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Using gas chromatography-mass spectrometry, we developed a sensitive and reliable technique to measure phenylacetic acid (PAA), an oxidatively deaminated metabolite of beta-phenylethylamine (PEA), in small amounts of cerebrospinal fluid (CSF). In a preliminary analysis, PAA concentrations in depressive patients were significantly lower than those in controls, while there were no differences in PAA levels between schizophrenic patients and controls. This suggests a possible link between the decreased PEA metabolism in the brain and the etiology of depression. However, further studies are needed to clarify the effects of neuroleptics and antidepressants on PAA levels in CSF, since the samples were obtained without regard to medication in the present study. In control subjects, a U-shaped distribution was obtained when the values of PAA were plotted as a function of age. There were no sex differences and no significant concentration gradients in CSF PAA levels.

Type IV collagen-degrading enzyme activity was measured in liver homogenate obtained from 10 patients with hepatocellular carcinomas. Type IV collagen, the enzyme substrate, was extracted from human placenta with pepsin digestion, and labeled with [1-14C] acetic anhydride. The homogenate was preincubated with p-aminophenylmercuric acetate to activate the latent form of the enzyme, and then the enzyme activity was measured at pH 7.5 by adding a substrate mixture. Referring to previous reports, the enzyme measured seemed to be a neutral metalloprotease. The enzyme activity of the homogenate was markedly reduced by omitting the p-aminophenylmercuric acetate pretreatment, indicating that the enzyme was present mainly in the latent form. The activity seemed to be higher in the peripheral portion of hepatocellular carcinoma than in the center. Further the activity was found to be the highest in a hepatocellular carcinoma patient with many metastatic nodules in the lung. The results might suggest that type IV collagen-degrading enzyme participates in tumor invasion and intrahepatic or remote metastasis.

The elimination of fibroblast-like cells from primary cultures of fetal human livers was studied. A fibroblast-like cell line (HuF), which was obtained by subculturing fetal human liver cells 4 or more times, was briefly treated with hydrocortisone (HC) or putrescine (PUT). The growth of HuF cells was inhibited by HC at a concentration of 10(-2) M and by PUT at a concentration higher than 10(-3) M. Long-term treatment of HuF cells with 10(-3) M HC inhibited the growth of the cells. Primary cultures of fetal human livers were made in medium containing HC or PUT, and morphological and functional examinations were made. The cultures were predominantly composed of epithelial-like cells, with few fibroblast-like cells, when the HC concentration was 10(-5)M to 10(-3) M. A high amount of albumin was secreted at these concentrations of HC. On the other hand, at 10(-3) M PUT, many epithelial-like cells were seen, but albumin was undetectable. The present results indicate that albumin-producing epithelial-like cells can be selectively maintained in medium containing HC, in primary cultures of fetal human livers.

The replicative responses of suckling and adult rat hepatocytes in primary culture to growth-stimulating factors were compared. By addition of L-proline alone, the [3H]-thymidine labeling of suckling rat hepatocytes was dramatically enhanced, but that of adult ones was not. Epidermal growth factor (EGF), insulin, triiodothyronine (T3) and glucagon also enhanced the labeling of suckling rat hepatocytes regardless of the presence or the absence of L-proline. On the other hand, in the absence of L-proline, only EGF enhanced the labeling of adult rat hepatocytes, and, in the presence of L-proline, insulin as well as EGF enhanced the labeling. In the presence of growth factors and L-proline, the number of suckling rat hepatocytes increased up to about 143%, whereas that of adult rat hepatocytes hardly increased. Thus, a remarkable difference in replicative responses to growth factors and L-proline was observed between suckling and adult rat hepatocytes in primary culture.

To study chromatin structure at the sites of DNA replicated in permeable cells, deoxyribonuclease I (DNase I) sensitivity of newly replicated DNA in permeable mouse sarcoma cells was compared with that of newly replicated DNA in intact cells. About 35% of the DNA replicated in permeable cells was hypersensitive to DNase I, and the remaining DNA showed the same DNase I sensitivity as that of parental chromatin DNA. The sensitivity of DNA replicated in permeable cells was higher than that of DNA newly replicated in intact cells, and was close to that of DNA replicated in the presence of cycloheximide. The sensitivity of DNA pulse-labeled with [3H]deoxythymidine triphosphate by replication in permeable cells was reduced significantly by chasing with cold deoxythymidine triphosphate. The present results suggest that chromatin structure at the sites of DNA replicated in permeable cells is similar to that at the sites of DNA replicated in living cells in the absence of protein synthesis, and that some structural change (possibly toward the maturation) of newly replicated chromatin occurs after the DNA replication in permeable cells.

This study was designed to determine the in vitro release of tegafur from a suppository and the in vivo bioavailability of tegafur in rats. Two different suppository preparations (product A-1 and product A-2) containing 750 mg of tegafur were tested for in vitro release of tegafur by the Muranishi Method (membrane diffusion method) and the partially modified paddle method (permeability through dialysis tubing). When determined by either method, the amount of tegafur released from product A-2 during the whole experimental period was significantly greater than that released from product A-1. When tested by the Muranishi method, however, the difference in the amount released during the first 10-min period was not significant. A greater bioavailability of tegafur after rectal administration was obtained by product A-2 more than product A-1. A significant correlation was observed between the in vitro release and the in vivo bioavailability. The present results indicate that there are considerable differences in physiochemical characteristics between product A-1 and product A-2.

Vital observation on the cellular morphology of the normal human blood cells was conducted by means of bone marrow culture successfully in conjunction with vital staining with Janus green B and neutral red. A special attention was paid for the alterations of the cellular structures in the course of the culture. The findings are summarized as follows : 1) Intracellular particles with affinity to Janus green B or neutral red were classified into minute granules, granules, vacuoles, and mitochondria. Morphologic features of each type of the particles were studied in detail. 2) Two types of granules are present in neutrophilic and eosinophilic blood cells, whereas one type of granules is present in basophilic blood cells. Eosinophilic and basophilic granules show characteristic pole formation in them at the terminal stage of the staining. 3) The rosette formation in the mature monocyte and the aggregations of neutral red vacuoles in the mature neutrophil and the mature lymphocyte were characterized. 4) The cluster of neutral red vacuoles is characteristic of the erythroblast. 5) The mitochondria of the mature neutrophil and the mature monocyte participate in producing neutral red vacuoles.

Within the range of our investigations the most important biochemical characteristics in the brain of idiopathic epileptic patients seem to be defect in the production of and the attendant decrease in free amino acids of the brain. On account of these phenomena there seem to occur the acceleration of the ChE activity and a poor utilization of glucose. Of the free amino acids in the brain the combined amount of glutamic acid, glutamine and γ-aminobutyric acid (GABA) will occupy the major portion of the total free amino acids found in brain, and thus diminution in the contents of glutamic acid and GABA in the brain of idopathic epileptic patients has quite an important meaning. At the present stage it is not yet possible to give any definitive answer to the question why such decrease occurs but it is believed that the most urgent problem facing us today is the amino acid metabolism that is associated with glutamic acid and the comparative studies of the amino acid metabolism in the epileptic brain to that in the non-epileptic brain are required. The fact that γ-amino-β-hydroxybutyric acid (GABOB), the substance that suppresses the central excitation, is decreased seems to indicate biochemically the existence of a defect in the processes of excitation in the brain of idiopathic epleptic patients.

1. The results of 245 pleural biopsies perfomed in 108 patients including 219 pleural needle biopsies and 26 pleural open biopsies were reported. The method of pleural biopsy seems to be superior to any other currently available diagnostic procedures for the etiological diagnosis of pleurisy. 2. When the pleural needle biopsy is compared with the pleural open biopsy, the former method has definite advantages over the open biopsy. The pleural needle biopsy is simple, repeatable and has almost no complication. The method of pleural needle biopsy is the initial method of choice as Donohoe correctly stated and should be employed in every cases of the pleurisy to confirm the etiological diagnosis. The open biopsy should be reserved only for those cases in whom the needle biopsy had not proved satisfactory. 3. Utilizing the method of needle biopsy, the pathological diagnosis was made in 86 per cent of our cases at the initial biopsy. By repeated needle biopsies, the results have improved to 91-92 per cent. 4. Most of the failures of the pleural needle biopsy were noted at the early stage of the study due to the unfamiliarity of the biopsy technique and later due to the incooperation of the patients. 5. The presence of the free pleural fluid serves as a convenient guide for the performance of the needle biopsy but successful needle biopsy was easily done without presence of pleural fluid when there is adequate pleural thickening. 6. 63-75 per cent of our diagnosed cases were proved to have granulomatous pleuritis, 13-31 per cent non-specific pleuritis and 5.4-5.8 per cent eosinophilic pleuritis due to paragonomiasis. The distribution of this pathological diagnosis seems to reflect quite well the actual picture of incidences of pleurisy of various different etiology in young adults in Korea. 7. The relationship of the success in obtaining adequate tissue by needle biopsy and interval between onset of symptom and biopsy was discussed. It was found that the interval has no significant effect on the production of adequate tissue by needle biopsy if the time elapsed is 4 weeks or more from the onset of symptom. 8. The significance of the pathological findings of ranulomatous pleuritis at one biopsy and non-specific pleuritis at another biopsy in the same patient was discussed. It is concluded that the single finding of nonspecific pleuritis at one needle biopsy cannot rule out the presence of granulomatous pleuritis and it is recommended that pleural biopsy be repeated whenever necessary. 9. The diagnostic significance of the chemical analysis of the pleural fluid was discussed in correlation with the results of the pleural needle biopsies. It is concluded that the number of examinations are not quite sufficient to draw any definite conclusion at the present stage of our study. 10. The finding of sanguinous pleural fluid in the patient of granulomatous pleuritis is quite high (72.7 %) and it was found that the sanguinous pleural fluid was most frequently found in the patients with granulomatous pleuritis in non-cancerous age. 11. Two groups of pleurisy patients with or without parenchymal lung lesion on chest X-ray were discussed in correlation with the results of the needle biopsy. It was found that the incidence of the pathological evidence of granulomatous inflammation on the biopsy specimens in these two groups is almost the same regardless of the presence of the demonstrable parenchymal lung lesion. 12. Histopathological finding of granulomatous pleuritis was discussed in conjunction with the significance of two types of tubercles, the soft tubercles and hard tubercles. In all specimens diagnosed as granulomatous pleuritis granulomas were demonstrated ranging from large, conglomerate tubercles with central caseation or giant cells to small granulomas without central caseation or Langhans' giant cells. 13. Histopathological significance of the finding of non-specific pleuritis on the biopsy specimens was discussed and the existence of a specific entity of "non-specific pleuritis" which is equivalent to the non-specific inflammation of the pericardium. 14. Cases of pleurisy due to paragonomiasis were discussed and the need of specific attention for search of new cases was emphasized.

1. Adrenalin, when acting directly on eosinophils, brings about a diminution in the wandering velocity of eosinophils but it has no influence on the number of the cells. Judging from the movement patterns of eosinophils this drug acts as to impede the motive function. 2. Acting directly on eosinophils, cortisone markedly decreases the wandering velocity of these cells and also brings about the diminution in the number of the cells. Likewise from the movement patterns of eosinophils, this drug markedly impedes the motive function of the cells. 3. ACTH (adrenocorticotropic hormone), when acting directly on eosinophils, enhances the wandering velocity of eosinophils but it in no way affects the number of eosinophils. Judging from the eosinophil movement patterns, this drug markedly promotes the motive function. 4. Although adrenalin brings about a decrease in the number of peripheral eosinophils in hypophysectomized dogs, the rate of the decrease is less than that observable in the case of normal dogs. 5. Cortisone brings about no significant change in the number of peripheral eosinophils in hypophysectomized dogs, but is induces a decrease in peripheral eosinophils of normal dogs. 6. ACTH acts as to decrease the number of peripheral eosinophils to an equal. degree in both hypophysectomized and normal dogs. 7. When cortisone is administered simultaneously with Adrex, a marked decrease in peripheral eosinophils is brought about in hypophysectomized dogs. 8. By means of the bone-marrow tissue culture of hypophysectomized dogs it has been confirmed that the blood plasma of hypophysectomized dogs lacks an essential factor for cortisone to induce eosinopenia in perpheral blood. 9. The decrease in eosinophils of peripheral blood induced by cortisone has been proved to be dependent upon the presence or absence of the pituitary body. 10. Taking the decrease in peripheral eosinophils by cortisone administration as the criterion, the author has carried out clinical observations with this method and obtained anticipated results.

The vector electrocardiographic method was applied on 126 healthy young Korean adults without any evidence of cardiac diseases. The range of the age of the subjects were between 19 and 34. The normal values of the magnitude and direction of the mean QRS, T, P vectors, ventricular gradient and QRS-T angle in frontal plane were presented and discussed in comparison with those previously reported in the literature. Considering the age of the subjects under study, our results were in general agreement with those previously reported by other authors.

Many studies have shown that a motif of 11 consecutive arginines (11R) is one of the most effective protein transduction domains (PTD) for introducing proteins into the cell membrane. By conjugating this "11R", all sorts of proteins can effectively and harmlessly be transferred into any kind of cell. We therefore examined the transduction efficiency of 11R in cerebral arteries and obtained results showing that 11R fused enhanced green fluorescent protein (11R-EGFP) immediately and effectively penetrated all layers of the rat basilar artery (BA), especially the tunica media. This method provides a revolutionary approach to cerebral arteries and ours is the first study to demonstrate the successful transductionof a PTD fused protein into the cerebral arteries. In this review, we present an outline of our studies and other key studies related to cerebral vasospasm and 11R, problems to be overcome, and predictions regarding future use of the 11R protein transduction method for cerebral vasospasm (CV).

There is little information available concerning the influence of right bundle branch block (RBBB) on the prognosis of patients with inferior myocardial infarction (MI). In this study we evaluated the influence of RBBB on the short-term prognosis of patients with inferior MI. Our study subjects were 1,265 hospitalized patients with Q wave MI. Patients were divided into 4 groups based on the presence or absence of RBBB and on the location of the infarction. RBBB was classified into 4 categories according to the timing of its appearance and its duration as new permanent, transient, old and age indeterminate. In-hospital death and pulmonary congestion were observed more frequently in patients with RBBB than in those without RBBB. Moreover, in inferior MI as in anterior MI, in-hospital death and pulmonary congestion occurred more frequently in new permanent RBBB patients than in patients with other types of RBBB. Multivariate regression analysis reveals that new permanent RBBB was a strong independent predictor for an adverse short-term prognosis in patients with inferior MI, as well as in patients with anterior MI. New permanent RBBB during inferior MI is a strong independent predictor for increased in-hospital mortality, regardless of the infarction location.

Surgical treatment of metastatic spinal cord compression is controversial. The purpose of this study was to investigate the effectiveness of our current surgical treatments and the use of spinal instrumentation. In this retrospective study covering the years between 1990 and 2006, 100 patients with spinal metastases which were secondary to various cancers underwent posterior and/or anterior decompression with spinal stabilization for the purposes of reduction of pain, and/or to help correct or improve neurological deficits. The group was made up of 60 men and 40 women whose ages ranged from 16 to 83 years (average of 60 years), and the average follow-up period was 14 months. The effect of treatment upon pain relief and neural deficits was assessed, and the cumulative survival rate was calculated by the Kaplan-Meier method. The average surgical time was 185min. This was calculated based on the following times, listed here with the surgery type:178min for posterior surgery;245min for anterior surgery;465 min for combined surgery;and 475min for total en bloc spondylectomy. Average blood loss during surgery was 1,630 ml for posterior surgery, 1,760 ml for anterior surgery, 1,930 ml for combined surgery, and 3,640 ml for total en bloc spondylectomy. Preoperative pain and paralysis were improved by 88% and 53%, respectively. In regards to surgical complications, postoperative epidural hematoma was observed in 2 patients, and instrumentation-related infection was observed in 1. Only 2 patients died within 2 months of surgery. In conclusion, posterior and/or anterior decompression with spinal stabilization is a safe and effective treatment for patients with spinal metastases, and can improve their quality of life.

The present study was performed to clarify the effect of hypertonic saline infusion into the lung parenchyma on radiofrequency ablation (RFA) of the lungs. A total of 20 ablation zones were created in 3 pigs. The ablation zones were divided into 3 groups. Group 1 (n6) consisted of ablation zones created by applying smaller radiofrequency (RF) power without saline infusion;group 2 (n5) zones were created by applying greater RF power without saline infusion;and group 3 (n9) zones were created by applying greater RF power with saline infusion. The techniques of saline infusion included administration of hypertonic saline 1ml before RFA, followed by continuous administration at a rate of 1ml/min during the first 2min after the initiation of RFA. The ablation parameters and coagulation necrosis volumes were compared among the groups. Group 3 had a tendency toward smaller mean impedance than group 1 (p0.059) and group 2 (p0.053). Group 3 showed significantly longer RF application time than group 2 (p0.004) and significantly greater maximum RF power than group 1 (p0.001) and group 2 (p0.004). Group 3 showed significantly larger coagulation necrosis volume (mean, 1,421mm3) than group 2 (mean, 858mm3, p0.039) and had a tendency toward larger necrosis volume than group 1 (mean, 878mm3, p0.077). Although this small study had limited statistical power, hypertonic saline infusion during RFA appeared to enlarge coagulation necrosis of the lung parenchyma.

Angiogenesis involves complex processes mediated by several factors and is associated with inflammation and wound healing. High mobility group box 1 (HMGB1) is released from necrotic cells as well as macrophages and plays proinflammatory roles. In the present study, we examined whether HMGB1 would exhibit angiogenic activity in a matrigel plug assay in mice. HMGB1 in combination with heparin strongly induced angiogenesis, whereas neither HMGB1 nor heparin alone showed such angiogenic activity. The heparin-dependent induction of angiogenesis by HMGB1 was accompanied by increases in the expression of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor-A120 (VEGF-A120). It is likely that the dependence of the angiogenic activity of HMGB1 on heparin was due to the efficiency of the diffusion of the HMGB1-heparin complex from matrigel to the surrounding areas. VEGF-A165 possessing a heparin-binding domain showed a pattern of heparin-dependent angiogenic activity similar to that of HMGB1. The presence of heparin also inhibited the degradation of HMGB1 by plasmin in vitro. Taken together, these results suggested that HMGB1 in complex with heparin possesses remarkable angiogenic activity, probably through the induction of TNF-alpha and VEGF-A120.

We report 2 cases of small cell carcinoma (SmCC) of the stomach with distant metastasis that were treated with the same chemotherapeutic regimens as used to treat small cell lung cancer. Although the mean survival of patients with SmCC of the stomach is reported to be only 7 months, our patients survived for 15 and 14 months, respectively. In our experience, these chemotherapeutic regimens might provide a survival benefit for patients with SmCC of the stomach, although they demonstrated no remarkable antitumor effects.

For many years, surgery alone was the standard treatment for patients with stage I-IIIA non-small-cell lung cancer (NSCLC). However, recent studies have demonstrated that adjuvant chemotherapy provides a survival benefit. The first adjuvant chemotherapy for NSCLC was performed in the 1960s using a key drug known as cyclophosphamide. In the 1980s and early 1990s, a new anti-cancer drug, cisplatin, was developed. The first meta-analysis of this drug was conducted by the Non-small Cell Lung Cancer Collaborative Group in 1995. This analysis comparing surgery with surgery plus chemotherapy containing cisplatin produced a hazard ratio of 0.87 and suggested an absolute benefit of chemotherapy of 5% at 5 years;this difference was not statistically significant (p0.08). Several clinical trials of adjuvant chemotherapy were planned after the meta-analysis conducted in 1995, but the efficacy of adjuvant chemotherapy remained a matter of controversy. However, useful evidence was reported after 2003. The International Adjuvant Lung Cancer Collaborative Group Trial (IALT) demonstrated a 4.1% improvement in survival for patients with stage I to III NSCLC. The JBR. 10 trial demonstrated a 15% improvement in 5-year survival for the adjuvant chemotherapy arm in stage IB or II (excluding T3N0) patients. The Adjuvant Navelbine International Trialist Association (ANITA) trial reported that the overall survival at 5 years improved by 8.6% in the chemotherapy arm and that this survival rate was maintained at 7 years (8.4%) in stage II and IIIA patients. A meta-analysis based on collected and pooled individual patient data from the 5 largest randomized trials was conducted by the Lung Adjuvant Cisplatin Evaluation (LACE). This analysis demonstrated that cisplatin-based adjuvant chemotherapy improved survival in patients with stage II or III cancer. Alterna-tively, uracil-tegafur has been developed and tested in Japan. The Japan Lung Cancer Research Group (JLCRG) on Postsurgical Adjuvant Chemotherapy reported a 5-year overall survival advantage of 11% in the uracil-tegafur group patients with stage IB cancer. The efficacy of adjuvant chemotherapy with uracil-tegafur was confirmed in a meta-analysis. In conclusion, the results of phase III trials and a meta-analysis have confirmed the benefit of adjuvant chemotherapy for resected stage IB, II, and IIIA NSCLC.

The first operative procedure in sex reassignment surgery (SRS) for female-to-male transsexuals (FTMTS) is mastectomy. This procedure includes the removal of mammary tissue, removal of excess skin, and reduction and proper repositioning of the nipple and areola complex. We have performed mastectomies in over 120 patients since January 2001 and want to describe the operative procedures we have developed. We classified our patients into 3 groups according to the patient's breast volume and the degree of ptosis, and we selected the operative procedure that was suitable for each group. At present all costs for SRS are assumed by the patient in Japan. If the FTMTS patient undergoes the entire series of SRS operations, he has to pay more than 3,000,000 yen. Thus the surgeon should select the proper operative procedure so that the patient can avoid unnecessary additional operations. We describe herein the techniques and the strategy for performing mastectomy in FTMTS.

Sporadic intestinal cryptosporidiosis is not easily diagnosed and might be overlooked. We present here a case of this disease in a 23-year-old Japanese military man with 3 days of abdominal pain, watery diarrhea, and nausea. The frequency of his diarrhea was more than 10 times per day. After his diarrheal bowel symptoms subsided, a colonoscopy was performed because inflammatory bowel disease was suspected. Although the endoscopic findings indicated non-specific ileitis, intestinal cryptosporidiosis was suspected from the histology of ileal biopsy specimens, and this was confirmed ultrastructurally. At that time, however, the patient was on active duty, and thus it was not possible to confirm this as a definitive diagnosis by an adequate stool examination for cryptosporidium. Routine practitioners should be encouraged to carefully inspect patients for this disease, supported by detailed knowledge of it and its diagnosis. If stool-examination results are negative or are not obtained at first, histological diagnosis by endoscopic biopsy could be a useful way to screen for intestinal cryptosporidiosis. Furthermore, stool or histological examination should be performed in recovered patients because the oocysts may continue to be shed for 1 to 4 weeks after the symptoms disappear. Therefore, endoscopic and histological examinations may be useful tools for the early diagnosis of intestinal cryptosporidiosis, although admittedly they are invasive procedures.