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The retinoblastoma gene (RB) plays important roles in the genesis of human cancers. Several pieces of evidence have shown that the retinoblastoma protein (Rb) has dual roles in gating cell cycle progression and promoting cellular differentiation. The molecular mechanisms involved in these roles have been elucidated in some biological systems: Rb sequesters the transcription factors of E2F-1 to regulate entry of cell cycle, but enhances the activities of transcription factors such as C/ EBPs to initiate terminal differentiation. Thus, the Rb protein can serve as a mediator of extracellular signals for growth or differentiation. RB also has a tumor suppression function. Introduction of wild-type RB into human tumor cells deficient for RB suppresses their tumorigenicity in nude mice. Similarly, mice with RB+/- genotypes created by gene knockout methods spontaneously develop melanotrophic tumors with complete penetrance. Immune-competent RB+/- mice benefited significantly from adenovirus-mediated RB gene therapy. The fundamental knowledge of Rb function will allow us to take the next steps toward the use of tumor suppressor genes in the treatment of human cancer.

We reported 2 cases of Mycobacterium avium complex lung disease occurred in middle-aged women without underlying disorders, which we could observe for more than 30 years. One case was a 42-year-old woman started with bloody sputum, and the other was a 43-year-old woman with cough and sputum. In both cases, chest X ray films were normal on their first visit. More than 15 years after their first visit, Mycobacterium avium complex was isolated from their sputum or bronchial washing. During the observation, a cluster of small nodules in the periphery of the lung and bronchiectasis appeared and deteriorated, and excretion of the bacilli increased gradually. Their past history and family history were normal. Since lung disease caused by Mycobacterium avium complex progresses very slowly, long-time observation would be necessary to consider its pathogenesis.

A 52-year-old man had been asymptomatic except for nasal speech since his third decade of life. A chest roentgenogram obtained during a health screening one year before admission revealed elevation of the right hemidiaphragm and infiltrates in the right lower lung field. Because the pulmonary shadows had gradually increased, he was admitted to the hospital, for further examination. Based on physiological findings and on the results of electromyography, myotonic dystrophy was diagnosed. The chest roentgenographic abnormalities were regarded as resulting from complications of this disease. Arterial blood gas analysis showed hypercapnic hypoxia and a spirogram showed that the vital capacity and maximum voluntary ventilation were about half of their respective predicted values. The hypercapnic ventilatory response was also abnormally low. An overnight study of oxygen saturation showed episodes of marked desaturation, and polysomnography revealed central sleep apnea. Inhalation of capsaicin showed an abnormally high cough threshold. Patients with undiagnosed myotonic dystrophy rarely present with chest roentgenographic abnormalities.

A 76-year-old male patient suffered from recurrent bacterial pneumonia of the right upper lobe and both lower lobes since 2 years after total gastrectomy for gastric cancer. He was treated with antibiotics repeatedly without complete remission. Meanwhile, chronic cough, purulent sputum, and persistent bilateral pulmonary infiltration developed gradually. Upper digestive tract endoscopy showed moderate reflux esophagitis. For diagnosis, we performed upper digestive tract scintigraphy, a "modified-salivagram", to detect aspiration and GER. Although aspiration was not detected, GER reaching to the upper portion of the esophagus was observed 46 min after taking radio-labeled albumin, and chronic aspiration pneumonia with GER was thus diagnosed. Bed blocks and gragling with ponvidone-iodine after meals and before sleep greatly improved the symptoms of cough and sputum. The bilateral infiltrative shadows disappeared with resolution of symptoms. Chronic aspiration resulting from GER is an important cause of chronic airway infection. Even if a patient with reflux esophagitis is asymptomatic, chronic aspiration pneumonia should be suspected in cases of recurrent or persistent pneumonia in both lower lobes. The "modified-salivagram" is a sensitive test to detect aspiration and GER in hypoacidic states, such as in total gastrectomy and elderly patients.

Ultrastructural changes in the rat endometrium under several conditions including experiments of the inhibition of implantation were studied to clarify the sequential changes of the endometrium and their endocrinologic background during ovoimplantation. The following pertinent findings were noted. 1) Normal pregnancy. In the luminal surfaces, the microvilli were short and arranged rather irregularly and lost their so-called glycocalyx on L3. The large fungus-like protrusions appeared on L4. On L5, the luminal surfaces were completely covered with small serrated cytoplasmic protrusions. They formed the interdigitation btween the apposed surfaces and the uterine lumen was disappeared when the uterus was fixed in situ by the arterial perfusion method. High ATP-ase activity was demonstrated at the site of interdigitation. In the apical cytoplasm, many apical vesicles, well developed Golgi apparatuses, and dilated cisternae of the granular endoplasmic reticulum were observed on L3. On L5, however, these apical vesicles decreased in number and the Golgi apparatuses were small. On the contrary, the semilunar and coated vesicles were numerous, and the lysosomes increased both in number and size. Acid phosphatase activity was detected in these lysosomes. In the glandular epithelium, progressive increase in the number of small granules and the amount of amorphous substance were observed in the glandular lumen from L2, to L4. But on L4, some autophagosomes had already appeared in the cytoplasm. Swollen and degenerated mitochondria as well as many vacuoles were recognized on L5. In the stromal cells, the cytoplasm was enlarged, and contained many polyribosomes, granular endoplasmic reticulum with markedly dilated cisternae, lysosomes and lipid droplets on L5. The cytoplasmic protrusions on L5 were elongated and showed various features; one of them was situated very closely to the basement lamina of the luminal epithelium, and the other surrounded the lumen. Some of these protrusions were connected with the desmosomes. High ATP-ase activity was localized in these cytoplasmic protrusions, on the surfaces of the stromal cells, and in the stroma itself. 2) Delayed implantation and estrogenic transformation. In delayed implantation, the luminal surfaces were covered with regular microvilli and several fungus-like cytoplasmic protrusions. The cytoplasm contained many apical vesicles and large Golgi apparatuses that were observed both on L3 and L4 in normal pregnancy. At 48 hrs after the injection of estrogen, the interdigitation between the apposed luminal surfaces was also established. In the glandular epithelium, a slight enlargement of the glandular lumen and the appearance of small granules similar to those observed in normal pregnancy were noted at the 4th hr of estrogen treatment. In the stromal cells, two cells apposed each other very closely at the 4th hr and formed large cell masses at the 48th hr of estrogen treatment...

This dissertation reports basic and clinical research performed on the value of magnetic resonance imaging (MRI) in the diagnosis of lumbar disc lesions. With the T2 weighted spin echo image (T2-W-SE), the center portion of normal discs showed high signal intensity, with gradual drop-off signal intensity toward the edges. Experiments using gelatine indicated that this change in signal intensity resulted from the change in water content of the disc. In contrast to discograms, the use of MRI allowed disc degeneration to be classified into the three levels of "normal", "mild degeneration" and "moderate or severe degeneration". MRI allowed excellent depiction of disc herniation, even where a myelogram showed a complete block, and it also readily distinguished recurrent disc herniation and post-operative scarring.