[Indications and problems of presymptomatic diagnosis and prophylactic surgery for hereditary cancers].
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Adenomatous Polyposis Coli↗
Biomedical subjects
T Akasu
Publications and source records attributed to T Akasu.
Interleukin-1beta causes a biphasic response in neurons of rat major pelvic ganglia.
The effect of interleukin-1beta (IL-1beta) on peripheral autonomic neurons was examined with intracellular microelectrodes, in vitro. Recombinant human IL-1beta (6-300 pM) produced a depolarization, associated with decrease in input resistance, followed by a hyperpolarization, associated with increase in input resistance, in neurons of rat major pelvic ganglia (MPG). IL-1beta 163-171 (10-100 pM), the active domain of human IL-1beta, also produced a biphasic response. The IL-1beta-induced responses reversed polarity at the equilibrium potential for Cl-. The IL-1beta-induced responses were blocked by picrotoxin (100 microM) but not by bicuculline (20 microM). Imidazole-4-acetic acid (14AA, 100 microM), a GABA(C) receptor antagonist, reduced the IL-1beta-induced responses. The results suggest that the IL-1beta-induced biphasic response is mediated through GABA(C) receptors in rat MPG neurons.
Animals↗
The relationship between prognosis and CEA-dt after hepatic resection in patients with colorectal carcinomas.
AIMS: CEA-doubling time (CEA-dt) was calculated by measuring serum CEA at two voluntary points. As CEA-dt is correlated with tumour doubling time the growth rate of liver metastasis could be determined. We investigated the relationship between CEA-dt and prognosis to determine the indications for resection of liver metastasis. METHODS: We examined 334 patients diagnosed with resected liver metastasis of colorectal carcinoma. Patients were divided into three categories based on CEA-dt; Group A, CEA-dt <30 days; Group B, 30 days </=cCEA-dt <80 days; and Group C, CEA-dt >/=s80 days. Clinicopathological parameters, the 3-year or 5-year survival rate and the rate of recurrence were compared among the three groups. RESULTS: In Group A, the survival time after hepatic resection was significantly shorter compared to the other groups. Furthermore, multiple liver metastasis showed slightly reduced CEA-dt levels compared with solitary metastasis, but even in patients with solitary liver metastasis, the rate of survival was poor. In 70% of Group A patients, recurrent tumour was recognized within 1 year of hepatic resection. CONCLUSION: When surgery for liver metastasis of colorectal cancer is considered. Group A patients should be recognized as having a poor prognosis and a high rate of recurrence after hepatic resection, and CEA-dt should be employed as a prognostic factor.
Adult↗
Role of GABAA and GABAC receptors in the biphasic GABA responses in neurons of the rat major pelvic ganglia.
The role of gamma-aminobutyric acid-A (GABAA) and GABAC receptors in the GABA-induced biphasic response in neurons of the rat major pelvic ganglia (MPG) were examined in vitro. Application of GABA (100 microM) to MPG neurons produced a biphasic response, an initial depolarization (GABAd) followed by a hyperpolarization (GABAh). The input resistance of the MPG neurons was decreased during the GABAd, whereas it was increased during the GABAh. The GABAd could be further separated into the early component (early GABAd) with a duration of 27 +/- 5 s (mean +/- SE; n = 11) and the late component (late GABAd) with a duration of 109 +/- 11 s (n = 11). The duration of the GABAh was 516 +/- 64 s (n = 11). The effects of GABA (5-500 microM) in producing the depolarization and the hyperpolarization were concentration-dependent. GABA (5-30 microM) induced only late depolarizations. The early component of the depolarization appeared when the concentration of GABA was >50 microM. Muscimol produced only early depolarizing responses. Baclofen (100 microM) had no effect on the membrane potential and input resistance of MPG neurons. Bicuculline (60 microM) blocked the early GABAd but not the late GABAd and the GABAh. Application of picrotoxin (100 microM) with bicuculline (60 microM) blocked both the late GABAd and the GABAh. CGP55845A (3 microM), a selective GABAB receptor antagonist, did not affect the GABA-induced responses. cis-4-Aminocrotonic acid (CACA, 1 mM) and trans-4-aminocrotonic acid (TACA, 1 mM), selective GABAC receptor agonists, produced late biphasic responses in the MPG neurons. The duration of the CACA responses was almost the same as those of the late GABAd and GABAh obtained in the presence of bicuculline. Imidazole-4-acetic acid (I4AA, 100 microM), a GABAC receptor antagonist, depressed the late GABAd and the GABAh but not the early GABAd. I4AA (100 microM) and picrotoxin (100 microM) also suppressed the biphasic response to CACA. The early GABAd and the late GABAd were reversed in polarity at -32 +/- 3 mV (n = 7) and -38 +/- 2 mV (n = 4), respectively, in the Krebs solution. The reversal potential of the GABAh was -34 +/- 2 mV (n = 4) in the Krebs solution. The reversal potentials of the late GABAd and the GABAh shifted to -20 +/- 3 mV (n = 5) and -22 +/- 3 mV (n = 5), respectively, in 85 mM Cl- solution. These results indicate that the late GABA(d) and the GABAh are mediated predominantly by bicuculline-insensitive, picrotoxin-sensitive GABA receptors, GABAC (or GABAAOr) receptors, in neurons of the rat MPG.
Animals↗
Effects of interleukin-1 beta on neurons in mammalian pelvic ganglia.
The effects of interleukin-1 beta (IL-1 beta) on the membrane potential and synaptic transmission were examined in neurons of mammalian pelvic ganglia. Bath-application of recombinant human IL-1 beta (6-300 pM) for 10 s-5 min produced a long-lasting hyperpolarization associated with increased input resistance in 11 neurons of rat major pelvic ganglia (MPG). In other 8 neurons, IL-1 beta (300 pM) produced a biphasic response that consists of an initial depolarization followed by a long-lasting hyperpolarization. IL-1 beta 163-171 (10-100 pM), a synthetic nonapeptide analog that contains the active domain of human IL-1 beta, mimicked the effect of IL-1 beta in MPG neurons. gamma-Aminobutyric acid (GABA, 300 microM) produced a depolarization followed by a hyperpolarization that was blocked by picrotoxin (100 microM). Db-cyclic guanosine monophosphate (db-cyclic GMP, 100 microM) also produced an initial depolarization followed by a long-lasting hyperpolarization. These results suggest that the IL-1 beta-induced biphasic response is mediated by a GABA receptor-cyclic GMP pathway. IL-1 beta and IL-1 beta 163-171 caused an initial facilitation followed by a long-lasting depression of the excitatory postsynaptic potential (EPSP) in rabbit VPG. The data suggest that IL-1 beta presynaptically depressed the EPSP by reducing the release of acetylcholine (ACh) from the pelvic nerve terminals.
Animals↗
Macroscopic intrabiliary growth of liver metastases from colorectal cancer.
BACKGROUND: The clinicopathologic features of colorectal liver metastases that invade the bile duct were evaluated. METHODS: From 1992 to 1996, 149 patients who underwent a first hepatic resection were studied for a total of 377 colorectal liver metastases. Twenty-one second hepatic resections in these patients were also analyzed. RESULTS: Bile duct invasion was histologically observed in 62 (42%) of 149 patients with first colorectal liver metastasis. Eighteen patients (12%) had gross extension of the tumor in the bile duct ranging from 4 mm to 42 mm (median 17.0 mm). Histologically, two thirds (12 of 18) of the tumors with macroscopic bile duct invasion were well-differentiated adenocarcinomas with a tendency for less vascular involvement. The actuarial 3- and 5-year survivals were 62% and 57% for patients with no bile duct invasion, 56% and 48% for patients with microscopic bile duct invasion, and 94% and 80% for patients with macroscopic bile duct invasion. The 5-year survival rate was better for patients with macroscopic bile duct invasion than for those with only microscopic (P = .02) or no bile duct invasion (P = .03). In a multivariate analysis, macroscopic bile duct invasion was an independent prognostic variable for favorable outcome after hepatic resection. CONCLUSIONS: Macroscopic bile duct invasion of colorectal liver metastases may reflect an indolent biologic behavior, warrants an aggressive surgical approach, and confers a better prognosis.
Adenocarcinoma↗
Resection of both hepatic and pulmonary metastases in patients with colorectal carcinoma.
BACKGROUND: More than 40% of patients who undergo curative resection of advanced colorectal carcinoma can be expected to have recurrence of the disease. The most frequent sites of recurrence are the liver (33% of patients) and lung (22%). Interest has therefore focused on treating hepatic or pulmonary metastases, or both, to improve the outcomes of these patients. Although surgical resection has become an increasingly accepted treatment for resectable localized hepatic or localized pulmonary metastases from colorectal carcinoma, the value of aggressive surgery for the removal of both hepatic and pulmonary metastases from patients with primary colorectal carcinoma remains to be clarified. METHODS: Data on 30 patients who had undergone resection of both hepatic and pulmonary metastases from colorectal carcinoma were included in the study. RESULTS: Independent, significant prognostic features were found to be the time that hepatic or pulmonary metastases occurred and the distribution of pulmonary metastases. Median survival times were 30 months (range, 7-108 months) after resection of both hepatic and pulmonary metastases and 48.5 months (range, 11-149 months) after excision of the primary colorectal tumor. Actuarial 1-, 3-, and 5-year survival after resection of both hepatic and pulmonary metastases was 86.7%, 49.3%, and 43.8%, respectively. No perioperative mortality occurred. There were three cases of minor morbidity, which the authors considered acceptable. CONCLUSIONS: Resection of both hepatic and pulmonary metastases from colorectal carcinoma may help to prolong the survival of a small group of patients with these metastases.
Adult↗
Abnormal expression of CD44 variants in the exfoliated cells in the feces of patients with colorectal cancer.
BACKGROUND & AIMS: Recent investigations have shown that CD44 variant exons are frequently overexpressed in human colorectal adenocarcinoma. The aim of this study was to investigate abnormal expression of the CD44 gene in exfoliated cells from patients with colorectal cancer. METHODS: Exfoliated cells in feces from 25 patients with colorectal cancer before and after surgery and from 15 healthy volunteers were analyzed. CD44 standard, variant 6, and variant 10 messenger RNA (mRNA) expressions were examined in the exfoliated cells in feces by using reverse-transcription polymerase chain reaction followed by Southern hybridization with exon-specific probes. RESULTS: CD44 standard mRNA was detected in all samples before and after surgery and in all healthy volunteers. CD44 variant 6 and variant 10 mRNA were detected in 17 of 25 patients (68%) and 15 of 25 patients (60%), respectively, in individual feces obtained before surgery. CD44 variant 6 mRNA and variant 10 mRNA were detected in postoperative samples in 3 of 25 patients (12%) and 7 of 25 patients (28%), respectively. Fifteen of 17 patients who were positive for CD44v6 based on preoperative fecal samples became negative after surgery (88.2%). Similarly, 12 of 15 patients who were CD44v10 positive in preoperative fecal samples were negative postoperatively (80%). CONCLUSIONS: These results suggest that analysis of CD44 variant expression in the exfoliated cells in feces can provide a noninvasive diagnostic test for colorectal cancer.
Adult↗
Perianal Paget's disease associated with rectal carcinoma: a case report.
A 58-year-old man was referred to us because of anal bleeding. Digital rectal examination revealed a 1.2 x 0.8 cm-sessile villous tumor located in the anal canal and lower rectum. Pruritus was lacking and there were no erythematous lesions or any skin lesion in the perianal region. Histologic examination of the excised lesion revealed the presence of an adenocarcinoma within a villous adenoma. The malignancy exhibited well, moderately and poorly differentiated areas with signet-ring cell elements. Because the carcinoma had massively invaded into the submucosa, additional abdominoperineal resection was performed. Microscopic examination of the obtained specimens showed incidental Paget's disease of the anal skin. Although perianal Paget's disease associated with rectal cancer is rare, cautious pathologic examination of the anal and perianal skin in cases with anorectal carcinoma is necessary, even if there are no suggestive clinical findings. If there is perianal Paget's disease, surgical resection with sufficient apparently normal skin and close follow-up are necessary.
Adenocarcinoma↗
Optical recording of neuronal excitability in the rat dorsolateral septal nucleus.
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Animals↗
GABAC receptors mediate slow membrane potentials in neurons of the rat major pelvic ganglia.
Effects of gamma-aminobutyric acid (GABA) on the neuronal membrane of the rat major pelvic ganglia (MPG) were studied using intracellular recording techniques, in vitro. Application of GABA (100 microM) to MPG neurons induced a depolarization (GABAd) associated with a decreased membrane input resistance and a slow hyperpolarization (s-GABAh) associated with an increased membrane input resistance. The GABA depolarization had two phases, a fast depolarization (f-GABAd) and a subsequent slow depolarization (s-GABAd). Bicuculline (60 microM) blocked the f-GABAd but not the s-GABAd and s-GABAh. Picrotoxin (100 microM) blocked all the GABA responses. Imidazole-4-acetic acid (I4AA, 100 microM), a GABAc receptor antagonist, depressed the s-GABAd and s-GABAh, but did not block the f-GABAd. Cis-4-aminocrotonic acid (CACA), a GABAc receptor agonist, produced a depolarization followed by a hyperpolarization in MPG neurons. I4AA (100 microM) depressed the CACA-induced responses. It was concluded that GABAA receptors mediate the f-GABAd and that GABAc receptors mediate the s-GABAd and s-GABAh, in neurons of the rat MPG.
Animals↗
[Effects of nonsteroidal anti-inflammatory drugs (NSAID) on colorectal polyps in patients with familial adenomatous polyposis: a review of clinical studies].
Experimental animal studies have demonstrated a protective effect of NSAIDs against intestinal tumorigenesis due to chemical carcinogens. Many epidemiological studies have also shown that regular aspirin use is associated with reduction of the risk of colorectal cancer. In familial adenomatous polyposis, numerous clinical studies have reported that sulindac and indomethacin are effective in reducing colorectal polyps. However, their effects are incomplete and they may cause severe toxicity. Therefore, they are unlikely to replace colectomy as primary treatment. Nevertheless, their unique effects on colorectal tumorigenesis warrant further basic and clinical research on NSAIDs, including COX-2-selective inhibitors.
Adenomatous Polyposis Coli↗
Solitary peritoneal metastasis from colon carcinoma.
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Adenocarcinoma↗
Opioid peptides modulate GABA(A) receptor responses in neurons of bullfrog dorsal root ganglia.
Effects of enkephalin and selective opioid-receptor agonists on GABA-induced current were examined in dissociated neurons of bullfrog dorsal root ganglia (DRG) by using whole-cell patch-clamp method. Leucine- (Leu)-enkephalin and methionine- (Met)-enkephalin depressed GABA(A) receptor-mediated currents. DPDPE, DAMGO and dynorphin-A (Dyn-A) also depressed the inward current produced by GABA; the order of agonist potency was DPDPE > DAMGO > Dyn-A. Naloxone blocked the inhibitory effects of enkephalins and other opioid agonists on the GABA current. Naltrindole (NTI), a delta-receptor antagonist, prevented the DPDPE-induced depression of the GABA current. beta-Funaltrexamine (beta-FNA), a mu-receptor antagonist, reduced the DAMGO-induced depression of GABA currents. Nor-binaltorphimine (nor-BNI), a kappa-receptor antagonist, reduced the effects of Dyn-A in depressing the GABA current. The results suggest that enkephalin down-regulates GABA(A) receptor function through mainly delta- and mu-opioid receptors in bullfrog DRG neurons.
Analgesics↗
Baclofen reduces GABAA receptor responses in acutely dissociated neurons of bullfrog dorsal root ganglia.
The effect of baclofen on the function of the gamma-aminobutyric acidA (GABAA) receptor was examined in acutely dissociated neurons of bullfrog dorsal root ganaglia (DRG) by using the whole-cell voltage-clamp method. Baclofen (0.1-100 microM) depressed the inward currents produced by GABA (100 microM) and muscimol (100 microM). Baclofen shifted the concentration-response curve for GABA (1 microM-1 mM) downward. Baclofen decreased the maximum response (Vmax) to GABA without changing the apparent dissociation constant (Kd), suggesting a noncompetitive antagonism. The effect of baclofen on the GABA current was blocked by antagonists for the GABAB receptor; the rank order of potency was P-[3-Aminopropyl]-P-diethoxymethylphosphinic acid (CGP 55845A) > > 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P- benzyl-phosphinic acid (CGP 35348) > saclofen > > phaclofen. Baclofen produced an irreversible depression of the GABA current in neurons dialyzed with an internal solution containing guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S, 100 microM). Intracellular guanosine 5'-O-(2-thiodiphosphate) (GDP beta S, 100 microM) blocked the inhibitory effect of baclofen on the GABA current. Forskolin (10 microM) and dibutyryl N6, 2'-O-dibutyryladenosine 3':5'-cyclic monophophate (db-cyclic AMP) (200 microM) depressed the GABA current. N-(2-aminoethyl)-5-isoquinolinesulfonamide (H-9, 40 microM) and N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004, 50 microM), protein kinase A (PKA) inhibitors, reduced the depressant effect of baclofen on the GABA current. The baclofen-induced depression of the GABA current was blocked by PKI(5-24), a specific PKA inhibitor, but not by PKC(19-36), a specific protein kinase C (PKC) inhibitor. We suggest that GABAB receptors regulate the GABAA receptor function through a G-protein linked to the adenylyl cyclase-PKA pathway in bullfrog DRG neurons.
Animals↗
Abdominal actinomycosis: barium enema and computed tomography findings.
A case of abdominal actinomycosis is described in a woman with recurrent right lower abdominal pain and low-grade fever without history of appendectomy. Past history included the use of an intrauterine device (IUD) until 10 years before manifestation of these symptoms. We followed up the patient, via diagnostic imaging, for 7 months. On initial barium enema, a polypoid lesion was visualized at the bottom of the cecum and there was constriction of the sigmoid colon; the appendix was not seen. Seven months later, poor extension at the cecum, severe constriction in the sigmoid colon, and narrowing of the terminal ileum were also visualized. On computed tomography (CT), the lesion was initially localized only in the ileocecal region adjacent to the sigmoid colon. After 7 months, the lesion had infiltrated adjacent anatomic components and showed direct infiltration of the pelvic space. Differential diagnosis was difficult, as it was not obvious whether this was a pelvic abscess due to inflammation or appendiceal carcinoma. Laparotomy was performed. Macroscopically, the lesion was not limited to the ileocecal region, but involved the right ureter, tubes the Fallopian and ovary, bladder, psoas muscle, and abdominal wall. Pathology findings showed, chronic inflammatory tissue with evidence of actinomycosis. Although previous reports have described a lack of specific findings in this disease. When actinomycosis is suspected, CT is recommended to define its extent.
Abdominal Abscess↗
Triple-stapled low colorectal anastomosis for the narrow pelvis.
Standard linear staplers for transverse occlusion of the rectum is sometimes too large to be applied in a narrow pelvis. A proximate TL 30 (Ethicon, Inc., Somerville, NJ) is easily introduced and applied twice for occlusion of the rectum, followed by anastomosis with a circular stapler. This triple-stapling technique is a safe and easy procedure for low colorectal anastomosis in a narrow pelvis.
Anastomosis, Surgical↗