[Surgical approaches for superior sulcus tumor].

Surgical approach is one of the most crucial aspects in the treatment of superior sulcus tumor (SST). Posterior approach as described by Paulson and coworkers is appropriate for the resection of SST invading posterior part of the 1st rib and the vertebrae, whereas anterior approaches as described by Masaoka, Dartevelle, Grunenwald, or Rusca are suitable for resection of SST involving subclavian vessels. We present 2 cases of SST who underwent complete resection through the posterior approach and a modified hemi-clamshell approach, respectively. We also discuss the surgical approaches for SST with referring to literatures.

Salmonella enterica serovar Typhi in Japan, 2001-2006: emergence of high-level fluoroquinolone-resistant strains.

The phage types and antimicrobial susceptibilities of 226 isolates of Salmonella enterica serovar Typhi from imported cases in Japan between 2001 and 2006 were investigated. Most (93.8%) had travelled to Asian countries, particularly South East Asia. Twenty-one phage types were identified with E1 (30.5%), UVS (15.9%) and B1 (9.3%) being the most common. The frequency of multidrug-resistant strains reached 37.0% in 2006 with phage types E1 and E9 predominating. Almost half (48.2%) of the isolates were resistant to nalidixic acid and two isolates displayed high-level fluoroquinolone resistance. Three mutations, two in gyrA and one in parC, were identified in both isolates.

Lipid-mediated transbronchial human interleukin-10 gene transfer decreases acute inflammation associated with allograft rejection in a rat model of lung transplantation.

BACKGROUND: Transferring genes with immunoregulatory capacity to transplanted organs has the potential to modify allograft rejection (AR). We examined the effect of ex vivo lipid-mediated transbronchial human interleukin-10 (hIL-10) gene transfer on acute AR in a rat model of lung transplantation. METHODS: Left single lung transplantations were performed between a highly histoincompatible rat combination: Brown Norway to Lewis. The extracted donor left lung was intrabronchially instilled with a plasmid encoding hIL-10 or Escherichia coli beta-galactosidase (control), mixed with a cationic lipid. On day 6 posttransplantation, the degree of AR was graded histologically (stages 1-4) based upon pathological categories of inflammation: perivascular, peribronchial, and peribronchiolar lymphocytic infiltrates, edema, intraalveolar hemorrhage, and necrosis. RESULTS: The stage of AR in the IL-10 group (3.1 +/- 0.4) was significantly lower than the control group (3.8 +/- 0.4). Pathological scores for edema, intraalveolar hemorrhage, and necrosis in the IL-10 group (2.3 +/- 0.8, 0.3 +/- 0.5, and 0.3 +/- 0.5, respectively) were also significantly decreased compared with those in the control group (3.2 +/- 0.4, 2.2 +/- 0.8, and 1.2 +/- 0.4, respectively). CONCLUSION: Ex vivo lipid-mediated transbronchial hIL-10 gene transfer attenuated acute inflammation associated with AR in a rat model of lung transplantation.

Fulde-Ferrell-Larkin-Ovchinnikov state in a perpendicular field of quasi-two-dimensional CeCoIn5.

A Fulde-Ferrell-Larkin-Ovchinnkov (FFLO) state was previously reported in the quasi-2D heavy fermion CeCoIn5 when a magnetic field was applied parallel to the ab plane. Here, we conduct 115In NMR studies of this material in a perpendicular field, and provide strong evidence for FFLO in this case as well. Although the topology of the phase transition lines in the H-T phase diagram is identical for both configurations, there are several remarkable differences between them. Compared to H parallelab, the FFLO phase for H perpendicularab is confined in a much narrower region at the low-T-high-H corner in the H-T plane, and the critical field separating the FFLO and non-FFLO superconducting states almost ceases to have a temperature dependence. Moreover, directing H perpendicularab results in a notable change in the quasiparticle excitation spectrum within the planar node associated with the FFLO transition.

Diagnostic results before and after introduction of autofluorescence bronchoscopy in patients suspected of having lung cancer detected by sputum cytology in lung cancer mass screening.

For the purpose of early detection, we have conducted population-based mass screening for lung cancer by sputum cytology since 1982. Although detection of lung cancer in its early stage is important for a good prognosis, it is often difficult to localize lesions in roentgenographically occult cancer. To clarify the role of autofluorescence bronchoscopy in localizing tumors in patients with roentgenographically occult cancer, we analyzed our diagnostic results. Fifty patients who had been detected by sputum cytology were screened by the light-induced fluorescence endoscope (LIFE)-Lung System from November 1997 to April 1999. We compared the results according to the screening methods: conventional bronchoscopy alone versus LIFE with conventional white-light bronchoscopy (November 1997 to April 1999). Twenty-eight cancerous lesions and 39 borderline lesions were detected by LIFE. Of the 39 borderline lesions, nine were detected only by LIFE. Multicentric lesions including cancer or dysplasia were also detected in 21 of the 50 patients by LIFE. The sensitivity by white-light bronchoscopy alone was 85.3%, whereas that of the LIFE-Lung System with white-light bronchoscopy was 94.1% (P=0.078). There were no cancerous lesions in the area observed as normal by LIFE. We also compared the diagnostic results of two localization methods: brushing of all bronchi (September 1986 to December 1990) and the LIFE-Lung System (November 1997 to April 1999). Although this was a historical comparison, the number of detected borderline lesions increased, which led to a high detection rate in patients with suspected-positive sputum (P=0.0006) by the LIFE-Lung System. In conclusion, the LIFE-Lung System is a safe and non-invasive system for detecting small intraepithelial lesions of the tracheobronchial tree. Autofluorescence bronchoscopy is more efficacious for localizing intraepithelial lesions and places fewer burdens on the patient than brushing of all bronchi.

[Present condition of lung transplantation candidates in eastern Japan].

We investigated the present condition of lung transplant candidates and the familiarity of doctors in eastern Japan by questionnaire. We shipped questionnaires to 614 hospitals in the Hokkaido district, the Tohoku district, the Kanto district and Niigata Prefecture, a received responses from 216 departments (200 hospitals). The percentage of respondents was 32.6%. There were 191 lung transplant candidates, 97 men and 94 women, in the past two years. Moreover, there were 45 patients with primary pulmonary hypertension (PPH), 38 with idiopathic pulmonary fibrosis, 23 with pulmonary emphysema, 20 with pulmonary lymphangiomyomatosis, among others. Currently, however, there are 88 patients who are lung transplant candidates, a large number, in eastern Japan. On the other hand, only 38 of 68 departments had informed their patients about lung transplantation. It was a lamentable result for transplant surgeons, and points urgently to the importance of giving information about lung transplantation.

[The pattern of mediastinal nodal involvement in lung cancer according to tumor-located lobe].

To clarify the pathway of the metastases from each pulmonary lobe to mediastinal nodes, we examined the pattern of mediastinal nodal involvement in 462 resected pN2 non-small cell lung cancer. Carcinomas of the right upper lobe frequently involved #3 (78/133) and #4 (70/133) nodes, whereas those of the right middle or lower lobe frequently metastasized to #7 nodes (18/23 and 86/113, respectively). On the other hand, carcinoma of left upper lobe frequently involved #5 nodes (81/118), whereas those of the left lower lobe most frequently metastasized to #7 nodes (50/75). Of 462 pN2 patients, 95 (20.6%) had skip metastases to the mediastinal nodes. Skip metastasis was observed more frequently in carcinomas of right upper and middle lobe. One of the reasons of skip metastasis may be the direct lymph drainage through subpleural space to mediastinum.

Goodpasture's syndrome associated with primary biliary cirrhosis.

A 73-year-old woman who had a history of primary biliary cirrhosis developed rapidly progressive glomerulonephritis and pulmonary-renal syndrome. She was found to have anti-mitochondrial antibody (AMA) and myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA). She also had weak anti-glomerular basement membrane (GBM) antibody. She was treated with methylprednisolone pulse therapy, but died of respiratory failure. On postmortem examination, both lungs showed diffuse hemorrhage and the immunofluorescence study of the kidney revealed linear immunoglobulin G (IgG) deposition along the glomerular basement membrane.

Studies on the mechanism of dimethylnitrosamine-induced acute liver injury in mice.

Male and female adult C3H- +/+, C3H-gld/gld.lpr/lpr (gld.lpr) and CBA-lprcg/lprcg (lprcg) mice were given a single i.p. dose of 30 mg/kg dimethylnitrosamine (DMN). Liver tissues were collected from mice killed 6, 12, 24 and 36 hrs post treatment, and the progression of the lesions was characterized morphologically and by the TUNEL method. DMN induced centrilobular hepatic injury accompanied with acute hemorrhage, and all mice died 36 to 48 hrs after the dosing. At 12 hrs after DMN administration, centrilobular hepatocytes revealed nuclear chromatin clumping. At 24 hrs, hepatocyte nuclei became fragmented to form apoptotic cells. Ultrastructurally, chromatin was condensed into a compact granular mass or crescent granular cap at the nuclear periphery. At 36 hrs, the number of apoptotic cells increased and they protruded into the sinusoid or were engulfed by the neighboring hepatocytes. A TUNEL-positive signal preceded the morphological changes and a few normal appearing centrilobular hepatocytes were positive 6 hrs post dosing. Endothelial damage was seen immunohistochemically at 24 hrs by disruption of type IV collagen and factor VIII-related antigen, resulting in massive hemorrhage in the centrilobular to mid zone. No inflammatory reactions were observed throughout the degeneration. The findings indicate that a single i.p. administration of DMN induced severe and fatal toxicity in liver tissues in mice which resembled human fulminant hepatitis. However, as gld-lpr and lprcg mice defective in apoptosis through the Fas system also showed similar severe liver damage, the Fas/Fas ligand system is not involved in DMN-induced liver apoptosis. No other organs or tissues were damaged, and the control mouse liver was intact.

Liver apoptosis after dimethylnitrosamine administration in shrews.

Female house musk shrews (Suncus murinus, Insectivora) were given a single i.p. dose of 30 mg/kg dimethylnitrosamine (DMN) at 8 weeks of age which was lethal 36 to 48 hrs after dosing. Liver tissues were collected from shrews killed 3, 6, 16, 24 and 36 hrs after treatment, and the sequential development of the lesions was characterized. DMN induced acute centrilobular cell injury. In 6 hrs, a few cells became apoptotic in the centrilobular area; the number increased at 16 hrs and 24 hrs, and was prominent at 36 hrs. There was no inflammatory reaction or necrosis and hemorrhage was not obvious. These apoptotic cells as well as normal appearing cells in the centrilobular area were labeled by the TUNEL method. In both hepatocytes and endothelial cells, apoptosis was confirmed electron microscopically as nuclear chromatin condensation at the periphery with no mitochondria swelling. When an i.p. dose of 10 mg/kg DMN was given twice at 8 and 9 weeks of age, no acute toxicity was induced, and the liver of shrews surviving for 50 weeks of age was normal with no tumor formation. These findings indicate that a single i.p. administration of 30 mg/kg DMN induced severe and fatal toxicity on liver tissues in shrews due to apoptosis, whereas 2 x 10 mg/kg DMN had no carcinogenic effect.

Immunohistochemical detection of estrogen and progesterone receptors performed with an antigen-retrieval technique on methacarn-fixed paraffin-embedded breast cancer tissues.

Immunohistochemical detection of estrogen and progesterone receptors (ER and PgR, respectively) was performed in 67 cases of Japanese female invasive breast carcinoma on methacarn-fixed paraffin-embedded sections using monoclonal antibodies against ER (1D5) and PgR (10A9) with an antigen-retrieval technique based on microwave exposure in citrate buffer solution. Staining localized in nuclei and specimens containing > or = 20% specifically stained tumor cell nuclei were considered ER- or PgR-positive; the positive rate was 37% (25/67) for ER and 45% (30/67) for PgR. The immunohistochemical (IHC) results were compared with cytosolic receptors obtained from tissue homogenates as measured by dextran-coated charcoal (DCC) assay, in which tumors were considered ER- and/or PgR-positive when receptor concentration was greater than 3 or 5 fmol/mg cytosolic protein, respectively, and agreement between the two methods was 71.6% for ER and 80.6% for PgR. The sensitivity and specificity were 53.5 and 91.7% for ER-IHC, and 77.4 and 83.3% for PgR-IHC, respectively. In relation to age of the patient and stage of the cancer, ER immunoreactivity correlated with patient's age (> or = 55 vs 55, P = 0.032), and proportionally increased with aging (P = 0.0084) using the Kruskal-Wallis statistics. PgR-immunoreactivity correlated with nodal involvement (P = 0.031) by the TNM system. However, no correlations were found between the results of the DCC assay and any of the clinical parameters examined. Thus, immunohistochemical assay may provide valuable information in predicting prognosis and response to endocrine therapy.

Experimental models for carcinogenesis in the house musk shrew, Suncus murinus, Insectivora.

Animal carcinogenicity studies have mainly been performed on rodents. From the phylogenetic point of view, animals closer to humans must be included in these studies. Insectivora are considered to be the most primitive placental mammals and much closer to the early primates than rodents. Among the insectivora, the house musk shrew (Suncus murinus, family Soracidae), has been bred under laboratory condition. This animal is small having a short life span, and a comparatively low incidence of spontaneous tumor provides a useful animal model for tumor induction studies. We have examined the carcinogenicity of several chemicals known to produce tumors in rodents and found shrews, in general, to be sensitive to these chemicals but often showed different targets compared to rodents, and some chemicals tested were demonstrated not to be carcinogenic. Here we describe the carcinogenic studies performed in our laboratory and review other works including the occurrence of spontaneous tumors in shrews. Shrew carcinogenesis may fill up the gap of knowledge existing between the rodents and human beings.

Induction of apoptosis in head and neck tumor-cell lines by anti-fas antibody.

Programmed cell death, currently termed apoptosis plays a key role in the maintenance of the steady state in continuously renewing tissues. Since little is known of apoptosis in head and neck tumors, we studied morphological changes in head and neck tumor-derived cell lines (KB, KBrc, HSC-2,3,4), induced by anti-Fas antibody. Light and electron microscopic examinations were carried out after culturing these cell lines with the antibody for 1-2 days. The antitumor effect of anti-Fas antibody on tumor cells differed with the cell lines. Most of the cell lines that were sensitive to anti-Pas antibody showed evidence of enhanced apoptosis when the cells were pretreated with interferon-gamma. The results suggest that the strategy of induction of apoptosis by anti-Fas antibody may be considered in treatment of some tumors of head and neck.

Morphogenesis of esophageal carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine in the house musk shrew, Suncus murinus (Insectivora).

The histological changes occurring in the esophageal mucosa of shrews (Suncus murinus) after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment were investigated sequentially. Six-week-old female shrews were given a 50 micrograms/ml MNNG solution as drinking water for 30 weeks, and 5 selected at random were killed at 10 and 20 weeks of age, and thereafter at 5-week intervals until 45 weeks of age. Controls were killed at 45 weeks of age. The MNNG-induced esophageal lesion in shrews began from basal cell hyperplasia at 20 weeks of age, followed by dysplasia occurring at 25 weeks of age, then progressed toward intraepithelial carcinoma to invasive squamous cell carcinoma at 35 weeks of age. Apparent sequential dysplasia-carcinoma transition was seen. Papillomas were seen from 25 weeks of age but there was no evidence of papilloma-carcinoma sequence. Five MNNG-untreated shrews killed at the end of the experiment were free of esophageal tumors.

Lectin-binding profiles in MNNG-induced shrew esophageal carcinomas.

The lectin-binding profiles of methacarn-fixed paraffin-embedded sections of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced shrew esophageal lesions (papillomas, dysplasia, and carcinoma) were studied histochemically with biotinylated lectins and compared with those in adjacent normal esophageal epithelia. The lectins used for demonstrating sugar residues were soybean agglutinin (SBA), peanut agglutinin (PNA), Helix pomatia agglutinin (HPA), wheat germ agglutinin (WGA) and Griffonia simplicifolia-I (GS-I). Lectin-binding in normal squamous epithelium showed suprabasal (SBA, PNA and HPA) or all layer (WGA and GS-I) types. Papillomas generally showed similar lectin-binding profiles to normal epithelium, with the exception of the loss of WGA staining in basal cells. There was a significant down-regulation of SBA, PNA, HPA and WGA binding in dysplasia and carcinoma cells, while GS-I binding was preserved.

Tenascin expression in normal human adult skin and skin appendage tumours.

The expression and distribution of tenascin, an extracellular matrix glycoprotein, was investigated immunohistochemically using an anti-human tenascin monoclonal antibody (RCB 1) in formalin-fixed paraffin-embedded tissues obtained from 79 patients with skin appendage tumours, and compared with adjacent normal skin. Tissue specimens were pretreated with actinase and processed by the labelled streptavidin-biotin method. In normal skin, tenascin immunoreactivity was consistently found around the ductal portion of the sweat glands, around the lower part of the hair follicle and hair bulbs, and around or within blood vessels. Immunoreactivity was also observed variably around secretory coils of the sweat glands, and below the epidermis. No immunoreactivity was seen around the sebaceous glands. Tumours originating from sweat glands and hair follicles expressed tenascin around the tumour cells nests, while sebaceous gland tumours were immunonegative. Thus, tenascin expression in skin appendage tumours generally resembled that in corresponding normal tissue.

Immunohistochemical characteristics of breast-carcinoma in patients receiving neuroleptic therapy.

The immunohistochemical characteristics of 17 cases of breast carcinoma in patients treated with neuroleptics (prolactin-releasing drug) are reported. Sixteen of the patients were female and one was male. Sixteen tumors in thirteen patients were invasive ductal carcinoma, two tumors in two patients were lipid-secreting carcinoma, one tumor was apocrine carcinoma, and two tumors in one patient were mucinous carcinoma. Elevated serum prolactin (Prl) levels (>15.0 ng/ml) were seen in all 7 patients whose preoperative serum prolactin levels had been determined. Immunohistochemical staining showed that 71% (15/21) of the carcinomas reacted positively for prolactin receptor (PrlR), while immunoreactive Prl was totally negative. Fourteen tumors were estrogen receptor (ER)-positive (67%; 14/21), and 12 were progesterone receptor (PgR)-positive (57%; 12/21). These results suggest that Prl secreted from the pituitary gland may interact with PrlR present on the cancer cells, but there was no evidence of de novo synthesis or uptake of Prl by cancer cells. ER and PgR status showed no characteristic immunoreactivity compared with unselected breast carcinoma patients not related to neuroleptic use.