Stereotyped axonal bundle formation and neuromeric patterns in embryos of a cyclostome, Lampetra japonica.

Early embryonic development of the nervous system of a lamprey, Lampetra japonica, was studied by using immunohistochemical techniques and by scanning electron microscopy. The earliest appearance of axons was detected at Tahara's stage 21-, when dorsolateral and ventral longitudinal fasciculi were present in the hindbrain and spinal cord regions. The branchiomeric nerve roots began to appear at stage 22; the fibers were joined to the dorsolateral fasciculus proximally and also extended distally into each pharyngeal arch. The anterior neural tube was divided into several neuromeres: the mid-hindbrain sulcus became apparent first, then the portion rostral to this sulcus was subdivided into two portions by the syn-parencephalic boundary. In the hindbrain around stage 23, rhombomeres developed transiently, of which, rhombomere 4 was the most distinctive. Putative crest cells forming the octavofacial nerve root anlage were selectively adhering to rhombomere 4, whereas no crest cells were found on rhombomere 3. The assignment of the crest-derived nerve anlage to rhombomeres is conserved between gnathostomes and L. japonica. The neuromerical scheme of the neural tube of L. japonica is also mostly in accordance with that in gnathostomes, sharing the basic developmental patterning of axon bundles at early developmental stages. The most distinct difference between these two groups is the topographical relationships between the hindbrain neuraxis and pharyngeal arches, as well as the otic placode.

Involvement of endogenous prostaglandins in pancreatic endocrine and exocrine secretion in dog pancreas.

The involvement of endogenous prostaglandins (PGs) in pancreatic endocrine and exocrine secretion was investigated, using the isolated and perfused dog pancreas. Spontaneous production of both PGE2 and 6-keto-PGF1 alpha was recorded in venous effluent. Prostaglandin production increased following stimulation with both 10 x 10(-11) and 20 x 10(-11) mol of CCK-8, but was not affected by a 5 x 10(-11) mol infusion. Insulin, glucagon, and amylase release was stimulated by 10 x 10(-11) mol of CCK-8. Indomethacin pretreatment with 10 mg/kg totally abolished endogenous PG production, but failed to suppress an insulin and glucagon response. On the other hand, an amylase response was accelerated by indomethacin pretreatment. Although low dose CCK-8 failed to stimulate endogenous prostaglandin production, a brisk exocrine secretion was not suppressed by indomethacin pretreatment. From the above results, we conclude that endogenous PGs do not appear to play an important role in pancreatic endocrine and exocrine secretion, but might have a cytoprotective effect on the pancreatic acinar cells damaged by CCK-8.

Evaluation of imaging examination for hepatic invasion of carcinoma of the gallbladder and postoperative patient outcome.

BACKGROUND: Hepatic invasion is an important factor in the selection of an operative procedure for patients with carcinoma of the gallbladder. Imaging modalities to detect the hepatic invasion were evaluated for accuracy, and postoperative patient outcome was analyzed. STUDY DESIGN: Thirty-six patients who were treated for carcinoma of the gallbladder at our institution between 1984 and 1993 were studied. The imaging results of ultrasonography (US), computed tomography, and angiography were compared with histologic findings regarding intrahepatic invasion of the carcinoma. RESULTS: Histologic examination of the operative specimens removed from 21 patients revealed that the detection of hepatic invasion with preoperative US was superior to that with the other two modalities. The preoperative US showed a diagnostic value that was almost the same as that of the intraoperative US. The postoperative patient outcome was not satisfactory, although extended radical operation was performed using image guidance in the 21 patients. The patients died as a result of nodal recurrence rather than hepatic recurrence. CONCLUSIONS: Preoperative US should be performed initially for detecting hepatic invasion from carcinoma of the gallbladder and can be substituted for intraoperative US. Considering the operative treatment for patients with carcinoma of the gallbladder, lymph node dissection is as important as the extent of hepatectomy.

[Usefulness of subcutaneously implanted reservoir for postoperative therapy in hepatocellular carcinoma and liver metastases of colorectal carcinoma].

Hepatectomy has been a treatment of choice for hepatocellular carcinoma and metastatic liver carcinoma. Recurrence in residual liver after hepatectomy is clinically a serious problem. Since 1987, postoperative hepatic arterial infusion chemotherapy using subcutaneously implanted reservoir has been undertaken to improve the prognosis after hepatectomy in hepatocellular carcinoma and liver metastasis of colorectal carcinoma. The indications for reservoir implantation were determined for high-risk cases in hepatocellular carcinoma and all cases in liver metastasis. The tip of a catheter was placed at the root of the common hepatic artery via gastroduodenal artery. Lipiodol-ADM was injected for hepatocellular carcinoma every 2 months and MMC-5-FU was injected for liver metastasis of colorectal carcinoma every one or two weeks. Complications of this procedure in every 2 cases of reservoir infection proved to be catheter obstruction and hepatic artery obstruction. In the process of this treatment, we observed 3 recurrences in residual liver of hepatocellular carcinoma and one case of peritoneal dissemination and 3 recurrences in residual liver of liver metastasis of colorectal carcinoma. All are still alive.

[A case of complete response of breast cancer with pulmonary metastases to combination therapy of 5'-DFUR and MPA].

This paper presents a case with lung metastases from breast cancer. Complete response was obtained by combined chemoendocrine therapy with 5'-DFUR and MPA. The patient was a 62-year-old female. She underwent a standard radical mastectomy in April, 1988. The primary legion was ER (-) and PgR (-). Postoperative treatments using CMF and CAF were eventually discontinued owing to profound damage to the bone marrow. An adjuvant chemotherapy with UFT has been employed since. Two years and 7 months later, hemosputum and coughing appeared, and metastases to the lung were revealed. Combined chemoendocrine therapy with 5'-DFUR and MPA was undertaken. A significant decrease in tumor size was observed 3 months after the chemoendocrine therapy was begun, and complete response was obtained at the 8th month. The state has been maintained for one year and 9 months. The use of combined chemoendocrine therapy with 5'-DFUR and MPA in patients for whom intensive chemotherapy is not possible due to damage to bone marrow function is considered effective for its antitumor effects or maintaining patients' quality of life.

[Treatment of liver metastases from gastric cancer].

Nine patients with liver metastases from gastric cancer were treated in our department since 1986. Hepatectomy was performed in 3 cases and hepatic arterial infusion chemotherapy was performed in 6 cases. In 3 patients in whom hepatectomy was performed, the extent of liver metastases showed 2 H1 and 1 H2. One has survived for 20 months, but the other 2 died after 5 and 7 months, respectively. In 6 patients in whom hepatic arterial infusion chemotherapy was performed, the extent of liver metastases was H3. These patients were treated with 5-FU.EPIR.MMC (3 cases), CDDP.MMC (1 case), MMC only (1 case) and 5-FU.ADM.MMC.CDDP (1 case). This treatment revealed a 50% response rate (CR 1, PR 2). The patient with CR has survived for 6 years and 2 patients with PR died after 8 and 12 months. The patient with CR showed high AFP level (55, 480 ng/ml), and 2 patients with PR showed high AFP level (24, 327 ng/ml) or high CEA level (3,903 ng/ml). The prognosis of hepatectomy for liver metastases from gastric cancer was not so good. Hepatic arterial infusion chemotherapy seemed to be a useful treatment for liver metastases from gastric cancer.

Developmental morphology of the head mesoderm and reevaluation of segmental theories of the vertebrate head: evidence from embryos of an agnathan vertebrate, Lampetra japonica.

Due to the peculiar morphology of its preotic head, lampreys have long been treated as an intermediate animal which links amphioxus and gnathostomes. To reevaluate the segmental theory of classical comparative embryology, mesodermal development was observed in embryos of a lamprey, Lampetra japonica, by scanning electron microscopy and immunohistochemistry. Signs of segmentation are visible in future postotic somites at an early neurula stage, whereas the rostral mesoderm is unsegmented and rostromedially confluent with the prechordal plate. The premandibular and mandibular mesoderm develop from the prechordal plate in a caudal to rostral direction and can be called the preaxial mesoderm as opposed to the caudally developing gastral mesoderm. With the exception of the premandibular mesoderm, the head mesodermal sheet is secondarily regionalized by the otocyst and pharyngeal pouches into the mandibular mesoderm, hyoid mesoderm, and somite 0. The head mesodermal components never develop into cephalic myotomes, but the latter develop only from postotic somites. These results show that the lamprey embryo shows a typical vertebrate phylotype and that the basic mesodermal configuration of vertebrates already existed prior to the split of agnatha-gnathostomata; lamprey does not represent an intermediate state between amphioxus and gnathostomes. Unlike interpretations of theories of head segmentation that the mesodermal segments are primarily equivalent along the axis, there is no evidence in vertebrate embryos for the presence of preotic myotomes. We conclude that mesomere-based theories of head metamerism are inappropriate and that the formulated vertebrate head should possess the distinction between primarily unsegmented head mesoderm which includes preaxial components at least in part and somites in the trunk which are shared in all the known vertebrate embryos as the vertebrate phylotype.

Embryology of the lamprey and evolution of the vertebrate jaw: insights from molecular and developmental perspectives.

Evolution of the vertebrate jaw has been reviewed and discussed based on the developmental pattern of the Japanese marine lamprey, Lampetra japonica. Though it never forms a jointed jaw apparatus, the L. japonica embryo exhibits the typical embryonic structure as well as the conserved regulatory gene expression patterns of vertebrates. The lamprey therefore shares the phylotype of vertebrates, the conserved embryonic pattern that appears at pharyngula stage, rather than representing an intermediate evolutionary state. Both gnathostomes and lampreys exhibit a tripartite configuration of the rostral-most crest-derived ectomesenchyme, each part occupying an anatomically equivalent site. Differentiated oral structure becomes apparent in post-pharyngula development. Due to the solid nasohypophyseal plate, the post-optic ectomesenchyme of the lamprey fails to grow rostromedially to form the medial nasal septum as in gnathostomes, but forms the upper lip instead. The gnathostome jaw may thus have arisen through a process of ontogenetic repatterning, in which a heterotopic shift of mesenchyme-epithelial relationships would have been involved. Further identification of shifts in tissue interaction and expression of regulatory genes are necessary to describe the evolution of the jaw fully from the standpoint of evolutionary developmental biology.

Effects of pentobarbital and cyproheptadine on brain ischemia induced by bilateral occlusions of carotid arteries and vertebral arteries of second cervical vertebra in rats.

The bilateral hemispheric ischemia in rats was induced by the occlusion of bilateral common carotid arteries after permanent electrocauterization of bilateral vertebral arteries at the level of the second cervical vertebra. In ischemic rats, (a) electroencephalograms became flat immediately after occlusion of carotid arteries, and (b) mortalities reached maximum levels at day 3 after recirculation. These results suggested that a constant level of cerebral ischemia was produced in this rat model. Pentobarbital markedly inhibited the mortality in these ischemic rats, whereas cyproheptadine did not.

The antitumor activity and immunosuppressive effects of 5-fluorouracil suppositories in rectal cancer patients.

The antitumor activity and immunological effects of the local administration of 5FU were investigated by determining the tissue concentration of 5FU, histological appearance of the primary tumor, and lymphocyte subsets of the regional lymph nodes in 23 rectal cancer patients. Twelve patients were treated with 5FU suppositories preoperatively, being the 5FU group, while 11 patients were given no preoperative treatment, being the control group. The 5FU concentrations in the primary tumors were higher than those in the regional lymph nodes and appeared to remain high for an extended period. No histological changes peculiar to the 5FU group were observed in the primary tumors. An analysis of the lymphocyte subsets in the pararectal nodes revealed that Leu2a+15- cells, or cytotoxic T lymphocytes, were significantly decreased in numbers in the 5FU group compared to the control group. These results suggest that the local use of 5FU may not only exert an antitumor effect against rectal cancer, but can also cause the suppression of antitumor immunity in the regional lymph nodes.

Gas-forming liver abscess after transcatheter arterial embolization for hepatocellular carcinoma: report of a case.

A case of a gas-forming liver abscess developing after transcatheter arterial embolization for recurrent hepatocellular carcinoma (HCC) in a 65-year-old man is presented herein. He was admitted to hospital with fever and jaundice, following which ultrasonography (US) and computed tomography revealed a gas-containing abscess in the posterior segment of the hepatic lobe with multiple HCC. Percutaneous transhepatic drainage was performed using US. Antibiotics which were sensitive to the Escherichia coli bacteria detected in the abscess were administered both intravenously and through the drainage tube into the abscess. Four months later, the abscess had diminished and the patient was discharged after receiving percutaneous ultrasonographically guided ethanol injection therapy for the recurrent HCC.

Development of cephalic neural crest cells in embryos of Lampetra japonica, with special reference to the evolution of the jaw.

Neural crest cells contribute extensively to vertebrate head morphogenesis and their origin is an important question to address in understanding the evolution of the craniate head. The distribution pattern of cephalic crest cells was examined in embryos of one of the living agnathan vertebrates, Lampetra japonica. The initial appearance of putative crest cells was observed on the dorsal aspect of the neural rod at stage 20.5 and ventral expansion of these cells was first seen at the level of rostral somites. As in gnathostomes, cephalic crest cells migrate beneath the surface ectoderm and form three major cell populations, each being separated at the levels of rhombomeres (r) 3 and r5. The neural crest seems initially to be produced at all neuraxial levels except for the rostral-most area, and cephalic crest cells are secondarily excluded from levels r3 and r5. Such a pattern of crest cell distribution prefigures the morphology of the cranial nerve anlage. The second or middle crest cell population passes medial to the otocyst, implying that the otocyst does not serve as a barrier to separate the crest cell populations. The three cephalic crest cell populations fill the pharyngeal arch ventrally, covering the pharyngeal mesoderm laterally with the rostral-most population covering the premandibular region and mandibular arch. The third cell population is equivalent to the circumpharyngeal crest cells in the chick, and its influx into the pharyngeal region precedes the formation of postotic pharyngeal arches. Focal injection of DiI revealed the existence of an anteroposterior organization in the neural crest at the neurular stage, destined for each pharyngeal region. The crest cells derived from the posterior midbrain that express the LjOtxA gene, the Otx2 cognate, were shown to migrate into the mandibular arch, a pattern which is identical to gnathostome embryos. It was concluded that the head region of the lamprey embryo shares a common set of morphological characters with gnathostome embryos and that the morphological deviation of the mandibular arch between the gnathostomes and the lamprey is not based on the early embryonic patterning.

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver.

To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%. HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.

Enhanced production of endogenous prostaglandin in obstructive jaundiced pancreas in dogs.

Endogenous pancreatic prostaglandin production in control and obstructive jaundice was investigated using isolated and perfused dog pancreas. In both groups, spontaneous production of prostaglandin E2 and prostaglandin I2 was recorded, and the levels did not change in both groups. The production of both prostaglandins in jaundice, however, was higher than that in the control on stimulation by 8 x 10(-11) mol of cholecystokinin-octapeptide. Amylase release with cholecystokinin-octapeptide at an amount of 8 x 10(-11) mol in jaundice was higher than in the control. The amylase release in both groups, however, showed further elevation on indomethacin pretreatment. On incubation of pancreatic dispersed cells in both groups, prostaglandin production in jaundiced cells was higher than that in control cells. These data showed that enhanced endogenous prostaglandin in obstructive jaundice might be caused by the characteristic change of pancreatic cells, which increased susceptibility to cholecystokinin-octapeptide because of long-term exposure to abnormal blood components, and enhanced prostaglandins might act as a cytoprotector of acinar cells in the pancreas damaged by cholecystokinin-octapeptide administration.