The microvasculature of the cerebral white matter: arteries of the subcortical white matter

The microvascular architecture of the human cerebral subcortical white matter was studied. Most of the subcortical arteries ran straight through the cortex, but upon entering the white matter, they began to coil, loop, and spiral. Vascular stains showed wide spaces between the adventitial sheaths and blood vessels. The blood vessels coiled, looped, and spiraled within these wide adventitial spaces. This phenomenon was observed in the brains from persons ranging from the first to ninth decades of life and there were no statistically significant age-related correlations. Furthermore, there was no evidence of a reduction in the volume of white matter after fixation. Therefore, the observed tortuosity does not appear to be the result of shrinkage of brain tissue following fixation. While the mechanisms responsible for the subcortical arteries circuitry remain undetermined, this coiling architecture may serve as a trap for tumor cells and microorganisms passing through the blood stream, suggesting that these coiling arterial blood vessels may play a significant role in the pathogenesis of tumor metastasis and the brain abscess that frequently occurs in the gray-white matter junction.     

Effects of oral befunolol on heart rate and systolic blood pressure during submaximal exercise in man

For the purpose of determining exercise intensity required for evaluating the effect of beta-blocking agents, the multi-stage treadmill exercise was carried out up to intensity of 85% of maximal oxygen intake (VO2max) after administration of beta-blocking agents in 7 healthy men. To obtain a stable dose response in the inhibitory effect of beta-blocking agents on heart rate (HR) and systolic blood pressure (S-BP), the exercise intensity more than 65% of VO2max (75% of maximal heart rate) was needed. In order to evaluate the effect of befunolol (BFE), a submaximal treadmill exercise of 75% of the age adjusted predicted maximal heart rate was loaded in 6 healthy men at 1.5, 4, and 8 hours following a single oral administration of 10 mg, 20 mg or 40 mg of BFE and 20 mg or 40 mg of propranolol. Simultaneously, the plasma concentration of BFE was determined 1.5, 4, 6 and 8 hours after the administration of BFE at each dose. In human serum, BFE was detected together with its metabolite, revealing a significant correlation between BFE and metabolite (r = 0.94, p < 0.001). Almost a certain rate of metabolite (4--5 times) was detected against BFE. As for the biological half life, it was 1.79 +/- 0.13 hours with BFE and 3.67 +/- 1.33 hours with metabolite. The inhibitory effect of BFE on HR and S-BP during exercise exhibited a dose response with the oral dose and its plasma concentration, and was almost twice as much as that of propranolol at the same dose. Accordingly, the myocardial oxygen consumption which may be represented as rate pressure product was inhibited twice as much as propranolol. BFE is characteristic of its more rapid elimination of its effect compared to the other beta-blocking agents. The decrease in the inhibitory effect of BFE or HR during exercise was about 1.8 times quicker than that of propranolol.     

Development of enrofloxacin ELISA using a monoclonal antibody tolerating an organic solvent with broad cross-reactivity to other newquinolones

Antibacterial reagents, especially quinolones, are widely used in animals and humans, and have caused serious problems to human health because of their residual contaminants in food. In order to screen for different kinds of newquinolones at the same time, a sensitive and specific enzyme-linked immunoassay (ELISA) has been developed. The anti-enrofloxacin monoclonal antibody was selected because of its ability to react with structurally related newquinolones in organic solvent. The antibody has 100% cross-reactivity with norfloxacin, ciprofloxacin and other newquinolones at 50% inhibition of control values IC₅₀, but not with nitroflazone, sulphadimethoxine. The lowest detection limit of this ELISA was 0.7 ng/ml (ppb) when enrofloxacin was used as the calibrator. Eel extracts were spiked with enrofloxacin and the average recoveries at 10, 50, 100 ng/ml were 98, 102 and 91%, respectively. The proposed ELISA is a useful method for the practical microquantitation of various newquinolones in biological and environmental specimens.     

Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays

Recent reports indicate that copy number variations (CNVs) within the human genome contribute to nucleotide diversity to a larger extent than single nucleotide polymorphisms (SNPs). In addition, the contribution of CNVs to human disease susceptibility may be greater than previously expected, although a complete understanding of the phenotypic consequences of CNVs is incomplete. We have recently reported a comprehensive view of CNVs among 270 HapMap samples using high-density SNP genotyping arrays and BAC array CGH. In this report, we describe a novel algorithm using Affymetrix GeneChip Human Mapping 500K Early Access (500K EA) arrays that identified 1203 CNVs ranging in size from 960 bp to 3.4 Mb. The algorithm consists of three steps: (1) Intensity pre-processing to improve the resolution between pairwise comparisons by directly estimating the allele-specific affinity as well as to reduce signal noise by incorporating probe and target sequence characteristics via an improved version of the Genomic Imbalance Map (GIM) algorithm; (2) CNV extraction using an adapted SW-ARRAY procedure to automatically and robustly detect candidate CNV regions; and (3) copy number inference in which all pairwise comparisons are summarized to more precisely define CNV boundaries and accurately estimate CNV copy number. Independent testing of a subset of CNVs by quantitative PCR and mass spectrometry demonstrated a >90% verification rate. The use of high-resolution oligonucleotide arrays relative to other methods may allow more precise boundary information to be extracted, thereby enabling a more accurate analysis of the relationship between CNVs and other genomic features.     

Mechano-active scaffold design of small-diameter artificial graft made of electrospun segmented polyurethane fabrics

To fabricate a "mechano-active" tubular scaffold of nonwoven mesh-type small-diameter artificial graft made of the synthetic durable elastomer, segmented polyurethane, the fabrication technique of electrospinning on a mandrel under a high rotation speed and transverse movement was used. Emphasis was placed on how the rotation speed of the mandrel and the fusion or welding states of fibers at contact points affect the compliance (ease of intraluminal pressure-dependent circumferential inflation) and Young's modulus determined by uniaxial stretching in the longitudinal and circumferential directions. The results showed that a high rotation speed is attributed to exhibit isotropic mechanical properties in the entire range of applied strain but reduces the compliance, and a high fusion state, which is produced using a mixed solvent with a high content of high-boiling-point solvent, reduces the compliance but is expected to exhibit high durability in a continuously loaded pulsatile stress field in an arterial circulatory system.     

Thrombocytosis in preterm infants: a possible involvement of thrombopoietin receptor gene expression

Transient thrombocytosis is commonly observed in preterm infants after birth, but its physiological mechanism is still unknown. To understand the mechanism of the transient thrombocytosis in preterm infants we firstly evaluated a correlation between platelet counts and thrombopoietin (TPO) levels in preterm infants and next c-mpl mRNA levels on platelets in healthy preterm infants longitudinally during a half-year of life. The mean platelet counts in 45 very low birth weight infants (mean gestational age 27.4±1.8 weeks, mean birth weight 1047±249 g) was 230±71×10⁹/l just after birth and thereafter gradually increased to 579±178×10⁹/l by 5 weeks of age. The platelet counts continued this level for about next 8 weeks. Serum TPO levels soon after birth and at 1 month of age were significantly higher than those at the age of 2–6 months. There was a significant negative correlation between platelet counts and serum TPO values. The c-mpl expression levels on platelets at birth and at 1 month of age tended to be lower than those on platelets from adults, and the c-mpl levels gradually increased through 6 months of age, although they were still lower than those of adults. Our results suggest that low expression of TPO receptor on platelets until 1 month after birth cause a decreased TPO clearance and keep a high level of free TPO in blood, thereby promoting platelet production from megakaryocytes or their progenitors in bone marrow, resulting in the subsequent thrombocytosis in preterm infants.     

Mucinous cystadenoma of the appendix with raised serum carcinoembryonic antigen concentration: clinical and pathological features.

A case of mucinous cystadenoma mimicking ovarian cancer is reported. Serum carcinoembryonic antigen (CEA) concentration was raised, and computed tomography of the abdomen and pelvis demonstrated a long oval shaped cystic mass measuring 9 cm in length on the right anterior side of the uterus. Because of possible right ovarian cancer, laparotomy was performed and the mass was found to be a mucinous cystadenoma of the appendix. This case indicates that mucinous cystadenoma of the appendix may show an unusual presentation including its location as well as the high serum CEA, mimicking ovarian cancer. Therefore, gynaecologists as well as gastroenterologists should consider its possibility as a differential diagnosis of the right adnexal mass in a patient without previous appendectomy.     

Effects of growth hormone treatment on thyroid function in pediatric patients with Prader–Willi syndrome

It is unclear whether hypothyroidism is present in patients with Prader–Willi syndrome (PWS). This study aimed to clarify the state of the hypothalamic–pituitary–thyroid axis and the effects of growth hormone (GH) treatment on thyroid function in pediatric patients with PWS. We retrospectively evaluated thyroid function in 51 patients with PWS before GH treatment using a thyroid‐releasing hormone (TRH) stimulation test (29 males and 22 females; median age, 22 months). We also evaluated the effect of GH therapy on thyroid function by comparing serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels at baseline, 1 year, and 2 years after GH therapy. TSH, fT4, and fT3 levels were 2.28 μU/ml (interquartile range [IQR]; 1.19–3.61), 1.18 ng/dl (IQR; 1.02–1.24), and 4.02 pg/dl (IQR; 3.54–4.40) at baseline, respectively. In 49 of 51 patients, the TSH response to TRH administration showed a physiologically normal pattern; in two patients (4.0%), the pattern suggested hypothalamic hypothyroidism (delayed and prolonged TSH peak after TRH administration). TSH, fT4, and fT3 levels did not change significantly during 1 or 2 years after GH treatment. The TSH response to TRH showed a normal pattern in most patients, and thyroid function did not change significantly during the 2 years after initiating GH treatment.