Glucose uptake by individual skeletal muscles during running using whole-body positron emission tomography

The purpose of this study was to examine, by positron emission tomography (PET), the distribution of [¹⁸F]fluoro-deoxy-glucose ([¹⁸F]FDG) uptake by human muscles during 35?min of running. Thirteen healthy male subjects were studied, seven of whom participated in the exercise study. Running intensity was kept constant such that the subjects' heart rates were maintained at between 140 and 150?beats per minute. [¹⁸F]FDG [62.9 (14.8)?MBq, mean (SD)] was injected after 15?min of running. PET imaging was started immediately after the running ended. The ratio of [¹⁸F]FDG uptake by muscles in runners to that in control subjects (r-c ratio) varied from three to six for the muscles of the foot and leg below the knee joint. The r-c ratio of the medial head of the gastrocnemius (MG) was higher than that of its lateral head (LG). The r-c ratio of the rectus femoris (RF) was lower than that of the other three muscles of the quadriceps femoris (QF). The r-c ratio of inactive muscles located above the waist was approximately 0.7. These results suggest that, during the moderate running of this study: (1) glucose uptake by muscles of the foot and leg below the knee joint clearly increases, (2) the r-c ratio differs significantly among the skeletal muscles, which act synergistically, and (3) glucose uptake by inactive skeletal muscles decreases.     

Freeze-fracture studies of muscle plasma membranes in myopathic patients with hypo-and hyperthyroidism

To examine the influence of thyroid hormone on the skeletal muscle plasma membrane, we analyzed the changes in ultrastructural architecture and membrane area complexed with digitonin of muscle plasma membrane in myopathic patients with hypo-and hyperthyroidism by the conventional freeze-fracture (F-F) technique and F-F cytochemistry using the sterol-specific ligand digitonin. The densities of flask-shaped invaginations, which are mainly thought to correspond to caveolae, intramembranous particles, and orthogonal arrays, and the changes of digitoninreacted membrane areas in the muscle plasma membranes in three patients with hypothyroid myopathy and one patient with both myasthenia gravis and hyperthyroidism were compared with those in age-matched controls. In the conventional F-F study, the muscle plasma membrane of hypothyroid patients showed increased invagination density, whereas that of the hyperthyroid patient was normal ultrastructurally. In the F-F cytochemistry study, however, the ratio of digitonin-reacted membrane areas versus fractured membrane areas was not different between hypothyroid patients and controls, whereas that of the hyperthyroid patient was lowered in comparison with that of control. These results suggest that thyroid hormone may alter the biochemical properties and ultrastructural architecture of muscle plasma membrane.This study was presented at the 29th annual meeting of the Clinical Electron Microscopy Society of Japan, Sapporo, October 2–3, 1997     

Therapy with nebulized beta2 agonists (procaterol) in asthmatic children: pulmonary function and plasma levels after inhalation]

BACKGROUND: Relationship between post administrative changes in plasma drug levels and bronchodilation remains unknown. In this study, we measured plasma levels of procaterol, a beta2-agonist, when being inhaled through nebulizers in children with bronchial asthma to examine relationship between improvement of pulmonary function and the plasma levels. METHOD: Six asthmatic children with the mean age of 9.8 years, inhaled 0.3 ml of 0.01% procaterol solution through a nebulizer. We examined changes in pulmonary function and plasma procaterol levels before and after inhalation. RESULTS: Procaterol was detected in the plasma 2 minutes after inhalation when it already rose to the maximum level, and kept the steady until showing a decline in 30 minutes. The measured highest value was 87.8+/-45.1 pg/ml. FEV 1.0 remarkably increased 2 minutes after inhalation and was maintained until 60 minutes after inhalation. Other lung function parameters also improved. There was no significant change in the heart rate, but serum potassium concentrations significantly dropped in all patients 60 minutes after inhalation. CONCLUSION: Plasma procaterol levels promptly rose to the peak at 2 minutes after inhalation and decreased 30 minutes later. Improvement of pulmonary function started promptly at minutes after inhalation and it became a peak 60 minutes later.     

Intriguing Case: Endolymphatic Stromal Myosis Coexisting with Adenocarcinoma of the Uterus

Carcinosarcoma of the uterine corpus containing endolymphatic stromal myosis (ESM) is extremely rare. This report describes the light- and electron-microscopic findings of ESM coexisting with adenocarcinoma of the uterus in a 58-year-old female. The polypoid tumor originated from the fundus uteri and filled the uterine cavity. In addition to papillary and medullary acinous adenocarcinoma at the apex of the polypoid mass, the major portion of the tumor specimen was composed of cells resembling endometrial stromal cells that infiltrated the myometrium and lymphatic channels, and a diagnosis of ESM was made due to the relative cell uniformity, rare mitoses, and the presence of invasive growth. There have been few reports on the ultra-structure of ESM and endometrial stromal sarcoma, and there are no reports on the ultrastructural difference between these tumors. In addition to the ultrastructural observations of our case, the electron-microscopic findings of previous reports are discussed.     

TPA-induced cohort migration of well-differentiated human rectal adenocarcinoma cells: cells move in a RGD-dependent manner on fibronectin produced by cells, and phosphorylation of E-cadherin/catenin complex is induced independently of cell-extracellular matrix interactions

 We have already presented a two-dimensional cell motility assay using a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1 as a motility model of tumour cells of epithelial origin. In this model, L-10 cells showed locomotion as a coherent sheet when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement ”cohort migration”. Electron and immunoelectron microscopic study of the migrating cell sheets demonstrated localized release from cell–cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosine phosphorylation of the E-cadherin–catenin complex, including β-catenin. Cell–extracellular matrix (ECM) interactions involved in this TPA-induced cohort migration and their effect on tyrosine phosphorylation of the E-cadherin-catenin complex have now been investigated. L-10 cell cohort migration was almost completely inhibited by addition of Arg-Gly-Asp (RGD) peptide into the medium, and thus RGD dependent. Cohort migration was stimulated on type I and IV collagens, fibronectin (FN)- and laminin-coated substratum, but was inhibited by RGD only on FN-coated surface. By using immunofluorescent techniques, FN was demonstrated preferentially around migrating cells, and a protein synthesis inhibitor, cycloheximide, inhibited the migration by about 75%. FN produced by L-10 cells were found to be mostly EDA+ FN when analysed by RT-PCR. Moreover, anti-FN antibody, but not anti-vitronectin antibody, inhibited the TPA-induced cohort migration almost completely. Thus, it was likely that L-10 cells produced FN themselves and moved on the FN substrate in an RGD-dependent manner. However, stimulation of migration by type I collagen coating and inhibition by RGD treatment did not affect the tyrosine phosphorylation of the E-cadherin–catenin complex induced by TPA, indicating that cell–cell interactions were adjusted to suit cell migration, irrespective of the condition of cell–ECM adhesion, during TPA-induced cohort migration. Received: 31 December 1997 / Accepted: 2 April 1998     

Immunohistochemistry and angiography in adenomatous hyperplasia and small hepatocellular carcinomas

The sinusoidal structure and blood supply of 38 liver nodules less than 2 cm In diameter were Investigated. There were 18 cases of adenomatous hyperplasia (AH) and 20 cases of hepatocetlular carcinoma (HCC). Growth pattern, encapsulation and vascularity were examined, and Immunohistochemistry performed for factor VIII related antigen (factor VIII), type IV collagen (collagen IV), lamlnln and CD68. There were significant differences between AH and small HCC, except for the expression of CD68. There were differences In tumor size, vasculartty and the components of the basement membrane between AH and small, well differentiated HCC. The cases of AH were supplied by the portal system and maintained the sinusoidal structure, but small well-differentiated HCC were supplied by a mixture of portal and arterial vessels. In spite of their small size, moderately and poorly differentiated HCC had capillary and were supplied by branches of the hepatic artery.     

Prototype heel effect compensation filter for cone-beam CT

The prototype cone-beam CT (CBCT) has a larger beam width than the conventional multi-detector row CT (MDCT). This causes a non-uniform angular distribution of the x-ray beam intensity known as the heel effect. Scan conditions for CBCT tube current are adjusted on the anode side to obtain an acceptable clinical image quality. However, as the dose is greater on the cathode side than on the anode side, the signal-to-noise ratio on the cathode side is excessively high, resulting in an unnecessary dose amount. To compensate for the heel effect, we developed a heel effect compensation (HEC) filter. The HEC filter rendered the dose distribution uniform and reduced the dose by an average of 25% for free air and by 20% for CTDI phantoms compared to doses with the conventional filter. In addition, its effect in rendering the effective energy uniform resulted in an improvement in image quality. This new HEC filter may be useful in cone-beam CT studies.     

Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypevascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mecha-nism under such a hypoxic state at high altitude.     

Apparent genotype–phenotype correlation in childhood,adolescent, and adult Chediak‐Higashi syndrome

Chediak‐Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10–15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype–phenotype relationship among the various clinical forms of CHS. © 2002 Wiley‐Liss, Inc.     

Hyperplastic foci in chronic liver disease: Their proliferative activity assessed by nucleolar organizing region

In the cirrhotic and precirrhotic liver, there may be small foci with increased cellularity and amphophilic cytoplasm. These are microscopic lesions that do not form macroscopically detectable nodules, which differ from the macroscopically apparent nodules of dysplastic nodules. In the present study, we assessed the proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or chronic hepatitis, by staining for agyrophilic nucleolar organizing regions (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from 0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08) in the controls. The AgNOR count In the hyperplastic foci was significantly higher than that In the controls (P> 30.01). Small hyperplastic foci show Increased proliferative activity. Further study on these foci is required to clarify their relation to hepatocarcinogenesis.