ADRENAL PHEOCHROMOCYTOMA WITH BOTH BENIGN AND MALIGNANT COMPONENTS

A case of adrenal pheochromocytoma Is reported characterized by polygonal basophilic granular cells of benign type, plump eosinophilic granular cells of transitional type, and spindle-shaped cells of malignant type. In the primary tumor the neoplastic cells of each type revealed a distinctive topographical distribution. All gradations between the latter two varieties of cells were found, especially in the vicinity of the transitional cell area. Multiple metastases were present in the liver and lungs, where only anaplastic spindle-shaped cells could be found. Ultrastructurally, the benign cells contained predominantly large, rather light, secretory granules with a coarsely granulated core. In the malignant cells, the number, size, and intensity of granules varied considerably from cell to cell or even within a single cell. In general, the malignant cells had a higher frequency of smaller granules with electron-dense homogeneous cores. Moderate amounts of noradrenalin but not significant dopamine or adrenalin could be demonstrated from a metastatic nodule In liver. We postulate that this adrenal medullary pheochromocytoma was benign originally and underwent malignant transformation shortly before the patient's death. This is based upon the patient's clinical features and the peculiar structures of the primary tumor.     

Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord

In the developing spinal cord, signals from the roof plate are required for the development of three classes of dorsal interneuron: D1, D2, and D3, listed from dorsal to ventral. Here, we demonstrate that absence of Wnt1 and Wnt3a, normally expressed in the roof plate, leads to diminished development of D1 and D2 neurons and a compensatory increase in D3 neuron populations. This occurs without significantly altered expression of BMP and related genes in the roof plate. Moreover, Wnt3a protein induces expression of D1 and D2 markers in the isolated medial region of the chick neural plate, and Noggin does not interfere with this induction. Thus, Wnt signaling plays a critical role in the specification of cell types for dorsal interneurons.     

Anaesthetic management of a neonate with prenatally diagnosed cervical tumour and upper airway obstruction

We report the anaesthetic management of a mother, and airway management of a neonate with a prenatal diagnosis of cervical cystic hygroma causing upper airway obstruction. The mortality of such neonates due to upper airway obstruction is reported to exceed 20% following deliveries. Elective Caesarean section was performed under general anaesthesia, and in utero tracheal intubation of the neonate was accomplished under uninterrupted maternal-fetal circulation. By utilizing isoflurane and ritodrine, the heart rate of the neonate remained between 120 to 150 bpm for four minutes following uterine incision. We believe that it is important that a multidisciplinary approach be initiated for planning of airway management of the neonate soon after the diagnosis is made. Laryngoscopy blades larger than normal for neonates, and a portable Doppler to monitor the viability of the neonate were found to be useful in the management of the neonate during in utero tracheal intubation. Although estimated blood loss was not increased, nor did uterine atony occur postoperatively despite the use of ritodrine during Caesarean section, the efficacy and safety of ritodrine to delay placental detachment have not been proved.     

Reproductive characteristics of transgenic (TG) chickens carrying an exogenous gene

An exogenous gene (lacZ/MiwZ) introduced into the germinal crescent region (GCR) of avian embryos was confirmed to be successfully transferred to the gonads via the primordial germ cells (PGCs). Following hatching, the chicks were raised until the stage of sexual maturation. The incorporation of MiwZ DNA was detected in male and female transgenic chickens, respectively. The normal male and female transgenic birds were subjected to artificial insemination according to routine methods. Fertilized eggs obtained from female transgenic chickens were incubated for 72 h and the embryos removed from the yolk were examined by X-gal staining to detect the introduction of MiwZ in the offspring. As a result, the expression of MiwZ was detected in the offspring. Furthermore, the presence of MiwZ in the extracts from embryos was also detected by polymerase chain reaction (PCR) analysis. In male transgenic chickens, the presence of injected MiwZ in the extracts from sperm was also confirmed. The exogenous gene introduced into the GCR migrated successfully to the gonad resulting in its incorporation into the offspring and spermatozoa of transgenic chickens.     

Optic-spinal form of multiple sclerosis and immune-mediated myelopathy in Japan

Optic-spinal form of multiple sclerosis (OS-MS) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) are two immune-mediated myelopathy relatively common in Japan. (1) Transverse myelitis, once seen in 60% of MS, mostly OS-MS, 30 years ago, drastically decreased (5%) recently in Japan. In contrast, frequency of conventional form of MS (C-MS) increased during this period of time. But unlike C-MS in white patients, cerebellar hemispheric lesions are uncommon in Japanese C-MS. These findings emphasize influence of changes in exogenous factors on manifestations of MS and distinct genetic factors related to MS in Japanese and white patients. (2) To clarify the reason of high HTLV-I proviral load in HAM/TSP, we studied cellular immune surveillance against HTLV-I and found that significant cytotoxic T lymphocyte activity, and suppressed natural killer activity and antibody-dependent cell-mediated cytotoxicity in the patients. These altered immune surveillance may be associated with the spread of HTLV-I infection and the pathogenesis of HAM/TSP.     

Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation

Aims: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. Methods: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using¹⁸fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day,n=16) for 12weeks.¹⁸F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. Results: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%).¹⁸F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of¹⁸F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. Conclusions: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.     

Dietary Vitamin B1 Intake Influences Gut Microbial Community and the Consequent Production of Short-Chain Fatty Acids

The gut microbiota is closely related to good health; thus, there have been extensive efforts dedicated to improving health by controlling the gut microbial environment. Probiotics and prebiotics are being developed to support a healthier intestinal environment. However, much work remains to be performed to provide effective solutions to overcome individual differences in the gut microbial community. This study examined the importance of nutrients, other than dietary fiber, on the survival of gut bacteria in high-health-conscious populations. We found that vitamin B1, which is an essential nutrient for humans, had a significant effect on the survival and competition of bacteria in the symbiotic gut microbiota. In particular, sufficient dietary vitamin B1 intake affects the relative abundance of Ruminococcaceae, and these bacteria have proven to require dietary vitamin B1 because they lack the de novo vitamin B1 synthetic pathway. Moreover, we demonstrated that vitamin B1 is involved in the production of butyrate, along with the amount of acetate in the intestinal environment. We established the causality of possible associations and obtained mechanical insight, through in vivo murine experiments and in silico pathway analyses. These findings serve as a reference to support the development of methods to establish optimal intestinal environment conditions for healthy lifestyles.     

The effects of thiopental and propofol on cell swelling induced by oxygen/glucose deprivation in the CA1 pyramidal cell layer of rat hippocampal slices

Cellular swelling has been implicated as an early process after cerebral ischemia. We compared the effects of two commonly used IV anesthetics, thiopental and propofol, on hippocampal CA1 pyramidal cell swelling induced by oxygen/glucose deprivation (OGD) in vitro. Experiments were performed in rat hippocampal slices. Cell swelling in the CA1 pyramidal cell layer was evaluated by determining light transmittance (LT) change through the slices and by histopathological examination. For LT experiments, OGD was induced for 10 min by superfusing slices with glucose-free artificial cerebrospinal fluid equilibrated with 95% nitrogen and 5% CO(2). Thiopental and propofol were present 10 min before and during the period of OGD. The results showed that thiopental (100 and 400 microM), but not propofol (40 and 160 microM), significantly prolonged latency to the peak of LT increase after the onset of OGD. Consistent with the LT experiments, histopathological examination revealed that thiopental, but not propofol, attenuated CA1 pyramidal cell expansion and the gap diminution between CA1 pyramidal cells induced by OGD. These results suggest that thiopental, but not propofol, reduces the neuronal cell swelling caused by OGD. Whether the reduction of cell swelling is related to reduction in cell injury caused by OGD remains to be investigated. IMPLICATIONS: We demonstrated that thiopental, but not propofol, attenuates ischemic neuronal swelling induced by oxygen/glucose deprivation in an in vitro ischemic model.     

FR177995, a novel vacuolar ATPase inhibitor, exerts not only an inhibitory effect on bone destruction but also anti-immunoinflammatory effects in adjuvant-induced arthritic rats

There is considerable evidence that osteoclasts are involved in the pathogenesis of juxta-articular bone destruction in rheumatoid arthritis. Vacuolar ATPases (V-ATPases), which are highly expressed in the ruffled border membrane of osteoclasts, play a central role in the process of bone resorption, and V-ATPase inhibitors are effective in preventing bone destruction in several animal models of lytic bone diseases. Here, we evaluated for the first time the effects of V-ATPase inhibition in rats with adjuvant-induced arthritis (AIA) using FR177995, a novel V-ATPase inhibitor. FR177995 completely inhibited H(+) transport driven by V-ATPase, but exerted no effect on the H(+) transport activities of F- and P-ATPase, indicating that FR177995 is a specific inhibitor of V-ATPase. FR177995 acted directly on osteoclastic bone resorption and equally inhibited in vitro bone resorption stimulated by IL-1, IL-6 or PTH. In addition, FR177995 dose-dependently reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats. When FR177995 was administered to AIA rats once a day, the loss of femoral bone mineral density was significantly improved. Moreover, indicators of cartilage damage (arthritis score and glycosaminoglycan content in the femoral condyles) and inflammation parameters (paw swelling volume, erythrocyte sedimentation rate and plasma sialic acid level) were found to be unexpectedly ameliorated. These results strongly suggest that V-ATPase may be an interesting drug target in the treatment of rheumatoid arthritis.     

Exaggerated response of arginine vasopressin-enhanced green fluorescent protein fusion gene to salt loading without disturbance of body fluid homeostasis in rats

We examined the effects of chronic salt loading on the hypothalamic expressions of the enhanced green fluorescent protein (eGFP), arginine vasopressin (AVP) and oxytocin (OXT) genes in AVP-eGFP transgenic rats that expressed eGFP in the hypothalamic AVP-containing neurones. In these rats, salt loading for 5 days caused a marked increase of the eGFP fluorescence in the magnocellular divisions of the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the internal layer of the median eminence. Expression of the eGFP gene was increased seven- to eight-fold in the PVN and SON of salt-loaded rats in comparison with euhydrated rats. By contrast, none of these changes were observed in the suprachiasmatic nucleus. The expression of the AVP and OXT genes was increased 1.5- to two-fold in the PVN and SON of salt-loaded nontransgenic (control) and transgenic rats. There were no differences in the expression levels of the AVP and OXT genes in the PVN and SON between nontransgenic (control) and transgenic animals under normal conditions and after salt loading. In the posterior pituitary gland, the intensity of the eGFP fluorescence did not change after salt loading for 5 days, but increased after 10 days of salt loading. Upon salt loading, significant increases in the plasma AVP concentrations, plasma osmolality and plasma Na+ were observed. Furthermore, there were no significant differences in changes of water intake, food intake, urine volume, urine osmolality, urine Na+ concentrations, and the body weights in both models under normal or salt-loaded conditions. Our results show that the response of the AVP-eGFP fusion gene to chronic salt loading is exaggerated, and humoral responses such as AVP and OXT and the body fluid homeostasis are maintained in AVP-eGFP transgenic rats. The AVP-eGFP transgenic rat gives us a new opportunity to study the dynamics of the AVP system in vivo.