[Heredity of diabetes in a family].
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Biomedical subjects
Publications and source records attributed to T Miyake.
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Scanning electron microscopy of vascular casts prepared by arterial injections of intentionally reduced amounts of resin showed that in the rat pancreas, the casting medium fills blood capillaries in the endocrine islets more promptly than those in the exocrine lobules and secretory ducts. Furthermore, the exocrine lobules containing endocrine islets allowed a more rapid resin flow through the insulo-acinar portal route than those lobules lacking an islet. The capillaries of secretory ducts were the last portions to be filled with resin. Since the resin used in this study was as viscous as blood and injected under a physiological pressure, the microcirculatory patterns demonstrated by the present method reflect the physiological flow pattern of blood in the pancreas.
We examined the hemodynamic changes induced by transient splenic arterial occlusion using a balloon catheter to investigate the hemodynamic effect of transcatheter splenic arterial embolization--a procedure that has been used since its introduction in 1973 as therapy for hypersplenism and more recently for portal hypertension. The blood flow volume was measured in 20 patients with liver disease using an ultrasonic duplex system (Toshiba SAL50A/SDL-01A). The portal venous pressure was also measured via a 3F catheter using a transducer. The catheter was placed in position by substituting it for a 25-gauge needle that had been inserted into the portal vein under ultrasonic guidance percutaneously and transhepatically. Splenic arterial occlusion caused a drop in splenic venous blood flow from 708 +/- 487 to 241 +/- 155 ml per min, in portal venous blood flow from 993 +/- 439 to 807 +/- 419 ml per min and in portal venous pressure from 17.4 +/- 7.2 to 14.4 +/- 6.1 mm Hg. The latter two reductions were less than expected from the decrease in the splenic venous blood flow volume. This phenomenon was caused by an increase in the mesenteric venous blood flow from 475 +/- 126 to 630 +/- 270 mm per min. This increase may be due to a compensatory mechanism under the control of a regulatory loop in the liver or portal vein, and there seems to be a relationship between splenic and intestinal circulation in portal hypertension that maintains hepatic circulation.
Evaluation of pulmonary arterial pressure is essential for the diagnosis and management of patients with congenital heart disease; it is usually done by cardiac catheterization. An alternative, noninvasive method may be clinically more useful. The purpose of this study was to assess the usefulness of the noninvasive determination of systolic pressure of the pulmonary artery and right ventricle by contrast-enhanced Doppler echocardiography. We selected 30 pediatric patients (28 with trivial or nonsignificant tricuspid regurgitant Doppler signals and 2 with significant tricuspid regurgitant Doppler signals) aged 2 months to 21 years. The flow velocity of tricuspid regurgitation was measured with continuous-wave Doppler of the right ventricular inflow view or left parasternal or apical four-chamber view before and after injection of two types of contrast medium (hand-agitated 5% glucose or sonicated albumin). The systolic pressure of the pulmonary artery was assessed as the estimated right ventricular systolic pressure (albumin method) minus the peak pressure gradient across the pulmonary valve (nonenhanced Doppler method). After injection of hand-agitated 5% glucose and sonicated albumin, trivial tricuspid regurgitation signals were enhanced in 25 of 28 patients (89%). In two patients, spectral envelopes were well defined enough to obtain the peak systolic velocity of the tricuspid regurgitation jet without contrast medium injection. Peak velocity was not altered by injection of contrast medium in these patients. There was significant correlation between the estimation by contrast-enhanced Doppler using hand-agitated 5% glucose and the cardiac catheterization measurement of the transtricuspid pressure gradient (r = 0.88). The transtricuspid pressure gradients obtained by continuous-wave Doppler during sonicated albumin enhancement corresponded closely to those measured by cardiac catheterization (r = 0.95). Pulmonary arterial and right ventricular systolic pressures measured by Doppler using sonicated albumin and those obtained by cardiac catheterization were highly correlated (right ventricle, r = 0.96; pulmonary artery, r = 0.95). In conclusion, this technique may be a valuable noninvasive method for determining accurate right ventricular and pulmonary arterial systolic pressures.
OBJECTIVES: The aim of this article is to examine the frequency, timing of formation of aneurysm of the ventricular membranous septum (AVMS), and prognosis in patients with a perimembranous ventricular septal defect (VSD). PATIENTS: One hundred forty-eight patients were diagnosed with a perimembranous VSD within 90 days after birth. They were classified into three groups: Group I, spontaneous closure; Group II, open; Group III, surgical closure. They were also divided into two further groups: 75 patients with congestive heart failure (CHF) and 73 patients without that. METHODS: An AVMS was observed by two-dimensional echocardiography, and spontaneous closure of the VSD was confirmed by color Doppler. RESULTS: An AVMS was formed in 69 (47%) of 148 patients: 50% in Group I, 66% in Group II, 15% in Group III. The timing of AVMS formation was at a median age of 6 months. In 14% of patients, AVMS was formed within 3 months of age. The frequency of AVMS at the time of the initial echocardiogram was low in patients with CHF (odds ratio, 3.23; 95% confidence interval, 1.19-8.79 p = 0.017). CONCLUSIONS: We believe that AVMS formation is related to avoidance of surgical closure during early infancy in patients with a perimembranous VSD, because the frequency of AVMS during early infancy is low in patients with CHF.
To assess the alteration of myocardial ischemic findings and the role of collateral vessels in patients with Kawasaki disease (KD), we used dipyridamole stress technetium-99m tetrofosmin (Tf) single photon emission computed tomography (SPECT). A comparison study of coronary angiography and dipyridamole stress (0.70 mg/kg) Tf-SPECT was repeated at least twice in 20 patients. The subjects included 7 patients with coronary stenosis, 1 with pre- and post-coronary artery bypass grafting (CABG) due to coronary stenosis, 1 with progression to coronary stenosis, and 11 with persistent coronary aneurysms. In the stenosis group, Tf-SPECT revealed that 6 of the 7 patients had some degree of ischemic findings, and 5 of these 6 did not show any change in their ischemic findings during follow-up. In 1 patient, the ischemic findings changed according to the collateral circulation changes. The patient who underwent CABG had pre-CABG ischemic changes that disappeared after CABG. In the patient whose coronary arteries progressed to stenosis, the ischemic findings progressed as the coronary stenosis progressed. In the persistent aneurysm group, there were no ischemic findings. In the future Tf-SPECT may become one of the most useful methods for monitoring the progressive changes of myocardial ischemia in KD.
Formation and inhibition of malonaldehyde (MA) from blood plasma lipids oxidized by Fenton's reagent in the absence or presence of probucol [4,4'-(isopropylidenedithio)bis(2,6-di-tert-butylphenol)] and L-ascorbic acid were investigated. The amount of MA formed was quantitatively analysed by gas chromatography. L-Ascorbic acid inhibited MA formation by about 30% at the level of 4.0/micromol, but the amount of MA formed was increased by the presence of probucol. When 3.0 micromol oxidized probucol was hydrolysed at pH 1. 3 and 5, 2616.5 nmol, 287.5 nmol and 103.9 nmol MA were recovered, respectively. This is the first report of quantitative analysis of MA formed from probucol on oxidation.
We investigated the role of alpha IIb beta 3 in microparticle generation by normal and thrombasthenic platelets stimulated with collagen plus thrombin. Microparticle generation by normal platelets was scarcely inhibited by monoclonal antibodies for glycoprotein Ib and glycoprotein IX. Although one monoclonal anti-alpha IIb beta 3 antibody (NNKY1-32) partly inhibited microparticle generation, 3 other monoclonal anti-alpha IIb beta 3 antibodies had little effect. However, the combination of 4 monoclonal anti-alpha IIb beta 3 antibodies or treatment with a polyclonal anti-alpha IIb beta 3 antibody significantly inhibited microparticle generation (p < 0.05). Microparticle generation by thrombasthenic platelets also occurred after stimulation with collagen plus thrombin, although at a significantly lower level compared with normal platelets. Monoclonal antibodies for resting alpha IIb beta 3, P-selectin, activated alpha IIb beta 3 and beta 2-glycoprotein I bound to microparticles from healthy platelets. In contrast, only a monoclonal antibody for beta2-glycoprotein I bound to thrombasthenic microparticles. These results suggest that microparticle generation by collagen plus thrombin occurs via two different mechanisms which are dependent and independent of alpha IIb beta 3, respectively. The alpha IIb beta 3-dependent mechanism appears to require activation of alpha IIb beta 3.
To study platelet-derived microparticle generation in diabetes mellitus, we injected alloxan into male Japanese white rabbits. Injection of alloxan induced diabetes, but did not cause any significant change in various biochemical and hematological parameters. However, diabetic rabbits showed a significant elevation of platelet-derived microparticles from 8 weeks after alloxan injection (week 0: 0.45 +/- 0.24%; week 8: 1.12 +/- 0.61%, p < 0.005). These microparticles are known to have prothrombinase activity, suggesting that they may promote vascular complications in diabetes and may be used as a marker of vascular disease.
To evaluate the sensitivity of MR imaging for acute cerebral infarction and the effectiveness of MR enhancement with Gd-DTPA, we created a canine model of cerebral infarction by transarterial embolization (TAE). The external and internal carotid arteries were embolized respectively through a transfemoral catheter. MR imaging was performed with the Yokogawa Medical System prototype superconducting MR machine "Resona" operating at 0.35 Tesla. MR enhancement was done with 0.4 mmol/kg of Gd-DTPA. Early detectability without Gd-DTPA was 60% (3/5) two hours after TAE and 67% (4/6) at three hours. MR imaging showed high-intensity lesions on the T2-weighted sequence (SE 2000/100). The T1-weighted sequence (SR 250-600/25-35) did not reveal any lesions four hours after TAE. Five animals which received Gd-DTPA showed abnormal enhancement in the brain parenchyma within 30 min after Gd injection on the T1 weighted sequence. Gd-DTPA enhancement not only improved early sensitivity for acute cerebral infarction when MR imaging without Gd-DTPA was negative, but also enhanced the size and number of lesions compared with SE 2000/100 images without enhancement. The breakdown of the blood-brain barrier was suggested to be an important factor in Gd-DTPA enhancement.
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A detailed staging table of inbred C57BL/6 embryonic mice was developed to facilitate a study of the stage-by-stage cellular and molecular mechanisms underlying cranial skeletal development and elucidation of the developmental mechanisms potentially involved in evolutionary changes in cranial skeletal morphology exhibited by different inbred strains of mice. Mice were mated for only 2 hr and embryos were recovered every 2 or 4 hr between 11 and 13 days of gestation. Theiler's [1972] stages 18 through 21 were divided into substages and divisions based on the development of five external structures--the frontonasal area, eyes, auditory meatus, mandibular and hyoid auricular hillocks/pinna, and vibrissae--and three internal histological structures--eyes, tongue, and vibrissae. Each substage and division was designated with a decimal point: e.g., substage 20.1 and division 20.11. Embryos were staged using the staging table and the relationship of the substages and divisions with days of gestation was examined. The results showed considerable intra- and inter-litter variation in stages of embryos, suggesting that days of gestation are not a good indicator for staging embryos. Our staging table offers a more reliable and precise method to standardize embryonic development. Regression analyses of substages on days of gestation showed that the duration of stages increased from stages 18 to 21. Estimated durations were 3.5 hr for stages 18 and 19, 8.8 hr for stage 20, and 38.8 hr for stage 21. Our staging table also provides baseline information on development of the frontonasal area (muzzle) and vibrissae and development and the transformation of the auricular hillocks into the pinna. The developmental sequence of mystacial and labial vibrissae indicated highly regulated differentiation and morphogenesis of vibrissal development at stages 20 and 21. Three hyoid auricular hillocks transiently became four hillocks at stage 19.1 before transforming to the pinna during stage 21. The second and third hyoid auricular hillocks were the major contributor to the pinna before stage 21.2, whereas mandibular auricular hillocks contributed to the pinna from stage 21.32 onward. The staging table has already served to demonstrate stage-specific skeletogenesis of the first arch cartilages in inbred C57BL/6 mice and to reveal differences in the onset of timing of skeletogenesis among inbred C57BL/6, C3H/He and CBA/J mice.
Condensation is a multistep process, involving cell recruitment, cell-to-cell contact by cell adhesions, and concomitant changes in cell shape. Condensation of prechondrogenic cells down-regulates and/or inactivates cell proliferation and enhances the activities of cartilage-specific genes. Timing of onset and duration of condensation are thus important regulatory processes mediating cellular and molecular events during chondrogenesis. The present study was undertaken to examine timing of onset and duration of condensation and onset of matrix formation for first arch cartilages in inbred C57BL/6 mice. Because timing can only be reliably assessed in very precisely staged embryos, mice were mated for only 2 hr, pregnancy was determined by weight increase, and embryos were assigned to substages and divisions of Theiler's [1972] stages on the basis of external development of the frontonasal area, eyes, vibrissae, mandibular and hyoid auricular hillocks (pinna) and some internal structures [Miyake et al., 1996]. Condensation and matrix formation were determined using PNA lectin histochemistry, type II collagen immunohistochemistry, Mallory's trichrome, Hall and Brunt's quadruple and toluidine blue stains on serially sectioned embryos, and 3-D reconstruction. A single, continuous, first arch chondrogenic condensation was identified. It consisted of three components: 1) a rostral component for the symphysis; 2) a core component for the major portion of Meckel's cartilage; and 3) a caudal component for the caudo-lateral area of Meckel's cartilage and the two ear cartilages, the malleus and incus. The caudal component was further divided into rostral and caudal subcomponents which gave rise to the malleus and incus, respectively. Cellular arrangement differed among the three components, probably reflecting major axes of matrix growth. The condensation was only weakly recognized by peanut agglutinin lectin (PNA), unless sections were pretreated with neuraminidase, showing the masking effects of sialic acid. The core and caudal components of the condensation appeared at stage 20.12 and ended at stage 21.14 and 21.32, respectively. The symphysial component began at stage 20.2 and ended at stage 21.32. Deposition of sulfated proteoglycans began at stage 21.14 in the core component of the condensation--preceding slightly deposition of type II collagen--and at stage 21.32 in the symphysial and caudal components.
We examined the relationships between litter size, embryonic growth, days of gestation, onset and duration of morphological stages and development of the first arch skeleton in three inbred strains of mice--C57BL/6, CBA/J and C3H/He. Detailed embryonic staging was based on craniofacial development between 11 and 18 days of gestation. Considerable intra- and interlitter variation of morphological stages of embryonic development exists in all three inbred strains. The relationship of morphological stages to days of gestation reveals that each stage has a different duration, being shortest at Theiler's stage 18 and longest at stage 21 in all three inbred strains. Embryos of CBA/J mice tend to reach each stage later than do embryos of the other two strains, i.e., morphological development is slowest in CBA/J. The greatest length, a measurement of embryonic growth, increases at a constant rate during gestation in all three strains. In C57BL/6 and CBA/J, more embryos tend to be implanted in the right horn of the uterus than in the left, whereas in C3H/He an even number of embryos tends to be implanted in both horns. Timing of the development of Meckel's cartilage differs between the three inbred strains: both condensation and onset of matrix deposition begin one stage earlier in C57BL/6 than in CBA/J and C3H/He. On the other hand, alkaline phosphatase, one of the earliest markers for bone development, is expressed at the same time in all three inbred strains. Differences in timing of skeletal development between the strains may be attributed in part to the genealogical closeness OF CBA/J and C3H/He mice.