Immunohistochemical investigation of lymphatic vessel formation control in mouse tooth development: lymphatic vessel-forming factors and receptors in tooth development in mice.

The presence of lymphatic vessels in dental pulp has recently been controversial, and no conclusion has been reached. In this study, we investigated the control of lymphangiogenesis with dental pulp development in the mouse mandibular molar using VEGF-C, VEGF-D, and VEGFR-3 as indices of lymphatic vessel-controlling factors. In addition, to distinguish blood and lymphatic vascular epithelial cells, we performed immunohistochemical analysis using von Willebrand factor (vWF) and statistical analysis. In dental papilla in the bell-stage non-calcified period, mesenchymal cells positive for VEGF-C, VEGF-D, and VEGFR-3 increased and lumen-forming endothelial cells were noted, but vWF was negative, suggesting that these were actively forming lymphatic vessels. Positive undifferentiated mesenchymal cells, an increase in endothelial cells in dental pulp, and lumen expansion were noted early after birth. Positivity was also detected in the odontoblast layer and sheath of Hertwig after birth, suggesting that these factors also play important roles in odontoblast differentiation and maturation and periodontal ligament and tooth root formation. We embryologically clarified lymphatic vessel formation in dental pulp and a process of lymphatic vessel formation from blood vessels, suggesting involvement of the surrounding tissue, odontoblasts, and sheath of Hertwig in vessel formation.

Magnetic X-ray absorption fine structure for Ni-Mn alloys.

Magnetic X-ray absorption fine-structure (XAFS) spectra have been measured for Ni-Mn alloys. The magnetic XAFS in the near-edge region (X-ray absorption near-edge structure, XANES) and X-ray magnetic circular dichroism (XMCD) of the Mn and Ni K-edge for Ni(1-x)Mn(x) (x = 0.25, 0.24 and 0.20) show that (i) the local magnetic structure around the Mn atom is quite different from that around the Ni atom, and (ii) the peak intensity in the magnetic XANES of the Mn K-edge depends on the magnetization of the sample in contrast to the Ni K-edge. The Mn K-edge magnetic EXAFS (extended XAFS) for Ni(0.76)Mn(0.24) is also measured. The second and fourth peaks in the Fourier transform are observed to be enhanced in comparison with the non-magnetic EXAFS, indicating that the second- and fourth-shell Ni atoms are replaced by Mn atoms due to heat treatment (atomic ordering). Semi-relativistic theoretical calculation explains the observed magnetic EXAFS.

Recurrent intracranial germinoma outside the initial radiation field with progressive malignant transformation.

A 19-year-old man with a pure germinoma in the pineal region was successfully treated with chemotherapy followed by 24 Gy local irradiation. Eight months later, magnetic resonance (MR) imaging detected ventricular wall dissemination outside the radiation field. Near complete response was achieved again after 28.8 Gy whole brain and 24 Gy whole spine irradiation. Two months later, MR imaging demonstrated recurrence of a mass at the corpus callosum. Gamma knife radiosurgery did not control this mass, so tumour resection was performed. Histological examination revealed immature teratoma. Enlargement of the recurrent mass at the trigone of the left lateral ventricle was found in spite of additional chemotherapy. Tumour extirpation was performed and histological examination revealed embryonal carcinoma. The patient died of tumour progression 34 months after the initial treatment. By a combination of chemotherapy regiments in use today, the initial radiation field to treat intracranial germinomas should not be confined to the tumour bed.

Adenocarcinoma at the site of ileoanal anastomosis in Crohn's disease: report of a case.

PURPOSE: Proctocolectomy with ileoanal anastomosis has gained acceptance for the treatment of patients with ulcerative colitis. However, there are some patients with Crohn's disease who received ileoanal anastomosis, because some Crohn's colitis is difficult to differentiate from ulcerative colitis. The risk of cancer development at the site of ileoanal anastomosis has not been emphasized in Crohn's disease. METHODS: A 12-year-old patient with Crohn's disease was treated by proctocolectomy with straight ileoanal anastomosis. Twenty-five years after the operation, the patient noticed the tumor that developed at the site of ileoanal anastomosis. RESULTS: This article presents a patient with Crohn's disease who developed invasive adenocarcinoma at the site of ileoanal anastomosis 25 years after proctocolectomy with ileoanal anastomosis. CONCLUSIONS: An ileoanal anastomosis does not eliminate the risk of cancer development, and surveillance after this operation seems advisable.

[New serum markers to monitor treatment of acute exacerbation of interstitial lung disease].

A 58-year-old woman was admitted to our hospital because of recurrent fever, severe cough and sputum. Chest radiological examinations showed diffuse reticulonodular opacities in both lung fields. Interstitial pneumonia with probable polymyositis was diagnosed. Serum surfactant protein (SP)-A, SP-D and KL-6, which are new interstitial lung disease markers, showed values significantly higher than cutoff levels. The markers increased more in parallel with the rapid development of respiratory insufficiency, CPK level, myalgia and proximal muscle weakness. Treatment with a high dose of corticosteroid and the following gradual decrease over 8 months led to clinical and radiological improvement, with normalization of values of the markers. These markers may therefore be reliable indicators of therapeutic success. However, these markers underwent different respective changes during the first 2 months. SP-A reached a maximum at the start of the treatment, while SP-D and KL-6 peaked at 5 and 10 days, respectively, after the treatment was initiated. This discrepancy demonstrates that the markers reach the bloodstream by diverse mechanisms and are useful for analyzing pathophysiological alterations in the lung in the early stages of treatment.

Identification of volatile selenium compounds produced in the hydride generation system from organoselenium compounds.

We report a novel aqueous derivatization of selenomethionine (Semet), selenoethionine (Seet) and trimethylselenonium ion (TmSe) by NaBH4 and HCI to volatile selenium species, namely, diethyldiselenide (DeDSe), dimethyldiselenide (DMDSe), dimethylselenide (DmSe) and ethylhydrogenselenide (ESeH), in the hydride generation (HG) system. The volatile selenium compounds produced in the HG system were on-line trapped and concentrated in a U-tube that was immersed in the liquid nitrogen trap. The trapped volatile Se compounds were volatilized at 80 degrees C in a water bath, and 50-500 microL of volatile gas was injected into the GC/AED and GC/MS, respectively. It has been established that DmSe, DmDSe, and DeDSe are the predominant Se compounds that are produced in the HG system from TmSe, Semet, and Seet, respectively, followed by ESeH from Seet. Analytical methods previously employed have stated that these compounds are inactive in the HG system. Prior decomposition of Semet, Seet, and TmSe to selenous acid is essential before HG. To the best of our knowledge, current findings for the production and identification of volatile selenium compounds in the HG system are new and different from existing reports; hence, direct estimation of Semet, Seet, and TmSe is possible when coupling with a HG system using a suitable Se-specific detector.

Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis.

Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)-A and SP-D as new serum markers for RP. Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT). RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP-A and SP-D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p = 0.0065, p = 0.0011, respectively). As with SP-A, ratios of SP-D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio > 1.6 was considered positive, the SP-A and SP-D assays showed an 83% and 85% specificity, respectively. In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint.

Churg-Strauss syndrome after reduction of inhaled corticosteroid in a patient treated with pranlukast for asthma.

Recently, various forms of Churg-Strauss syndrome (CSS) have been reported in association with the use of leukotriene receptor antagonists. A 53-year-old woman with a 5-year history of asthma associated with chronic sinusitis presented mononeuropathy, hypereosinophilia, and positive P-ANCA in October 1999. She had been treated with pranlukast (450 mg/day) and beclomethasone dipropionate (BDP) at a dose of 1,200 microg/day which had gradually been tapered to 800 microg/day over the previous 17 months. She was found to have CSS, and 60 mg/day of prednisolone was administered instead of pranlukast, resulting in an improvement of her symptoms and eosinophilia. Later, we confirmed that serum P-ANCA had been positive before the pranlukast treatment, but CSS vasculitis had not appeared at that time. We speculated that an underlying incomplete form of CSS was being masked in this case and that the reduction of inhaled corticosteroid might have been responsible for the unmasking of CSS.

Severe subarachnoid hemorrhage with pulmonary edema successfully treated by intra-aneurysmal embolization using Guglielmi detachable coils--Two case reports.

A 48-year-old male and a 39-year-old female presented with subarachnoid hemorrhage (SAH) due to ruptured anterior communicating artery aneurysms. Both patients were comatose on admission. Chest radiography disclosed pulmonary edema. They were conservatively treated under controlled ventilation, but cardiopulmonary dysfunction persisted over 2 days. The patients were then treated by intra-aneurysmal embolization with Guglielmi detachable coils (GDCs) 2 days after the onset. The postoperative courses were uneventful, and the patients showed full recovery from pulmonary edema and were discharged without neurological deficits. Neurogenic pulmonary edema is one of the serious complications of SAH, and is a leading cause of poor clinical outcome. The favorable outcomes of the present cases suggest that intra-aneurysmal embolization with GDCs is an excellent choice for the patients with severe aneurysmal SAH complicated with pulmonary edema, in whom conventional surgical treatment under general anesthesia is difficult to perform in the acute stage.

Blunted peripheral vasodilatory response is a hallmark of progressive deterioration in mild to moderate congestive heart failure.

BACKGROUND: Several reports have shown that dilatory response to acetylcholine (ACh) and nitroprusside (SNP) is blunted in the limb vasculature in patients with congestive heart failure (CHF). However, it is not yet known whether this vascular dysfunction is related to clinical outcome. We have examined the relationship between peripheral vasodilatory response and prognosis of CHF. METHODS AND RESULTS: A total of 46 patients with mild to moderate CHF were enrolled (mean age 56 years). Changes in forearm blood flow (FBF) during intra-arterial infusion of ACh and SNP were determined by plethysmography. FBF changes above baseline for each dose were cumulated and used as an index of endothelium-dependent (ACh) response and endothelium-independent (SNP) response, respectively. During the follow-up period (mean 32 months), 9 patients were admitted to the hospital for treatment of worsening refractory CHF, and 6 patients died suddenly or developed life-threatening arrhythmia. By Kaplan-Meier analysis, when all cardiac events were included, no significant differences were observed between any levels of vascular response in terms of prognosis. However, when deterioration events were analyzed separately, patients with SNP responses below the median (7.4 mL/min/dL) had significantly higher rates of hospital admission caused by worsening CHF than those with above the median responses (P <.05). This relationship was not found between ACh response and clinical outcome. By Cox multivariate analysis, blunted vasodilatory response to SNP was a significant predictor of worsening CHF (chi(2) = 3.95; P <.05). CONCLUSION: This study has shown that patients with mild to moderate CHF showing a blunted vascular response to SNP rather than ACh were admitted to the hospital more frequently because of deterioration of CHF. This finding suggests that changes in vascular smooth muscle and/or vascular structure in the peripheral vasculature may be a critical element in the worsening of CHF.

Abdominal involvement in neurofibromatosis 1: sonographic findings.

BACKGROUND: Neurofibromatosis 1 (NF1) has been studied from many viewpoints, but its abdominal involvement has rarely been reported. Sonography (US) is now the initial diagnostic tool for abdominal exploration, which prompted us to determine the clinical manifestations and US findings of abdominal involvement in NF1. METHODS: We analyzed the US findings and clinical data of eight NF1 cases with abdominal involvement. RESULTS: Abdominal involvement included neurofibromatous tumor growth in the liver, mesentery, and retroperitoneum, in addition to mesenteric leiomyomatosis and gastric carcinoma. Color Doppler US was useful not only in detecting blood flows in the lesions but also in preventing hazardous vascular injury during tumor biopsy. CONCLUSION: A better understanding of the clinical manifestations and US findings of abdominal involvement in NF1 translates into improved NF1 patient care.

Microsatellite instability and the PTEN1 gene mutation in a subset of early onset gliomas carrying germline mutation or promoter methylation of the hMLH1 gene.

High-frequent microsatellite instability (MSI-H) was detected in two of the 80 gliomas examined, whlie the other 78 gliomas showed microsatellite stable (MSS) phenotype. Both of the two MSI-H tumors were glioblastomas which developed in teenage patients. One of the patient was diagnosed as having Turcot's syndrome and had a germline mutation in the hMLH1 gene. Loss of expression due to promoter methylation was selectively observed in the wild type allele of the hMLH1 gene in the tumor of this patient. The other patient had neither a family history nor a past personal history of malignancy. Although no mutation in the mismatch repair genes was detected in the tumor of this patient, the level of expression of the hMLH1 gene was markedly decreased and the promoter sequence of the gene was highly methylated. In the tumor of this patient, the PTEN1 gene, one of the genes carrying microsatellite sequences in their coding regions, was altered by a slippage mutation within five adenine repeat sequences. These findings indicate that the genetic or epigenentic inactivation of the hMLH1 gene is involved in a subset of early-onset gliomas and the PTEN1 gene could be a downstream target for mutation as observed in glioblastoma without MSI.

Mucosal carcinoma within a colonic diverticulum.

We report a case of a mucosal carcinoma and adenoma within a diverticulum in the cecum. Radiographic, endoscopic, and pathologic evaluation of the tumor is presented. Surgical resection was undertaken because of the size and shape of the lesion, risk of perforation, and the possibility of malignancy. A recent review of the literature with respect to clinical signs, diagnosis, growth of the carcinoma, and treatment of tumors around or within diverticula is also presented. A carcinoma or adenoma arising within the diverticulum is very rare. Endoscopic resection of the tumor could entail the risk of perforation, because of the lack of muscular coats in the diverticula. Surgical treatment may be the procedure of choice for lesions near or within the diverticula.

Allergic bronchopulmonary aspergillosis due to Aspergillus niger without bronchial asthma.

A 65-year-old woman was admitted to our hospital with a dry cough and pulmonary infiltrates. Chest radiograph and CT revealed mucoid impaction and consolidations. Peripheral blood eosinophilia and elevated serum IgE were observed. Aspergillus niger was cultured repeatedly from her sputum, but A. fumigatus was not detected. Immediate skin test and specific IgE (RAST) to Aspergillus antigen were positive. Precipitating antibodies were confirmed against A. niger antigen, but not against A. fumigatus antigen. She had no asthmatic symptoms, and showed no bronchial hyperreactivity to methacholine. Thus, this case was diagnosed as allergic bronchopulmonary aspergillosis (ABPA) without bronchial asthma due to A. niger, an organism rarely found in ABPA. The administration of prednisone improved the symptoms and corrected the abnormal laboratory findings.

Metabolism of prostaglandins in porcine liver transplantation with a graft harvested after 30- and 60-minute warm ischemia.

The influence of warm ischemia on the metabolism of prostaglandins was investigated using a pig liver transplantation model employing the temporary portal arterialization technique. Eighteen pigs were divided into three groups according to warm ischemia time: 0 min (group I, n = 6), 30 min (group II, n = 6), and 60 min (group III, n = 6). During portal arterialization, the hepatic venous prostaglandin E2 (PGE2) level in group III (3356.0 +/- 1011.8 pg/ml) was significantly higher than that in group I (831.7 +/- 182.1 pg/ml; P = 0.0285). The hepatic venous PGE2 levels were significantly higher than the arterial counterparts in all groups both at the beginning and during portal arterialization. At 60 min after portal revascularization, the arterial PGE2 level in group III (886.7 +/- 268.0 pg/ml) was significantly higher than that in group I (99.0 +/- 18.6 pg/ml; P = 0.0116) and II (204.2 +/- 65.4 pg/ml; P = 0.0282). Neither thromboxane B2 (TXB2) nor 6-keto PGF1 alpha showed any significant differences. In conclusion, the intraoperative changes of PGE2 thus reflected the degree of warm ischemic damage, and PGE2 could also be released from the graft. On the other hand, the increased levels of TXB2 and 6-keto PGF1 alpha were thought to have an extrahepatic origin.

Structural and functional evidence for the presence of tumor suppressor genes on the short arm of chromosome 10 in human gliomas.

Loss of heterozygosity (LOH) observed at polymorphic loci on both arms of chromosome 10 in many human gliomas suggests the presence of multiple tumor suppressor genes on this chromosome. Recently, the PTEN/MMAC1 gene on 10q23 was isolated as one of these putative glioma suppressors. To determine the subchromosomal localization of others, we analysed 79 gliomas for LOH using 30 polymorphic microsatellite markers on the short arm and 10 markers on the long arm of chromosome 10. Twenty tumors showed LOH at all the loci examined, while 17 others showed LOH at loci on a portion of chromosome 10. Deletion mapping of the latters demonstrated that two distinct regions, encompassing genetic distances of 5.6 cM on 10p15 and 5.5 cM on 10p14, were lost frequently. Introduction of chromosomal fragments 10p14-p15, which included the entire region on 10p15 and a portion of that on 10p14 assigned by deletion mapping, into the human glioblastoma cell line T98G through microcell-mediated chromosome transfer markedly suppressed colony forming ability in soft agar compared with parental T98G cells. The combined results of structural and functional analyses strongly suggest that aberrations of the tumor suppressor gene(s) within chromosomal region 10p14-p15 are involved in development of human gliomas.

[Evaluation of intra-arterial infusion chemotherapy for liver metastasis from gastric cancer].

We evaluated the result of intra-arterial infusion chemotherapy on liver metastasis from gastric cancer. Of 92 cases of metastatic liver tumor, 17 cases received intra-arterial infusion chemotherapy after primary resection. For comparison, we assigned the 17 cases to two groups according to the infused agents. One group was treated with the combination therapy of 5-FU, epirubicin and MMC (FEM group: n = 7), and another with other antineoplastic agents (non-FEM group: n = 10). In the FEM group, the response rate, 1-year survival rate and 50% survival period were 33.3%, 51.4%, 430 days, respectively, while those of the non-FEM group were 10.0%, 10.0%. 147 days. Although there was no significant difference (p = 0.0951), improvements in survival rate and survival period were observed. This implies the possibility that intra-arterial infusion chemotherapy, especially the combination therapy of FEM, is an effective treatment for liver metastasis from gastric cancer.

[Complication due to arterial infusion chemotherapy for liver metastasis from colorectal cancer].

OBJECTIVES: Arterial infusion chemotherapy is considered to be an extremely effective treatment for liver metastasis from colorectal cancer in terms of its tumor reduction and preventing recurrence in residual liver after resection. However, there still remain some unclear points as to the influence on hepatic artery and bile duct when this treatment is used over the long term. We report some conclusions obtained by examining cases of hepatic arterial occlusion (stenosis) and biliary complication who received this treatment. MATERIALS AND METHODS: Thirty-six cases who received this treatment over 3 months were the objects of this study, with the aim of direct effect against metastatic focus (21 cases) and prevention of recurrence in residual liver (15 cases). The ages were from 27 to 81; 22 cases were male and 14 were female. Indwelling routes of catheter were gastroduodenal artery (GDA) in 28 cases and femoral artery (FA) in 8 cases. Intermittent high-dose infusion (WHF: 5-FU 1,000 mg/m2/5 hrs qw) was adopted as the method. RESULTS: Hepatic arterial occlusion or stenosis was observed in 12 cases (GDA: 10; FA: 2). There seemed to be no correlation with the total dosage of 5-FU or the number of administrations. Even when hepatic arterial occlusion or stenosis occurred, no change was observed in liver function, and there no death was caused by this. However, CT showed a low-density area followed by atrophy in the right lobe in one case with right hepatic arterial stenosis, despite normal portal blood flow. Of the 6 cases which developed obstructive jaundice, 4 were due to the increase of metastatic focus or lymph nodes, and 1 case without dilatation of bile duct died from suspected sclerosing cholangitis. In this case, ALP had been increasing since 1 month before the onset of jaundice. Another case which developed biloma accompanied by the increase of serum bilirubin improved by discontinuance of chemotherapy. CONCLUSION: Since arterial infusion chemotherapy for liver metastasis from colorectal cancer causes hepatic arterial occlusion (stenosis) at a high rate, early detection of abnormalities by liver function test and imaging diagnosis which leads to early treatment is important.