Ninety patients with carcinoma of the pancreas treated between 1976 and 1990 were reviewed retrospectively. Intraoperative radiation therapy (IORT) in combination with external beam radiation therapy (EBRT) for localized but unresectable tumors (n = 29) prolonged survival significantly more than IORT alone (n = 16) (p < 0.01); it seems EBRT enhanced or contributed to the better results obtained with IORT plus EBRT. Moreover, IORT, alone or in combination, relieved pain. Adjuvant IORT for residual tumors (n = 20) might not effectively prolong survival, because the difference in survival rate between noncurative resection plus IORT and nonresection plus IORT in combination with EBRT was not significant. Curative tumor resection of stage III disease in combination with IORT (n = 9) resulted in significantly longer survival as compared with curative tumor resection alone (n = 8) (p < 0.05). It may be advisable to administer IORT in combination with EBRT to patients with advanced pancreatic carcinoma, avoiding aggressive tumor resection, when curative tumor resection cannot be performed.

Autopsy↗

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MRCP of congenital pancreaticobiliary malformation.

BACKGROUND: Congenital pancreaticobiliary malformations are sometimes associated with acute or chronic pancreatitis and biliary carcinoma. Currently, magnetic resonance cholangiopancreatography (MRCP) is one of the first choices for investigating and diagnosing pancreaticobiliary diseases noninvasively. We compared the accuracy of conventional MRCP and endoscopic retrograde cholangiopancreatography (ERCP) in making the diagnosis of congenital pancreaticobiliary malformations. METHODS: In patients with pancreas divisum (n = 17), pancreaticobiliary maljunction (n = 12), choledochocele (n = 2), and annular pancreas (n = 1) who underwent ERCP and MRCP, the diagnostic accuracy and findings on MRCP were compared with those on ERCP. RESULTS: Of the 32 patients with congenital pancreaticobiliary malformations diagnosed on ERCP, 23 (72%) presented the same diagnosis on MRCP. Complete pancreas divisum was diagnosed in 73% on MRCP based on the finding of a dominant dorsal pancreatic duct crossing the lower bile duct and emptying into the duodenum without communicating with the ventral pancreatic duct. Pancreaticobiliary maljunction was diagnosed in 75% on MRCP based on the finding of an anomalous union between the common bile duct and the pancreatic duct and the existence of a long common channel. CONCLUSIONS: Conventional MRCP is a useful, noninvasive tool for diagnosing congenital pancreaticobiliary malformations; and the diagnostic accuracy can be increased with three-dimensional MRCP or dynamic MRCP with secretin stimulation.

Bile Ducts↗

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Identification of neuropeptide-degrading enzymes in the pancreas.

Neutral endopeptidase (NEP) and aminopeptidase M (APM) were identified in the pancreas by enzymatic assays and Western blotting. The NEP activity, assessed by the phosphoramidon- and DL-thiorphan-inhibitable degradation of glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine, was 28.8 pmol/h/micrograms of pancreatic membrane protein and 124 pmol/h/10(6) pancreatic acinar cells. The APM enzymatic activity, assessed by the actinonin- and amastatin-inhibitable degradation of Ala-4-methoxy-2-naphthylamine, was 633 pmol/h/micrograms pancreatic membrane protein and 17.4 nmol/h/10(6) pancreatic acinar cells. Proteins corresponding to NEP (95 kDa) and APM (140 kDa) were identified in membranes by Western blotting. Both NEP and APM on acinar cells may degrade neuropeptides and regulate their effects on exocrine secretion.

Amino Acid Sequence↗

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IGFBP1 and Follistatin-like 3 genes are significantly up-regulated in expression profiles of the IUGR placenta.

To date, the clinicopathological features of intrauterine growth restriction (IUGR) are not clearly understood, and no effective therapy has been established for IUGR. This is the first study that uses microarray analysis to identify differentially expressed genes in the IUGR placenta. The expression profiles of a total of 9121 genes were examined by cDNA microarray analysis, using mRNA from an appropriate gestational age (AGA) placenta and an IUGR placenta from discordant dichorionic twins. Up-regulation of the IGFBP1 and Follistatin-like 3 genes was detected in the IUGR placenta, with a balanced differential degree of 20.7+/-1.3 and 13.1+/-2.1, respectively, while the balanced differential degrees of other genes were 2.6 or less. The expressions of the IGFBP1 and Follistatin-like 3 genes in four single IUGR and four AGA placentas were also examined by RT-PCR. Consistent with our data in discordant chorionic twin placentas, three of four IUGR placentas showed up-regulation of the IGFBP1 and all four IUGR placentas showed upregulation of Follistatin-like 3 genes when compared to the AGA placentas. Our results suggest that IGFBP1 and Follistatin-like 3 are highly up-regulated in IUGR in the placenta. IGFBP1 and Follistatin-like 3 are known critical regulators of fetal growth and differentiation. Pathways associated with these genes might be important for the pathogenesis of IUGR.

Female↗

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Mls determinants and anti-Mls receptors.

We review evidence from this laboratory that T cell recognition of Mlsa determinants is not controlled solely by the alpha-beta T cell receptor (TcR) molecule. We propose a model in which Mlsa recognition reflects a receptor-ligand interaction between two sets of complementary accessory molecules, one molecule (Mlsa) being expressed on B cells and the other (the anti-Mlsa receptor) on T cells; this interaction augments recognition of self class II molecules by the TcR. The biological role of Mls molecules might be to facilitate physiological T-B interaction.

Animals↗

PubMedDate not supplied

Embryology of the pancreatic duct system.

BACKGROUND/AIMS: It has been suggested that the distal portion of the dorsal pancreatic duct and the ventral pancreatic duct usually merge into the main pancreatic duct, and the proximal portion of the dorsal pancreatic duct becomes the accessory pancreatic duct. In this study, we investigated the embryology of the accessory pancreatic duct roentgenographically and immunohistochemically. METHODS/RESULTS: The accessory pancreatic duct shows two different patterns in pancreatograms: the long and the short type. The accessory pancreatic duct of the long type forms a straight line and joins the main pancreatic duct at the neck portion of the pancreas. The accessory pancreatic duct of the short type joins the main pancreatic duct near its first inferior branch. Long inferior branches from the accessory pancreatic duct were found in 74.6% with the long type, significantly more often than in the short type (29. 3%). Patency of the long type was (74.5%) significantly greater than in the short type (36.2%). Immunohistochemically, we found the main pancreatic duct between the junction with the accessory pancreatic duct and the neck portion of the autopsy pancreas in the short type was located within the ventral pancreas, characterized by pancreatic polypeptide-rich islets. CONCLUSION: The long type represents a continuation of the main duct of the dorsal primordium. The short type is very likely formed by the proximal main duct of the dorsal primordium and its long inferior branch, with the main duct of the dorsal primordium at the point of connection with the main duct of the ventral primordium being obliterated and replaced by this additional communication.

Cadaver↗

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Blood pressure and cochlear blood flow in the guinea pig.

The relationship between blood pressure and cochlear blood flow was investigated in 68 guinea pigs, using the vasoactive drugs angiotensin II, norepinephrine, phentolamine, isoproterenol, dobutamine, salbutamol, propranolol, bradykinin, papaverine, vinpocetine dilazep, and brovincamine. Cochlear blood flow increases markedly and proportionately to increases in blood pressure. By contrast, cochlear blood flow shows various responses toward a fall in blood pressure. In general, cochlear blood flow appears relatively resistant to blood pressure decrease.

Animals↗

PubMedDate not supplied

Effect of vasodilating agents on cochlear blood flow under loud sound exposure.

Loud sound has been proved by means of laser Doppler flowmetry to decline cochlear blood flow. The purpose of this study was to investigate the effect of a vasodilating agent on cochlear blood flow under loud sound exposure, i.e. whether the drug can impede blood flow decrease or not. As a vasodilating agent, dilazep dihydrochloride in a dose of 5 mg/kg was used. This drug caused a stable and significant increase of cochlear blood flow when intravenously injected into guinea pigs. When guinea pigs were exposed to loud sound (120 dB SPL at 10 kHz) for 10 min, cochlear blood flow promptly declined at the onset of sound stimulation and promptly recovered at its cessation. Then, dilazep dihydrochloride 5 mg/kg was injected intravenously into the same animal and loud sound (120 dB SPL at 10 kHz) was exposed for 10 min. Dilazep did not fully block a prompt decline of cochlear blood flow. However, the blood flow level was kept much higher than at pre-injection level. This study shows that a vasodilating agent which normally enhances blood flow probably does not completely block the sound-induced drop response in cochlear blood flow.

Animals↗

PubMedDate not supplied

Effect of loud sound exposure on the cochlear blood flow.

The effect of loud sound exposure on cochlear blood flow was studied in the guinea pig by the laser Doppler method. Fourteen guinea pigs with normal Preyer reflex were anesthetized and tracheotomy was performed. A tracheotomy tube was connected to a ventilator and the experiment was performed with artificial ventilation. After exposure of the tympanic bulla and complete removal of the mucosa, a probe of a laser Doppler flowmeter was attached to the lateral wall of the basal turn of the cochlea. A specially-designed ear piece connected with a speaker was inserted into the external ear canal and loud sound (10 kHz at 120 dB SPL) was delivered to the ear for 30 min. Thirteen of the 14 exposed guinea pigs showed a prompt decrease in cochlear blood flow at the onset of the sound exposure and 12 of the 13 guinea pigs showed a prompt recovery of the cochlear blood flow after the cessation of the sound exposure.

Acoustic Stimulation↗

PubMedDate not supplied

A case-matched control study of intrahepatoarterial chemotherapy in combination with or without regional hyperthermia for treatment of primary and metastatic hepatic tumours.

The efficacy of the combined application of intrahepatoarterial (IHA) chemotherapy and regional hyperthermia for the treatment of unresectable hepatic tumours was studied in a case-matched, retrospective control study. Well-matched pairs of patients with the same or similar background factors, who had been treated with IHA chemotherapy plus hyperthermia (group A; n = 32) and with IHA chemotherapy alone (group B; n = 32) were included in this study. In group A, partial responses (PRs) were found in 2 of 8, 4 of 8, and 5 of 16 patients with hepatocellular carcinoma, metastatic gastric cancer, and metastatic colorectal cancer, respectively. In group B, PRs were found in 1 of 8, 3 of 8, and 5 of 16 patients with those diseases, respectively. Overall, PRs were found in 12 (37%) and 9 (28%) of 32 patients in groups A and B, respectively; progressive disease was found in 6 (19%) in group A and in 12 (38%) in group B. These results indicate that this combination therapy is of therapeutic benefit in the treatment of unresectable hepatic tumours.

Antineoplastic Agents↗

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Viscoelasticity of hyaluronic acid with different molecular weights.

Storage and loss moduli of hyaluronic acid solutions with different molecular weights were observed as a function of frequency in the presence of sugars and salts. The hyaluronic acid solutions of higher molecular weight (Mw > 17 x 10(6)) fractions showed entanglement, whereas lower molecular weight fractions did not. For inducing the entanglement of molecular chains of hyaluronic acid, increasing the molecular weight of hyaluronic acid was more effective than increasing the concentration of the lower molecular weight fractions (Mw = 7. 8 x 10(5). Glucose, fructose, galactose, and sucrose increased both storage and loss moduli, while NaCl, KCl and CaCl2 decreased both moduli. It is suggested that sugars create hydrogen bonds and strengthen the transient network. Cations shield the electrostatic repulsion of hyaluronic acid molecules, and the polymer chains are shrunk into compact coils from expanded stiffened coils.

Carbohydrates↗

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Combination therapy with podophyllin and vidarabine for human papillomavirus positive cervical intraepithelial neoplasia.

Our aim was to establish an effective non-surgical treatment for cervical intraepithelial neoplasia (CIN) through inactivation of human papillomavirus (HPV), the major etiological agent for this disease. We show that vidarabine, a DNA polymerase inhibitor, suppressed growth and HPV gene expression in human cervical keratinocytes immortalized by HPV or in cervical cancer cell lines. Expression of HPV-16 E6 and E7 proteins in normal cervical keratinocytes sensitized cells to apoptosis in the presence of podophyllin or vidarabine. We applied vidarabine ointment and/or podophyllin to cervical epithelium in 28 cases of CIN I-II to evaluate the therapeutic effectiveness of these agents. Co-application of vidarabine and podophyllin in six treatments caused regression of lesions cytologically and histologically, and disappearance of HPV-16 or -18 DNA in 17 of 21 (81%) women. Our results suggest that the combination of vidarabine and podophyllin therapy is an effective non-surgical treatment for HPV-positive CIN.

Adult↗

PubMedDate not supplied

Telomerase activity in gynecological tumors.

The aim of this study was to define the clinical implications of semi-quantitative telomerase activity in gynecological tumors by comparing the telomerase activity of cancerous lesion and the adjacent non-cancerous lesion. In 118 cases of gynecologic tumors, including 41 uterine cervical tumors, 43 uterine body tumors and 34 ovarian tumors, telomerase activities were determined using TRAPeze telomerase detection kit for the extension reaction of the telomere sequence and the PCR reaction for amplification of the sequence, and using fluorecence-based telomere repeat amplification protocol (F-TRAP) method for the detection. In all gynecologic cancers examined, telomerase activity of the cancerous lesion was significantly higher than that of the non-cancerous lesion. Telomerase activity in the uterine cervix increased in the following order of the normal uterine cervix, cervical dysplasia and cervical cancer. Regarding the endometrial cancer, telomerase activity at the primary lesion in patients with lymph node metastases was significantly higher than that in patients without lymph node metastases. When telomerase activity was compared by histologic subtypes of the ovarian cancer, clear cell adenocarcinoma showed significantly lower telomerase activity than the other subtypes, especially endometrioid adenocarcinoma. In all gynecologic cancers examined, there was no clear correlation between the telomerase activity and age at diagnosis or age of menopause. Although all tumors with 100 units or more telomerase activity were cancerous, the sensitivity was 39% in cervical cancer, 41% in endometrial cancer and 21% in ovarian cancer, respectively. Cervical intraepithelial neoplasia (CIN) had already increased telomerase activity and endometrial cancer with lymph node metastases had also greater activity than that without lymph node metastases. Although telomerase activity in ovarian cancer tended to increase as stage advances, it is noteworthy that clear cell adenocarcinoma showed significantly lower telomerase activity than endometrioid adenocarcinoma.

Cervix Uteri↗