A case of supravalvular aortic stenosis with spontaneous remission of peripheral pulmonary stenosis

A 14-year-old junior high school boy was admitted to our institute. Previously he had been diagnosed as having peripheral pulmonary stenosis (Gay's classification, type IV) at the age of 2 years and 10 months. On this occasion, however, a diagnosis of supravalvular aortic stenosis was made, with a pressure gradient of about 120 mmHg, and all examinations showed spontaneous remission of peripheral pulmonary stenosis. He underwent a successful standard aortoplasty. This is the first reported case of spontaneous remission of peripheral pulmonary stenosis.     

Veno-arterial ECLA (extracorporeal lung assist) for severe respiratory failure due to meconium aspiration

A full term newborn female, 3262g, aspirated meconium at birth and began to suffer from severe hypoxia and acidosis due to progressing pneumonitis, pneumothorax and pneumomediastinum. She also had severe hypotension and anuria. Venoarterial ECLA with a Kolobow membrane lung via the right internal jugular vein and the right common carotid artery was initiated. Blood gas parameters and blood pressure improved, and urine output increased to normal. ECLA permitted a reduction in FIO2 and airway pressure of mechanical ventilation, as well as frequent lavage of the lung. As the physical condition improved, the bypass flow was gradually decreased from 200 ml.kg-1.min-1 at the start to 130 ml.kg-1.min-1 for maintenance, then to 25 ml.kg-1.min-1 at the end. Bleeding throughout the ECLA for 69 hours could be minimized by a meticulous control of the activated coagulation time with a minimum dose of heparin and the transfusion of fresh frozen and platelet rich plasma. After ECLA, the carotid artery was simply ligated, and mechanical ventilatory support was carried out for 5 days. Her condition improved and she left the hospital without any neurological sequelae. ECLA will become an effective means of life support for a baby with severe MAS irresponsive to conventional ventilatory support.     

Temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat

We investigated the temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat by immunohistochemistry. The mid-portion of the medial half of the patellar ligament in 14-week-old male Wistar rats was cut transversely with a scalpel. On day 1 after ligament injury, diffuse staining for transforming growth factor-β was observed in the extracellular matrix filling the wound, and the staining in the adjacent ligament tissue was as weak as it was in the normal ligament. On day 3, the intensity of the diffuse extracellular staining decreased, and the staining was observed in correspondence with the cellular distribution in the wound site and in the adjacent uninjured ligament tissue. On day 7, the intense staining was widely distributed over the whole length of the ligament tissue. On day 28, the staining for transforming growth factor-β was still observed at the wound site and in the adjacent uninjured ligament tissue, where the staining was reduced in intensity but still stronger than it was in the normal ligament. On day 56, the expression of transforming growth factor-β was still detectable at the wound site: however, in the adjacent uninjured ligament tissue, it had almost subsided to the normal level. The results of the present study suggest that ligament healing may be accompanied by extensive changes in the expression of transforming growth factor-β over the whole length of ligament tissue.     

Induction and activation of the aryl hydrocarbon receptor by IL-4 in B cells

It is widely known that IL-4 and IL-13 act on various kinds of cells, including B cells, resulting in enhancement of proliferation, class switching to IgE and expression of several surface proteins. These functions are important for the recognition of the various antigens in B cells and are known to be involved in the pathogenesis of allergic diseases. However, it has not been known whether IL-4/IL-13 is involved in the metabolism of various kinds of xenobiotics including 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), and it remains undetermined whether TCDD, an environmental pollutant, influences IgE production in B cells, exaggerating allergic reactions. We identified IL-4- or IL-13-inducible genes in a human Burkitt lymphoma cell line, DND-39, using microarray technology, in which the AHR gene was included. The AHR gene product, the aryl hydrocarbon receptor (AhR), was induced by IL-4 in both mouse and human B cells in a STAT6-dependent manner. IL-4 alone had the ability to translocate the induced AhR to the nuclei. TCDD, a ligand for AhR, rapidly degraded the induced AhR by the proteasomal pathway, although IL-4-activated AhR sustained its expression. AhR activated by IL-4 caused expression of a xenobiotic-metabolizing gene, CYP1A1, and TCDD synergistically acted on the induction of this gene by IL-4. However, the induction of AhR had no effect on IgE synthesis or CD23 expression. These results indicate that the metabolism of xenobiotics would be a novel biological function of IL-4 and IL-13 in B cells, whereas TCDD is not involved in IgE synthesis in B cells.     

Three-dimensional organization of the hepatic microvasculature in hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic fibrovascular dysplasia. Although hepatic vascular shunts are often observed in HHT, the responsible pathological mechanism is unknown. This issue was addressed by performing a 3-dimensional reconstruction study of the hepatic microvasculature of an HHT-involved liver in a 79-year-old woman. Clinical observation revealed high-output congestive heart failure and hepatic encephalopathy due to arteriovenous and portovenous shunts, respectively. Angiography revealed tortuous dilation of hepatic arterial branches and intrahepatic arteriovenous shunts. The 3-dimensional analysis of the autopsy liver revealed focal sinusoidal ectasia, arteriovenous shunts through abnormal direct communications between arterioles and ectatic sinusoids, and portovenous shunts due to frequent and large communications between portal veins and ectatic sinusoids. Type 1 HHT was suggested by the lack of endoglin immunoreactivity in the liver. The 3-dimensional reconstruction study of hepatic microvasculature was successful in identifying the pathological changes responsible for the intrahepatic shunts in HHT.     

Lack of ubiquitin immunoreactivities at both ends of neuropil threads. Possible bidirectional growth of neuropil threads.

Immunocytochemically, neuropil threads (curly fibers) were investigated in the Alzheimer's disease brain using a confocal laser scanning fluorescence microscope by double labeling with tau/ubiquitin antibodies. Ubiquitin immunoreactivities were found to be lacking at one or both ends in more than 40% of tau-positive threads. Immunoelectron microscopy showed that bundles of paired helical filaments, which constitute neuropil threads, were positive for ubiquitin around their midportions, but often negative at their ends. Since it is reasonable to postulate that tau deposition as paired helical filaments precedes ubiquitination, the aforementioned observation suggests that the ends of the threads are newly formed portions, and thus the threads are often growing bidirectionally in small neuronal processes.     

Immunohistochemical characteristics of duodenal adenomas in familial adenomatous polyposis with special reference to cell kinetics

The duodenum is the second most frequent site of cancer in patients with familial adenomatous polyposis (FAP). The main objective of this study was to evaluate the cell kinetics in duodenal and ampullary adenomas in FAP. The endoscopic and biopsy findings of duodenal adenomas in 22 FAP subjects and 18 non-FAP subjects were compared. Adenomas in FAP included 15 ampullary adenomas and 17 nonampullary adenomas. The cell kinetics was evaluated by immunohistochemistry for Ki-67, p53, bcl-2, and cyclooxygenase 2 (COX2), and the apoptotic index (AI) as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) method. Any correlations between the indices for cell kinetics and the endoscopic findings were identified. All 50 adenomas were histologically verified to be tubular adenoma with low-grade dysplasia. Neither the expression of Ki-67, p53, bcl-2, and COX2 nor the AI differed substantially between FAP and non-FAP subjects. In patients with FAP, duodenal adenoma tended to have a higher Ki-67-labeling index than the ampullary adenoma (54.3 +/- 11.3 versus 46.8 +/- 12.7; .05 < P < .1). In addition, the Ki-67-labeling index in endoscopically normal or slightly enlarged ampullary adenoma was significantly higher than that in markedly enlarged ampullary adenoma (51.8 +/- 11.4 versus 39.4 +/- 11.3; P < .05). Duodenal adenoma in FAP subjects was not found to have a higher proliferative activity or a smaller degree of apoptosis compared with those in non-FAP subjects. The smaller proliferative activity in larger ampullary adenoma may thus be related to the static nature of ampullary adenoma in FAP.     

Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities

Background  

CD4+ T lymphocyte (CD4) cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART), but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs) have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb), and body mass index (BMI) to identify patients who require ART.