Perforin expression in lymphocytes infiltrated to human colorectal cancer

Perforin (PFP) is a cytotoxic protein released from killer cells. PFP immunoreactivity in human peripheral blood lymphocytes (PBL) and tumour infiltrating lymphocytes (TIL) was investigated immunocytochemically with the aid of an anti-PFP monoclonal antibody. PFP was detected in the cytoplasm of 10% of PBL. We performed a double staining of PFP+ cells with Leu11b/CD16, Leu2a/CD8, or Leu3a/CD4 and showed that PFP was produced by 9% of CD8+ cells and 18% of CD16+ cells but not by CD4+ cells. In 28 colorectal cancer tissues, PFP immunoreactivity was observed in the lymphocytes infiltrating to the tumour stroma. The PFP+ cells were most numerous in Dukes A and decreased in number according to the progression of tumours. The PFP+ cells in TIL exhibited the same phenotypes as those in PBL but the PFP+ cells were more numerous in CD8+ cells than in CD16+ cells at all stages. This study represents the first evidence that PFP is mainly secreted from CD8+ cells in tumour tissues. It is hypothesised that the decrease in the number of PFP+ cells in accordance with tumour progression may reflect the suppression of the hosts local immunity.     

Comparison of characteristics of esophageal squamous cell carcinoma associated with head and neck cancer and those with gastric cancer

In ongoing reviews of 339 patients with surgically treated primary squamous cell carcinoma, there were 19 (5.6%) with concurrent gastric cancer and 11 (3.2%) with head and neck cancer. The incidences of intra-esophageal multiple occurrence of esophageal cancer are 27.3% and 26.3% in those with associated head and neck cancer and gastric cancer, respectively, and higher than 7.1% in those without such a concurrent cancer. There was no difference in the clinicopathological characteristics of those with concurrent head and neck and gastric cancers, except for the higher incidence of metachronous occurrence in the former. These findings suggest that, in cases of esophageal cancer associated with concurrent head and neck cancer and gastric cancer, intraesophageal multiplicity of the esophageal carcinoma is frequent and that preoperative serial evaluations is most important to design treatment and estimate the prognosis.     

Effects of 2,4-dichlorophenoxyacetic acid on Rhizobium sp. in pure culture

The effects of 2,4-Dichlorophenoxyacetic acid on the growth rate, chemical composition, ¹⁴C-2,4-dichlorophenoxyacetic acid and ⁴⁵Ca²⁺ uptake by Rhizobium sp. M 4 able to nodulate Arachis hypogaea were determined. Cellular growth was diminished by the presence of 10^?3 M 2,4-dichlorophenoxyacetic acid in the medium. Alterations in cellular chemical composition, in ¹⁴C-2,4-dichlorophenoxyacetic acid and in ⁴⁵Ca²⁺ uptake were found.     

Metabolic fate of 125I-labeled batroxobin in rats and dogs

125I-Labeled batroxobin was prepared and following its intravenous and subcutaneous administrations to rats and dogs, the blood radioactivity was determined. In the both species following the intravenous injections, the decrease in radioactivity was biexponential. Following subcutaneous administration, radioactivity became maximal at 6h and decreased in a manner similar to that of the beta-phase of the intravenous injection. The blood concentration of fibrinogen in dogs was also determined. After the intravenous injection, fibrinogen became undetectable 1h later, and appeared again in the blood at 24h. After the subcutaneous injection, the decrease was not so rapid. Fibrinogen resumed its original levels at 7 day after the administration in both the routes. Radioactivity after the both injections was excreted generally in the urine in about the same amounts. The total urinary and fecal excretions in rats and dogs were 80 and 95%, respectively. The distribution of radioactivity in the tissues was examined by counting technique and whole-body autoradiography. Radioactivity predominantly accumulated in the thyroid and stomach and could also be found in the kidneys and liver in fair amounts. The distribution patterns of radioactivity for both the routes of administrations and also for male and pregnant rats were basically the same. In fetus rats, a slight distribution was noted. From the results of gel filtration chromatography and trichloroacetic acid fractionation, [125I] batroxobin was metabolized soon after the administration to afford low molecular substances such as 125I-ion in the plasma and urine.     

Induction chemoradiotherapy prior to surgery for non-small cell lung cancer invading the left atrium.

We present a case of a 58-year-old man with diagnosis of lung adenocarcinoma invading the left atrium. He was treated with induction chemoradiotherapy for T4N1M0 disease, showing objective response. Then, a left upper lobectomy with a partial resection of the left atrium was performed without cardiopulmonary bypass. No residual tumor cells existed in the resected specimens, showing pathological complete response. Our case suggests that induction chemoradiotherapy prior to surgery can be an appropriate strategy among carefully selected patients with non-small cell lung cancer invading the left atrium.     

A case of chronic hepatitis C virus-related advanced hepatocelluar carcinoma surviving more than 8 years]

A 64-year-old man was admitted for further examinations of a liver tumor. The patient was diagnosed as chronic hepatitis C complicated with advanced hepatocelluar carcinoma (HCC) with left portal vein tumor thrombosis. As he refused surgical treatment, hepatic arterial infusion chemotherapy (HAIC) using cisplatin and 5-fluorouracil was performed initially. Administration of ursodesoxycholic acid (UDCA) was also started. Following HAIC, microwave coagulation therapy for residual tumor was added. Consequently, viable lesions of HCC disappeared completely. At present, after more than 8 years, neither signs of tumor recurrence, nor elevation of hepatic enzymes has been observed. Although the precise reason for long survival of this patient is not known, we speculate that suppression of levels of hepatic enzymes, as well as HAIC for subclinical intrahepatic metastasis, contributed to the good outcome. Therapeutic strategy for hepatic inflammation seems to be important for long-term prevention of hepatocarcinogenesis.     

A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis]

A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.     

A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivation

A 65-year-old Japanese man was hospitalized because of acute hepatitis and severe cholestasis due to hepatitis E virus (HEV) infection combined with a drug reaction to a cold preparation. He died of disseminated intravascular coagulation and severe intestinal bleeding due to systemic cytomegalovirus reactivation following the development of severe eruptions with marked eosinophilia due to drug hypersensitivity to taurine and ursodeoxycholate preparations. The close interaction between viral infection or reactivation and drug hypersensitivity was considered as a pathophysiology in this case, which emphasizes the need for further study of the immunological mechanism of the interaction.     

Pressure overload-induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II.

Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 [MCP-1] induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.