An Electron Microscopic Study of Pathological Changes of the Great Occipital Nerve Following Local Cooling

On electron microscopy the great occipital nerve of the rabbit was studied in its relation to local cooling of the head on the occipital region of the scalp to learn the ill effect of unduly prolonged bed rest using ice pillow following head injury as a part of investigation of chronic post-traumatic headache. After three hours of occipital cooling in the temperature ranging between 2°C. and 5°C. the mylin sheath is swollen, the lamella is torn and vacuoles are formed. The axon becomes atrophic, axon-Schwann interface is enlarged, and spiral invagination of the lamella is common. Endoplasmic reticulums are increased in the axon and mitochondria are swollen and cristae are destroyed. These changes are found in all fibers with no discrimination of their size. After 6 hours of cooling, these changes are brought to the extreme, and most of these changes remain long after cooling is stopped, or they are irreversible. Recovery after three hour cooling is much better. Swelling of the axon and vacuoles in the lamella disappear within two weeks, and axon-Schwann interface returns to their normal relation within two months, although spiral invagination of the lamella may remai

Immunohistochemical Characteristics of Histiocytes in Lymph Node Associated with Yellow-Brown Bodies

Yellow-brown bodies were observed in the sinusoids of lymph nodes and histiocytes. The authors confirmed immunohistochemical reactivity of alpha-1-antichymotrypsin, lysozyme, and alkaline phosphatase in non-phagocytic histiocytes, and phagocytic histiocytes which contained yellow-brown bodies. Histiocytes with yellow-brown bodies were not reacted to alpha-1-antichymotrypsin, lysozyme, and alkaline phosphatase. On the other hand, histiocytes without yellowbrown bodies were reacted to alpha-1-antichymotrypsin, lysozyme, and alkaline phosphatase

Time-Dependent Changes in Risk of Progression During Use of Bevacizumab for Ovarian Cancer

卵巣がんに対する分子標的薬「ベバシズマブ」の効果を解析 投与終了後に悪化リスクが高まることを確認、最適な投与法を提案. 京都大学プレスリリース. 2023-08-03.[Importance] Although bevacizumab has been used in the treatment of ovarian cancer, its optimal use is unknown. [Objective] To investigate time-dependent changes in the outcomes of bevacizumab therapy. [Design, Setting, and Participants] This cohort study was conducted using published data from 7 previous randomized phase 3 clinical trials with bevacizumab (ICON7, GOG-0218, BOOST, GOG-0213, OCEANS, AURERIA, and MITO16B) from January 10 to January 31, 2023. From 2 ancillary analyses of the ICON7 trial with individual patient data and tumor gene expression profiles, an ICON7-A cohort was generated comprising 745 cases. From other studies, published Kaplan-Meier curves were graphically analyzed. [Exposures] Bevacizumab treatment vs placebo or no treatment. [Main Outcomes and Measures] Restricted mean survival time and relative risk of progression at a given time point between bevacizumab treatment and control groups. [Results] In the ICON7-A cohort (n = 745), restricted mean survival analysis showed that bevacizumab treatment (n = 384) had significantly better progression-free survival (PFS) than the control (n = 361) before bevacizumab discontinuation (restricted mean survival time ratio, 1.08; 95% CI, 1.05-1.11; P < .001), but had significantly worse PFS after bevacizumab discontinuation (0.79; 95% CI, 0.69-0.90; P < .001), showing rebound. In a post hoc analysis, the rebound was similarly observed both in homologous recombination deficiency (HRD) (before, 1.05; 95% CI, 1.02-1.09; P < .001; after, 0.79; 95% CI, 0.63-0.98; P = .04) and non-HRD tumors (before, 1.08; 95% CI, 1.03-1.15; P < .001; after, 0.71; 95% CI, 0.56-0.90; P < .001) of the serous subtype, but not in the nonserous subtype (before, 1.11; 95% CI, 1.05-1.18; P < .001; after, 0.94; 95% CI, 0.78-1.15; P = .57). In Kaplan-Meier curve image–based analysis, the trend of rebound effect was consistently observed in the overall ICON7 and GOG-0218 cohorts and their subgroups stratified by prognostic factors, homologous recombination–associated mutations, and chemotherapy sensitivity. In contrast, no such trend was observed in the studies GOG-0213, OCEANS, AURERIA, and MITO16B, in which patients who experienced relapse received bevacizumab until progression. [Conclusions and Relevance] In ovarian cancer, bevacizumab may reduce progression for approximately 1 year after initiation, but discontinuation may increase subsequent progression in the serous subtype regardless of HRD status. The results suggest that in the first-line treatment, bevacizumab may be more beneficial in patients with a shorter prognosis who are less likely to experience the rebound outcome

Histochemical and Immunohistochemical Studies on the Relationship Between Severe Iron Accumulation and Liver Cell Injury

Histochemical and immunohistochemical analysis was carried out to determine the relationship between iron accumulation and hepatic cirrhosis, using 10 autopsy cases of. severe iron accumulation in the hepatocytes obtained from Kenya, including cases of Bantu siderosis. These severe iron accumulation specimens were divided into two groups ; one group consists of five cases with cirrhosis with or without hepatocellular carcinoma, and the other five cases with non-cirrhosis. All cirrhosis cases included hepatitis B surface antigen. Chronic infection caused by hepatitis B virus may lead to necrosis of the liver cells, resulting in the formation of hepatic fibrosis or cirrhosis. On the other hand, none of the non-cirrhosis cases include hepatitis B virus. This finding indicates that iron accumulation does not lead to cellular injury. Therefore, it is suggested that chronic iron toxicity is not recognized in Bantu siderosis. The reached conclusion is that there is no correlation between iron accumulation and hepatic fibrosis or cirrhosis

The Fine Structure of the Pancreatic Endocrine Cells of Salamander, Hinobius nebulosus

The pancreatic endocrine cell of adult salamanders, Hynobius nebulosus, was studied with light and electron microscopy. The following results were obtained. 1. The endocrine cells were distributed individually or in small groups, islets, and were located either in the acinus or in the duct epithelium. 2. Two types of endocrine cell group, the A cell islet and B cell islet, were observed. Each islet was light-microscopically composed of two to five cells, but electron-microscopically, only two or three cells were in direct contact with each other. 3. These islets were not always composed of the same cell type, but frequently were mingled with other cell types. 4. A and B cells were easily distinguished on the basis of the morphology of secretory granules. 5. In the B cells, the secretory granule core did not show a typical crystalline pattern. Crystalloid structures originated from mitochondria were occasionally encountered and intracytoplasmic filaments were most prominent. 6. D cells were identified by the correlative observation of thin sections with an adjacent semithin section stained with silver impregnation by HELLMAN and HELLERSTROM. The D cell secretory granules were electron low dense to moderately dense and showed varying numbers of elongate profiles besides round ones. 7. F-like cells contain electron dense, elliptic secretory granules except for spherical ones. 8. Another type of cells was distinguished. They had a scanty cytoplasm which contained extremely dense, secretory granules with different shapes. 9. The average long and short diameters of secretory granules of each cell type were measured using Reiz-ASM image analyzers

CXCL13-producing CD4⁺ T cells accumulate in the early phase of tertiary lymphoid structures in ovarian cancer

卵巣がんにおける新たな免疫の仕組みを発見 --三次リンパ様構造の形成メカニズムと予後への影響を解明--. 京都大学プレスリリース. 2022-08-05.Tertiary lymphoid structures (TLSs) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. However, how TLSs are induced in the tumor microenvironment (TME) and how they affect patient survival are not well understood. We investigated TLS distribution in relation to tumor infiltrating lymphocytes (TILs) and related gene expression in high grade serous ovarian cancer (HGSC) specimens. CXCL13 gene expression correlated with TLS presence and the infiltration of T cells and B cells, and was a favorable prognostic factor for HGSC patients. Coexistence of CD8⁺ T cells and B-cell lineages in the TME significantly improved the prognosis of HGSC and was correlated with the presence of TLSs. CXCL13 expression was predominantly coincident with CD4⁺ T cells in TLSs and CD8⁺ T cells in TILs, and shifted from CD4⁺ T cells to CD21⁺ follicular dendritic cells as TLS matured. In a mouse ovarian cancer model, recombinant CXCL13 induced TLSs and enhanced survival by the infiltration of CD8⁺ T cells. These results suggest that TLS formation was associated with CXCL13-producing CD4⁺ T cells and that TLSs facilitated the coordinated antitumor response of cellular and humoral immunity in ovarian cancer

An Electron Microscopic Study of Pathological Changes of the Great Occipital Nerve Following Local Cooling

On electron microscopy the great occipital nerve of the rabbit was studied in its relation to local cooling of the head on the occipital region of the scalp to learn the ill effect of unduly prolonged bed rest using ice pillow following head injury as a part of investigation of chronic post-traumatic headache. After three hours of occipital cooling in the temperature ranging between 2°C. and 5°C. the mylin sheath is swollen, the lamella is torn and vacuoles are formed. The axon becomes atrophic, axon-Schwann interface is enlarged, and spiral invagination of the lamella is common. Endoplasmic reticulums are increased in the axon and mitochondria are swollen and cristae are destroyed. These changes are found in all fibers with no discrimination of their size. After 6 hours of cooling, these changes are brought to the extreme, and most of these changes remain long after cooling is stopped, or they are irreversible. Recovery after three hour cooling is much better. Swelling of the axon and vacuoles in the lamella disappear within two weeks, and axon-Schwann interface returns to their normal relation within two months, although spiral invagination of the lamella may remai