The lung transplantation has come to be done in Japan

After the establishment of transplantation law, the right pulmonary transplantation was done from the brain dead donor for the first time in Japan at the attached hospital of Institute of Development, Aging and Cancer, Tohoku University on March 29, 2000. The woman in 30's had been deteriorated from progressive lymphangiomyomatosis since 1984. She was waiting for the right lung transplantation in the related hospital of the Institute Hospital since May, 1999. A brain dead donor appeared in Tokyo. After receiving the information from Japan Organ Transplant Network, we immediately started for Tokyo in order to procure the lung. We carried the right lung by Shinkansen. The lung of the donor was transplanted to the patient under the partial extracorporeal circulation on March 29, 2000. The total operating time was 6 hours and 7 minutes: 5 hours and 20 minutes for total ischemic period of the lung and 2 hours and 7 minutes for using extracorporeal circulation. The total amount of bleeding during the operation was 3,695 ml. Postoperative course of the transplanted patient was fair except chylothorax in the operated side, which was successfully controlled by intrathoracic infusion with OK-432. The transplanted patient was discharged from the hospital after 75 days postoperatively.     

Near‐infrared photoimmunotherapy through bone

Near‐infrared photoimmunotherapy (NIR‐PIT) is a molecularly targeted cancer phototherapy that is based on injecting a conjugate of a silicon‐phthalocyanine derivative, IRdye 700DX (IR700), and a monoclonal antibody that targets an expressed antigen on the cancer cell surface. Subsequent local exposure to NIR light results in the rapid and highly selective immunogenic cell death of targeted cancer cells. Because many cancers grow in bones through which light does not penetrate well, the goal of this study was to determine if NIR‐PIT can effectively treat cancers in bone. A bovine rib was used as a bone sample. Because the sample’s NIR light transmittance was shown to be approximately 4.52% in preliminary tests, it was hypothesized that a maximum radiation dosage of 128 and 1500 J/cm² would be sufficient to induce cell death in in vitro target cells and in vivo mouse tumor models, respectively. Cell viability was measured through bioluminescence studies comparing relative luciferase activity, as well as a cytotoxicity assay. In the in vitro model, tumor cell viability was significantly decreased after 64 and 128 J/cm² NIR light irradiation through the bone. An in vivo mouse tumor model also showed that 1500 J/cm² NIR light irradiation through the bone significantly reduced tumor viability at both 24 and 48 hours posttreatment compared to the control group (P = .026 and .040 respectively). Therefore, despite limitations in light transmission, NIR‐PIT nevertheless is capable of effectively treating cancers within bone.     

Correlation between overexpression of c-met gene and the progression of gastric cancer

The c-met oncogene encodes a receptor of hepatocyte growth factor (HGF), which has both mitogenic and motogenic activities. We have studied the c-met gene expression in gastric cancer by immunohistochemical method using an antibody specific to the c-met beta-chain. c-met immunoreactivity was preferentially localize on the cell membrane, and 55 (43%) of 127 primary gastric cancers showed c-met immunoreactivity. Strong correlation was found between c-met expression in large tumors, lymph node involvement, serosal invasion, as well as peritoneal dissemination. Furthermore, c-met positive tumors had a tendency to metastasize to more distant lymph node sites. Regarding the macroscopic type, Borrmann type 4 gastric cancer showed the highest incidence (12/16, 76%) of positive c-met expression. Patients with c-met positive tumor ran a significantly poorer prognosis than those with c-met negative one. These results indicate that the c-met protein participates in the progression and invasion of stomach cancer, and that c-met tissue status is a useful biological marker in gastric cancer.     

Effects of crude drugs on experimental hypercholesterolemia. I. Tea and its active principles

The effect of methanol extractives from tea leaves on hypercholesterolemia was examined in animal models. It was found that orally administered (-)-epicatechin gallate and (-)-epigallocatechin gallate from tea leaves lowered the serum cholesterol level in mice fed a high fat emulsion. Quantitation of tissue cholesterol and examination of liver tissues in mice fed a high cholesterol diet revealed that these constituents also significantly lowered the amount of cholesterol crystallization. These results support the reputed effectiveness of tea use in hypercholesterolemia.     

Detection of New H5N1 High Pathogenicity Avian Influenza Viruses in Winter 2021–2022 in the Far East,Which Are Genetically Close to Those in Europe

Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021–2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020–2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 10^4.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs.     

Effect of carbon on the co-presence of metallic tungsten as a nucleation agent and Eu2+ in glass: crystallization of CaO–Al2O3–SiO2 glass probed with Eu2+ luminescence

This study demonstrated simple redox control in glasses by improving the method used to added glass raw materials. Specifically, the effect of carbon on the co-presence of metallic tungsten (W) particles as nucleation agents and Eu²⁺ ions in CaO–Al₂O₃–SiO₂ (CAS) glass was investigated via their crystallization to form CAS glass-ceramics (GCs). In this study, the glass specimens were prepared by mixing glass cullet containing metallic W particles and Eu²⁺ ions, respectively, with a glass batch containing carbon. Whereas the glass specimen was yellowish because of the presence of Eu²⁺ when carbon was not added during the remelting process, the glass specimen prepared with carbon was black because of the presence of metallic W particles. In addition, this specimen displayed the 470 nm emission band in its fluorescence spectrum recorded under 393 nm excitation, which was attributed to the presence of Eu²⁺. According to the fluorescence and transmission spectra, the glass specimen showed a darker coloration and more intense 470 nm emission band compared with the specimen prepared by the conventional melting method that included a remelting process. These results indicated that metallic W and Eu²⁺ were reduced with greater efficiency by the melting method that involved mixing the glass cullet and batch. In addition, the heat-treated glass specimen prepared by the aforementioned mixing method contained a greater amount of metastable CaAl₂Si₂O₈ with increasing heat treatment time as revealed by X-ray diffraction analysis and scanning electron microscopy observation. The intensity of the 470 nm emission band decreased with increasing intensity of the band at 420 nm because of the incorporation of Eu²⁺ into the crystalline phase, and the increase in intensity of the 420 nm band was lineally proportional to the volume fraction of the crystallized glass specimens. The results therefore indicated that the co-presence of metallic W particles as nucleation agents and Eu²⁺ as a probe for tracking the crystallization process was achieved by the addition of carbon during the remelting process of mixed cullet containing W and Eu²⁺ through crystallization of the CAS glass. The results thus demonstrate the importance of improving the method used to added glass raw materials.

Effect of carbon on the co-presence of metallic tungsten (W) as nucleation agents and Eu²⁺ ions as a probe for tracking crystallization in CaO–Al₂O₃–SiO₂ (CAS) glass was demonstrated by efficient reduction method of Eu²⁺ and metallic W.     

Biodistribution of Insulin Following Massive Insulin Subcutaneous Injection

A man in his 30s injected insulin several times into his abdomen and was found dead several hours later. Micropathological findings showed alveolar injury with hemorrhaging and cerebral parietal lobe nerve cell edema. Biochemical examinations showed that the blood insulin level was high, significantly so at the insulin injection sites. The blood glucose and C-peptide levels were low. The insulin level in the kidneys was low. In forensic medicine, a postmortem diagnosis of insulin subcutaneous injection is often difficult. When insulin injection is suspected, particularly high insulin levels can be expected at the insulin injection site, rather than in the blood.