Biomedical subjects

M Saeki

Publications and source records attributed to M Saeki.

At least 55 records · Page 3Linked to original sources

PubMed1998

The combined method: a novel access technique for fetal endoscopic surgery.

BACKGROUND/PURPOSE: To develop practical and less invasive techniques for fetal endoscopic surgery, new methods of lifting the uterine wall to allow fetal surgery without maternal laparotomy were developed and assessed. METHODS: Fetal endoscopic surgical procedures, including tracheostomy and umbilical vascular cannulation, were performed using one of the three methods to enter the uterus without maternal laparotomy in pregnant goats (n = 6; 105 to 115 days' gestation): (1) direct uterine lifting with an air-cushion device; (2) indirect uterine lifting, in which the uterine wall was fixed to the maternal abdominal wall using balloon tip ports inserted percutaneously by Seldinger's method, then the maternal abdomen was lifted mechanically; and (3) combined method, in which low pressure CO2 (5 mm Hg for initial inflation and 2 mm Hg for maintenance) was insufflated into the uterus in addition to the indirect uterine lifting cited above. RESULTS: The direct uterine lifting caused massive injury of myometrium and uterine membranes. The creation of intrauterine space and the protection of the membranes were not accomplished effectively by the indirect uterine lifting only. The combined method provided the adequate intrauterine space and excellent endoscopic visibility for completion of the endoscopic procedures with minimal uterine injury. CONCLUSION: The fetal endoscopic surgery may be accomplished simply and safely by the combined method, a novel technique of uterine lifting to allow fetal surgery without maternal laparotomy.

Animals↗

PubMed1998

Hair cells in mammalian utricles.

Two morphological classes of mechanosensory cells have been described in the vestibular organs of mammals, birds, and reptiles: type I and type II hair cells. Type II hair cells resemble hair cells in other organs in that they receive bouton terminals from primary afferent neurons. In contrast, type I hair cells are enveloped by large cuplike afferent terminals called calyces. Type I and II cells differ in other morphological respects: cell shape, hair bundle properties, and more subtle ultrastructural features. Understanding the functional significance of these strikingly different morphological features has proved to be a challenge. Experiments that correlated the response properties of primary vestibular afferents with the morphologies of their afferent terminals suggested that the synapse between the type I hair cell and calyx ending is lower gain than that between a type II hair cell and a bouton ending. Recently, patch-clamp experiments on isolated hair cells have revealed that type I hair cells from diverse species have a large potassium conductance that is activated at the resting potential. As a consequence, the voltage responses generated by the type I hair cells in response to injected currents are smaller than those generated by type II hair cells. This may contribute to the lower gain of type I inputs to primary afferent neurons. Studies of neonatal mouse utricles show that the type I-specific potassium conductance is not present at birth but emerges during the first postnatal week, a period of morphological differentiation of type I and type II hair cells.

Animals↗

PubMed1998

Cloning of human polyubiquitin cDNAs and a ubiquitin-binding assay involving its in vitro translation product.

During large-scale in vitro translation analysis of a human full-length cDNA bank, we found a clone producing a remarkably smaller translation product than that expected from the open reading frame. The cDNA encodes a polyubiquitin, UbC, composed of nine tandem repeats of the ubiquitin unit. The bank contained twelve UbC cDNAs including four full-length ones. Sequencing analysis of these clones showed that UbC cDNAs can be classified into two types, UbC1 and UbC2, in each of which there are six polymorphic nucleotide variations. The present UbC cDNA was in vitro translated in a rabbit reticulocyte or wheat germ extract to produce a free ubiquitin labeled with [35S]methionine. The labeled ubiquitin could be used as a substrate for thiol ester formation with ubiquitin-activating enzyme E1 or ubiquitin-conjugating enzyme E2.

Amino Acid Sequence↗

PubMed1998

[TNM classification--pediatric tumors].

The clinical and postsurgical TNM classifications (cTNM and pTNM) for neuroblastoma (NB), nephroblastoma (WT) and soft tissue sarcomas were presented in 1982 by the TNM Committee in UICC in collaboration with SIOP. The Japanese TNM Committee proposed new pTNM systems (J-pTNM) for NB and WT, and new cTNM and pTNM system for primary liver carcinoma in infants and children (HT). These pTNMs were based on the staging systems developed by the Malignant Tumor Committee of the Japanese Society of Pediatric Surgeons. The proposal of subdivision of M category in NB was presented for testing the new telescopic ramifications of TNM. The TNM for HT was added as a new classification recommended for testing. The effectiveness of these TNM systems was assessed using NB, WT and hepatoblastoma (HB) cases which were registered in collaborating institutes. The analyses suggested that pTNM, especially the J-pTNM system in NB, WT and HT were effective for the assessment of prognoses, although cTNM systems were not enough to assess the extent of the disease.

Child↗

PubMed1998

Effects of loxiglumide on pancreatic exocrine secretion stimulated by cholecystokinin-8 in conscious dogs.

The effects of loxiglumide (CAS 107097-80-3, CR 1505), a novel cholecystokinin-A(CCK-A) receptor antagonist, on pancreatic exocrine secretion stimulated by exogenously administered CCK-8 were examined in conscious dogs with chronic pancreatic fistula. Pancreatic exocrine secretion in dogs was significantly increased by intravenous infusion of CCK-8 at a dose of 0.06 microgram/kg/h. Loxiglumide inhibited CCK-8-augmented outputs of pancreatic protein, trypsin and amylase at intravenous doses of 1, 3, 10 mg/kg/h (p < 0.05 or 0.01), and inhibited pancreatic juice volume at a dose of 10 mg/kg/h (p < 0.05). These results demonstrated that the selective CCK-A antagonist loxiglumide inhibited the increase of pancreatic exocrine secretion stimulated by CCK-8 based on selective blockade of receptor binding of CCK in dogs.

Amylases↗

PubMed1998

Effects of loxiglumide on pancreatic exocrine secretion stimulated by meal in conscious dogs.

The effects of loxiglumide (CAS 107097-80-3, CR 1505), a novel cholecystokinin-A(CCK-A) receptor antagonist, on pancreatic exocrine secretion stimulated by meal were examined in conscious dogs with chronic pancreatic fistula. Pancreatic exocrine secretion was stimulated by intraduodenal infusion of a liquid test meal and postprandial plasma CCK levels were apparently elevated. Loxiglumide inhibited the meal-stimulated outputs of pancreatic protein, amylase and bicarbonate at an intravenous dose of 10 mg/kg/h (p < 0.05). However, loxiglumide did not show apparent inhibition of pancreatic juice volume and trypsin output. These results show that the selective CCK-A antagonist loxiglumide may inhibit the increase of pancreatic exocrine secretion based on selective blockade of receptor binding of CCK endogenously induced by meal in dogs.

Amylases↗

PubMed1997

Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents.

The alpha7 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) is abundantly expressed in hippocampus and is implicated in modulating neurotransmitter release and in binding alpha-bungarotoxin (alpha-BGT). A null mutation for the alpha7 subunit was prepared by deleting the last three exons of the gene. Mice homozygous for the null mutation lack detectable mRNA, but the mice are viable and anatomically normal. Neuropathological examination of the brain revealed normal structure and cell layering, including normal cortical barrel fields; histochemical assessment of the hippocampus was also normal. Autoradiography with [3H]nicotine revealed no detectable abnormalities of high-affinity nicotine binding sites, but there was an absence of high-affinity [125I]alpha-BGT sites. Null mice also lack rapidly desensitizing, methyllycaconitine-sensitive, nicotinic currents that are present in hippocampal neurons. The results of this study indicate that the alpha-BGT binding sites are equivalent to the alpha7-containing nAChRs that mediate fast, desensitizing nicotinic currents in the hippocampus. These mice demonstrate that the alpha7 subunit is not essential for normal development or for apparently normal neurological function, but the mice may prove to have subtle phenotypic abnormalities and will be valuable in defining the functional role of this gene product in vivo.

Aconitine↗

PubMed1997

Trends of survival in neuroblastoma and independent risk factors for survival at a single institution.

To assess the progress of survival in neuroblastoma which varies with many risk factors and to evaluate the influence of these factors on survival as independent risk factors. The study subjects were 159 neuroblastoma patients seen from 1965-1994 at the oldest and largest children's hospital in Japan. Trends of survival in three treatment eras-1965-81, 1982-86, 1987-94-were assessed by the Kaplan-Meier method for different sex, age at diagnosis, the clinical stage, the site of onset, and the histological type. Then the influence on survival of these factors as independent prognostic variables was evaluated by the Cox proportional hazards regression analysis. Age at diagnosis, the clinical stage, the site of onset, the histological type, and the treatment era were independent risk factors in the order of their influence on survival. Unfavorable survival outcomes were obtained for patients with age at diagnosis above 1 year, the clinical stage of VI by the Evans classification, adrenal onset, and neuroblastoma rather than ganglioneuroblastoma. Survival improved from the first to the second and from the second to the third treatment era. Improvement of survival in neuroblastoma took place during the past 3 decades. Age at diagnosis, the clinical stage, and the histological type have still remained overwhelming prognostic factors over the progress in treatment.

Adrenal Gland Neoplasms↗

PubMed1997

Clinical application of minimal residual neuroblastoma cell detection by reverse transcriptase-polymerase chain reaction.

The highly sensitive method to detect neuroblastoma (NB) cells using reverse transcriptase polymerase chain reaction (RT-PCR) was applied in the practical clinics, and its efficacy was assessed in the present study. Human tyrosine hydroxylase (TH), a rate-limiting enzyme in the catecholamine biosynthesis, was used as the marker for NB cells, and the expression of THmRNA was examined in 13 samples (four peripheral blood and nine bone marrow) harvested from seven patients (four with stage IV, one with stage III, two with stage II) using RT-PCR with our original primers. The positive signals for NB cells were detected in four samples (one peripheral blood and three bone marrow) by the PCR method, but were undetectable by the conventional histological examinations. In the present series, a case that showed a positive signal for NB cells in the peripheral blood showed a remarkably unfavorable clinical course, indicating that the circulating NB cells detected by the PCR method can be a sign of the progressively advanced NB, and may define a new prognostic factor suggesting higher risk. In another case, the PCR detection for the residual NB cells in the bone marrow provided important supporting evidence to determine the necessity of the additional chemotherapy and the suitable timing for bone marrow transplantation. This detection also guaranteed the safety of the bone marrow for transplantation. The PCR method was considered to be very beneficial in the selected cases. However, some problems such as the false-negative results in the negative urinary vanillylmandelic acid secretor were also highlighted in the present study.

3-Iodobenzylguanidine↗

PubMed1997

Pentaerythritol tetranicotinate (niceritrol) decreases plasma lipoprotein(a) levels.

We determined the most effective dosage of pentaerythritol tetranicotinate (niceritrol) to reduce plasma lipoprotein(a) [Lp(a)] levels in 44 Japanese patients (16 men and 28 women; mean age, 59.2 +/- 10.8 years) with hyperlipidemia types IIa, IIb, and IV. Patients received oral niceritrol at a dosage of 750 mg (3 tablets)/d for 8 weeks, followed by 1,500 mg (6 tablets)/d for 8 weeks. Administration of niceritrol 750 mg/d for 8 weeks decreased total and low-density lipoprotein (LDL) cholesterol in patients with type IIa hyperlipidemia and decreased triglycerides in patients with type IV hyperlipidemia, but did not affect Lp(a). However, niceritrol 1,500 mg/d for 8 weeks decreased Lp(a) in patients with initial Lp(a) levels greater than 30 mg/dL in addition to decreasing total and LDL cholesterol and triglycerides. These results suggest that the effective dosage of niceritrol to reduce the serum Lp(a) concentration in Japanese hyperlipidemic patients with a high Lp(a) level (> or = 30 mg/dL) is greater than 1,500 mg/d.

Aged↗

PubMed1997

Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta.

Recently, we developed a simple method for detecting a secretory signal sequence encoded by a cDNA fragment. In this study, we used this method to select cDNA clones encoding secretory proteins from a human full-length cDNA library. Full-sequencing analysis of the candidate clones revealed that one clone encoded a novel TGF-beta superfamily protein. The clone encodes a protein of 308 amino acids of which the C-terminal region shows a characteristic feature of TGF-beta superfamily proteins: seven conserved cysteine residues at the C-terminal preceded by a putative processing site composed of a basic amino acid repeat. The corresponding transcripts are highly expressed in the placenta, so the novel protein may play an important role in reproduction.

Amino Acid Sequence↗

PubMed1997

The activity of 17alpha-hydroxylase/C17-C20 lyase in the ovaries of immature hypophysectomized rats treated with recombinant FSH combined with various doses of human chorionic gonadotropin.

The activity of 17alpha-hydroxylase/C17-C20 lyase (17alpha-hydroxylase) in the ovaries and steroid hormone levels in the plasma were studied in immature hypophysectomized rats (IH-rats) treated with human recombinant follicle-stimulating hormone (rec-FSH) alone or combined with various doses of human chorionic gonadotropin (hCG). Eleven days after hypophysectomy, rats were given rec-FSH alone (total dose, 40 IU), or combined with various doses (0.1 to 10 IU in total) of hCG, twice daily for 4 days. Plasma levels of progesterone, testosterone and estradiol, and ovarian 17alpha-hydroxylase activity were measured 18 h after the last injection. Histology showed that the ovaries treated with rec-FSH alone had large antral follicles, the theca interna cells of which were small in size compared with those treated with rec-FSH combined with hCG. The activity of 17alpha-hydroxylase in the ovaries of IH-rats treated with rec-FSH alone was lower than that in the control IH-rats. It was markedly increased by treatment with rec-FSH combined with 1 or 10 IU hCG. Immunohistochemistry revealed that 17alpha-hydroxylase was localized only in the oocyte in the ovaries of control IH-rats and those treated with rec-FSH alone. When the IH-rats were treated with rec-FSH plus hCG, the number of immunopositive theca interna cells and interstitial cells, and their immunointensity were increased in an hCG dose-dependent manner. The plasma estradiol levels in the IH-rats treated with rec-FSH alone were low, but significantly higher than those in the control IH-rats, and estradiol levels were noticeably elevated in IH-rats treated with rec-FSH plus hCG. These results suggest that a synergism between hCG (LH) and FSH is essential for follicular development and steroidogenesis in the ovaries, implying paracrine effects among granulosa cells, theca cells and probably oocytes. The functional significance of 17alpha-hydroxylase in the oocytes is discussed in relation to estradiol production.

Animals↗

PubMed1997

Japanese Biliary Atresia Registry, 1989 to 1994.

The Japanese Biliary Atresia Society founded in 1980 for the aim of investigations of all aspects of biliary atresia (BA), started a nationwide registry of BA patients in 1989. A total of 626 cases were registered from 1989 to 1994. The male to female ratio was 0.58. Corrective surgery was performed in 603 patients. Regarding the type of obstruction, 63 cases were Type I, atresia of the common bile duct, 9 were Type II, atresia of the hepatic ducts, and 543 were Type III, atresia of the porta hepatis. As initial corrective procedures, original Roux-en Y, Suruga II and Roux-en Y with intestinal valve were mainly employed. Jaundice cleared in 346 patients (57%) and decreased in 131, while it persisted in 120. The 5-year-follow-up showed that 34 patients, 49% of the patients who were followed up, were alive without jaundice, while 28 (41%) are dead. Thirty five, 33% of the patients who were entered to the Registry, were lost to follow-up.

Biliary Atresia↗

PubMed1997

[Diagnostic imaging of renal pedicle injury].

We reviewed the radiological findings of 8 patients with renal pedicle injury admitted to our emergency center from January 1986 through September 1995 and compared them with the previously reported findings. The patients included 3 with renal artery occlusion and 5 with avulsion or disruption of renal pedicle vasculature. Extended retroperitoneal hematoma such as contralateral pararenal or central parahilar hematoma was visualized in all 5 cases with avulsion or disruption of renal pedicle vasculature. Although lack of contrast enhancement of injured renal parenchyma is a hall-mark of renal pedicle injury, three cases did not demonstrate this typical finding. In these three cases, one showed partial and the others showed total enhancement of the injured renal parenchyma on contrast enhanced CT. Partial enhancement in one case was found to represent total occlusion of the main renal artery and an intact accessory polar branch on angiography. The other two cases showed total enhancement of the renal parenchyma, with renal vein perforation done and complete disruption of the main renal artery and vein in the other. The latter findings were thought to be due to the maintenance of vascular flow surrounded by hematoma. In conclusion, when central parahilar hematoma is identified, the possibility of renal pedicle injury should be considered even if the renal parenchyma is well enhanced.

Adolescent↗

PubMed1997

[Organ preservation in the treatment of malignant solid tumors in children].

Organ preservation is one of the requirements for maintaining the high quality of life after the treatment of malignant solid tumors in children. We analyze our recent results of renal preservation in the abdominal neuroblastoma and describe 3 cases of successful organ preservation in pelvic malignancy. Between 1982 and 1996, 29 patients with adrenal or retroperitoneal neuroblastoma, that extended into the surrounding tissues and organs and/or to the contralateral side, underwent delayed primary excision. Before 1982, 9 patients were treated and only one ipsilateral kidney was preserved. On the other hand, 13 of 20 kidneys were preserved after 1987. Adoption of cis-platinum deepened our awareness of preserving the kidney. Furthermore, we have altered our strategy since 1987 to continuing preoperative chemotherapy until the size of the tumor becomes as small as it is estimated completely resectable by our own index, which is derived from computed tomography. Kidneys are shielded during intraoperative irradiation, and the tumor relapsed from the shielded area of retroperitoneum in one patient. Four of 14 preserved kidneys became atrophic and lost their function. The bladder and the rectum were left intact at tumor resection after intensive chemotherapy in two patients with pelvic (one retroperitoneal and one vaginal) rhabdomyosarcoma. A yolk sac tumor of the vagina responded completely to chemotherapy with cis-platinum, etoposide and bleomycin. The patient has survived 7.5 years without any local and distant relapse in spite of the fact that surgery, aside from several diagnostic biopsies, was not undertaken.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Cholecystokinin antagonistic activities of loxiglumide.

Cholecystokinin (CCK) antagonistic activities of loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR1505, CAS 107097-80-3) were investigated in the gastrointestine and gallbladder in vivo. Intravenous administration of loxiglumide antagonized the CCK-induced reduction of gastric emptying in rats, acceleration of intestinal transport in mice, increase in ileal motility in rabbits, gallbladder contraction in guinea pigs and acceleration of gallbladder emptying in mice. Orally administered loxiglumide also antagonized the CCK-induced gallbladder emptying in mice. Furthermore, egg yolk-stimulated gallbladder emptying in mice was also inhibited by loxiglumide, indicating that this agent antagonizes not only exogenous but also endogenous CCK. These results demonstrate that loxiglumide is an intravenously and orally effective, potent CCK antagonist.

Animals↗

PubMed1997

General pharmacological profile of the novel cholecystokinin-A antagonist loxiglumide.

The general pharmacological properties of a novel cholecystokinin-A antagonist, loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR 1505, CAS 107097-80-3) on central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems were investigated in experimental animals. 1. Central nervous system: At a dose of 30 mg/kg, i.v. loxiglumide showed ptosis in one of 6 mice, but at doses of 3 and 10 mg/kg, i.v. no change on gross behavior in mice. Loxiglumide had no effect on locomotor activity and thiopental-induced hypnosis, anti-convulsive activity, analgesic activity in mice and rectal temperature changes in rats. 2. Autonomic nervous system: In vitro, loxiglumide at concentrations of 10(-4) and 3 x 10(-4) mol/l slightly inhibited agonist-induced contractions in the isolated guinea pig ileum and spontaneous rhythmic contractions in the isolated non-pregnant rat uterus. But loxiglumide had no effect on oxytocin-induced contraction in isolated non-pregnant rat uterus. 3. Cardio-respiratory system: Loxiglumide had no effect on heart rate and electrocardiogram in anesthetized dogs. But it slightly increased blood pressure and decreased the frequency of respirations at a dose of 30 mg/kg, i.v. Furthermore, loxiglumide slightly decreased femoral arterial blood flow at doses of more than 3 mg/kg, i.v. On the other hand, it had no effect on contractile force or contraction rate in the isolated guinea pig atrium and resting tension in the isolated rabbit aorta. 4. Gastrointestinal system: Loxiglumide increased bile secretion at doses of 10 and 30 mg/kg, i.v. in anesthetized rats and at doses of 3, 10 and 30 mg/kg, i.v. in anesthetized dogs. However, total bile acid output was not affected by loxiglumide. On the other hand, loxiglumide had no effect on pancreatic secretion, gastric secretion and gastric emptying in rats and intestinal transport activity in mice. 5. Hematology: In vitro, in the case of samples without bovine serum albumin, at concentrations of more than 1.9 x 10(-3) mol/l loxiglumide showed hemolysis, while in the case of samples with bovine serum albumin, at concentrations of more than 6.9 x 10(-3) mol/l loxiglumide showed hemolysis, and its maximal potency was weak compared to albumin-free conditions. On the other hand, in vivo, loxiglumide had no effect on hemolysis. In addition, it had no effect on platelet aggregation, prothrombin time and activated partial thromboplastin time. 6. Miscellaneous pharmacological actions: Loxiglumide had no effect on local anesthetic activity in guinea pigs and renal function in mice. These results suggest that loxiglumide seems to produce no serious side effects on the central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems at pharmacologically effective doses.

Animals↗

PubMed1996

cDNA cloning and functional analysis of the p97 subunit of the 26S proteasome, a polypeptide identical to the type-1 tumor-necrosis-factor-receptor-associated protein-2/55.11.

Molecular cloning of cDNA for a new regulatory subunit, designated p97, of the human 26S proteasome showed that the polypeptide consists of 908 amino acid residues with a calculated molecular mass of 100184 Da and an isoelectric point of 4.94. Computer analysis showed that p97 is very similar to type-1 tumor-necrosis-factor (TNF)-receptor-associated protein (TRAP)-2 and 55.11, both of which were identified recently as binding proteins of the cytoplasmic domain of type-1 TNF receptor by yeast two-hybrid screening. This finding suggests that the 26S proteasome might serve as a mediator molecule in the TNF signaling pathway in cells. Computer-assisted similarity analysis also revealed the high sequence similarity of p97 with a yeast protein whose function is yet unknown, the gene for which is here termed NAS1 (non-ATPase subunit 1). Disruption of NAS1 resulted in several phenotypes, including lethality and temperature-sensitive growth, depending on the genetic background of the cells used. The human p97 cDNA suppressed the growth defect of nas1 disruptant cells, when expressed from single-copy or multi-copy vectors, indicating that p97 is functionally equivalent to yeast Nas1p. Culturing of the temperature-sensitive nas1 cells at the restrictive temperature promoted the accumulation polyubiquitinated cellular proteins, implying that the 26S proteasome requires a functional Nas1p subunit for ubiquitin-dependent proteolysis. These results indicate that p97/Nas1p plays an important regulatory role in the function of the 26S proteasome.

Amino Acid Sequence↗