MALIGNANT LYMPHOEPITHELIAL LESION

A case of undifferentiated carcinoma arising from benign lymphoepithelial lesion (BLEL) of the parotid gland was studied by light and electron microscopy. Histopathologically, the carcinoma was composed of pleomorphic anaplastic cells showing an undifferentiated type among abundant lymphoid tissue forming germinal center. Among the prominent lymphoid tissue, epithelial hyperplasia, dysplasia, and squamous metaplasia of the duct epithelium were found. Dysplastic epithelium revealed a transition with carcinomatous component in some areas. On the electron microscopic observation, the tumor cells were poorly differentiated, possessing desmosomes and intracytoplasmic filaments. The patient is alive and well 2 months after resection of the tumor, but has a high titer of serum Epstein-Barr virus capsid antigen in IgG. Eighty five cases of the malignant lymphoepithelial lesion (MLEL) including the present case are summarized.     

Experience with microsurgical epididymovasostomy (specific tubule technic: end-to-end anastomosis by the Silber method)

Here, we report 2 cases of epididymovasostomy operation in which good results were obtained. These operations were done for patients whose complaints were male sterility due to obstructive azospermia after bilateral epididymitis. The method of this operation was reported by Silber in 1978 as "specific tubule technique", and excellent results have been reported. Herein, we introduce this technique perhaps for the first time in Japan, and the characteristics of this method are considered. The important factors and characteristics of this method are that it is very reasonable with a high success rate, it is more difficult than microsurgical vasovasostomy, it is a time-consuming operation. Epididymovasography should not be done preoperatively but intraoperatively, if possible and chronic epididymitis should be ruled out by serological study and culture study.     

The National Health Plan 2030: Its Purpose and Directions of Development

The National Health Plan 2030 (HP2030) started to be prepared in 2017 and was completed and announced in December 2020. This study presents an overview of how it was established, the major changes in policies, its purpose, and future directions. This study analyzed the steps taken in the past 4 years to establish HP2030 and reviewed major issues at the international and governmental levels based on an evaluation of HP2020 and its content. HP2030 establishes 6 divisions and 28 topic areas, and it will continue to expand investments in health with a total budget of 2.5 trillion Korean won. It also established goals to enhance health equity for the first time, with the goal of calculating healthy life expectancy in a way that reflects the circumstances of Korea and reducing the gap in income and healthy life expectancy between regions. The establishment of HP2030 is significant in that it constitutes a sustainable long-term plan with sufficient preparation, contains policy measures that everyone participates in and makes together, and works towards improvements in universal health standards and health equity. With the announcement of HP2030, which includes goals and directions of the national health policy for the next 10 years, it will be necessary to further strengthen collaboration with relevant ministries, local governments, and agencies in various fields to concretize support for prevention-centered health management as a national task and to develop a health-friendly environment that considers health in all policy areas.     

Metabolism and distribution in the rat of peak E substance,a constituent inl-tryptophan product implicated in eosinophilia-myalgia syndrome

Peak E substance, 1,1-ethylidenebis[tryptophan], a contaminant found inl-tryptophan tablets, has been suggested as a causative agent for eosinophilia-myalgia syndrome (EMS). Peak E substance (50 mg/kg) was administered perorally to Wistar rats to determine its metabolism and distribution. A purification procedure using Bond Elut C₈ cartridges followed by HPLC was developed for the determination of peak E substance. The plasma concentration of peak E substance was 136 ng/ml at 1 h, and urinary excretion was 717 ng at 5 h and 10342 ng for 5–24 h, showing slow excretion of peak E substance into urine. The amount of peak E substance in the contents of the large intestine at 5 h, however, was 3136 g, much greater than urinary excretion for 24 h, indicating considerable transfer of peak E substance to large intestine without decomposition by gastric fluid in the stomach. We have detected for the first time not only the occurrence of peak E substance in plasma and urine, but also 1-methyl-tetrahydro--carboline-3-carboxylic acid (MTCA) in blood and organs of rats treated with peak E substance, thereby suggesting MTCA as one of the the metabolites of peak E substance. The amount of MTCA in the contents of the large intestine as well as in urine of rats treated with peak E substance was significantly greater than inl-tryptophantreated rats (50 mg/kg p.o.), demonstrating that MTCA was more readily produced from peak E substance than froml-tryptophan. Finally, we propose acetaldehydeinduced production of MTCA from peak E substance.     

Accumulation of 1-methyl-tetrahydro-Β-carboline-3-carboxylic acid in blood and organs of rat. A possible causative substance of eosinophilia-myalgia syndrome associated with ingestion ofl-tryptophan

1-Methyl-tetrahydro--carboline-3-carboxylic acid (MTCA) may cause eosinophilia-myalgia syndrome (EMS) associated with ingestion ofl-tryptophan. The distribution and excretion of MTCA were studied in rats which had received perorally a single 1.6 mg/kg dose of MTCA. MTCA concentrations in blood, kidney, liver, brain, heart, spleen, lung and gastrocnemius muscle were measured by HPLC combined with fluorometric detection. The concentration of MTCA in each organ reached a maximum at 1 h and then gradually declined. However, a significant level of MTCA still remained at 5 h, when 52% of ingested MTCA remained in the contents of the large intestine. Twenty-nine percent of the ingested MTCA was excreted in urine over the course of 24 h. A higher dose (10 mg/kg) of MTCA resulted in significant elevations in the concentrations and amounts of MTCA in the various organs. In addition, chronic treatment with a 10 mg/kg dose of MTCA for 6 weeks further increased the concentrations and amounts of MTCA in each organ. However, no histological changes were observed in any of the organs after chronic treatment. This is the first report which demonstrates accumulation of MTCA in the blood and various organs, including muscle, of rats.     

The effect on the bones of condensed phosphate when used as food additives: Its Importance in Relation to Preventive Medicine

Based on the fact that chemical products such as binding agents are produced by mixing three kinds of phosphates with different ratios, we mixed metaphosphate, polyphosphate and pyrophosphate. Each was made to Na-phosphate, K-phosphate, and Ca-phosphate and each was mixed with commercial feeds so that the content of P would be approximately 0.1, 0.15, 0.3, 0.4, 0.6 and 1.0%. The prepared pellets were given to ICR, CF # 1 and AKR strains of mice at 29 days of age for 680 days and observations were made through this experimental period at different stages. The observations were also carried out on the mice administered with the experimental feeds for 1.5 months from 9 to 10.5 months of age. The observations were compared with those of the control group at all times. As a result, plasma 1 α, 25 (OH)₂ D₃ and P levels were always significantly higher in the phosphate administered groups relative to the control. Urine P and Fe increased while urine Ca decreased in the phosphate-treated groups. The effect of phosphates on the bones was studied taking soft X-ray pictures of hind legs and applying microdensitometry to them. Through these observations we recognized thinning of the cortex of bones, reduction of marrow trabecules and development of osteophyte. Histological observations disclosed that changes in knee joint tissues were apparent; that is, a decrease in or an irregular loss of the number of cells in superficial, intermediate, and radial strata of the joint cartilage, proliferation of subchondral bone, and the development of osteophytes were noted. As for muscles, diameters of musclar fibers became smaller; in particular, type II fibers showed greater shrinkage. Regarding kidneys, swelling and atrophy of glomerular capillaries, proliferation of mesangial cells, nephroselerosis, swelling, thinning, and loss of tubular epithelium, interstitial tissue inflammation, development of cylindruria, and deposition of calcium were observed. All these changes seem to be a particularly advanced aspect of the changes which are more pronounced with increasing dose and age. These changes were found even in the group administered with the feed containing 0.1% phosphorus, and, these changes were dependent on the concentration level of P. It was observed that administration to older subjects for a short term (1.5 months) produced effects stronger than those to younger subjects administered for a long term (10.5 months). The effects of condensed Ca-phosphate on bones were similar to those of condensed Na- and K-phosphates, and, hence, it was supposed that these effects were caused by phosphate radicals. An erratum to this article is available at .     

Efficacy of an echo contrast agent, SH/TA-508, in color doppler sonography of mass lesions in urology

We performed a clinical phase III study with a galactosebased ecoo contrast agent, SH/TA-508, to evaluate its efficacy, safety, and usefulness for mass lesions in urology. SH/TA-508 was prepared as a suspension containing stabilized micro-air bubbles by adding water for injection just before use. SH/TA-508 was administered into the antecubital vein at an initial dose of 300 mg/ml × 5 ml followed by higher doses of 400 mg/ml × 4 ml, 300 mg/ ml × 10 ml or 400 mg/ml × 8 ml when a sufficient effect was not obtained. Efficacy was evaluated by color Doppler signal enhancement, the duration of blood flow signal enhancement, and improvement of diagnostic capacity. Fifty-nine patients with mass lesions in the kidney, prostate, testis, adrenal gland, and bladder were enrolled in the study. Up to the third dose the cumulative efficacy rates (≥2+) of color Doppler signal enhancement and duration of blood flow signal enhancement were 92% and 87%, respectively. Consequently, diagnostic capacity in 76% of the patients was remarkably improved. A light transient angialgia occurred in one patient but no other clinically significant changes were observed. It was confirmed that SH/TA-508 is a safe echo contrast agent that offers satisfactory color Doppler signal enhancement in the urologic organs mentioned above.     

Correlation between the blood supply and grade of malignancy of hepatocellular nodules associated with liver cirrhosis: evaluation by CT during intraarterial injection of contrast medium

OBJECTIVE: The purpose of this study is to evaluate the correlation between the intranodular blood supply revealed by CT during intraarterial injection of contrast medium, mainly using helical CT, and the grade of malignancy of hepatocellular nodules associated with liver cirrhosis as classified by the International Working Party of the World Congress of Gastroenterology. SUBJECTS AND METHODS: We studied 201 histologically proven nodules (101 resected and 100 biopsied nodules), including 47 low-grade dysplastic nodules (low-DNs), 56 high-grade dysplastic nodules (high-DNs), 24 well-differentiated hepatocellular carcinomas (wd-HCCs), and 74 moderately or poorly differentiated HCCs (mp-HCCs), in 139 cirrhotic patients. Findings on CT during arterial portography (n = 201) and CT during hepatic arteriography (n = 74) were reviewed and compared with the histologic diagnosis. RESULTS: CT findings were classified into four types relative to the surrounding liver: type A (isodense), type B (slightly hypodense), type C (partially hypodense), and type D (markedly hypodense) on CT during arterial portography and type I (isodense), type II (hypodense), type III (partially hyperdense), and type IV (hyperdense) on CT during hepatic arteriography. On CT during arterial portography, the distributions of each type were low-DN (n = 47 [A, n = 36; B, n = 8; C, n = 3]), high-DN (n = 56 [A, n = 18; B, n = 20; C, n = 10; D, n = 8]), wd-HCC (n = 24; [B, n = 4; C, n = 13; D, n = 7]), and mp-HCC (n = 74 [D, n = 74]). On CT during hepatic arteriography, the distributions were low-DN (n = 26 [I, n = 18; II, n = 7; III, n = 1]), high-DN (n = 19 [I, n = 6; II, n = 7; III, n = 4; IV, n = 2]), wd-HCC (n = 15 [I, n = 1; III, n = 8; IV, n = 6]), and mp-HCC (n = 14 [IV, n = 14]). We found a statistically significant correlation between the four types and the grade of malignancy of these nodules. CONCLUSION: Findings on CT during arterial portography and CT during hepatic arteriography correlated positively with histologic grading when overlap in appearance between dysplastic nodules and HCCs occurred. The concept revealed in this study can apply to diagnoses made on the basis of Doppler sonography, dynamic CT, and MR imaging.     

Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity

Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)₂ reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1.     

Complete repair of severe penoscrotal hypospadias in 1 stage: experience with urethral mobilization, wing flap-flipping urethroplasty and "glanulomeatoplasty"

We describe our experience with complete repair of severe penoscrotal hypospadias in 1 stage. The operative technique includes several innovative points, such as release of chordee by urethral mobilization (without detaching it from the glans) after penile degloving of dartos chordee, wing flap-flipping urethroplasty to the tip of the glans and incrimination of "glanulomeatoplasty" for better cosmetic and functional results. Our technique is compared to other 1-stage methods.