[Direct instillation of the fibrin glue into the ruptured bulla is an effective treatment for uncontrolled pneumothorax occurred from severe emphysematous bullae].

From May 2005 to October 2010. 9 patients with severe emphysematous bullae suffered from uncontrolled pneumothorax had been successfully treated by a new surgical method in our hospital. By using direct instillation of fibrin glue into the ruptured bulla following ligation of the ruptured bulla hole, 8 of 9 patients revealed no recurrence of new rupture and pneumothorax. Although the ligation of ruptured bulla hole tended to increase tension of surface of the bulla around the ligation and caused new rupture of the bulla, the fully instilled glue reduced intra air pressure of the ligated bulla and prevented new rupture. Additionally, the direct instillation of the glue immediately stopped the air leakage by itself. This direct instillation method of the glue encouraged us to challenge the surgery for the patients suffered from uncontrolled pneumothorax with severe emphysematous bullae.

[Characteristics of postoperative period in children with funnel chest deformity after thoracoplasty].

The efficiency of postoperative analgesia using the epidural infusion of bupivacaine (0.2 mg/kg/hr) in 42 children and with opioid analgesics (1 mg per year of life) was studied in 17 children after Paltia thoracoplasty for funnel chest deformity. Analysis of hemodynamic and external respiratory parameters and visual pain scores demonstrated the high postoperative efficiency of analgesia using the epidural infusion of bupivacaine. By causing respiratory depression, opioid analgesics did not deteriorate alveolar ventilation during active postoperative management.

Comparison between dexmedetomidine and midazolam as a sedation agent with local anesthesia in inguinal hernia repair: randomized controlled trial.

PURPOSE: In Japan, inguinal hernia repair is widely performed with local anesthesia. The objective of this study was to evaluate safety and efficacy of intravenous dexmedetomidine as a sedation agent with local anesthesia in inguinal hernia repair. METHODS: We performed this randomized, single-blind study for 200 patients who were scheduled to undergo inguinal hernia repair with local anesthesia. Patients were randomly divided into two groups (dexmedetomidine group: Group D, midazolam group: Group M). The primary outcome was to evaluate the safety of intravenous dexmedetomidine. Secondary outcomes were to analyze results of operators' surveys and patients' questionnaires and evaluate implementation of conscious sedation. RESULTS: Incidence of respiratory depression was significantly higher in Group M than Group D (p = 0.03). Other adverse events examined did not differ significantly. All three operators' questionnaires indicated that results were better in Group D than Group M. More than 70% of patients in both groups were satisfied with the surgery. More than 80% of Group D patients and 74% of Group M patients achieved a state of conscious sedation. CONCLUSION: This study demonstrated that intravenous dexmedetomidine during hernia repair with local anesthesia is safe and the results were satisfactory to both operators and patients.

Hierarchical viscosity of aqueous solution of tilapia scale collagen investigated via dielectric spectroscopy between 500 MHz and 2.5 THz.

Aqueous solutions of biomolecules such as proteins are very important model systems for understanding the functions of biomolecules in actual life processes because interactions between biomolecules and the surrounding water molecules are considered to be important determinants of biomolecules' functions. Globule proteins have been extensively studied via dielectric spectroscopy; the results indicate three relaxation processes originating from fluctuations in the protein molecule, the bound water and the bulk water. However, the characteristics of aqueous solutions of collagens have rarely been investigated. In this work, based on broadband dielectric measurements between 500 MHz and 2.5 THz, we demonstrate that the high viscosity of a collagen aqueous solution is due to the network structure being constructed of rod-like collagen molecules surrounding free water molecules and that the water molecules are not responsible for the viscosity. We determine that the macroscopic viscosity is related to the mean lifetime of the collagen-collagen interactions supporting the networks and that the local viscosity of the water surrounded by the networks is governed by the viscosity of free water as in the bulk. This hierarchical structure in the dynamics of the aqueous solution of biomolecules has been revealed for the first time.

Altered p16INK4 and retinoblastoma protein status in non-small cell lung cancer: potential synergistic effect with altered p53 protein on proliferative activity.

p16INK4 protein (p16) and retinoblastoma protein (pRB), like p53 protein, are important tumor suppressors that regulate the cell cycle. We immunohistochemically examined fresh-frozen specimens of 114 resected non-small cell lung cancers (NSCLCs) for loss of p16 and pRB expression, together with aberrant accumulation of p53 protein and the proliferative activity determined by the Ki-67 index. Three pRB-positive tumors were uninterpretable for p16 status. Of the remaining 111 tumors, 30 (27%) lacked p16 expression, and 10 (9%) lost pRB expression. No tumors showed coincident loss of both proteins, supporting the hypothesis that they function in a single pathway. Of 25 tumors, including 4 p16-negative tumors, examined by Southern blot analysis, only 2 p16-negative tumors were considered to have reduced gene dosage consistent with possible homozygous deletion of the CDKN2 gene encoding p16, suggesting that immunohistochemistry is a sensitive and suitable method to screen for p16 alteration. Loss of p16 expression did not correlate with any clinical factors or p53 status, whereas loss of pRB expression correlated with heavy smoking (P = 0.03 by Fisher's exact test and P = 0.01 by the multivariate logistic regression analysis). Proliferative activity was considerably higher in p53-positive tumors than in p53-negative tumors (P < 0.001). Loss of p16 or pRB expression was associated with a further increase in proliferative activity in the p53-positive tumors (P = 0.009) but not with proliferative activity in the p53-negative tumors. These results suggest that alteration of the p16/pRB pathway is relatively frequently involved in the development and progression of NSCLCs and that its effect on the proliferative activity is potentially synergistic with altered p53 protein.

A risk-stratification model of non-small cell lung cancers using cyclin E, Ki-67, and ras p21: different roles of G1 cyclins in cell proliferation and prognosis.

A large number of biological factors that seem to have important prognostic significance have been identified in non-small cell lung cancers (NSCLCs). In the present study, we have characterized expression of cyclin D1 and cyclin E in a cohort of 217 resected NSCLCs from a single institution by immunohistochemistry to analyze their expression in relation to the growth fraction determined by Ki-67 and to prognosis, and then we have constructed a risk-stratification model of cancer death by multiple biological factors in p-stage I NSCLCs. The cyclin E labeling index (LI) was significantly associated with the Ki-67 LI (r = 0.45; P < 0.001). Tumors having high-level cyclin E expression (cyclin E LI > or =30%) showed a significantly higher Ki-67 LI than tumors having low-level cyclin E expression (cyclin E LI <30%; P < 0.001), whereas positive or negative cyclin D1 expression was not associated with the Ki-67 LI (P = 0.1). Cyclin E expression was a significant and independent unfavorable prognostic factor (hazards ratio = 2.09; P = 0.03), as reported previously (Clin. Cancer Res., 6: 11-16, 2000), whereas cyclin D1 expression was not. These findings indicate different roles of cyclin D1 and cyclin E in cell proliferation and in the prognosis of NSCLCs. Furthermore, we stratified this cohort of p-stage I NSCLCs into different survival groups by using biological factors, including cyclin E, Ki-67, and ras p21, which previously we have found to be independent prognostic factors among 10 factors studied in p-stage I NSCLCs. Four groups of patients with markedly different survivals were identified with 5-year survival rates that ranged from 96% for patients with no factors altered to 41% for patients with all three factors altered (P < 0.001). This combination of biological factors was a significant and independent prognostic factor (hazards ratio = 7.94; P = 0.001).

Prognostic significance of p27KIP1 protein and ki-67 growth fraction in non-small cell lung cancers.

We immunohistochemically examined specimens of 215 surgically resected non-small cell lung cancers (NSCLCs) for p27KIP1 protein (p27) expression and the growth fraction determined by the Ki-67 labeling index (LI). The NSCLCs analyzed showed considerable heterogeneity in both p27 and Ki-67 LIs; 25 of 207 (13%) lacked p27 expression (p27 LI < 5%), and 116 of 215 (54%) showed a high Ki-67 LI (>30%). The p27 LI was not significantly associated with the Ki-67 LI. A chi2 test showed that loss of p27 expression was inversely correlated with smoking (P = 0.01) and that a high Ki-67 LI was significantly associated with male gender, squamous cell carcinoma histology, and smoking (P < 0.0001 each). Prognostic values of p27 and Ki-67 expression were evaluated in 109 tumors of postsurgical pathological stages I and II. Patients with tumors lacking p27 expression survived for a significantly shorter time than patients with tumors expressing p27 (5-year survival rates, 38% and 68%, respectively; P = 0.02). Patients with tumors having a high Ki-67 LI survived for a significantly shorter time than patients with tumors having a low Ki-67 LI (5-year survival rates, 48% and 78%, respectively; P = 0.005). Multivariate analysis showed that loss of p27 expression tended to be an unfavorable prognostic factor (P = 0.054), whereas a high Ki-67 LI was a significant and independent unfavorable prognostic factor (P = 0.004). When analyzed by cell types, loss of p27 expression was a significant and independent unfavorable prognostic factor in squamous cell carcinomas (P = 0.01), whereas a high Ki-67 LI was a significant and independent unfavorable prognostic factor in nonsquamous cell carcinomas (P = 0.007). We further evaluated the importance of p27 expression in clinical outcome in combination with the Ki-67 LI and ras p21 protein (ras) expression, which we previously reported as an important prognostic factor in NSCLCs. Patients with tumors lacking p27 expression and having a high Ki-67 LI survived for a significantly shorter time than those with tumors expressing p27 and having a high Ki-67 LI (5-year survival rates, 17% and 52%, respectively; P = 0.003). Patients with p27-negative and ras-positive tumors survived for a significantly shorter time than those with both p27- and ras-positive tumors (5-year survival rates, 0% and 38%, respectively; P < 0.0001). These results indicate the pivotal roles of p27 and Ki-67 expression in the clinical outcome of NSCLCs.

Cyclin E expression, a potential prognostic marker for non-small cell lung cancers.

Cyclin E is a G1 cyclin that has been shown to be one of the key regulators of the G1-S transition and could consequently be a deregulated molecule in tumors. In the present study, we have characterized cyclin E expression by immunohistochemistry in 217 resected non-small cell lung cancers (NSCLCs) and found large variations in cyclin E expression among tumors. High-level cyclin E expression (a cyclin E-labeling index > or =30%), observed in 115 (53%) of 217 NSCLCs, was more frequently found in tumors from smokers than from nonsmokers (P = 0.001), in squamous cell carcinomas than in nonsquamous cell carcinomas (P = 0.0002), and in pT2-4 tumors than in pT1 tumors (P = 0.04) by the chi2 test. Multivariate logistic regression analysis for the correlation between cyclin E expression and various characteristics showed a significant association of high-level cyclin E expression with squamous cell carcinomas (P = 0.005). Patients with tumors having high-level cyclin E expression survived a significantly shorter time than patients with tumors having low-level expression, both among the 151 patients with potentially curatively resected NSCLCs (5-year survival rates, 48 and 63%, respectively; P = 0.03) and the 103 patients with p stage I NSCLCs (5-year survival rates, 57 and 81%, respectively; P = 0.007). High-level cyclin E expression was also a significant and independent unfavorable prognostic factor in both patients with potentially curatively resected NSCLCs (P = 0.01) and in those with p stage I NSCLCs (P = 0.03) by Cox's proportional hazards model analysis. These findings indicate that cyclin E may play a pivotal role for the biological behavior of NSCLCs, and that a high level of cyclin E expression may be a new prognostic marker for NSCLCs.

Synthesis and immunosuppressive activity of 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols.

A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.

Stimulatory and inhibitory effects of guanine nucleotides on arginine-vasotocin-sensitive adenylate cyclase in the epithelial cell membranes of the bullfrog bladder.

The effects of arginine-vasotocin and nucleotides on the steady-state kinetics of the adenylate cyclase activity in the epithelial cell membranes of the bullfrog (Rana catesbiana) bladder were studied. Arginine-vasotocin stimulated adenylate cyclase more effectively than oxytocin or arginine-vasopressin, with respect to both the maximal hormonal activation ratio relative to basal, and the hormone concentration yielding a half-maximal response (apparent Km). Arginine-vasotocin, GTP and its analogue guanyl-5'-yl imidodiphosphate (Gpp(NH)p) increased the Vmax of the basal adenylate cyclase activity, but showed no effect of the apparent Km of the system for ATP. In addition, Gpp(NH)p enhanced the arginine-vasotocin-stimulated adenylate cyclase activity, further increasing the Vmax, while GTP showed no statistically significant effect. Dual effects of GDP were apparent: it was stimulatory at 1 x 10(-5) mol/l and inhibitory at 1 x 10(-3) mol/l, on both the basal and the arginine-vasotocin-stimulated adenylate cyclase activity. Guanosine 5'-monophosphate, CTP, UTP and ITP showed no apparent effect on the enzyme activity. Sodium fluoride acted in the same manner as GTP on the adenylate cyclase system, increasing only basal activity. Adenylate cyclase activities exhibited pH optima that were less distinct in the presence than in the absence of Gpp(NH)p. The Arrhenius plot of the temperature experiment showed that a high-energy step was involved for activation by Gpp(NH)p or arginine-vasotocin. When the relative activation ratios by arginine-vasotocin at different ATP concentrations were studied, a distinct activation optimum was shown at 2.5 x 10(-4) mol ATP/l, either in the absence or presence of Gpp(NH)p. The possibility that GTP, GDP nd ATP play a regulatory role in the epithelial cells of the bullfrog bladder by adjusting the responsiveness of the system to a natural hormone, arginine-vasotocin, is discussed.

Frequent cyclin D1 expression in chromate-induced lung cancers.

Ex-chromate workers are frequently afflicted with lung cancers, especially central-type squamous cell carcinomas (SCCs) of the lung. However, little is known about the molecular and cellular biologic characteristics of chromate-induced lung cancers. We investigated expression of cyclin D1, bcl-2, and p53 proteins in chromate-induced lung cancers by immunohistochemistry, compared with those in lung cancers from nonexposed individuals and those in individuals with pneumoconiosis. Of 19 chromate-induced lung cancers, 16 tumors were SCCs, including 11 central and 5 peripheral types. Eleven (69%) of 16 chromate SCCs showed cyclin D1 expression. In contrast, cyclin D1 expression was observed in only 3 (12%) of 26 SCCs from nonexposed individuals and 6 (16%) of 37 SCCs that developed in patients with pneumoconiosis, respectively. The frequency of cyclin D1 expression proved to be significantly higher in chromate-induced SCCs than in SCCs from nonexposed individuals and from those with pneumoconiosis (P < .001). When comparisons were extended to all histologic types of lung cancer, cyclin D1 expression was observed significantly more often in chromate-induced lung cancers than in lung cancers from nonexposed subjects and those from patients with pneumoconiosis (11 [58%] of 19 v 5 [10%] of 52, P < .001, and 7 [11%] of 63, P < .001, respectively). Frequencies of bcl-2 and p53 expression were not significantly different among lung cancers from ex-chromate workers, nonexposed individuals and those with pneumoconiosis. The current study suggests that cyclin D1 expression may be involved in the development of chromate-induced lung cancers, although its underlying mechanism remains to be determined.

Absorption of anticancer drugs through bladder epithelium.

Fundamental and clinical evaluations of ten anticancer drugs were performed. The required qualities of an anticancer drug ideal for bladder instillation therapy are thought to be as follows: (1) a high sensitivity for bladder tumor cells; (2) a pKa which provides a high percentage of nonionized molecules in a pH 6-7 solution; (3) a log P in the range from -0.4 to -1.2 or from -7.5 to -8.0; and (4) a molecular weight over 200.

Intravesical instillation of adriamycin for bladder tumors.

In the present series of trials, Adriamycin (ADM) intravesical instillation therapy was found to be effective against tumors of papillary morphology measuring less than 10 mm in diameter that were of low pathological stage and low histological grade. The rate of complete disappearance increased in proportion to the concentration of ADM and the duration of retention of the drug, although the efficacy rates were almost the same in each trial. On the other hand, side effects on the bladder were reduced when the instilled solution was lower in concentration and the retention time was short.

Development and clinical application of an AFC regimen (adriamycin, futraful, cytosine arabinoside) for superficial bladder tumors.

Our AFC regimen was originally developed to treat superficial bladder tumors. It consists of a daily intravesical administration of 20 mg Adriamycin (ADM) and 200 mg Cytosine arabinoside (CA) dissolved in 20 ml of sterilized distilled water, simultaneously with a daily rectal suppository of 750 mg tegafur (Futraful) for a total of 20 applications. Our study demonstrated the following characteristics of the AFC modality: (1) It is simple; (2) it is completed in 3 weeks, which is shorter than conventional bladder instillation therapy; (3) the effective rate is reasonable (70%); (4) no local side-effects were observed because the concentrations of ADM and CA were low; (5) interruption of therapy was unnecessary, because whatever general side-effects were caused, they disappeared within several days of completion of treatment.

Synthetic cephalosporins. The synthesis and antibacterial activities of 7-[2-(2-(amino-1,3,4-thiadiazol-5-yl)acetamido]-cephalosporins.

Synthesis and antibacterial activities of 7-[2-(2-amino-1,3,4-thiadiazol-5-yl)acetamido]-cephalosporins and their derivatives having the methoxyimino group at the 2-position of the 7-acyl moiety are described. These compounds are of interest as structural analogues of potent antibiotics, 7-[2-(2-aminothiazol-4-yl)acetamido]cephalosporins. 7-[2-(2-Amino-1,3,4-thiadiazol-5-yl)acetamido]cephalosporins showed comparable activity with cefazolin. Introduction of methoxyimino group to the 7-side chain resulted in a lowering of activity.

Virtual cancer image data warehouse.

We previously developed a system with which we have created more than 100 virtual cancer images from CT or MR data of individual patients with cancer (Cancer Edutainment Virtual Reality Theater: CEVRT). These images can be used to help explain procedures, findings, etc. to the patient, to obtain informed consent, to simulate surgery, and to estimate cancer invasion to surrounding organs. We recently developed a web-based object-oriented database both to access these cancer images and to register medical images at international research sites via the Internet. In this report, we introduce an international medical VR data warehouse created using an object-oriented database.

[Clinical statistics on outpatients and operations at Mishina Urological Office between July 1984-June 1986].

The total number of outpatients was 2,012. There were 1,402 males and 610 females. The male to female ratio being 2.3:1. The major diseases seen in outpatients were benign prostatic hypertrophy, chronic prostatitis, prostatic stone, chronic cystitis, chronic pyelonephritis and ureteral stones. The total number of patients operated on was 347; 281 males and 66 females. These operations were performed at 11 hospitals using our semi-open system. Major operations were transurethral resection of prostate, subcapsular prostatectomy, transurethral resection of bladder tumor, YV plasty of bladder neck, ureterolithotomy and partial cystectomy.

[Histopathological study of secondary ureteral tumors occurring in 4 cases of bladder tumors].

Ureteral tumors were found in 4 out of 88 patients with bladder tumors who had been followed up at our clinic between July 4, 1984 and June 30, 1986. Radical nephroureterectomy and partial cystectomy were performed in 3 of them, and transurethral resection in the remaining one. The pathogenesis of the secondary ureteral tumors was discussed from the standpoints of implantation by vesicoureteral reflux, multicentricity, lymphatic or vascular spread and direct extension along the mucosa in these 4 cases. The ureteral tumor might have occurred in cases with multiple, recurrent or high grade bladder tumors and in cases with bladder tumors suffering from vesico-ureteral reflux. This study suggests that urine cytology, cystoscopy, retrograde cystography and excretory urography might be necessary in the cases of bladder tumors that had been treated with surgery with bladder preserved.

[A case of sigmoidovesical and ileovesical fistula with bladder papilloma complicating colonic diverticulitis].

The clinical course of sigmoidovesical and ileovesical fistula due to rupture of colonic diverticulitis is reported. The patient, a 41-year-old male, who had been suffering from intestinocutaneous fistula for 16 months since drainage of abdominal abscess had chief complaints of cloudy urine and fecaluria. Cystoscopic examination revealed bladder papilloma land edema at the apex area of the bladder. Abscess and fistula were identified with transurethral ultrasonotomography and fistulography, respectively. Primary resection was performed after intravesical instillation of mitomycin-C and postoperative course was uneventful. Histological findings of the specimen revealed disappearance of bladder papilloma for the instillation therapy. Statistical analysis was made on 73 cases of sigmoidovesical fistula due to colonic diverticulitis reported in Japan including my own case.

[Clinical statistics on outpatients at Mishina urological office between July, 1984 and December, 1990].

The total number of outpatients was 6,298. There were 4,293 males and 2,005 females, the male to female ratio being 2.1:1. The major diseases seen in the outpatients were benign prostatic hypertrophy, bladder dysfunction, chronic prostatitis, prostatic stones, ureteral stones, chronic cystitis, urethral stricture, and essential renal bleeding. The 102 (5.1%) patients with urethral diverticulum among 2,005 female patients were discovered by high pressure urethrography. There were 373 cases of urogenital malignancies including 205 of bladder tumor, 85 of prostatic carcinoma and 29 of renal tumor, 11 of which were incidentally found. Twenty of the 205 bladder tumors were found among the 703 cases of microhematuria.