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The pathogenesis of progressive spongy degeneration in zitter rats with genetic spongiform encephalopathy was examined histopathologically and biochemically in the context of edematous change in the central nervous system (CNS). Histopathological studies revealed that vacuolation in the CNS of zitter rats progressed with aging and the severity of spongy degeneration was markedly divergent in different areas in the CNS. Edematous change was confirmed by a consistently higher water content in the brain of zitter rats than in that of normal SD/J rats at all ages. Furthermore, a close relationship between spongy degeneration and edematous change in the CNS was demonstrated by regional measurement of specific gravity (SPGR) of brain tissues and quantification of the spongy degeneration by computer-image analysis. The brain regions with lighter SPGR were more severely affected by spongy degeneration. These results suggest that edematous change is related to the pathogenesis of spongy degeneration in the CNS of the zitter rat.

Two characteristic cases of Reiter's syndrome are reported. One (case T.M) was a 64-year-old female with ulcerative colitis and the other (case O.M) was a 20-year-old male with serum antistreptococcal lysine O (ASLO) and antistreptokinase (ASK) titers of 480x and 2560x, respectively. These cases were both histocompatibility antigen HLA-B27 positive. The ulcerative colitis and iritis were inactive in case T.M. However, case O.M required aggressive treatment for fever and arthralgia. These patients have recently shown no evidence of Reiter's syndrome; however, case T.M has had recurrent bowel hemorrhages due to ulcerative colitis.

Exactly why N-acetyl-beta-D-glucosaminidase (NAG) excretion is increased in patients with nephrotic syndrome with glomerular lesions is poorly understood. Glomeruli contain less NAG than do proximal tubules. In this study, we have tried to measure the NAG isoenzymes automatically by use of the recently developed fast protein liquid chromatography (FPLC) system, followed by column chromatography on DEAE cellulose (Mono Q). Three isoenzyme peaks--B, I + II, and A--were observed for urine from both healthy subjects and nephrotic patients. The B isoenzyme usually constituted about 10% of the total NAG in healthy controls, 30% in nephrotic patients. In contrast, the proportion of the A isoenzyme was inversely related to that of the B isoenzyme when healthy controls and nephrotic patients were compared. Our system for measuring NAG isoenzymes is reproducible and fast, and it should be useful in further studies.

In vitro cultivation of primed T cells with antigen resulted in the induction of a regulatory T cell that nonspecifically augmented the in vitro antibody responses of H-2-compatible T and B cells. This T cell, designated as the augmenting T cell (Ta), was unable to help B cells by itself but enhanced the antibody response of B cells to several multitudes only when conventional helper T (Th) cells or cloned Th cells from the same H-2 haplotype coexisted. Ta was radioresistant and belonged to Lyt-1+, 2-, L3T4+, I-J- T cell lineage. Ta exhibited interesting H-2-restricted activities: when primed T cells from (A X B) F1 were cultured with the antigen in the presence of parent A type antigen-presenting cells, the induced Ta was able to augment the antibody response of (A x B) F1 B cells in the presence of Th cells from F1----A but not from F1----B radiation bone marrow chimeras. This indicates that the induction of Ta in an F1 T cell population is dependent on the H-2 haplotype of antigen-presenting cells during in vitro cultivation. The restriction specificity of the established Ta is, however, not directed to the class II antigen itself but to the restriction specificity of Th cells that recognize class II antigen. In support of this is the fact that the elimination of A-restricted Th cells during cultivation by treatment with anti-I-J mAb, which is known to react with H-2-restricted Th cells, resulted in failure of induction of Ta cells having the augmenting activity for the A-restricted response.

More than 1,900 patients of advanced and inoperable malignant tumor were treated with fast neutron radiotherapy using 30 MeV (d-Be) and 14 MeV (d-Be) beams at NIRS and IMS between 1975 and 1986. Protocols were largely nonrandomized. Some results have been obtained: 1) results with mixed beam studies for advanced squamous cell carcinoma of the uterine cervix have been equivocal compared with the photon controls. 2) some trends of local control have been observed in the trial of esophageal cancer, early cases of adenocarcinoma of the lung and malignant melanoma. 3) significant better results were observed in the pancoast type lung cancer and osteo sarcoma which was treated by the systemic multimodal treatment. It is concluded that neutrons are efficacious for certain specific tumor types owing to some biological effects, however the problem of inferior dose distribution was the weakness of neutron therapy at present.

An analysis of prognostic factors for stage 3 carcinoma of the uterine cervix was performed using multivariate analysis. Such factors were closely related to prognosis of the patients as follows; 1) risen temperature during the treatment, kidney function before treatment and age which were concerned in local recurrence 2) risen temperature, leucocytosis, hypertension and kidney function which were concerned in distant metastasis. Since the patients have various factors which have correlation between one another, it is important to investigate each factors separately more detail aspect.

A synthetic human growth hormone (hGH) gene was efficiently expressed under the control of the repressible acid phosphatase promoter in yeast (Saccharomyces cerevisiae). More than 10(6) molecules of hormone were formed per cell despite the fact that the gene was constructed with codon preference for Escherichia coli.

Eighty-nine patients with carcinoma of the cervix received radical radiation therapy from May 1981 through 1983 at the hospital of the National Institute of Radiological Sciences. After a 2 to 4 year follow-up, primary cancer was found to be controlled in 59 patients, a recurrence was noted in 16 patients but 12 patients had died without precise information concerning recurrence. We examined the correlation between recurrence and seven prognostic factors. Among these factors, the tumor volume, age, and the red blood corpuscle sedimentation rate showed a relatively strong correlation. A multivariable analysis (quantification methods II) was undertaken in order to integrate these prognostic factors and the score that was calculated from this analysis showed a strong correlation to local control. We believe that this score can be used for predicting recurrences and can be applied to the selection of patients for new treatments like hyperthermia or high LET irradiation.

Eleven hundred and seventy one patients, 921 previously untreated and 250 recurrent, have been treated with 30 MeV (d-Be) fast neutron beam between 1975 and 1984 at NIRS. Some trends have been identified: non-randomized results have been at least as good as those of photons in carcinomas such as: supraglottic carcinoma in the larynx, pancoast type tumor of the lung, malignant melanoma of the skin and so on. Randomized results with mixed beam studies for carcinoma of the uterine cervix have indicated no significant advantages against those of photons. Treatment technique for the beam concentration must be improved to demonstrate the merit of neutrons in the next step.

The gene for insulin-like growth factor I (IGF-I) was constructed from chemically synthesized deoxyoligonucleotides and expressed in Escherichia coli, under the control of a trp promoter, as a set of fusion proteins which were connected with a portion of human growth hormone through the recognition sequence for a sequence-specific protease, either blood coagulation factor Xa or alpha-thrombin. Upon induction with 3-indoleacrylic acid, fusion proteins accumulated with a yield of 10-30% of the total protein. A fusion protein connected through a tetradecapeptide (Asp-Asp-Pro-Pro-Thr-Val-Glu-Leu-Gln-Gly-Leu-Val-Pro-Arg) was efficiently and correctly cleaved by alpha-thrombin, and the purified IGF-I possessed somatomedin-like activity, as determined by the enhancement of sulfation of glycosaminoglycans in cultured costal chondrocytes from rabbits.

Thirty-seven patients with recurrent cancer of the uterine cervix were treated with interstitial radiotherapy between 1966 and 1983 at NIRS. The 1-, 3- and 5-year survival rates after the salvage treatment were 57%, 30% and 24%, respectively. A local control rate of more than 80% was achieved in smaller-than-thumb-sized lesions. However, the rates decreased to 27% in larger tumors. The local control rate of all patients was 58%. A dosage of 60-70 Gy was required to control the smaller lesions, while the larger ones were difficult to control irrespective of the dosage. Therefore, early detection of recurrent cancer is most important for this treatment.

The results of irradiation therapy for nasopharyngeal carcinoma in 49 patients treated at the Department of Radiology, Jikei University of Medicine, between 1968 and 1981 are reviewed. The CR rate increased in proportion to increased dosage, especially in well-differentiated squamous cell carcinoma. The five-year cumulative survival rate was 40% in all stages. Severe late radiation injury occurred in two patients.

Blood pressure of 251,742 schoolboys and schoolgirls aged 7 to 18 years was measured in the year 1970. Analyzing these data, the authors obtained the percentile values classified by age. The lowest hypertensive systolic blood pressures, which are represented by the 95th percentile, are 123, 126, 128, 128, 129, 134, 138, 144, 149, 152, 155, and 154 mmHg in boys from 7 to 18 years of age, respectively. The corresponding values are 123, 126, 128, 130, 134, 138, 139, 143, 144, 142, 142, 141 mmHg in girls of the same ages. Girls' systolic blood pressure is higher than that of boys between the ages of 10 and 13 years. After the 14th year of age, girls' systolic blood pressure does not increase any further, whereas boy's blood pressure continuously increases until 18 years. The present results differ in the following two points from the study in USA (1977): 1) The uniform rise of blood pressure with age is not observed. 2) Blood pressure, especially systolic pressure, is higher in girls than in boys between the ages of 10 and 13 years, although it is higher in boys thereafter until 18 years.

Human epidermal growth factor (urogastrone; UG) is a 53-amino acid polypeptide hormone. A 192-bp DNA fragment containing the coding sequence for methionyl UG (Met-UG) and the ribosome-binding site (RBS) was chemically synthesized and placed downstream from the promotor for the Escherichia coli outer-membrane lipoprotein gene (lpp) on a plasmid. E. coli cells harboring the plasmid directed the synthesis of Met-UG at 10(2)-10(3) molecules per cell. Next, the coding sequence for Met-UG was inserted in a runaway-replication plasmid and expressed under the control of the lpp promoter and the RBS derived from bacteriophage Mu cII gene. Upon heat induction, the cells harboring the recombinant plasmid synthesized 10(5) molecules of Met-UG per cell.

Thirty-three patients suffering from squamous cell carcinoma of the vulva were treated with radiation therapy alone between 1961 and 1980 at the NIRS. The five-year survival rate and local control rate in each stage were 91% and 36% in T2 and 71% and 64% in T3, respectively. These results indicated that the early detection of recurrent tumor by close follow-up and an adequate retreatment procedure is very important for prolonging survival. Late recurrence, more than five years after treatment, appeared in 30% of the patients and this may be one of the special figures of postirradiated vulval carcinoma. The primary site was irradiated with external electron beams or radium needles, and better results were obtained with the later. Irradiation to the lymph node area in the pelvic cavity was necessary in patients with a more advanced stage of disease than T2.

A case of a three years old boy with subaortic stenosis caused by accessory tissue of the mitral valve is presented. We can find only four similar cases in the literature. In surgery of this anomaly, it is a peculiar problem that the most of stenotic tissues can not be identified through the aortotomy only. We opened the left atrium and pulled up the mitral valve with threads, so that we could distinguish the stenotic tissue from true mitral valve through the aortotomy.