Somatic mutation in constant regions of mouse lambda 1 light chains.

To study the distribution of somatic mutation, we determined nucleotide sequences of rearranged lambda 1-chain genomic DNA from four hybridomas obtained from C57BL/6 mice that had been immunized with (4-hydroxy-3-nitrophenyl)acetyl-conjugated chicken gamma globulin. In total, 114 nucleotide substitutions were observed, with neither insertion nor deletion. Sixty-one mutations occurred in the variable-joining region genes (V lambda 1-J lambda 1) and 49 in joining-constant (J lambda 1-C lambda 1) introns. Although frequency decreased with distance from the V lambda 1-J lambda 1 coding region, somatic mutations occurred in the entire J lambda 1-C lambda 1 intron and even in the C lambda 1 region. We found four nucleotide substitutions in C lambda 1 genes, all of which were replacement mutations. Therefore, the mechanism responsible for somatic mutation is operative into the C lambda 1 exons. Nucleotide sequences of rearranged but inactive lambda 2-chain genes from two hybridomas were also examined and compared with those of lambda 1-chain genes. The clustering of replacement mutations in complementarity-determining regions in the inactive lambda 2-chain genes similar to the active lambda 1-chain genes suggested a mechanism that induces somatic mutation preferentially in this region even in the absence of antigenic selection.     

Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease

We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean ± SD) of 8.2 ± 1.2 years to the age of 15.1 ± 1.6 years. They had been born at 29.1 ± 1.9 weeks of gestation, with a birthweight of 1120 ± 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 ± 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air-trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV₁), and the ratio FEV₁/FVC remained at or above the predicted normal range in all patients. FEF_25–75, FEF₅₀, and FEF₇₅ were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. In contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity. Pediatr Pulmonol. 1996; 21:28–34 . © 1996 Wiley-Liss, Inc.     

Investigation of poststroke epilepsy (INPOSE) study: a multicenter prospective study for prediction of poststroke epilepsy

Journal of Neurology - Poststroke epilepsy is a common problem in clinical practice. This study aimed to determine the predictors of poststroke epilepsy and to identify the risk factors. A total of...     

Ovarian Sertoli-Leydig cell tumor with heterologous gastrointestinal epithelium as a source of alpha-fetoprotein: a case report

Ovarian Sertoli-Leydig cell tumors (SLCT) are rare sex cord stromal neoplasms. To date there have been approximately 25 case reports of ovarian SLCT expressing alpha-fetoprotein (AFP). In such cases, AFP was immunohistochemically detected in the Sertoli cells, Leydig cells, or hepatocytes. This case report confirms heterologous gastrointestinal epithelium expression of AFP. A 20-year-old woman presented with complaints of abdominal enlargement and irregular menstrual cycles over one year. A right ovarian tumor was detected and the patient's serum AFP was elevated. A right salpingo-oophorectomy was performed. On microscopic examination, the tumor was composed of a fibrosarcoma-like area and a poorly differentiated SLCT area with heterologous gastrointestinal epithelium. Immunohistochemical analysis detected AFP in the gastrointestinal epithelium only. Postoperatively, serum AFP levels fell to normal. A recurrent tumor was discovered in the omentum after adjuvant chemotherapy, but serum AFP remained normal. A second laparotomy was performed and the recurrent tumor showed only fibrosarcoma-like features. The patient received second line chemotherapy and is currently in remission. This is the first case of AFP production by heterologous gastrointestinal epithelium in SLCT.     

Initial panel of immunocytochemical markers for identification of primary carcinoma site for effusions and peritoneal washings from women

Introduction: In women, most malignant effusions are from breast and ovary primary carcinomas that have metastasized to body cavity fluids (pleural, peritoneal and pericardial). When carcinoma is diagnosed in effusions, it is not possible to identify its site of origin solely by cytology (morphology); therefore, immunocytochemistry is used as a complementary method. There are no immunocytochemical markers with 100% sensitivity and specificity for identifying carcinoma primary site. The markers most used are TTF-1 for the lung, GATA-3 for the breast, and PAX-8 for the ovary. The aim of this study was to evaluate the sensitivity and specificity of a panel including these markers for detecting the primary site of carcinoma in effusions. Methods: Samples of pleural, pericardial, and peritoneal effusions and peritoneal washings with carcinoma of known primary site from women (n = 60) and men (n = 18) were prepared by using the cell block method, and immunocytochemistry was performed to evaluate the expression of primary site markers (TTF-1, PAX-8, and GATA-3). Results: In women, the breast was the most frequent primary site of metastatic carcinoma to both pleural and pericardial cavities, followed by the lung, whereas the ovary was the most frequent primary site of carcinoma within peritoneal effusions and washings, followed by the gastrointestinal tract (stomach or intestine). The expected profiles for carcinomas of the most common primary sites were: breast (GATA-3 (+), PAX-8 (-), TTF-1 (-)), ovary (PAX-8 (+), GATA-3 (-), TTF-1 (-)), lung (TTF-1 (+), PAX-8 (-) GATA-3 (-)) and gastrointestinal tract (PAX-8 (-), GATA-3 (-), TTF-1 (-)). These were observed in 88.23% (45/51) of women’s samples with carcinoma from these primary sites. By using TTF-1 as the sole primary site marker, 6.25% of carcinomas of primary site other than the lung would have been misdiagnosed. Conclusion: An initial panel of markers including GATA-3, PAX-8, and TTF-1 allows, with high sensitivity and specificity, the identification or exclusion of frequent primary sites of carcinoma in effusions from women. Our results highlight the importance of using a panel of markers to avoid misidentification of the primary site of tumor.     

Clinical characteristics after surgery of non-small cell lung cancer which measures 20 mm or less in diameter

Today's advances in diagnostic image-technologies often enable us to find small lung cancers. However, we have few definite strategies including how to diagnosis and treat them. In this study, we performed a retrospective analysis of 122 consecutive patients who underwent surgery for non-small cell lung cancer 20 mm or less in diameter to clarify the clinical features of small lung cancer. Of 122 patients, there were 114 patients of pN0, and 8 patients with lymph node metastasis. Seventy three patients underwent lobectomy, 45 underwent segmentectomy, and 4 underwent wedge resection based on the findings of preoperative CT and anatomical and oncological view during operation. Overall survival rate( OS) and progression free survival( PFS) at 3-year was, 94% and 84%, respectively. There were no differences in OS or PFS between lobectomy group and limited resection group, which might suggest that we adapted appropriate surgical procedures. Multivariate analysis revealed that pathological pleural invasion, lymphatic vessel invasion, and vascular vessel invasion were likely to be unfavorable prognostic-factors. We believe that further investigations should be required to clarify the characteristics of small lung cancer.     

Soluble and Cell-Associated Forms of Some Yet to be Identified Factor in Transfused Blood Which Promotes Solid Tumor Growth in Mice

Purpose The mechanism underlying the immunomodulation caused by blood transfusion has yet to be elucidated. The aim of the present study was to determine whether the transfusion of a soluble or insoluble factor present in stored blood can induce immunomodulation, which would thereby promote solid tumor growth.Methods C57Bl/6J mice were subcutaneously inoculated with B16-CG melanoma cells, which secrete -human chorionic gonadotropin (-hCG). Following inoculation, each of three different products of allogeneic and syngeneic blood were transfused on days 0 and 1: fresh whole blood, stored whole blood, and supernatants from the stored blood. Tumor growth was then monitored by measuring urinary -hCG. All mice were killed on day 15, and the tumor weight and volume were measured.Results Transfusion of all allogeneic blood products enhanced tumor growth, as did the stored syngeneic whole blood. Neither fresh syngeneic blood nor the supernatant from stored syngeneic blood promoted tumor growth. Although the tumors were not visually detectable until day 10 after inoculation, by day 7 the levels of urinary -hCG were significantly higher in the mice that received allogeneic blood supernatant than in the mice that received saline.Conclusions A soluble alloantigen enhances solid tumor growth, as does an insoluble factor present in stored syngeneic whole blood. The immunomodulation associated with this factor begins to enhance tumor growth within 7 days after transfusion.