Early asbestosis: evaluation with high-resolution CT

To determine the earliest stage at which lesions in asbestosis can be diagnosed and to assess their progression, 23 asbestos-exposed patients with minimal or no abnormalities at plain radiography were examined with high-resolution computed tomography (HRCT) twice, with an interval of 12-37 months between examinations. In 21 of the patients, parenchymal abnormalities were found. Major parenchymal features seen at CT included thickened intralobular and interlobular lines, subpleural curvilinear lines, pleural-based nodular irregularities, hazy patches of increased attenuation, small cystic spaces, and small areas of low attenuation. At paired serial CT, subpleural isolated dots or branching structures connected with the most peripheral branch of the pulmonary artery started to appear in lower subpleural zones and then became confluent to create pleural-based nodular irregularities. CT-pathologic correlation led to the conclusion that the confluence of subpleural peribronchiolar fibrosis creates subpleural fibrosis.     

CT and 123I-IMP SPECT findings of head injuries with hyponatremia]

CT and SPECT findings were examined and the relationship between development of hyponatremia and lesions was studied in cases who developed hyponatremia following head injury. Six cases of hyponatremia after head injury in the last two years were used as the subjects. SPECT was performed by the 123I-IMP intravenous injection method using Tomomatic 64. Slice 2 of 4 to 6 cm on the OM line in the early image was used as the subject site. The data of development of hyponatremia was 5.8 patients days, duration 9.2 days, minimum serum Na level 117.2 mEq/l and minimum plasma osmotic pressure 247.6 mOsm/lH2O. CT findings in the hyponatremic stage showed frontal subdural effusion in all the cases. SPECT findings revealed a decrease of CBF in the frontal region on both sides and in the central region. CBF in the central region also tended to improve at a time when hyponatremia improved. In hyponatremia after head injury, lesions are often found in the frontal region on CT, and CBF in the central region is also decreased bilaterally on SPECT, which is presumed to be concerned with the development of hyponatremia.     

Accelerator mass spectrometry of 36Cl produced by neutrons from the Hiroshima bomb

Accelerator mass spectrometry was performed at the Munich tandem laboratory to determine 36Cl/Cl ratios of samples from a tombstone exposed to neutrons from the Hiroshima bomb. The ratios were determined from the surface to deeper positions. The depth profile of 36Cl/Cl can be used for estimating the neutron energy distribution and intensity near the hypocentre in Hiroshima.     

Clinical investigation of pulmonary tuberculomas diagnosed by video-assisted thoracoscopic biopsy]

We investigated the clinical characteristics of pulmonary tuberculomas and discussed strategies for their diagnosis. We compared a group of patients with lesions that had been diagnosed by bronchoscopy (the BF group: 15 patients, 17 lesions) with a group whose lesions had been diagnosed by thoracoscopy (the VATS group: 19 patients, 20 lesions). The VATS group included patients with lesions that could not be diagnosed by bronchoscopy alone. The 2 groups did not differ significantly in terms of patient age, gender, lesion size, number of bronchoscopic examinations, or tuberculin test findings. In both groups, the lesions always existed just below the pleural surface and were mostly located in the upper lobes of the lungs. Lesion locations in the middle lobe and lingular segment were observed only in the BF group, whereas locations in the lower lobes were observed only in the VATS group. Tuberculomas in 2 BF group patients (11%) and 10 VATS group patients (50%) were diagnosed on the basis of histopathologic findings in the absence of bacteriological evidence. No postoperative complications were observed in the VATS group, and all patients in this group were discharged from the hospital within 1 week. No relapse of tuberculosis was observed in either group following anti-tuberculous therapy. Video-assisted thoracoscopic biopsy is a reliable and minimally invasive diagnostic procedure, and should be performed on any solitary pulmonary lesion that cannot be diagnosed by bronchoscopy. It is important that tuberculomas be quickly and accurately diagnosed not only in order to distinguish them from lung cancer, but also to treat the patient's tuberculosis at an early stage and prevent it from spreading.     

PD-L1 blockade exhibits anti-tumor effect on brain metastasis by activating CD8+ T cells in hematogenous metastasis model with lymphocyte infusion

Brain metastases are common complication in cancer patients. Immune checkpoint inhibitors show therapeutic benefits also in patients with central nervous system (CNS) metastases. However, their antitumor effects on metastatic tumors and their underlying mechanisms are still poorly understood. In this study we investigated the antitumor effect of anti-programmed death-ligand 1 (PD-L1) antibody on metastatic brain tumors and evaluated immune responses during treatment. We employed a hematogenous brain metastasis xenograft model using immunodeficient mice with murine lymphocyte infusions. A human non-small-cell lung cancer (NSCLC) cell line stably expressing NanoLuc^® reporter (Nluc-H1915) was inoculated from the internal carotid artery of SCID mice. After metastases were established (24 days after inoculation), splenocytes prepared from H1915-immunized BALB/c mice were injected intravenously and mouse IgG or anti-PD-L1 antibody treatment was started (day 1). Evaluated by Nluc activity, tumor volume in the brain on day 14 was significantly lower in anti-PD-L1-treated mice than in mouse IgG-treated mice. Furthermore CD8⁺ cells were primarily infiltrated intratumorally and peritumorally and anti-PD-L1 treatment induced a significantly higher proportion of Granzyme B (GzmB)⁺ cells among CD8⁺ T cells. The antitumor effect of anti-PD-L1 antibody on brain metastasis is thought to be achieved by the enhanced activation of infiltrated CD8⁺ T cells into metastatic brain tumor. These results suggest that anti-PD-L1 antibody-containing regimens may be promising treatment options for cancer patients with brain metastases.

     

The hotei mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development

We previously performed mutant screens in the medaka for defects in gonadal development and identified a mutant of interest in this regard, which was designated as hotei (hot). This mutant manifests a number of remarkable phenotypic abnormalities including: (i) excessive proliferation of germ cells that initiates at around the hatching stage regardless of the genetic sex of the fish; (ii) initiation of premature meiosis in phenotypically male hot homozygotes; (iii) one-half of the hot-homozygous XY fish undergo sex reversal, which accompanies the expression of the female-characteristic aromatase gene in the somatic cells of the gonad; and (iv) in phenotypically female homozygotes, follicular development is arrested at an early stage. We have also performed genetic mapping, chromosome walking, and candidate gene sequencing analysis of hot and demonstrate that the underlying mutation occurs in the recently identified medaka anti-Müllerian hormone (Amh) receptor type II (amhrII) gene. Moreover, this gene was found to be responsible for each of the hot phenotypes, as an amhrII transgene rescues these abnormalities. In addition, the amhrII gene is expressed in the somatic cells of the gonads of both sexes. The phenotypes of the hot homozygotes indicate that there are multiple regulatory functions of the AMH/AMHRII signaling system in the development of the gonad, including the sex-dependent regulation of germ cell proliferation and follicular development. These presumably represent the basic roles of Amh, which precede Müllerian duct evolution during phylogeny.     

Overexpressed cyclo-oxygenase-2 in the background liver is associated with the clinical course of hepatitis C virus-related cirrhosis patients after curative surgery for hepatocellular carcinoma

BACKGROUND: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC. METHODS: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53-73 years; follow-up period; range 22-159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin-biotin-peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery. RESULTS: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann-Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann-Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival. CONCLUSIONS: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.     

Case of local recurrence of the periurethral proximal-type epithelioid sarcoma successfully treated by repeated regional excision

Proximal-type epithelioid sarcomas are rare soft tissue neoplasms occuring in the soma or thigh and often repeat recurrence and metastasis. We present a case of locally recurrenced proximal-type epithelioid sarcoma that could be treated by regional excision alone. A 62-year-old man visited our institute for a growing mass in the perineal region. Computed tomography (CT) showed a periurethral tumor 22 x 13 mm in diameter in the perineal region. The tumor was excised regionally, and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. Local recurrence of the tumor occurred 2 years 7 months later without any metastatic lesion, and regional excision was performed again. Pathological diagnosis was proximal type epithelioid sarcoma and it was identical to the primary tumor. The patient is free of the disease 1 year after the second surgery of the tumor.