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Biomedical subjects

T Naitoh

Publications and source records attributed to T Naitoh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hand-assisted laparoscopic digestive surgery provides safety and tactile sensation for malignancy or obesity.

BACKGROUND: Some of the persistent problems associated with laparoscopic surgery stem from the inability of the surgeon to palpate the abdominal contents during the operation. This lack of tactile sensation can lead to poor abdominal exploration, difficulty in extracting the organs, and a relatively long operation time compared to conventional procedures. The Dexterity Pneumo Sleeve is a new device that allows the surgeon to insert his or her hand into the abdominal cavity through a small incision while preserving the pneumoperitoneum. METHODS: Recently, 13 of our patients underwent hand-assisted advanced laparoscopic surgery using this device. In this series, we had two cases of gastrectomy, two cases of gastric bypass for morbid obesity, two Whipple cases for periampullary tumor, and seven cases of bowel resection. On the basis of this series, we were able to assess the utility of this device. RESULTS: Satisfactory pneumoperitoneum was maintained in 12 of 13 cases. The length of the skin incision was 7.8 cm on average, which was almost the same size as surgeon's glove. The device proved to be very useful for tissue retraction and abdominal exploration in all cases and for intracorporeal knot tying in some cases. CONCLUSIONS: We found that the device permitted an easier dissection, resection, and anastomosis. It also helped to decrease the operation time.

Adult↗
PubMed1999

Molecular characterization and functional regulation of a novel rat liver-specific organic anion transporter rlst-1.

BACKGROUND & AIMS: Recently, we isolated a new complementary DNA (cDNA) encoding human liver-specific organic anion transporter (LST-1), representing the multispecificity of human liver. The aim of this study was to isolate a rat counterpart of human LST-1 and examine the expression regulation of its messenger RNA (mRNA) to clarify the molecular basis of cholestasis. METHODS: A rat liver cDNA library was screened with human LST-1 cDNA as a probe. Xenopus oocyte expression system was used for functional analysis. Northern blot analyses were performed using the isolated cDNA (termed rlst-1). The bile duct ligation model and the cecum ligation and puncture model were used for expression analyses. RESULTS: rlst-1 encodes 652 amino acids, predicting at least 11 transmembrane regions. The overall homology with human LST-1 was 60.2%, which is the highest among all known organic anion transporters. rlst-1 also belongs to the same new gene family as human LST-1, located between the organic anion transporter family and the prostaglandin transporter. rlst-1 preferably transports taurocholate (K(m), 9.45 micromol/L) in an Na(+)-independent manner. The rlst-1 mRNA is exclusively expressed in the liver. In both the bile duct ligation model and the cecum ligation and puncture model, mRNA expression levels of rlst-1 were down-regulated. CONCLUSIONS: rlst-1 is a counterpart of human LST-1 and is one of the important transporters in rat liver for the clearance of bile acid. The expression of rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.

Amino Acid Sequence↗
PubMed1999

Allometry in vestibular responses of anurans.

Frogs and toads turn either their heads or bodies opposite to angular accelerations applied around the yaw axis. Thresholds exist for the minimum angular acceleration that induces this vestibulomotor response in individual frogs. These thresholds were recorded for several anuran species that cover a broad range of sizes and life styles. Interspecific variation in the magnitude of the thresholds, which correlated with the ecology and behavior of the species, was documented. Also an allometric relationship was observed between this threshold and body size; the larger the frog, the lower the threshold. In many species, the threshold value for reflexive vestibulomotor responses to angular acceleration was proportional to the -0.4 (+/-0.2) power of body mass. Physical dimensions of the semicircular canals determine, in part, vestibular sensitivity to angular acceleration. Hence changes with growth in the semicircular canals are believed to contribute to the slope of -0.4. The biological significance of this allometry in vestibular responses is discussed and compared to trends in vestibular sensitivity and semicircular canal morphology of other vertebrate classes.

Acceleration↗
PubMed1998

Endoscopic endocrine surgery in the neck. An initial report of endoscopic subtotal parathyroidectomy.

BACKGROUND: The fervor surrounding minimally invasive surgery, which began with laparoscopic cholecystectomy in the late 1980s, has spread to nearly all surgical specialties. METHODS: After experimental success in an animal model, we recently performed our first case of endoscopic subtotal parathyroidectomy in a 37-year-old man. The patient, who had a history of severe pancreatitis and pancreatic calculi, was diagnosed as having hyperparathyroidism. The option of endoscopic parathyroidectomy was proposed and accepted. After placing the first trocar directly under the platysma, a space was created by bluntly dissecting with the tip of a 5-mm endoscopic camera. Four parathyroid glands were identified, and after a frozen-section diagnosis of parathyroid hyperplasia, three-and-one-half of the glands were resected. RESULTS: The patient developed slight hypercarbia and subcutaneous emphysema during the procedure, but no other problems were noted. His postoperative course was otherwise unremarkable. CONCLUSIONS: This is the first case reported of an endoscopic parathyroidectomy. This experience makes us optimistic about the future of endoscopic neck surgery.

Adult↗
PubMed1998

Inhibitor and temperature effect on catalase in the liver of adult diploid and haploid Rana rugosa.

The authors succeeded in raising a single mature haploid Rana rugosa female to the age of 2 years from an egg artificially fertilized with ultraviolet-irradiated sperm. In order to discover why this particular haploid individual should survive so long, hydrogen peroxide detoxifying catalase in the liver of this individual and age-matched diploids was examined and compared for total activity, temperature stability, and chemical inhibition. Total activity was found to be significantly higher in the haploid frog than in the diploids, suggesting that this particular haploid had a unique system for hydrogen peroxide detoxification which protected the liver against cell death, preventing hepatic failure, and leading to a prolonged survival. Liver catalase from the haploid proved to be more labile to aminotriazole and urea, losing 60-70% of its original activity after 30 min treatment, whereas diploid catalase lost only 40% under the same conditions. Haploid and diploid catalase responded similarly to heat, however. It seems likely that inhibitor-binding sites differ considerably between the catalase of normal diploids and the catalase of this particular haploid, while overall structure is generally similar.

Amitrole↗
PubMed1998

Species differences and mechanism of the epimerization of a new MAO-A inhibitor.

1. (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl-2-oxazolidinone (E2011) has two chiral centers in its structure. In vivo optical inversion of the hydroxy group at one of the chiral centers converts E2011 to a diastereoisomer (ER-20593). Pharmacokinetic parameters of E2011 and ER-20593 were determined after administration of E2011 to rat at 10 mg/kg, and the plasma concentration ratios of E2011 to ER-20593 were almost constant after Tmax of the plasma concentrations. 2. E2011 and ER-20593 were separately administered orally to six species in addition to rat, and the species differences in both directions of epimerization (i.e. from E2011 to ER-20593 and from ER-20593 to E2011) were studied by measuring the plasma concentrations of both compounds. In mouse, guinea pig, dog, and squirrel monkey, the epimerization of E2011 to ER-20593 did not occur, but the epimerization of ER-20593 to E2011 did. In rat, pig and rhesus monkey, the inversion of E2011 to ER-20593 occurred, but the ratios of this inversion were smaller than those for the inversion in the opposite direction. E2011 underwent about 15% inversion to ER-20593 in rat, which was the largest inversion in the seven species examined. 3. To study the mechanism of the epimerization, deuterium-labelled E2011 and ER-20593 (created by substituting the proton at the chiral center of the parent compounds for deuterium) were orally administered (separately) to rat and dog, and the concentration ratios and molecular weights of E2011 and ER-20593 in the plasma were determined by hplc and FAB(+)-mass spectrometry respectively. The results indicated that the major mechanism of the epimerization was oxidation to the carbonyl form followed by reduction to the original epimer and/or the other epimer. 4. The carbonyl form of E2011 (CO-E2011) was reduced to E2011 and ER-20593 (alcohol forms) by liver cytosol and microsomes from rat and dog in vitro with NADH or NADPH. The resultant epimeric ratios (E2011:ER-20593) were consistent with the in vivo results in rat and dog. 5. In conclusion, species differences in the epimerization of E2011 would result from product stereoselectivity of the reductase activity with the carbonyl intermediate.

Administration, Oral↗
PubMed1998

A porcine model for laparoscopic ventral hernia repair.

Ventral hernia repair is one of the most common abdominal operations. Recurrence rate remains high despite all preventive measures. "Tension-free" repair has been postulated as the surgical method of choice. A laparoscopic approach to ventral hernia repair has been described recently. Theoretical advantages of a laparoscopic repair include faster recovery, less postoperative pain, less morbidity, and a better cosmetic result. However, the approach requires advanced laparoscopic skills and familiarity with its technique. An animal model of ventral hernia, suitable for laparoscopic repair, was developed to be used for educational and experimental purposes. The model is simple, reliable, and reproducible in any minimally invasive surgery facility. We conclude that the pig can be used as an excellent model to learn the technique and evaluate a variety of endpoints for laparoscopic ventral hernia repair.

Animals↗
PubMed1997

Stereoselective determination of a new antidepressant, E2011, and its diastereoisomer as a metabolite by high-performance liquid chromatography.

A stereoselective HPLC method has been developed for the determination of E2011 (compound I) and one of its metabolites and diastereoisomers, ER-20593 (compound II), in plasma. The two substances and the internal standard were extracted from plasma, followed by two purification steps. In the first step, a minicolumn, Bond Elut C18, was used and in the second step, another minicolumn, Bond Elut Si, was used for purification of the compounds. After the purification, the compounds were analyzed by HPLC with two Chiralpak AD columns. In this procedure, compounds I and II were stable and there was no chiral inversion. The within-day and the between-day assays were performed in rat plasma, where compounds I and II existed simultaneously. The within-day and the between-day precisions of compound I were 2.0 approximately 10.1% and 1.3 approximately 7.1%, and the within-day and the between-day accuracies were -8.2 approximately +3.0% and -6.6 approximately +4.0% in the concentration range 0.003-10 microg ml(-1). The within-day and the between-day precisions of compound II were 1.7 approximately 16.9% and 0.9 approximately 4.5% and the within-day and the between-day accuracies were -9.0 approximately +2.4% and -5.6 approximately +3.8% in the concentration range of 0.005-0.5 microg ml(-1). QC samples for compound I and II were stable for at least 3 months. The method was applied to measure the levels of compound I and II in the rat plasma after oral administration of compound I.

Animals↗
PubMed1997

Laparoscopically assisted gastric surgery using Dexterity Pneumo Sleeve.

BACKGROUND: Laparoscopic surgery has been successfully applied to several gastrointestinal procedures. Although the totally laparoscopic gastrectomy is feasible, tactile sensation and manipulation of the organ as well as the lesion are decreased when compared to open surgery. The Dexterity Pneumo Sleeve is a new device which allows the surgeon to insert a hand into the abdominal cavity while preserving the pneumoperitoneum. This device was used for patients who underwent laparoscopic gastric surgery. METHODS: The first patient presented with a non-Hodgkin's lymphoma of the stomach. A laparoscopically assisted distal gastrectomy was performed with Roux-en-Y reconstruction. The second patient had a 5-cm leiomyoma involving the greater curve of the stomach, and this device was used for manipulation of the tumor. The last patient suffered from morbid obesity with its associated medical complications and a ventral hernia. The Sleeve was applied at the hernia site and a laparoscopically assisted gastric bypass was performed. RESULTS: The Pneumo Sleeve was useful in these cases for tactile localization of the tumor and for retraction and manipulation of the stomach and surrounding upper abdominal organs. CONCLUSIONS: The utilization of this device resulted in a more easily performed dissection, resection, and anastomosis and was felt to decrease operation time.

Adult↗
PubMed1997

Limb allografts in rats treated with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.

This study examined whether administration of anti-ICAM-1 mAb (monoclonal antibody) and anti-LFA-1 mAb were effective for inhibition of the acute rejection reaction in a rat-limb allograft model. The grafts were carried out using major histocompatibility complex mismatch pairs of rats: ACI rats as the donors and Lewis rats as the recipients. The subjects were of species with completely different major histocompatibility complexes. The average length of survival in this combination was 4.7 +/- 0.6 days. When anti-ICAM-1, anti-LFA-1 mAb, or a combination of both were administered intraperitoneally at 1 mg/kg body weight daily for 7 days after the graft, the mean survival times were 4.3 +/- 0.6, 4.7 +/- 0.6, or 4.7 +/- 0.6 days, respectively. The agents were found to exercise no beneficial effects for transplants. Transplants were then carried out with a single intramuscular administration of FK506 at 3mg/kg body weight on the day of the operation to observe the effect of this adjunct therapy. The mean survival time averaged 16.0 +/- 5.5 days with FK506 alone. Administration of anti-ICAM-1, anti-LFA-1, and both antibodies together with FK506 resulted in mean survival times of 15.4 +/- 3.0, 25.0 +/- 5.8 and 13.2 +/- 5.8 days, respectively. Thus, a significant prolongation of survival time was observed when the combination of anti-LFA-1 mAb and FK506 was used. In contrast, anti-ICAM-1 mAb and FK506 or both mAb and FK506 showed no beneficial effects.

Animals↗
PubMed1997

Absorption, distribution, metabolism and excretion of a new, 14C-labelled oxazolidinone MAO-A inhibitor in rat and dog.

1. After oral administration of 14C-labelled (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-metho xymethyl -2-oxazolidinone (E2011) at a dose of 1 mg/kg, the blood level of radioactivity reached a maximum concentration (Cmax) of 0.545 microgram eq./ml after 0.25 h in the rat and of 0.900 microgram eq./ml after 0.5 h in the dog. In dog plasma, Cmax for radioactivity and unchanged E2011 were 0.862 microgram eq./ml and 0.650 microgram/ml respectively with corresponding Tmax (time at Cmax) of 0.75 and 0.25 h. The unchanged drug in dog plasma was below the detection limit (5 ng/ml plasma) after 24 h. 2. The tissue levels of radioactivity were measured at 0.25 (Tmax), 6, 24, and 168 h after administration to the rat and at 0.5 (Tmax), 24, and 168 h in the dog. The radioactivity was distributed in all tissues examined at Tmax in the rat and dog. The radioactivity levels of the cerebral cortex in the rat and dog were 26 and 36% of the plasma level at Tmax. The radioactivity in tissues decreased at almost the same rate as that in plasma. Plasma protein binding of the unchanged drug in the rat in vitro were about 70% in the range of 0.1-10 micrograms/ml, and those in the dog were about 45% in the same concentration range. 3. Cumulative excretion of radioactivity in the rat was 74.5% in urine and 22.5% in faeces after 7 days. In the dog, 55.5 and 36.5% of the radioactivity administered were excreted in urine and faeces respectively after 7 days. The biliary excretion of radioactivity in the cannulated rat was 23.0% within 48 h. 4. In tlc analysis of plasma and tissues of the rat and dog, the radioactivity for the unchanged drug was much higher than metabolites. In tlc analysis of urine, the same metabolites were detected in the rat and dog, and the radioactivity of a metabolite, IM1, was the highest in the both animals. Eight metabolites were detected in the plasma, tissues and excreta of the rat, and four metabolites in the dog. 5. In conclusion, the absorption, distribution, metabolism and excretion of 14C-labelled E2011 in the rat and dog have been established, and only minor differences were observed between these species.

Absorption↗
PubMed1997

Identification of the metabolites of a new oxazolidinone MAO-A inhibitor in rat.

1. Six metabolites present in rat urine after the oral administration of E2011 ((5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5-meth oxymethyl-2- oxazolidinone) were isolated with an Amberlite XAD-4 column and hplc, and termed HPM-1, HPM-2, HPM-31, HPM-32, HPM-33 and HPM-4. 2. To determine the correspondence of the findings of the metabolites between tlc (which was used in our previous study) and hplc, the six metabolites were isolated from rat urine after the administration of 14C-labelled E2011 with an Amberlite XAD-4 column and hplc, and then analysed by tlc. HPM-1, HPM-2, HPM-31, HPM-32, HPM-33 and HPM-4 were identified as IM7, IM3, IM4, IM2, IM1 and E2011, respectively. 3. The structures of the metabolites were identified with nmr and mass spectrometry. One of the compounds identified, HPM-4, was the unchanged drug, E2011, and HPM-2 was O-desmethyl-E2011. Another metabolite (HPM-33), the main metabolite in the urine, was identified as (4S)-hydroxy-E2011, and the others were (4S)-hydroxy-O-desmethyl-E2011 (HPM-1), 2"-hydroxy-E2011 (HPM-31) and (4R)-hydroxy-E2011 (HPM-32). 4. In conclusion, the main metabolic pathway of E2011 in the rat consisted of O-demethylation and hydroxylation.

Animals↗
PubMed1997

Effects of specific antagonists of angiotensin II receptors and captopril on diabetic nephropathy in mice.

We investigated whether angiotension II was involved with diabetic nephropathy in the mouse model. Twelve days after streptozotocin (STZ) injection, the urinary albumin excretion (UAE) level was increased by 118% of the baseline value. On days 21, 28, 35 and 42 after STZ injection, the UAE levels were significantly increased compared with the level at day 12. A marked elevation of creatinine clearance and diabetic-induced renal hypertrophy were also observed on day 49 after STZ injection. The 35-day treatments of captopril and Dup 753 (angiotensin II type 1 receptor antagonist) significantly attenuated the increment of UAE levels (26.4% on day 14 and 34.6% on day 28). PD123177 (angiotensin II type 2 receptor antagonist) also attenuated the increment of UAE (24.7% on day 14) at the dose of 150 mg/kg. Furthermore, Dup 753 partially prevented diabetic-induced renal hypertrophy. These results suggest that angiotensin II type 2 receptor as well as type 1 receptor may be involved in the development of diabetic nephropathy in the STZ-induced diabetic mice, and these mice are beneficial models of early diabetic nephropathy.

Albuminuria↗
PubMed1997

The Frog in Space (FRIS) experiment onboard Space Station Mir: final report and follow-on studies.

The "Frog in Space" (FRIS) experiment marked a major step for Japanese space life science, on the occasion of the first space flight of a Japanese cosmonaut. At the core of FRIS were six Japanese tree frogs, Hyla japonica, flown on Space Station Mir for 8 days in 1990. The behavior of these frogs was observed and recorded under microgravity. The frogs took up a "parachuting" posture when drifting in a free volume on Mir. When perched on surfaces, they typically sat with their heads bent backward. Such a peculiar posture, after long exposure to microgravity, is discussed in light of motion sickness in amphibians. Histological examinations and other studies were made on the specimens upon recovery. Some organs, such as the liver and the vertebra, showed changes as a result of space flight; others were unaffected. Studies that followed FRIS have been conducted to prepare for a second FRIS on the International Space Station. Interspecific diversity in the behavioral reactions of anurans to changes in acceleration is the major focus of these investigations. The ultimate goal of this research is to better understand how organisms have adapted to gravity through their evolution on earth.

Acceleration↗