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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 937 records · Page 52Linked to original sources

Stimulating effects of bovine small intestine mucosal factors on rat hepatocyte development.

A mass of pure adult rat parenchymal hepatocytes, obtained by a newly devised isolation technique, developed into organized micro-liverlike layered multicellular colonies in long-term primary cultures grown in the presence of bovine small intestine mucosal factors (SIMFs). These factors stimulated proliferation, aggregation, and orderly arrangement of the hepatocytes, and differentiation into partially functional micro-livers in vitro. SIMFs derived from other mammalian species affected rat hepatocytes in the same manner. Studies of the effects of mammalian SIMFs on hepatocytes may provide new insights into the kinetics and mechanisms of liver regeneration.

Animals↗

A case report of transcatheter arterial embolization of cholestatic type of hepatoma.

A 57-year-old man with hepatocellular carcinoma (HCC) invading the hepatic duct was treated with transcatheter arterial embolization (TAE). The dilated hepatic duct was decompressed his jaundice disappeared and he survived for 10 months after the first TAE, succumbing due to bleeding from gastric erosion. Although total bilirubin was 26.7 mg/dl and massive ascites was noted on occasion of the first TAE, hepatic dysfunction did not worsen and both icterus and ascites decreased, disappearing one month after the therapy. Autopsy revealed HCC with trabecular arrangement originating in the left lobe and growing into the left hepatic duct accompanied by liver cirrhosis and follicular carcinoma of the thyroid gland. Severe icterus caused by bile duct obstruction does not correlate with the grade of hepatic failure in HCC with liver cirrhosis, so TAE was effective and should be tried as a first choice therapy in such a poor risk case.

Carcinoma, Hepatocellular↗

In situ hybridization analysis of the somatostatin-containing neuron system in developing cerebellum of rats.

We used in situ hybridization histochemistry to examine the postnatal development of the somatostatin (SRIF) synthesizing system in the cerebellum of rats. There are numerous hybridizing neurons from 1 to 9 days after birth. These occur throughout the cerebellum including the developing medulla and cortex except in the external granular cell layer. The lateral cerebellar nucleus also contains SRIF gene-containing cells. The intensity of the signals for SRIF mRNA in the cerebellum decreases with age. There is a drastic decrease in SRIF mRNA in the lateral cerebellar nucleus. SRIF cells cannot be detected in the lateral cerebellar nucleus of adult rats, whereas a small, yet significant number of SRIF cells are scattered in the cerebellar medulla. However, the cerebellum of adult rats still contains a significant number of labeled cells in the granular cell layer, although the intensity for SRIF mRNA decreases from 14 days after birth to adulthood. SRIF gene-expressing cells in the cerebellar cortex are located primarily in the granular cell layer and appear to correspond to Golgi cells judging from their characteristic features. These results are consistent with our previous immunohistochemical study on the decrease of SRIF immunoreactivity in the cerebellum of adult rats. These findings, together with a recent study of transient SRIF receptor-expressing cells in the developing cerebellum suggest that SRIF acts during cerebellar development.

Aging↗

Coexistence of peptides (corticotropin releasing factor/neurotensin and substance P/somatostatin) in the bed nucleus of the stria terminalis and central amygdaloid nucleus of the rat.

Coexistence of corticotropin releasing factor and neurotensin and also of substance P and somatostatin was demonstrated in the lateral bed nucleus of the stria terminalis and the central amygdaloid nucleus of the rat, by means of a light microscopic mirror method or immunofluorescent double staining. Using the former technique, a major proportion of corticotropin releasing factor-like immunoreactive cells were found to display neurotensin-like immunoreactivity in the dorsal subdivision of the lateral bed nucleus of the stria terminalis and the lateral subdivision of the central amygdaloid nucleus. On the other hand, the immunofluorescent method showed that a significant number of neurons with both substance P- and somatostatin-like immunoreactivity were located in the ventral subdivision of the lateral bed nucleus of the stria terminalis and the medial subdivision of the central amygdaloid nucleus. Distribution patterns of such co-localized peptides may indicate that there are morphological and biochemical similarities between the dorsal subdivision of the lateral bed nucleus of the stria terminalis and the lateral subdivision of the central amygdaloid nucleus, as well as between the ventral subdivision of the lateral bed nucleus of the stria terminalis and the medial subdivision of the central amygdaloid nucleus. Previous studies have demonstrated that peptide-containing neurons in the lateral bed nucleus of the stria terminalis and central amygdaloid nucleus, such as corticotropin releasing factor-, neurotensin-, substance P- and somatostatin-like immunoreactive cells, project to the lower brainstem. The results of the present study suggest that corticotropin releasing factor/neurotensin and substance P/somatostatin neurons may be part of the lateral bed nucleus of the stria terminalis/central amygdaloid nucleus-lower brainstem pathways.

Amygdala↗

Stimulus specificity of peripherally evoked substance P release from the rabbit dorsal horn in situ.

Characteristics of in situ substance P release from the lumbar dorsal horn were investigated in decerebrated rabbits. Noxious mechanical stimuli produced by pinching the skin of a hind leg ipsilateral to the perfusion site remarkably and significantly increased the release of immunoreactive substance P, which was identified as substance P itself, using separation with high-performance liquid chromatography and radioimmunoassay. The noxious pinch did not affect the release of immunoreactive substance P, when applied to the contralateral hind leg. Both the basal and pinch-evoked release of immunoreactive substance P were largest in the dorsolateral part of the dorsal horn. The pinch-evoked release of immunoreactive substance P was abolished when the dorsal horn was perfused with a Ca2+-free medium containing 7 mM Mg2+ or with a medium with 10 microM tetrodotoxin added. The evoked release of immunoreactive substance P was also abolished following pretreatment of a stimulated region with the local anesthetic dibucaine, a procedure which inhibited the pinch-evoked aversive behavior in freely-moving rabbits. Among a variety of natural stimuli applied to the hind leg, noxious pinch and a subcutaneous injection of formaldehyde solution significantly evoked the release of immunoreactive substance P from the dorsal horn. The most intense heat or scalding stimulation increased the immunoreactive substance P release in two out of five experiments. However, other natural stimuli such as ice-cold, warm, noxious heat and innocuous mechanical stimuli produced no apparent changes in the release of immunoreactive substance P. These results suggest that among the noxious stimuli, only mechanical and inflammatory but not thermal stimuli lead to a release of substance P from the primary afferent terminals in the dorsal horn. The present findings suggest that, at least in rabbits, substance P-containing primary afferents have high-threshold mechanoreceptors. Substance P may participate in the transmission of information related to noxious mechanical and inflammatory stimulation from the periphery to the dorsal horn.

Animals↗

A light and electron microscopic study of calcitonin gene-related peptide in the rat caudate putamen.

Calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRP-IR) structures have been studied in the rat caudate putamen using avidin-biotin peroxidase immunohistochemistry. Immunoreactivity was found in the axons of this nucleus but not in the perikarya. CGRP-IR fibers were most densely concentrated along the ventral border and in the caudal portion of the rat caudate putamen. CGRP-IR fibers were sparsely distributed throughout the rest of this nucleus. Almost all immunoreactive boutons which contained small clear vesicles had formed asymmetrical synapses. Postsynaptic targets included dendritic spines and shafts. Asymmetrical synapses in the caudate putamen are supposed to be extrinsic in origin. These observations, together with the results of other investigations, suggest that CGRP-IR boutons form synapses with spiny striatal neurons, which, most likely, are medium-sized spiny projecting neurons. Moreover, evidence indicates that these boutons are of extrinsic origin.

Animals↗

The role of Pro-239 in the catalysis and heat stability of subtilisin E.

Site-directed mutagenesis was employed to analyze the role of an alpha-helix containing catalytic Ser-221 of subtilisin E. Pro-239 located at the carboxy-terminal end of the alpha-helix was first replaced with Gly to examine the role of Pro-239 in the catalysis and stability of subtilisin E. The mutation was found to decrease both the catalytic rate (kcat) and the heat stability. This result strongly suggests that Pro-239 plays an important role in the maintenance of the alpha-helix, affecting the functioning of the active site. Various amino acid substitutions at position 239 were attempted to obtain the active subtilisins from Gly-239 subtilisin. Lys- and Arg-substitutions were found to result in more active and stable subtilisins than the Gly-239 subtilisin. In particular, the Arg-239 mutant showed enhanced heat stability compared with the wild type. These results demonstrate the important role of the alpha-helix containing catalytic Ser-221 in the catalysis as well as in the heat stability of subtilisin.

Catalysis↗

Clinicohistopathologic and immunohistochemical studies of intrapancreatic development of carcinoma of the head of the pancreas.

Clinicohistopathologic and immunohistochemical studies of intrapancreatic development of duct cell carcinoma of the head of the pancreas to the body and tail were done in 34 cases in which total pancreatectomy accompanied by portal vein resection were performed from July 1981 to June 1987. In studies of hematoxylin and eosin (HE) staining, intrapancreatic development from the head to the body or tail was observed in 14 cases of 34 cases (41.1%). Multicentricity or skip development was observed in two of 14 cases. However, by using immunostaining of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and DUPAN2, small cancer nests surrounded by dense fibrous connective tissues could be easily and accurately diagnosed, and finally, in 25 of 34 cases (73.5%), intrapancreatic continuous development from the head to body or tail was observed. The intrapancreatic development correlated with portal invasion and perineural invasion of carcinoma, hardness of body and tail, obstruction of the main pancreatic duct, and irregular pancreaticogram. The intraoperative quick immunostaining on the cryostat sections, together with HE staining, is useful to determine the intrapancreatic development of the carcinoma. The indication of total pancreatectomy or pancreatoduodenectomy for carcinoma of the head of the pancreas can be determined by these results.

Adenoma, Islet Cell↗

[Acoustic neurinoma presenting with repeated intratumoral hemorrhage. Case report].

A case of acoustic neurinoma with multiple intratumoral hemorrhages is reported. A 56-year-old male noted sudden hearing reduction in his left ear in October of 1985. The diagnosis of a local physician was sudden deafness. About 10 months later, he had two episodes of severe headache without nausea or vomiting. The patient was hospitalized in October of 1986. Neurological examination cerebellar ataxia. cerebellar ataxia. Plain and enhanced computed tomography revealed only an unremarkable low-density area at the left cerebellopontine angle. In contrast, magnetic resonance imaging (MRI) clearly demonstrated a large (3 x 4 x 5 cm), multicystic tumor in the site. On exposure of the tumor at surgery, most of the cysts were found to be filled with a dark red or xanthochromic fluid. The tumor was completely removed following numerous cyst punctures to decrease its volume. There was no evidence of subarachnoid hemorrhage. Histological examination showed a typical acoustic neurinoma. The cyst wall contained numerous telangiectasia-like lesions. The initial symptom of this patient was sudden hearing loss, which is an atypical manifestation of acoustic neurinoma. The massive intratumoral hemorrhage was thought to be caused by telangiectatic lesions in the cyst wall. MRI clearly demonstrated the hemorrhagic cysts within the tumor, especially in the posterior fossa.

Cerebellar Neoplasms↗

Acute pancreatitis after transcatheter arterial embolization (TAE) for hepatocellular carcinoma.

Transcatheter arterial embolization (TAE) has been widely used for treatment of hepatocellular carcinoma. Acute pancreatitis occasionally occurs as a complication of TAE. We have investigated the possible effects of TAE on the pancreas by monitoring serum pancreatic enzyme activities following TAE with various embolic materials. Serum amylase activity was increased very little in the patients treated with chemotherapy alone or plus TAE with lipiodol, slightly increased in many of the patients treated with chemotherapy plus TAE with gelatin sponge, and increased in all of the patients treated with chemotherapy plus TAE with gelfoam powder. The activity was increased to a level as high as 700 U/dl or more in most individuals of the last category. In one of them acute pancreatitis developed, probably because the gelfoam powder regurgitated into the pancreaticoduodenal artery, and occluded a very peripheral portion of the pancreatic vascular bed, leading to ischemia of the pancreas. These results suggest that choosing the correct particle size is important for prevention of acute pancreatitis.

Acute Disease↗

Subcellular localization of benzodiazepine/GABAA receptors in the cerebellum of rat, cat, and monkey using monoclonal antibodies.

Two monoclonal antibodies, bd-17 and bd-24, specific for the beta- and alpha-subunit of the GABAA/benzodiazepine receptor/chloride channel complex, respectively, were used to determine the subcellular distribution of immunoreactivity in the cerebellum by electron microscopy. The 2 antibodies showed similar antigen distribution on the plasma membrane (except in the rat; bd-24 does not recognize the rat antigen), but intracellular immunoreactivity was more prevalent for the alpha-subunit. The plasma membrane of all neuronal types was immunopositive. The degree of immunoreactivity varied greatly between different types of cell, but it was stereotyped among individual cells of the same type. Granule cells showed the strongest immunoreactivity, not only on their dendrites which receive synapses from GABA-containing Golgi cell terminals, but also on their somata which do not receive synapses. Stellate and basket cells were somewhat weaker in immunoreactivity. Purkinje cells were only weakly positive on their somatic membrane but stronger on their dendritic shafts and spines. Golgi cells showed negligible if any immunoreactivity. Neurons of the deep cerebellar nuclei were strongly immunopositive along their plasma membrane. Immunoreactivity was strong in cisternae of the endoplasmic reticulum and in the Golgi saccules of stellate and basket cells, variable in Purkinje cells, while granule cells were rarely immunoreactive intracellularly. It is suggested that these differences reflect differences in the turnover of the receptor complex in the different cell types. The synaptic clefts established by boutons of the GABAergic stellate, basket, and Golgi cells were immunopositive, as were many synapses in the deep cerebellar nuclei. However, immunoreactivity was also present along the nonjunctional plasma membrane, and it was concluded that this reflected the distribution of the antigen. The synaptic clefts at the presumed glutamate-releasing parallel and mossy fiber terminals were almost always immunonegative. No immunoreactivity was detected on axons, nerve terminals, or glial cells. The results demonstrate that different neuronal types express the GABAA/benzodiazepine receptor/chloride channel complex to different degrees. The distribution of the receptor complex suggests that the cellular topography of GABAergic influence is not governed by the precise spatial arrangement of the receptors but by the precise placement of the GABA-releasing terminals, a characteristic of the cerebellar circuit.

Animals↗

[Radiation therapy of hepatocellular carcinoma].

After the transhepatic arterial therapy, irradiated 11 patients with hepatocellular carcinoma were investigated clinically and pathologically. As the effect to the main tumors except for 3 cases who dropped out because of the side effect of irradiation, partial response (PR) was found in 1 case, minor response (MR) was in 2. There was no change (NC) in 4 and 1 had progressive disease (PD), so the rate of effectiveness was 12.5%. Irradiation to the tumor thrombosis of the portal vein were done for seven cases, 2 of them (28.6%) showed the decrease of the thrombosis or improvement of the blood stream in the portal vein on angiography or histology. AFP decreased in four of seven measurable cases within one month after the irradiation. Side effects were jaundice, fever, appetite loss and so on, which were seen especially in cases of Child's B or C. Liver dysfunction and bone marrow suppression were also observed though not so severe. For the cases received lipiodol injection before radiation, lipiodol collection to the tumor was beneficial for the determination of the irradiated field.

Aged↗

[Studies on drug release from anti-cancer drug suspended Lipiodol].

In case of an arterial infusion chemoembolization therapy for primary or metastatic liver cancer, gradual release of the anti-cancer drug from lipiodol is a very important factor for a higher drug concentration in the tumor and for longer contact. We studied basic points about what kind of drug form has a gradual drug release. We prepared 3 forms of drugs. (1) Powder form: Powder of ADM, MMC and CDDP was suspended in lipiodol with ultrasonic suspender. (2) URO form: ADM and MMC were dissolved with Urografin and mixed with lipiodol. (3) Surfactant form: ADM and MMC were dissolved with water and then mixed with lipiodol using surfactant. We put lipiodol suspension into physiological saline and then stirred water at 100 rpm with the paddle method, measuring drug release from the suspension or emulsion. Powder form had a lowest drug release. In clinical trials, we administered intra-arterially (1) ADM, MMC dissolved with physiological saline water as usually used (physiological saline water form) (2) Powder form; (3) URO from; (1) CDDP solution as usually used was administered; (2) Powder form. Then we studied the changes of serum concentration of ADM, MMC and CDDP. The results indicated that powder form had the lowest drug release. Thus, the water-soluble anti-cancer drugs ADM, MMC and CDDP should be used in powder form.

Antineoplastic Agents↗

[Extended surgery for advanced colo-rectal carcinoma (stage IV and V)].

Two hundred fifty-five patients with colo-rectal carcinoma underwent operations in our department between January 1980 and December 1988. The five-year survival rate of stage IV patients (30 cases) was 58%, and the three-year survival rate of stage V patients (44 cases) was 8%. The study for the expression of blood group-related cancer-associated antigens (Lea, CA19-9, etc.) in colo-rectal cancers using immunohistological method and a series of mouse monoclonal antibodies revealed that the stromal staining pattern of CA19-9 means high malignancy with poor prognosis. Nineteen patients with locally invading rectal cancer were submitted to total pelvic exenteration with urinary diversion. The operative mortality rate was 5.3%. A determinate 5-year survival rate of 4.5 was achieved. Fourteen patients with local recurrent lesions of rectal cancer following abdominoperineal resection were submitted to pelvic exenteration combined with sacral resection. Two patients are alive disease free for longer than four years at this writing. This operation assures a better quality of life, lessening of symptoms, disease control and, in selected patients, a cure.

Antigens, Tumor-Associated, Carbohydrate↗

[Long-term results of mechanical valves in aortic position and biological valves in mitral and tricuspid positions].

The long-term results of patients undergoing aortic valve replacement (AVR) with a mechanical valve (AM), mitral valve replacement with a biological valve (MB), and tricuspid valve replacement (TVR) with a biological valve (TB) operated upon from 1977 to 1988 were retrospectively analysed. A total of 899 patients received 1117 valves (381 AM, 633 TB, 103 TB) with a follow-up 3778 patient-years and 4582 valve-years. A significant incidence of thromboembolism, hemorrhage, and endocarditis was not found among AVR, MVR, TVR, or multiple valve replacement. We found a significantly decreased incidence of survival rate in multiple valve replacement compared with AVR or MVR, and a significantly increased incidence of reoperation in MB compared with AM and TB. We use AM and TB in any adult patients as a first choice. However, we prefer a mechanical valve in the mitral position except in patients over 65 years old, who have a short life expectancy, in whom anticoagulation is thought to be difficult, and who desire a biological valve.

Adolescent↗