation developed tumors dysontogenetically. Out of 127 operated rats, 103 rats gave rise to tumors, which were histologically yolk sac carcinomas (52 cases), adenocarcinomas (34 cases), choriocarcinomas (8 cases) and teratomas (74 cases). Induction of malignant tumors was dependent on the male rats used for mating and the time of fetectomy. Killing of primordial germ cells by low-dose irradiation before fetectomy decreased the occurrence of tumors. These findings indicate that malignant tumors, including yolk sac carcinoma, might be of germ cell origin.

Adenocarcinoma↗

[Serum ferritin levels in patient with gynecological malignancy--especially the judgement of therapeutic response and the monitor during the post-therapeutic follow-up period (author's transl)].

Serum ferritin levels in patients with gynecological malignancy were measured by radioimmunoassay and in addition CEA, AFP and CRP were measured simultaneously. No samples had elevated values more than 200 ng/ml in none malignancy. The serum ferritin levels was elevated (greater than 200 ng/ml) in many patients with advanced cervical cancer and its recurrence, while early stage were almost within normal ferritin range. Patients with ovarian cancer showed normal ferritin levels, but its recurrence showed almost within normal levels than other groups. Serial measurements of serum ferritin showed a fall in patients who responded to radiation therapy or chemotherapy. In patients with tumor progression during therapy, ferritin values increased. The highest ferritin levels were found in patients with the time of recurrence and death. Ferritin levels showed low values in 5 cases of ovarian cancer without symptoms of recurrence on follow-up over 18 months. No correlation was found between ferritin and CEA or AFP levels in different patients except some cases. These results suggest that determination of serum ferritin may be useful to detect recurrence and to monitor the result of treatment.

Adult↗

Left atrial ball thrombus diagnosed by two-dimensional echocardiography.

The diagnosis of the ball thrombus in the left atrium has been very difficult by conventional clinical techniques. In the present case, two-dimensional echocardiography successfully demonstrated a spherical tumor moving in unpredictable directions in the left atrium. M-mode echocardiography did not clearly identify the tumor because of the limited visual width and spatial orientation of the technique; however, simultaneous recordings of the M-mode echocardiogram with phonocardiogram, carotid pulse wave, and electrocardiogram provided some diagnostic clues to the occlusive left atrial tumor. In the absence mitral valve occlusion by the tumor, a logarithmic correlation between the ejection time and the preceding R-R interval, and a negative lines correlation between Q to the first sound interval and the preceding R-R interval were found. In the beat following the appearance of the tumor in the mitral orifice, the sudden shortening of the ejection time and the prolongation of Q to the first sound interval were noted. Both of these findings are indirect evidence of decreased left ventricular filling associated with an elevated left atrial pressure resulting from the sudden mitral orifice obstruction by the tumor. Detailed analysis of the data obtained by the conventional noninvasive techniques could provide critical clues for the diagnosis of the occlusive left atrial tumor.

Blood Coagulation↗

A comparison of diameters of micronuclei induced by clastogens and by spindle poisons.

To compare the size of micronuclei induced by clastogens and by spindle poisons, bone-marrow smears were prepared 24 h after a single intraperitoneal injection of triethylenemelamine (TEM) (0.3 mg/kg) or vincristine (VCR) (0.125 mg/kg) into male mice. 100 micronucleated erythrocytes (MNEs) were randomly selected from each group and photomicrographed. Diameters of the cytoplasm (D) and the micronucleus (d) of each MNE were measured on the photographs. Relatively large micronuclei (d greater than or equal to D/4) were frequent (74%) in the VCR-treated group, and infrequent (2%) in the TEM-treated group. The frequencies of MNEs resulting in d greater than or equal to D/4 were determined for several other mutagens. All clastogens tested could be classified as TEM type, and all spindle poisons as VCR type. These findings indicate that it is possible to analyze the action site of micronucleus-inducing agents on the basis of the relative sizes of micronuclei.

Animals↗