Retardation of skeletal development and cervical abnormalities in transgenic mice expressing a dominant-negative retinoic acid receptor in chondrogenic cells

Skeletal formation is a fundamental element of body patterning and is strictly regulated both temporally and spatially by a variety of molecules. Among these, retinoic acid (RA) has been shown to be involved in normal skeletal development. However, its pleiotropic effects have caused difficulty in identifying its crucial target cells and molecular mechanisms for each effect. Development of cartilage primordia is an important process in defining the skeletal structures. To address the role of RA in skeletal formation, we have generated mice expressing a dominant-negative retinoic acid receptor (RAR) in chondrogenic cells by using the type II collagen α1 promoter, and we have analyzed their phenotypes. These mice exhibited small cartilage primordia during development and retarded skeletal formation in both embryonic and postnatal periods. They also showed selective degeneration in their cervical vertebrae combined with homeotic transformations, but not in their extremities. The cervical phenotypes are reminiscent of phenotypes involving homeobox genes. We found that the expression of Hoxa-4 was indeed reduced in the cartilage primordia of cervical vertebrae of embryonic day 12.5 embryos. These observations demonstrate that endogenous RA acts directly on chondrogenic cells to promote skeletal growth in both embryonic and growing periods, and it regulates the proper formation of cervical vertebrae. Furthermore, RA apparently specifies the identities of the cervical vertebrae through the regulation of homeobox genes in the chondrogenic cells. Great similarities of the phenotypes between our mice and reported RAR knockout mice revealed that chondrogenic cells are a principal RA target during complex cascades of skeletal development.     

Unilateral pulmonary agenesis associated with oesophageal atresia and tracheoesophageal fistula: A case report with prenatal diagnosis

We describe herein a case of unilateral pulmonary agenesis (PA) with oesophageal atresia (EA)/tracheoesophageal fistula (TEF) that was diagnosed prenatally and repaired by esophagoesophagostomy with stable postoperative course. The patient was born at 34 weeks gestation, after ultrasonography at 22 weeks gestation showed possible right-sided diaphragmatic eventration or PA and EA was subsequently suspected due to hydramnios. The initial X-ray showed mediastinal shift to the right, and coil up sign of the nasogastric tube, without intracardiac anomaly. Immediately after the diagnosis of EA/TEF and unilateral PA on day 0, the patient was intubated in the operating room, and a gastrostomy tube was placed. After pulmonary status stabilized, at 4 days old, EA/TEF was repaired through a thoracotomy in the right 4^th intercostal space. The right main bronchus was noted to continue into the distal oesophagus; this fistula was ligated and divided, and a single-layer esophagoesophagostomy was performed under mild tension with one vertebral gap. The neonate was maintained on mechanical ventilation and gradually weaned to extubation at 7 days old. The postoperative course was uneventful, with the exception of prolonged jaundice that emerged at 3 months old. Laparoscopic cholangiography at that time excluded biliary atresia, and jaundice resolved spontaneously. The patient has not shown any respiratory symptoms or feeding difficulties as of the 12-month follow-up.     

Hepatic steatosis and the elevated plasma insulin level in patients with endogenous hypertriglyceridemia

Among 31 nonobese or obese patients with endogenous hypertriglyceridemia, hepatic steatosis was found by histologic examination of the biopsied specimen in 17 patients, and it was severe in six patients. They had no history of excessive alcohol intake. Chemical analysis revealed that the lipid accumulated in the liver was triglyceride. The hypertriglyceridemic patients, with or without histologic steatosis, showed significantly increased responses of both plasma insulin and blood glucose to oral glucose load compared with control subjects. The responses were more exaggerated in the hypertriglyceridemic patients with steatosis than in the hypertriglyceridemic patients without steatosis. Analysis of correlations between five variables (liver triglyceride, plasma insulin, blood glucose, body weight index, and serum triglyceride) was done on 15 subjects whose liver triglyceride values were quantified, and highly significant correlations were found between liver triglyceride and plasma insulin, blood glucose, or body weight index. A stepwise multiple regression analysis performed on the five variables with liver triglyceride as the dependent variable revealed that the plasma insulin level was the most closely related variable, and the blood glucose level the next. The prediction equation for liver triglyceride as a function of plasma insulin and blood glucose levels (r = 0.91, p < 0.001) accounted for 84% of the total variance of liver triglyceride. It was shown that the decay of intravenously injected insulin in plasma was not delayed in the hypertriglyceridemic patients with steatosis, while the insulin sensitivity examined after intravenous insulin injection significantly decreased in the hypertriglyceridemic patients with or without steatosis, thus suggesting that the hyperinsulinemia in the hypertriglyceridemic patients was due to an increased insulin secretion associated with the decrease in the insulin sensitivity. Therefore, the elevated plasma insulin and blood glucose levels—or the insulin insensitivity by itself—might be the essential abnormalities in patients with endogenous hypertriglyceridemia, which, in extreme cases, might lead to massive triglyceride accumulation in the liver.     

Metastasis of rectal cancer to lymph nodes and tissues around the autonomic nerves spared for urinary and sexual function

PURPOSE: To clarify the indications for autonomic nerve-sparing operations for rectal cancer, the presence of lymph nodes and metastasis in the tissue around the autonomic nerve were examined in 28 rectal cancer patients. These were staged as pT2 in 8 patients, pT3 in 19 patients, and pT4 in 1 patient histopathologically. METHODS: The specimens of the autonomic nerve including the inferior mesenteric plexus, preaortic plexus, superior hypogastric plexus, hypogastric nerve, and pelvic plexus were removed with radical abdominopelvic lymphadenectomy after the autonomic nerve-sparing rectal cancer operation. RESULTS: In the tissue around the autonomic nerve, lymph nodes were 11.2±9.6 in number and 2.6±2.4 mm in size (mean ± standard deviation). The frequency of presence of lymph nodes was higher and the number of lymph nodes was larger in the inferior mesenteric plexus (70.4 percent; 3.6) and the preaortic plexus (66.7 percent; 2.1) than in the left and right pelvic plexuses (39.1 percent, 1; 36 percent, 1). Metastasis to the lymph nodes or lymphatic permeation in the tissue around the autonomic nerve were observed in four cases (14.3 percent) of lower rectal cancer, consisting of three with Stage III cancer (pT3, pN1-3, and M0) and one with Stage IV cancer (pT4, pN1, and pM1 (HEP)). CONCLUSION: Radical rectal excision that includes lymph nodes and adjacent tissue around the autonomic nerves may result in metastatic tumor removal that would otherwise be left in situ with nerve-sparing techniques for advanced rectal cancer in Stage III.     

Left atrial conduit function for left ventricular filling dynamics in patients with myocardial infarction

This study observed the left atrial function in determining filling dynamics of the left ventricle in patients with myocardial infarction. The study consisted of eight control subjects and ten patients with myocardial infarction. The left ventricular filling volume is considered to be composed of the left atrial passive emptying, active emptying, and conduit volumes. The change of left ventricular filling volume was correlated with that of conduit volume (r = .87, P < .01). However, the change of left ventricular filling volume did not have any correlation to those of left atrial passive emptying and active emptying volumes. These results suggested that the left atrial conduit function was important in determining filling dynamics of the left ventricle.     

Interleukin 2 stimulates the T-cells from patients with eosinophilia to produce CFU-Eo growth stimulating factor

Patients with immune thrombocytopenia have an increased percentage of microthrombocytes/platelet fragments and megathrombocytes. It has been suggested that increased levels of platelet associated IgG (PA-IgG) found in these patients might be related to the presence of this abnormal platelet size distribution. In this study we used flow cytometry to investigate the distribution of PA-IgG within a population of platelets and, in particular, we examined the relationship between platelet size and PA-IgG determined simultaneously on individual platelets. Platelet samples from 10 normals and 31 thrombocytopenic patients were studied. PA-IgG was estimated using immunofluorescent FITC anti-IgG antibody. Binding of FITC anti-IgG to the platelets was quantitated in the flow cytometer as relative mean fluorescence (RMF) which was calibrated against values (in fg/plt of FITC anti-IgG) obtained by spectrofluorometry after solubilization of the platelets. A high correlation (r = 0.89) was found between flow cytometric RMF value and spectrofluorometric FITC anti-IgG values. The flow cytometric studies showed that platelet samples with abnormally elevated levels of FITC anti-IgG (greater than 1.7 fg/plt) not only have a higher percentage of platelets with elevated FITC anti-IgG, but that these platelets also have increased levels of FITC anti-IgG as compared to platelets from normal samples. Platelet size was measured by the amount of forward light scatter in the flow cytometer. A low but significant correlation (r = 0.33 +/- 0.12) was found between size (FALS) and fluorescent signals in samples with elevated FITC anti-IgG. The contribution of 10% of the smallest platelets by FALS and 10% of the largest platelets by FALS to the total levels of flow cytometer platelet fluorescence in these samples was only 4.4% and 19.4% respectively which was not higher than obtained with samples with normal levels of FITC anti-IgG. In conclusion, this study showed that increased levels of PA-IgG found among thrombocytopenic patients were not confined to any particular size class of platelets.