Report on a national survey of cytologic facilities.
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Biomedical subjects
Publications and source records attributed to G Watanabe.
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We assessed the clinical utility of circulating angiogenic factors as a predictor for tumor angiogenesis in primary lung cancer. Circulating vascular endothelial growth factor (VEGF) and intratumoral VEGF were assessed by enzyme-linked immuno-sorbent assay (ELISA). There was a significant increase in the mean value of both plasma and serum VEGF concentration in primary lung cancer patients (n=97) compared to those of healthy controls (n=59). There was a significant correlation between plasma VEGF levels and microvessel density (MVD), and also between plasma VEGF and intratumoral VEGF levels. Plasma VEGF in patients with lung cancer appears to be a useful indicator of tumor angiogenesis.
Artificial insemination (AI) was conducted using the second fraction of semen, which was collected from 15 male dogs, diluted to a total sperm count of 100x10(6) for each insemination with egg-yolk Tris (eyT) citrate acid buffer and incubated at 4 degrees C for 48 hours. Luteinizing hormone (LH) surge was detected to determine the optimal time for mating using canine LH assay kits. Artificial insemination using 100x10(6) sperm was performed on the fourth and sixth days or the fifth and seventh days after the LH surge. The conception rates were 33% (4/12) and 89% (8/9), respectively; the whelping rates also showed similar results. Serum LH and follicle stimulating hormone (FSH) concentrations were measured in nine dogs, and the mean LH concentration (+/- standard deviation) at LH surge was 15.77+/-7.66 ng/ml. The time of the LH surge detected by the canine LH assay kit was very similar to that measured by radioimmunoassay (RIA).
The roles of inhibin and testosterone in the regulation of gonadotropin secretion were investigated in young adult male Shiba goats (8-12 months of age). Plasma levels of inhibin but not testosterone abruptly decreased after hemicastration (75% of the initial level), concomitant with a progressive rise in plasma levels of FSH. Removal of the remaining testis at 33 days after the hemicastration quickly decreased plasma levels of both inhibin and testosterone and induced a progressive increase in plasma FSH and LH. Implantation of testosterone sheets immediately after castration suppressed the increase in plasma FSH in part only, whereas the increase in LH secretion was almost completely suppressed. An i.v. injection of antiserum against [Tyr30] porcine inhibin alpha(1-30) resulted in a significant increase in plasma FSH in a dose-dependent manner, without altering plasma concentrations of LH. These findings clearly indicate that both inhibin and testosterone physiologically regulate FSH secretion and that testosterone is the principal gonadal factor regulating LH secretion in the adult male goat.
BACKGROUND/AIMS: Because the disappearance rate of indocyanine green depends not only on hepatocyte function but also hepatic blood flow, the disappearance rate of indocyanine green is considered to be affected by the systemic circulation. Although the disappearance rate of indocyanine green is slower in cirrhotic patients, a hyperdynamic state is reported to be present. Purpose of this study was to evaluate hepatic function and systemic circulation simultaneously with reference to the hyperdynamic state of cirrhotic liver. METHODOLOGY: Forty-six patients were selected randomly for this study. Simultaneous measurement of effective hepatic blood flow and systemic circulation using an indocyanine green clearance meter was performed. We calculated the effective hepatic blood flow using the early disappearance rate of indocyanine green movement, cardiac output, and circulating time simultaneously with indocyanine green clearance meter. RESULTS: Hepatic function and hyperdynamic circulation could be evaluated quantitatively. The indocyanine green disappearance rate was dependent on cardiac index in normal subjects, whereas the indocyanine green disappearance rate was lower in cirrhotic patients, although the cardiac index was relatively high. CONCLUSIONS: Hepatic function and systemic circulation could be evaluated simultaneously with this indocyanine green clearance meter. Hyperdynamic circulation was suggested to compensate the impaired hepatic function of cirrhotic liver. Simultaneous measurement of hepatic function and systemic circulation may be essential to studying liver function.
To identify the cellular source of inhibin in the male golden hamster, we have used complementary approaches, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Strong positive staining of the inhibin alpha subunit was observed in both the Sertoli and Leydig cells of the testes. No specific staining was observed for the inhibin betaA subunit, whereas specific staining for the inhibin betaB subunit was strongly positive in the Leydig cells. Inhibin pro-alphaC and inhibin B were detected in peripheral plasma, and testicular homogenate also contained large amounts of inhibin pro-alphaC and inhibin B. However, inhibin A was not detected either in peripheral plasma or in testicular homogenate. Plasma concentrations of inhibin pro-alphaC and inhibin B were significantly (P < .001) decreased 24 hours after orchidectomy. These results strongly suggest that the Leydig cells are the main source of dimeric inhibin B in the male golden hamster.
The folate pool in cancer tissue is a critical factor for the effect of 5-FU-based chemotherapy. Methylenetetrahydrofolate reductase (MTHFR) plays a role in the metabolism of folate. The gene of MTHFR is polymorphic (C667T, alanine-to-valine), and this is related to the activity of the enzyme. We analyzed the association between MTHFR genotype and the folate pool in gastrointestinal cancer tissues. MTHFR genotypes were determined in 67 surgically-resected gastrointestinal cancer tissues by PCR-RFLP analysis. Forty-five patients received no treatment and 22 patients received oral administration of UFT, a combination of Uridine and Tegafur, before surgery. 5,10-Methylenetetrahydrofolate (CH2FH4) and tetrahydrofolate (FH4) were measured by fluoro-dUMP (FdUMP) binding assay as representative values of the folate pool. The number of FdUMP binding sites on Thymidylate synthase (TS) was quantified in the samples from UFT-administered patients. The incidences of MTHFR genotype were as follows: Ala/Ala, 27; Ala/Val, 30; Val/Val, 10. In the UFT(-) group, the amount of FH4 in Ala/Val-type cancer tissue was higher than that in Ala/Ala-type (1.50 +/- 1.13 versus 0.72 +/- 0.64, p < 0.05). This relationship was also observed on the sum of CH2FH4 and FH4 (2.88 +/- 1.85 versus 1.75 +/- 1.06, p < 0.05). Val/Val-type cancer tissue had higher amount of either CH2FH4 and FH4 than Ala/Ala-type, although this finding did not reach statistical significance. In the UFT(+) group, no relationship between MTHFR genotype and the free folate pool was observed, presumably due to the influence of the amounts of FdUMP and TS in the tissue. The calculation of total CH2FH4 from the value of free CH2FH4, free TS and total TS showed a weak genotype-dependent difference in total CH2FH4. The TS inhibition rate also showed a weak genotype-dependent difference. These results suggest a link between MTHFR genotype and the folate pool in gastrointestinal cancer, leading to the association of MTHFR genotype with TS inhibition rate upon 5-FU exposure. The MTHFR genotype might be considered in the design of 5-FU-based chemotherapy, especially in patient-specific strategies with leucovorin supplementation.
PURPOSE: In only a very limited number of cultured cell lines, epidermal growth factor (EGF), a potent mitogen for many kinds of cells, was shown to activate STAT1 (signal transducer and activator of transcription 1) protein, which can transmit signals that cause cell growth arrest and apoptosis. The purpose of this work is to elucidate the physiologic and/or pathological significance of this EGF-STAT1 pathway. MATERIALS AND METHODS: A series of cultured cell lines that had been established from surgical specimens of esophageal squamous cell carcinoma was studied for the existence of the EGF-STAT1 pathway. Normal esophageal squamous epithelial cells either explanted from non-neoplastic portions of surgically removed human esophageal tissue or in bovine esophageal epithelium in situ were examined as well. RESULTS: EGF treatment leads to a strong growth arrest in three of the 30 esophageal squamous cell carcinoma cell lines. STAT1 was found to be activated by EGF in the three cell lines but not in the others. EGF can also activate STAT1 in cultured normal esophageal squamous epithelial cells. STAT1 is at the activated state in the basal cell layer of the bovine esophageal epithelium. Notably, patients who had harbored the cancer cells with the EGF-STAT1 pathway had a dramatically better prognosis. DISCUSSION: The EGF-STAT1 pathway may be intrinsic to esophageal epithelial lineage of cells and is lost in a considerable fraction of the carcinomas. This loss appears to cause a significantly more malignant clinical course. These findings may point out a critical step in the progression of esophageal cancer and could lead to the development of useful clinical applications.
This study was undertaken to investigate the endocrine changes that occur in male Tig:Wistar rats with Leydig cell tumors, with special reference to immunoreactive inhibin (ir-inhibin) and its dimeric forms. Adult male rats from 2 to 28 months of age were used. Blood samples were taken to measure plasma concentrations of ir-inhibin, inhibin-A, inhibin-B, 17beta-estradiol (E2), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Inhibin bioactivity in both peripheral plasma and testicular extracts was also measured. Rats aged 18 months and older had testicular Leydig cell tumor. Testicular tissue sections from 27-month-old rats examined immunohistochemically showed strong positive staining for all 3 inhibin subunits, in particular inhibin alpha and betaA subunits, in the tumor cells. Plasma concentrations of ir-inhibin began to rise significantly (P < .05) at 18 months of age. High bioactivity of inhibin was detected not only in testicular extracts but also in peripheral plasma of aged rats. Thus, plasma concentrations of bioactive inhibin-A, but not inhibin-B, were significantly elevated with increasing age. The concentrations were significantly higher than those in normal male (P < .01) or normal female (P < .05) rats. Plasma concentrations of E2 were significantly (P < .05) elevated only at 23-24 months of age. A marked reduction (P < .05 to .001) in plasma LH and FSH concentrations was observed at 18 months of age and older. Plasma concentrations of testosterone were highest at 2 months of age and then decreased gradually and significantly (P < .05 to .001) afterward. Significant (P < .05 to .001) positive (testosterone vs LH) and negative (ir-inhibin vs FSH, ir-inhibin vs LH, and E2 vs FSH) correlations were observed. It is suggested that plasma inhibin-A levels are elevated in male Tig:Wistar rats with Leydig cell tumor, and thus inhibin-A may be used as a specific marker of testicular Leydig cell tumors. The present results also suggest that the age-related decline in plasma gonadotropins and thus testosterone levels in Tig:Wistar rats may be due to the development of tumors of the Leydig cells rather than to aging per se.
A muscle powered cardiac assist device (MCAD) for right ventricular support requires optimized diastolic filling to obtain full stroke and acceptable fluid dynamics. A valved and spring-assembled skeletal muscle ventricle (SMV) was designed as a prototype MCAD, regardless of fluid dynamics. The present study addresses the optimal bypass method for right ventricular support, and predicts the future design for an implantable MCAD. Latissimus dorsi muscle (LDM) of 11 dogs were conditioned electrically for a one year maximum, and transformed into fatigue-resistant muscles (Type I fibers). Superior and inferior vena cavae were anastomosed using one arm of a Y-shaped vascular graft, as an inflow conduit, and the outflow conduit was placed on the main pulmonary artery. SMV was wrapped with transformed LDM and the bypass method was varied by SVC and/or IVC ligation. SMV demonstrated sufficient right ventricular support on total bypass (70% compared with control output), and the maximum pump off-to-on flow ratio (200%) was obtained. Maximum SMV power output was 0.27 X 10(6) erg, which was equivalent to that of canine right ventricle. Right atrial-to-pulmonary artery bypass was also constructed by using SMV in another 14 dogs, and also showed that total bypass was preferable for optimal SMV diastolic filling. In conclusion, specific requirements for a future MCAD include a subsystem assembly such as a spring, magnet, or alternative auxiliary muscle pump assembly for MCAD filling, and total bypass with optimized fluid dynamics and anatomic fitting.
Two cases of symptomatic myocardial bridging of the left anterior descending coronary artery (LAD) requiring surgery for relief of exertional angina are reported. High-frequency intraoperative echocardiography was used for imaging of the intramyocardial coronary artery lesions before and after supraarterial myotomy performed under cardiopulmonary bypass. The constricting band of the myocardial bridge could be clearly demonstrated. Supraarterial myotomy was successfully carried out in each patient. We conclude that intraoperative echocardiography for detecting myocardial bridge is a useful tool for supraarterial myotomy.
A case of acquired tracheoesophageal fistula (TEF) is reported. The cause of TEF was thought to be multiple bronchial artery infusions of anticancer drugs which presumably caused necrosis of the trachea and esophageal wall. Recurrent aspiration pneumonia was the main finding. Definite diagnosis was made by esophagoscopy and confirmed by bronchoscopy and chest CT scan. Successful palliative treatment was achieved by bypassing the esophagus with the stomach via the retrosternal route under epidural anesthesia.
The pancreas is an uncommon site for metastasis from renal cell carcinoma. In most cases, pancreatic metastases occur as part of widespread nodal and visceral involvement, and there is thus evidence of metastatic disease elsewhere in the body. We present 4 cases with resectable pancreatic metastases arising from renal cell tumors without involvement of the regional lymph nodes at the operation. Three cases out of 4 were asymptomatic and the pancreatic metastases were detected by routine follow-up examination of renal cell carcinoma. Aggressive surgical treatment for the solitary metastatic lesion is advocated. Spread of renal cell carcinoma to the pancreas is, however, via the hematogenous route, and even solitary pancreatic metastasis may be one of the manifestations of the systemic metastasis of renal cell carcinoma. No pancreatic regional lymph nodes metastases were noted. Pancreatectomy should be undertaken to remove the tumor with adequate resection margins while preserving as much of the gland as possible. The prognosis of pancreatic metastases arising from a renal cell carcinoma is discussed with a review of the literature. Adjuvant chemo- and endocrine therapy should also be considered in these cases.