A 2,7-diamino-1,4,8-triazanaphthalene derivative selectively binds to cytosine bulge DNA only at a weakly acidic pH.

The synthesis and properties of 2,7-diamino-1,4,8-triazanaphthalene (azaDANP) are described. AzaDANP is protonated only at a weakly acidic pH to bind to the cytosine bulge DNA duplex selectively. Upon binding of azaDANP to the cytosine bulge DNA, a new absorption band at 407 nm appears, and the absorption change of azaDANP on binding to the target is very sensitive to environmental pH with a bell-shaped pH-absorption profile.

[Descending necrotizing mediastinitis].

We treated of 3 patients with descending necrotizing mediastinitis that is often to be fatal. There are 3 important issues regarding the treatment of this disease. First, the precise sites of abscess should be determined by computed tomography (CT) scans from the neck to diaphragm. Second, effective drainage of the neck and mediastinal abscess should be carried out immediately when the sites of abscess are determined. Third, drainage under video-assisted thoracic surgery (VATS) is an appropriate treatment because VATS is less invasive and provides an easier placement of the drainage tubes at abscess sites.

[Complete resection of an advanced mediastinal nonseminomatous germ cell tumor with multiple distant metastases after down-staging by chemotherapy].

A mediastinal nonseminomatous germ cell tumor was completely resected after down-staging by chemotherapy despite the presence of multiple distant metastases. A 22-year-old female was admitted for superior vena cava (SVC) syndrome. Her SVC was obstructed by a large anterior mediastinal tumor; she also exhibited distant metastases on a left rib, in the liver, and multiple in the lung. The blood alpha-fetoprotein (AFP) level was extremely elevated to 57,530 ng/ml. Four courses of BEP therapy [cisplatin (CDDP), bleomycin (BLM), etoposide (VP-16)] and a high dose chemotherapy followed by a peripheral blood stem cell transplantation made the tumor become smaller and effected its down-staging. Residual mediastinal tumor with an intravascular tumor in SVC was completely resected. The SVC was reconstructed by an artificial vessel graft. A mediastinal nonseminomatous germ cell tumor, even though it has multiple distant metastases, can achieve down-staging and complete resection by a chemotherapy based on scientific evidence.

[Congenital bronchoesophageal fistula in an adult; an undiscribed mechanism of symptom tolerance].

We present a case of a congenital bronchoesophageal fistula in a 61-year-old woman. She was referred to hospital because of postprandial heart burn. Three-dimensional (3D) computed tomography (CT) demonstrated an anastomosis between her right intermediate bronchus and esophagus. In spite of direct communication between her bronchus and esophagus, she has never suffered severe infection. We visualized the orifice of fistula closed with mucosal flap in swallowing by means of a bronchofiberscope. The delay of a diagnosis was explained by symptom tolerance. Some theories as to the symptom tolerance are found in literatures, but we supposed to find an undiscribed mechanism; closure of the orifice in swallowing. The fistula was surgically closed.

[Comparison of the images in virtual bronchoscopy under different conditions].

OBJECTIVE: We report herein the comparison of the virtual bronchoscopy (VB) images which were constructed with 2 different computed tomography (CT) scanners combined with 3 different applications in 2 healthy adult volunteers. METHODS: CT scanners were multi-detector row CT (MDCT) [64 detectors] and MDCT (16 detectors). Applications, by which VB images were made, were Leonardo (Leo), Ziostation (Zio), and Plus XNVZ2 (Plus). The image quality was evaluated by 3 expert bronchoscopists. RESULTS: The change of the threshold value was necessary in Leo for practical use in subsegmental bronchi and more distal area, but unnecessary in Plus or Zio. When Plus was used, the VB images from the data obtained with MDCT (16 detectors) and MDCT (64 detectors) had almost equal quality. CONCLUSIONS: Although the process to construct VB images was different in each application, it was regarded that Plus was not inferior to Zio or Leo in VB image quality.

Spontaneous improvement of persistent ulceration after carotid artery stenting.

BACKGROUND AND PURPOSE: Because carotid plaque ulceration is associated with an increased risk of cerebral embolism, residual carotid plaque ulceration directly around a stent (persistent ulceration) after carotid angioplasty and stent placement (CAS) could still be a risk factor for a stroke. The purpose of this study is to understand the morphologic and clinical prognosis of persistent ulceration. PATIENTS AND TECHNIQUES: CAS was attempted on 91 consecutive stenotic lesions (80 patients). Of these, 54 lesions (48 patients) had ulceration before CAS. Angiograms were evaluated immediately after the procedure. Persistent ulceration was found in 34 lesions (30 patients). The mean depth and length of persistent ulcers were 2.1 mm (range, 1-4.7 mm) and 8.9 mm (range, 1.5-22 mm), respectively. All patients with persistent ulceration were followed with antiplatelet therapy. RESULTS: No ischemic event due to the lesions occurred during the mean follow-up period of 25.5 months (range, 3-48 months). Angiography on 25 lesions (21 patients) at a mean of 5.8 months (range, 1-21 months) after CAS showed that persistent ulceration disappeared in 12 lesions (48%), improved in 11 lesions (44%), and remained unchanged in 2 lesions (8%). Nine lesions (36%) showed restenosis, which were < or =30% and did not require any additional intervention. New ischemic lesions were not detected in any of the 14 patients (17 lesions) who underwent follow-up MR imaging at a mean of 9 months (range, 1-32 months) after CAS. CONCLUSION: We conclude that persistent ulceration after CAS improves spontaneously and is not a risk factor for cerebral embolism.

Direct carotid puncture for the endovascular treatment of anterior circulation aneurysms.

We report the usefulness of Guglielmi detachable coil (GDC) embolization by direct carotid puncture for anterior circulation aneurysms. For all 27 patients, GDC embolization by direct carotid puncture was safely performed by using a 5F sheath introducer 5 cm long and a Tracker-38 catheter. Neurologic deficits and hemorrhage were not found in any patient during the follow-up period. If the transfemoral approach cannot be applied, GDC embolization should be considered as an alternative method.

The significance of incomplete stent apposition in patients undergoing stenting of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Incomplete stent apposition after carotid angioplasty and stent placement (CAS) is often seen but little is known about how the incomplete attachment goes after stent placement. For example, some may change into restenosis around the stent edge and some may remain unchanged. The purpose of this study is to clarify the morphologic prognosis of an incomplete stent apposition at the stent edge. METHODS: CAS was attempted on 135 consecutive stenotic lesions (124 patients). Angiograms were then evaluated immediately after the procedure. An incomplete stent apposition at stent edge was found in 15 patients, and all of them were followed up by angiography and MR imaging with antiplatelet therapy. RESULTS: No ischemic event caused by the lesions occurred during the mean follow-up period of 11 months (from 4 to 32 months). The angiography findings of 15 lesions at a mean of 8.8 months (from 2 to 28 months) after CAS showed that all remained unchanged. No patients required any additional intervention. No new ischemic lesions were detected in any of the 15 patients who underwent follow-up MR imaging at a mean of 10 months (from 2 to 32 months) after CAS. CONCLUSION: In this study, the existence of a segment of incomplete stent apposition had no adverse morphologic or clinical effect.

[Large cell carcinoma with chest wall infiltration combined with contralateral giant bulla].

A 48-year-old male consulted the department of respiratory medicine for right precordial pain occurring from the beginning of May 2004. Chest X-ray indicated a tumorous shadow in the right upper lung field and a large left lung cyst. Although chest wall infiltration was suspected based on computed tomography (CT) demonstrating a mass lesion in the right S2, there was no significant swelling of the mediastinal lymph node. On the left side, the lung was markedly compressed by a large cyst in the left upper lobe. Since bronchoscopy failed to establish a definitive diagnosis, the patient was referred to our department for surgery based on a suspicion of malignant pulmonary tumor. Considering both the risk of perioperative complications due to the left cystic lesion at surgery for right lung lesion and the improvement of respiratory function by removing cystic lesion of the left lung, the left side operation was preceded by the right side. Although postoperative examinations of respiratory function did not demonstrate any particular improvement, the results of selective right pulmonary artery obstruction test supported the possibility of pulmonary lobectomy. Therefore, the right upper lobectomy and ND 2a mediastinal dissection combined with chest wall resection was subsequently performed. Postoperative pathological diagnosis revealed that the tumor was a stage IIB large cell carcinoma of pT3N0M0 with costal infiltration.

[Pulmonary actinomycosis developing diffuse phregmone after pneumonectomy].

The patient was a 75-year-old male who consulted the department of respiratory tract internal medicine in our hospital for left chest pain occurring from the beginning of December 2003. Chest X-ray indicated a tumorous shadow in the left lower lung field. A chest CT also revealed an irregularly shaped mass shadow in the left lower lobe. Since bronchoscopy failed to establish a definitive diagnosis, the patient was referred to our department for surgery to undertake thoracotomy. After left pneumonectomy being performed based on a suspicion of lung abscess, pathological examination of specimen from the resected left lung showed sulfur granules which led to the diagnosis of pulmonary actinomycosis. Because of the diffuse phregmone developing around the surgical wound, benzylpenicillin potassium administration was started, and was continued for a further 6 months on an outpatient basis. Pulmonary actinomycosis is a relatively rare chronic pulmonary infection. It is often difficult to distinguish pulmonary actinomycosis from other pulmonary disease such as lung cancer because of the similarity of their appearance on X-ray or CT, and almost all cases of pulmonary actinomycosis are diagnosed by thoracotomy.

[Abdominal organ infarction encountered immediately after surgery of primary lung cancer].

Very rare cases of abdominal organ infarction after surgery of primary lung cancer were reported. Case 1: Patient 1 was a 70-year-old man who underwent left upper lobectomy and ND 2a in June 1999 based on the clinical diagnosis of stage IA lung cancer. On the 4th postoperative day, the patient developed fever and right flank pain. Abdominal computed tomography (CT) demonstrated a specific finding compatible with renal infarction. The etiology could not be determined. The patient was treated conservatively. However, severe atrophy of right kidney was demonstrated by following CT performed 3 years later. Case 2: Patient 2 was a 70-year-old woman who underwent left upper lobectomy and ND 2a in December 2002 based on the clinical diagnosis of stage IA lung cancer. On the 4th postoperative day, the patient developed abdominal pain in the left upper quadrant, nausea and vomiting which had lasted for 10 days. Abdominal CT demonstrated a wedge-shaped filling defect at spleen compatible with splenic infarction. The etiology could not be determined. The patient was treated conservatively with prophylactic antibiotic therapy and followed closely. Partial atrophy of spleen was demonstrated by following CT performed 4 months later.

Hemorrhage of thiamine-deficient encephalopathy.

Hemorrhagic lesions of pyrithiamine-induced acute thiamine-deficient encephalopathy of the mouse (PIATDEM) consisted of petechiae, which often coalesced to form small hematomas. Electron microscopy showed the typical petechial lesion to be composed of a perivascular necrotic zone containing fibrin-platelet clot surrounded by a ring of erythrocytes. Endothelial cells were intact and tight junctions were closed. A study of permeability to horseradish peroxidase (HRP) revealed only a slight increase in the number of transport vesicles in the endothelial cells. A large amount of HRP present in the lesions seemed to have entered the brain by a hemorrhagic route which remains unclarified. Spherical latex particles, 0.23 micrometer in diameter, were injected intravenously into encephalopathic mice at a time when intracerebral hemorrhages frequently occurred. Two to 24 hours after the injection, a large number of latex particles penetrated the blood vessels at sites of hemorrhage. There were many particles in the phagosomes of the endothelial cells, which suggested transendothelial transport by the organelle. The possibility of endothelial phagocytic transport of erythrocytes as a main route of diapedesis is discussed.

6-Aminonicotinamide-induced hydrocephalus in suckling mice.

Following a single intraperitoneal injection of 6-aminonicotinamide (6-AN, 50 mg/kg of body weight) into newborn mice of the Institute of Cancer Research strain, hydrocephalus consistently developed nine days after injection, with rapid progression. All of these mice died before reaching adulthood. The most striking early histologic change in these mice was cytoplasmic vacuolation of ependymal cells, which was observed as early as 24 hours after injection. Vacuolation of subependymal astrocytes appeared during the next few days. After day seven, the aqueduct was obliterated by swollen vacuolated ependymal cells and subependymal astrocytes. The aqueduct remained obliterated even after the vacuolation of the ependymal cells subsided after day nine, when vacuolation of subependymal astrocytes was still pronounced. These morphological observations reveal that, in newborn mice, the ependymal cells are the most sensitive to the toxic action of 6-AN and suggest that the pathogenesis of 6-AN-induced hydrocephalus is likely to be due to the combination of ependymal cell damage and compression of the lumen by the edematous periaqueductal gray matter. This is a highly reproducible animal model of drug-induced hydrocephalus.

Low energy levels in thiamine-deficient encephalopathy.

Pyrithiamine-induced acute thiamine-deficient encephalopathy was produced in adult male Wistar rats. Twenty-four hours before the onset of neurological signs the brain showed no morphological abnormalities. Encephalopathic rats had symmetrical lesions of edematous necrosis localized in the thalamus, mammillary body, and pontine tegmentum. Biochemically, encephalopathic rats had brain thiamine levels less than 20% of controls. For the assay of the concentrations of adenosine triphosphate (ATP) and phosphocreatine, the brains were fixed using 5 KW microwave irradiation and were divided into four parts: cerebral cortex, diencephalon, lower brainstem, and cerebellum. In the lower brainstem of the encephalopathic rats ATP concentrations were 89.5% of normal controls. Phosphocreatine levels were lowered to 70% of controls in the diencephalon and to 75% in the lower brainstem. Total high energy phosphate levels were decreased to 89% of controls in the diencephalon and 91% in the lower brainstem before the onset of neurological signs and to 76% and 79%, respectively, after the onset. In the cerebral cortex and cerebellum high energy phosphates were not significantly reduced. Lower high energy phosphate levels and the distribution of edematous lesions were coincident in the brain. These findings suggest that a low energy state is closely related to the formation of edematous lesions in thiamine-deficient encephalopathy.

What kind of hilar lung cancer can be a candidate for segmentectomy with curative intent?: Retrospective clinicopathological study of completely resected roentgenographically occult bronchogenic squamous cell carcinoma.

Although a randomized control trial demonstrated that limited surgery for small peripheral lung cancers was not as curative as lobectomy, there have been no reports concerning segmentectomy for small hilar lung cancers. In this study, we analyzed the clinicopathological features of roentgenographically occult bronchogenic squamous cell carcinomas in order to select candidates for limited resection with curative intent. From April 1982 through June 1995, 105 roentgenographically occult bronchogenic squamous cell carcinomas whose proximal edge of the lesion was more peripheral than the orifice of the segmental bronchus were completely resected. The bronchoscopic findings of the lesions were classified into three categories: remarkable, minute and hidden. Moreover, in terms of the range of endoscopic visibility, the lesions were classified into two categories: lesions within the range of endoscopic visibility and those beyond it. If lymph nodes show no signs of metastasis, roentgenographically occult bronchogenic squamous cell carcinoma is regarded as localized carcinoma and can be a candidate for segmentectomy with curative intent. In cases with minute or hidden bronchoscopic findings or of lesions within the range of endoscopic visibility, metastatic lymph nodes were never observed. Accordingly, roentgenographically occult bronchogenic squamous cell carcinomas with minute or hidden bronchoscopic findings or those within the range of endoscopic visibility can be candidates for curative segmentectomy.

Postnatal mitotic division of endothelial cells in the brain.

Ultrastructural details of capillary endothelial cells undergoing mitosis in the central nervous system are reported. These mitotic endothelial cells were seen in the brain of 10-day-old mice treated with 6-aminonicotinamide, an antagonist of niacin. Electron microscopy revealed these cells to be characterized by segregated chromosomal materials and the absence of a nuclear membrane. They possessed well-formed tight junctions with adjacent endothelial cells. Numerous microtubules radiated from a centriole toward the chromosomal material. The basal lamina of these dividing endothelial cells was not always well defined and, in some portions was discontinuous. We believe this to be the first ultrastructural demonstration of mitotic endothelial cells in the postnatal brain.

Usefulness of ultrasonography in operation for pulmonary arteriovenous fistula.

A 54-year-old woman presented with nonhereditary, bilateral pulmonary arteriovenous fistulas. One of them was small (10 x 10 mm) and embedded in the parenchyma; it was neither visible nor palpable from the pleural surface. We therefore used intraoperative ultrasonography and succeeded in detecting and enucleating the small fistula with minimal resection of the normal lung tissue.

Enteric gliopathy in niacin-deficiency induced by CNS glio-toxin.

6-Aminonicotinamide (6-AN), an antagonist of niacin and a potent CNS glio-toxin, selectively caused degeneration of glial cells in the central nervous system (CNS) of rodents. Suckling mice treated with 6-AN developed diarrhea clinically and displayed vacuolated degenerating glial cells in the myenteric plexus as well as in the CNS. Myenteric neurons were well preserved. These findings provide further evidence for possible functional similarities between the glial cells in the central and enteric nervous systems.

Aqueduct stenosis induced by a single injection of antivitamin.

Hydrocephalus with aqueduct stenosis was a consistent feature in mice which received a single intraperitoneal injection of 6-aminonicotinamide (6-AN) on day 5 postnatal. Chronological investigation revealed that 6-AN-treated mice had aqueductal obstruction with edematously swollen ependymal cells and spongy changes in the periaqueductal gray matter in the early stage (on days 5 and 7 postinjection). However, these cytoplasmic edema of the ependymal and glial cells totally subsided by day 30 postinjection, leaving an obliterated aqueduct with a few remnants of ependymal cells without reactive gliosis. This abnormality of aqueductal lesions in the chronic stage was similar to those of human congenital hydrocephalus. These findings raise the possibility that some form of human congenital hydrocephalus may result from ependymal cell degeneration due to exposure to certain noxious substances in the perinatal period.

D-penicillamine-induced copper deficiency in suckling mice: neurological abnormalities and brain mitochondrial enzyme activities.

Brain mitochondrial enzyme activities were examined in 15-day-old suckling mice which were daily injected with D-penicillamine (DP), a chelating agent of copper. Newborn mice treated with DP (1 g/kg/day) showed retarded weight gain, hyperelasticity of skin, and a bizarre forelimb posture with subcutaneous edema on experimental day (ED) 7. Paraparesis or dragging of the hindlimbs was observed by ED 15. Brain copper contents of DP-treated mice decreased to 34% of the controls of ED 15. Cytochrome c oxidase activity (complex IV) in the brain showed 51% decrease of the controls, on the contrary, rotenone-sensitive NADH cytochrome c reductase (complex I + III) and succinate cytochrome c reductase (complex II + III) were normal. Histochemistry of cytochrome c oxidase in the cerebellum of DP-treated mice disclosed diffuse reduction of staining, especially in Purkinje cells. These data show that DP-induced copper deficiency in the brain subsequently disturbs mitochondrial electron transport system, selectively cytochrome c oxidase activity. This seems to be a useful animal model not only for Menkes' kinky hair disease but also for mitochondrial encephalomyopathy.