Establishment of a mouse thymic epithelial cell line, IT-76MHC and a brief review on cultured thymic epithelial cells.

Interactions between thymocytes and thymic stromal cells are essential for thymocyte differentiation, but little evidence has been presented to directly show in vivo functions or interactions of the stromal cells. Among the stromal cells, the thymic epithelial cell has been considered to have profound effect on thymocyte differentiation and maturation. The calcium-depleted medium, originally developed for the culture of mouse epidermal cells, was applied for the culture of the mouse thymic epithelial cells, and successfully, an epithelial cell line, IT-76MHC was obtained from the mouse thymus. IT-76MHC cells were identified as distinct mouse thymic epithelial cells by 1/ mosaic-like arrangement, 2/ presence of well-developed desmosome and 3/ tonofilaments, 4/ positivity for cytokeratin, and 5/ induced expression of MHC class I and II by IFN-gamma treatment. IGF-1, IGF-2, oxytocin and vasopressin were also detected immunohistochemically in IT-76MHC cells. Furthermore, the IT-76MHC thymic epithelial cells, when injected intrathymically in the allogeneic mouse, prolonged the survival of skin graft from the same donor strain that IT-76MHC cells were derived. These results demonstrate that the thymic epithelial cell line IT-76MHC produces modest thymocyte survival factors as well as a growth suppressor, and that IT-76MHC cells have the ability to induce transplantation tolerance probably through their expression of MHC class I and II molecules. Taken altogether, the IT-76MHC thymic epithelial cells have been proved to be useful tools to better understand the in vivo functions of thymic epithelial cells, and to gain a deep insight into their involvement in the critical selection process of thymocytes which still remains obscure. Finally and additionally, literatures so far reported on thymic epithelial cells in culture, especially lines and clones, are reviewed and their identity as well as their functions are discussed.

Microsatellite instability in double cancers of the esophagus and head and neck.

It is generally accepted that patients with squamous cancers of the esophagus are known to have a high risk of concomitant head and neck cancer. However, there have been only a few reports describing microsatellite instability (MSI) in patients with both esophageal squamous cell carcinoma and head and neck cancers. To evaluate the role of genetic instability in carcinogenesis in such patients, we analyzed six microsatellite loci in 21 tumors from 10 patients who had developed primary cancers of both the esophagus and the head and neck. MSI was detected in 6 out of 10 patients. In five patients with double cancer, MSI was observed at the same microsatellite loci in both the esophageal and the head and neck tumors obtained from the same individuals. These data suggest that such patients may have the same underlying defect in the mismatch repair system, providing insight into possible mechanisms for field carcinogenesis.

Esophageal cancer in patients with head and neck cancers.

Nine male patients with separate primary cancers of the esophagus and head and neck (pharynx, larynx) presented with a mean age of 56 years (41-69). They included 7 pharyngeal cancer patients and 2 laryngeal ones. Esophageal cancer was discovered synchronously in 6 patients and metachronously in 3 (1, 4, and 11 years later, respectively). The head and neck cancer was stage-I in one patient, stage-II in 4 and stage-IV in 4. The esophageal cancer was cervical in 2, thoracic in 6 and abdominal in 1. It was early cancer (stage-0) in 6 patients and advanced (stage-IV) in 3. The esophageal cancer was more advanced in the metachronous group, while it was early in the synchronous group. Since the head and neck cancer was advanced, all patients underwent a total laryngectomy for their head and neck cancers. As for esophageal surgery, a transhiatal esophagectomy was, in principle, performed for early cancers while a total thoracic esophagectomy was done for advanced cancers. For the reconstruction of the esophagus, a gastric tube was used. Four patients are still alive with a mean survival time of 25 months, whereas five died of cancer recurrence of either type a mean of 19 months after surgery. As compared with the survival rates of the patients with esophageal cancer alone, the 5-year survival rate was 18.2% for patients with double cancers in this series and 27.9% for those with esophageal cancer alone.

[Developing the portable type sleep apnea detector, and verifying the usefulness of the device].

Polysomnographic recording is indispensable in the diagnosis of sleep apnea syndrome (SAS). However, this method has a number of drawbacks, for example, subjects cannot sleep naturally like at their homes, and the methodology involved is complicated. We have now developed Portable Type Sleep Apnea Detector (PSD) that needs to equipment to provide subject's body. This study was done to verify the usefulness of this device. Subjects were 50 patients (42 male and 8 female, average and S.D. of age: 47.0 +/- 14.5), who were suspected to have SAS. Polysomnography and sleep recording using PSD were performed simultaneously. PSD consisted of three sensors for respiratory movements, a sensor for breathing sounds and a data recorder. The recorder was an 8K32 type 4-channel Handycorder (Nippon Denki Sanei, 370 mm x 115 mm x 200 mm, 7.5 kg) and the sensor for respiratory movements was a thin plate (180 mm x 100 mm). The three sensors for respiratory movements were placed between the mattress and bedsheet, hence the subjects did not feel them during sleep. A sound sensor detected breathing sounds such as snoring. We defined whether a subject is in sleep or awake by the number of body movements recorded by this device. Apnea was defined as depressed or stopped respiratory movement with no snoring for a period longer than 10 seconds. Standard polysomnography which consisted of electroencephalogram (2 channels), electrooculogram (2 channels), electromyogram (2 channels), electrocardiogram (1 channel), oral (1 channel) and nasal airflow (1 channel) and chest movements (1 channel) were performed. Sleep stages were evaluated according to the standard methods. The apnea hypopnea index (AHI) was defined as the number of apneas and hypopneas per sleep-hour. Significant correlation between each type of sleep apneas, AI and AHI as measured by two methods, was found (obstructive type: r = 0.929; p < 0.001, central type: r = 0.880; p < 0.001, mixed type: r = 0.952; p < 0.001, AI and AHI: r = 0.956; p < 0.001). It was concluded that this device is useful for screening SAS.

Prognostic factors for local control in hypopharyngeal cancer treated with radical irradiation.

PURPOSE: We retrospectively analyzed prognostic factors for local control in hypopharyngeal cancer. PATIENTS AND METHODS: Twenty-five patients with hypopharyngeal cancer treated with radical irradiation were entered into analyses. Local control according to clinical T stage and subsites of hypopharynx were analyzed. For 8 clinical T2 patients, local control according to findings assessed by pretreatment CT was also evaluated. RESULTS: The 2-year local control rates were 40% for all, 1/2 for T1, 8/11 (73%) for T2, 1/8 (12%) for T3, and 0/4 for T4. Two-year local control rates were 28% for pyriform sinus cancer and 66% for pharyngeal wall cancer. Local control analysis according to CT findings for patients with T2 hypopharyngeal cancer showed that patients without specified involvement beyond the hypopharynx or in the apex had good local control. CONCLUSION: Our preliminary analysis suggested that clinical T2 hypopharyngeal cancer patients without invasion beyond the hypopharynx or in the apex demonstrated on CT had favorable local prognosis when treated with radical irradiation.

[High tissue concentration of 5-FU reduced local recurrence after administration of tegafur suppositories].

Forty-two patients with head and neck cancer were treated with tegafur suppository for 7 days preoperatively and clinical value of this treatment was assessed. In a group which indicated tumor tissue concentrations of 5-FU were more than 0.5 micrograms/g, local recurrence decreased in the period of postoperative observation for 42 months. A survival rate of this group was better than others. From these results, preoperative tegafur suppository treatment seemed to have a role in expectation of improvement of local control in head and neck cancer therapy.

[Tissue concentration of tegafur suppository in patients with head and neck cancer--concentration of 5-FU in cancer tissue].

Fifty patients with head and neck cancer were treated with tegafur suppository for 7 days preoperatively. The tissues were obtained during surgical operation and the concentrations of 5-FU in cancer tissue, normal tissue and blood were measured. It was revealed that a high concentration of 5-FU was seen in cancer tissue and then metastatic lymph nodes. The 5-FU concentration in cancer tissue was parallel with T stage of the patients. Subsites which showed a high concentration of 5-FU were nasal-paranasal cavity, tongue and mesopharynx. The tegafur suppository was useful because of the high concentration in cancer tissue and metastatic lymph nodes without any obvious side effects in the head and neck region.

Identification of a plasminogen activator derived from nasopharyngeal carcinoma.

The activity of plasminogen activator (PA) in tissue extracts from nasopharyngeal carcinoma (NPC) was determined by means of the fibrin plate method. Development of PA activity was observed in 16 out of 25 cases investigated. Furthermore, using tissue extract of NPC with PA activity, characterization and identification of the activator were carried out by means of electrophoretic analysis, fibrin zymography and immunological analysis. The molecular weight of this PA was found to be 38,000 daltons. Additionally, a urokinase type of plasminogen activator was contained in the tissue extracts.

[The lymphocyte transformation test for detecting immunologic inner ear deafness]. / Der Lymphocytentransformationstest zum Nachweis einer immunologischen Innenohrschwerhörigkeit.

The basis and performance of the lymphocyte transformation test for proving an immunologically induced inner ear hearing loss are described and documented. In 6 out of 14 patients with inner ear hearing loss of unknown origin an immunological etiology could be elaborated by using this test. The relevance of this test as well and its further application by using collagen type II as antigen are discussed.

Fibrinolytic activity in medium from tissue culture of paranasal mucous membrane.

It is known that a remarkable fibrinolytic activity of plasminogen activator (PA) can be seen in extracts of wet tissue and acetone powder preparation of paranasal mucous membrane evidencing chronic sinusitis. However, the origin of the PA in extract of paranasal mucous membrane has not yet been clarified up to the present time. In this experiment, using a tissue culture of paranasal mucous membrane, it was observed that two species of cells, epithelial cells and fibrocytes, proliferated in the implanted tissue. PA was isolated from the conditioned medium on the fifth day after culture. From these results, it appears that the PA may be released from epithelial cells and/or fibroblasts.