Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants.

Immunity to collagen V [col(V)] contributes to lung 'rejection.' We hypothesized that ischemia reperfusion injury (IRI) associated with lung transplantation unmasks antigenic col(V) such that fresh and well-healed lung grafts have differential susceptibility to anti-col(V)-mediated injury; and expression of the autoimmune cytokines, IL-17 and IL-23, are associated with this process. Adoptive transfer of col(V)-reactive lymphocytes to WKY rats induced grade 2 rejection in fresh isografts, but induced worse pathology (grade 3) when transferred to isograft recipients 30 days post-transplantation. Immunhistochemistry detected col(V) in fresh and well-healed isografts but not native lungs. Hen egg lysozyme-reactive lymphocytes (HEL, control) did not induce lung disease in any group. Col(V), but not HEL, immunization induced transcripts for IL-17 and IL-23 (p19) in the cells utilized for adoptive transfer. Transcripts for IL-17 were upregulated in fresh, but not well-healed isografts after transfer of col(V)-reactive cells. These data show that IRI predisposes to anti-col(V)-mediated pathology; col(V)-reactive lymphocytes express IL-17 and IL-23; and anti-col(V)-mediated lung disease is associated with local expression of IL-17. Finally, because of similar histologic patterns, the pathology of clinical rejection may reflect the activity of autoimmunity to col(V) and/or alloimmunity.

Completion pneumonectomy of the residual left lung to treat lung cancer in a patient with hemophilia A: report of a case.

Hemophilia A is a sex-linked recessive hereditary disease that is relatively rare and the number of patients with this disorder who undergo major surgery is limited. Although replenishing coagulation factors can allow hemophiliac patients to undergo similar surgery to that performed for patients without hemophilia, there have been few reports on major surgery and none on the resection of lung cancer in patients with hemophilia A. We recently performed completion pneumonectomy of the left lung in a 70-year-old man with hemophilia A, for squamous cell carcinoma in the residual left lung. The administration of a recombinant DNA coagulation factor VIII preparation allowed this operation to be successfully carried out. This case serves to demonstrate that the recombinant DNA coagulation factor VIII preparation described may enable us to safely perform major surgery on hemophiliac patients, since there is no risk of viral infection or any other adverse effects, such as deterioration of immunocompetence or hemolysis, which are occasionally encountered with human plasma-derived preparations.

[Expression of brain-derived neurotrophic factor gene in retina following vitreous tap].

PURPOSE: Mechanical injuries to the retina following vitreous tap are reported to protect photoreceptor cells in a rat model of the retinal degeneration and enhance the survival rate of retinal ganglion cells in the optic nerve transection. Neurotrophic factors are presumably involved in the protective mechanisms. In order to see whether neurotrophic factors are synthesized in the retina, we studied the expression of neurotrophic factors in the retina following vitreous tap in rats. MATERIALS AND METHODS: One eye each of 20 mature rats received transscleral vitreous taps at three points of entry and retinal injury. The retinas were removed and examined at day 0 to 14 of treatment. RESULTS: Following injury, the retina showed increased expression of glial fibrillary acidic protein (GFAP) mRNA and brain-derived neurotrophic factor (BDNF) mRNA. There was no enhancement of neurotrophin-3 (NT-3) mRNA when examined by reverse transcription-polymerase chain reaction (RT-PCR). CONCLUSIONS: Activated retinal glial cells may produce BDNF which prevents retinal neuronal cell damage following injury.

All-trans retinoic acid reverses phorbol ester resistance in a human myeloid leukemia cell line.

Treatment of human HL-60 leukemic cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with activation of protein kinase C (PKC) and induction of monocytic differentiation. An HL-60 variant cell line, termed HL-525, derived from long-term exposure to TPA (Homma et al, Proc Natl Acad Sci USA 83: 7316, 1986) is resistant to TPA-induced differentiation and displays decreased PKC beta expression compared with the HL-60 parent line. However, this variant exhibits features of granulocytic differentiation, including nitroblue tetrazolium reduction, when exposed to all-trans retinoic acid (ATRA). Whereas treatment of HL-525 cells with ATRA or TPA alone had no effect on features of monocytic differentiation, these agents in combination resulted in cellular adhesion, nonspecific esterase staining, and induction of the c-fms (monocyte growth factor receptor) gene. In order to measure PKC expression associated with the reversal of TPA resistance by ATRA, we exposed HL-525 cells to ATRA and analyzed PKC-mRNA and protein levels. Exposure of HL-525 cells to ATRA for 3 days resulted in induction of PKC beta transcripts, whereas there was little change in PKC alpha mRNA levels. ATRA treatment was also associated with an increase in PKC activity and an induction of cytosolic PKC beta protein levels. These findings are consistent with the hypothesis that ATRA reverses TPA resistance in HL-525 cells by enhancing the expression of PKC.

Changes in alpha-tubulin and actin gene expression during optic nerve regeneration in frog retina.

The optic nerve of the bullfrog was transected and the regeneration process was investigated. We previously reported that alpha-tubulin mRNA in the retina increased to a maximum 1-2 h after optic nerve transection with no specific change in actin mRNA. In the present investigation, we examined the long-term effect of optic nerve transection. Northern blot analysis revealed that alpha-tubulin mRNA increased again gradually after the rapid and transient increase and actin mRNA increased to a maximum at 7 days (more than twofold compared to the control retinas). The period during which actin mRNA reaches a maximal increase almost corresponds to the time lag between the axotomy and the initiation of axonal outgrowth. The main cytoskeletons of neuronal growth cones have been shown to consist of actin-containing microfilaments. Therefore, the transient increase of actin mRNA may have a relationship to the initial outgrowth of axons. On the other hand, the rapid and transient increase of alpha-tubulin mRNA observed in our previous studies is probably one of the initial responses of retinal ganglion cells to the axotomy, and the gradual increase in alpha-tubulin mRNA observed in this study can probably be interpreted as provision of the structural materials necessary for axonal elongation.

[A case of lymphangiomas arising contiguously from the rib and thoracic spine].

Reported is a rare case of lymphangiomas arising contiguously from the left 6 th rib and thoracic spine of a 33-year-old female. The localization of the osteolytic lesions that had been observed by chest X-rays were more precisely detected by subsequent computed tomography. Histologically, dilated vessels lined with endothelial cells were observed in the bone marrow. Immunostaining uncovered factor VIII-related antigens in the endothelial of the small vessels, but not in those of the larger vessels. In order to differentiate lymphangiomas from hemangiomas of the bone, not only should the histological features of the lymph vessels be observed at time of operation also the ability these vessels to retain lymph is important. Primary lymphangioma of the bone should be differentiated from lymphangiomatosis and massive osteolysis, which show a poor prognosis.

[A case of malignant transformation of gastric hyperplastic polyp with metaplastic bone formation].

A case of malignant transformation of a gastric hyperplastic polyp with a metaplastic bone formation is reported. A large gastric polyp was revealed by X-ray examination and by endoscopy in the cardia of a 89-year-old female who had complained of nausea. A polypectomy was performed since the biopsied materials had contained some atypical glands intermingled with hyperplastic glands. Histologically, the polyp, 1.7 x 1.0 x 0.6 cm in size, was a hyperplasic polyp that was found to contain superficial dysplastic foci associated with a moderately differentiated type of a tubular adenocarcinoma. A metaplasic bone formation was found in stroma beneath the hyperplastic glandular epithelium. Thus, polypectomy of hyperplastic polyps of the stomach of more than 1 cm with dysplastic foci is recommended.

c-Fos mRNA induction under vitamin B6 antagonist-induced seizure.

c-Fos mRNA expression was studied in mouse brain after vitamin B6 antagonist-induced seizure. The vitamin B6 antagonists used were hydrazine, thiosemicarbazide, penicillamine and deoxypyridoxine. Only deoxypyridoxine was effective in increasing c-fos mRNA and c-fos protein expression in nerve cells. The other 3 antagonists had levels of c-fos mRNA below or equal to basal level. The seizure activity induced by several vitamin B6 antagonists resulted in different effects on c-fos gene expression.

Duodenal carcinoid (somatostatinoma) combined with von Recklinghausen's disease. A case report and review of the literature.

We report the immunohistochemical and ultrastructural features of a case of duodenal carcinoid (somatostatinoma) combined with cutaneous-type von Recklinghausen's disease in a 65-year-old woman. The duodenal tumor located at the 2nd portion was composed of tumor cells arranged in a trabecular, glandular or nest-like pattern, occasionally associated with eosinophilic globules in the glandular structures. The tumor cells mostly showed strong immunoreactivity with anti-somatostatin antibody. Electron microscopy revealed that every tumor cell contained intracytoplasmic granules with electron-dense cores, 100-300 nm in size, in varying numbers, and intracytoplasmic lumina were rarely detected. The present case including identical cases reported so far suggest that the disease entity is likely to be a combination of duodenal somatostatinoma and von Recklinghausen's disease and/or phaeochromocytoma. This is the tenth case of duodenal carcinoid associated with von Recklinghausen's disease and/or phaeochromocytoma in the world literature and the third case reported as duodenal somatostatinoma.

Increased tubulin messenger RNA in the frog retina after optic nerve transection.

The optic nerve of the bullfrog (Rana catesbeiana) was transected and the regeneration process was investigated. The nerve regeneration was confirmed by observing the extension of the axon and by examining the recovery of axonal transport. Following optic nerve transection, the rapid and transient increase of messenger RNA of alpha-tubulin gene was observed in the retina, but no specific change of actin messenger RNA was observed.

An elevated type of gastric ulcer scar in patients treated with cimetidine.

An elevated type of gastric ulcer scar (EUS) (A) was noted in 8 out of 227 ulcer patients treated with cimetidine. These were compared with 15 patients with EUS (B), not treated with cimetidine and the etiology of the lesion was discussed. The incidence of EUS (3.5%) and the average age of the patients were higher (61 years) in the A group than in the B group. The scar was seen all over the stomach in the A group. The period from detection of gastric ulcer to confirmation of EUS averaged 4 weeks, and there was no difference between the two groups. No difference was seen in the histological findings of elevated lesions either. In the A group, it appears that EUS was induced by rapid tissue regeneration due to the strong anti-ulcer effect of cimetidine in ulcer lesions, since it was noted in the regions where it had previously been considered unlikely to occur.

[A case of lobular carcinoma of the breast containing endocrine granules].

A case of lobular carcinoma containing many endocrine granules in the breast of a 76-year-old woman is reported. Histologically, tumor cells proliferated in solid or nest-like patterns featuring lobular carcinoma. Although argyrophilic and immunohistochemical reactions for peptide hormones were negative, electron microscopic observation revealed endocrine granules, 200-400 nm in diameter, associated with a limiting membrane and a halo in every tumor cell examined. It was suggested that this case might be considered a variant of lobular carcinoma and that breast cancer showing lobular patterns should be searched for the possibility of endocrine differentiation.

[Case report of lipoleiomyoma of the uterus].

A 64-year-old woman with a lipoleiomyoma of the uterus is reported. Histologically, the tumor was predominantly composed of mature fatty tissue and intermingled with irregular-shaped fibromuscular tissue. The fibromuscular tissue showed mast cell infiltration. Ultrastructural study revealed the smooth muscle component to have irregularly indented nuclei, there were cytoplasmic fusiform dense patches, discontinuous external lamina, and occasional fat vacuoles in the nuclei and cytoplasma. The histogenesis of this tumor is most likely metaplasia of the fibromuscular component of fatty tissue.