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Biomedical subjects

T Imai

Publications and source records attributed to T Imai.

At least 667 records · Page 37Linked to original sources

Structure of the bovine endothelin-B receptor gene and its tissue-specific expression revealed by northern analysis.

We have isolated and characterized the gene encoding the bovine endothelin (ET) receptor ETB with seven putative membrane-spanning domains. The gene exists as a single copy of the bovine genome and extends over 36 kilobases. The coding region is divided into seven exons separated by six introns; the first exon encodes the first and second transmembrane domains and each of the following transmembrane domains is encoded by a separate exon. The 5' region of the transcript was examined by the ribonuclease protection analysis; multiple start sites were deduced with no apparent "TATA" box in the expected upstream region. Northern blot analysis demonstrated a widespread but tissue-specific distribution of the ETB receptor in bovine tissues.

Amino Acid Sequence↗

Polymerase chain reaction-based DNA fingerprinting in the spontaneously hypertensive rat: potential source of cDNA library probes.

1. Using the Polymerase Chain Reaction with a primer homologous to a repetitive unit found at irregular distances in the rat genome, we were able to synthesize DNA fragments spanning such units and visualize them as a ladder of discrete bands following electrophoresis. 2. Differences between fingerprint patterns generated using SHR, WKY and SD DNA, in the form of band deletions or duplications, were readily detected. 3. Unlike traditional fingerprinting, PCR fingerprints allow the ready extraction and characterization of polymorphic bands. Such bands could then be used as probes with which to screen a cDNA library that might, in turn, identify expressed genes involved in the development of hypertension.

Animals↗

L-arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans.

1. The vascular endothelium produces endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of L-arginine (L-Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para-aminohippuric acid (PAH) and inulin was studied in five normal subjects. 2. Infusion of L-Arg (30 g) caused a significant fall in MBP (-8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters. 3. Neither L-Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7-fold) and after (1.9-fold) L-Arg infusion, but only slightly (1.3-fold) during saline infusion. 4. Urine flow increased more remarkably following L-Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after L-Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary Nox excretion showed positive correlations with urinary flow (r = 0.69, P less than 0.001) and with urinary cGMP excretion (r = 0.60, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Motor neuron disease with slow eye movements and vertical gaze palsy.

Two middle-aged patients with motor neuron disease showed common eye movement disorders and intellectual impairment in the later stage of the illness. Eye movement disorders were characterized by slow saccades and vertical glaze palsy, which seemed to be supranuclear ophthalmoplegia. Neuropathological examination of one patient revealed degeneration of the substantia nigra without pathological changes in the ocular motor nuclei, in addition to findings compatible with motor neuron disease. These cases appear to raise a possibility of a distinct group of multiple system degenerations.

Amyotrophic Lateral Sclerosis↗

[A case of miliary tuberculosis presenting as fever and jaundice with hepatic failure looking like the course of fulminant hepatitis].

A 79-year-old male was admitted to the Metropolitan Hiroo Hospital with chief complaints of icterus and fever. A few weeks prior to admission, he developed fever and swelling of right side of the neck and was seen at a local hospital where an anti-inflammatory agent was prescribed. The fever subsided in a few days, but recurred together with development of icterus a few weeks later, precipitating this hospitalization. After admission, hepatic failure progressed rapidly, indicating a fulminant hepatitis. Renal failure also developed and he died. Autopsy revealed diffuse caseous necrosis with demonstration of acid-fast bacilli in the liver, as did in the spleen, kidney and bone marrow. This case epitomizes a subset of miliary tuberculosis in which the hepatic failure predominates the clinical presentation while lacking the ante-mortem chest X-ray features suggestive of pulmonary tuberculosis and post-mortem macroscopic changes indicative of tuberculosis.

Aged↗

[The 5th report on long-term chemotherapy using erythromycin (EM) for chronic lower airway infection--cases followed over 7 years].

Clinical studies were made over 7 years on 9 cases to whom long-term chemotherapy with EM was administered for chronic airway infection. 1) Clinical effectiveness: Highly effective in 8 cases; Improvement in QOL was observed in 8 cases. Bacteriological effect: In 7 cases, pathogenic bacteria disappeared. 2) No side effects were observed. 3) Changes in PaO2 levels with the passage of time: In most cases, PaO2 reached a plateau within 1 year. Although in some cases, there was subsequent elevation. 4) The frequency of catching cold over the 7 years period was low with an average of 1.2 times/year per subject. In only 2 cases were subject hospitalized due to acute exacerbation triggered by a cold. 5) Mucociliary transport improved in 7 out of 8 cases examined. However, only 4 of these recovered normal transport. The effect of EM in the other cases in which clinical improvement was not demonstrated was deemed slightly effective. On the basis of the above findings, it was suggested that long-term chemotherapy using EM was clinically efficacious. This is based on the fact that its efficacy, including amelioration of QOL appeared within one year of the initiation of therapy, and continued without decline for over 7 years.

Administration, Oral↗

Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation: altered glycosylation of C33 antigen in HTLV-1-positive T cells.

We isolated four monoclonal antibodies (MAbs), M38, M101, M104, and C33, which were capable of inhibiting syncytium formation induced in a human T-cell line, MOLT-4-#8, by coculture with human T-cell leukemia virus type 1 (HTLV-1)-positive human T-cell lines. The MAbs had, however, no inhibitory activity on syncytium formation induced in a human osteosarcoma line, HOS, by HTLV-1-positive T-cell lines. They also did not inhibit syncytium formation induced in MOLT-4-#8 by human immunodeficiency virus type 1-positive MOLT-4. All MAbs reacted with various human cell lines of lymphoid and nonlymphoid origins, including HTLV-1-positive T-cell lines. Furthermore, they all reacted with a murine A9 clone containing human chromosome 11 fragment q23-pter. Two MAbs, M104 and C33, immunoprecipitated a membrane antigen with the same molecular size. The antigen (henceforth called C33 antigen) was about 40 to 55 kDa in HTLV-1-negative Jurkat, CEM, MOLT-4, and normal peripheral blood CD4-positive human T cells and about 40 to 75 kDa in HTLV-1-positive C91/PL, TCL-Kan, MT-2, and in fresh HTLV-1-transformed CD4-positive human T-cell lines. Pulse-chase experiments revealed that C33 antigen was synthesized as a 35-kDa precursor that was then processed to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL. In the presence of tunicamycin, a 28-kDa protein was synthesized. The conversion from 35 kDa to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL was inhibited by monensin. Treatment with N-glycanase alone, but not with sialidase and O-glycanase in combination, completely removed the sugar moiety of C33 antigen from both HTLV-1-negative Jurkat and HTLV-1-positive C91/PL. Therefore, C33 antigen has only N-linked carbohydrates, the modification of which appears to be substantially altered in the presence of the HTLV-1 genome.

Antibodies, Monoclonal↗

Mast cell response to formaldehyde. 2. Induction of stress-like proteins.

Previously we established that immediately after pretreatment with low concentrations (5-10 micrograms/ml) of formaldehyde antigen- and ionophore-induced histamine secretion was enhanced from peritoneal mast cells (PMC) isolated from rats infected with Nippostrongylus brasiliensis. In contrast to immediately following pretreatment with low concentrations of formaldehyde, 3 h after a 30-min treatment with formaldehyde (10, 50 and 100 micrograms/ml) antigen-induced histamine secretion from PMC was significantly depressed, and 35S-methionine incorporation was also decreased. To further explore the effects of formaldehyde on mast cells, we investigated protein biosynthesis of PMC following formaldehyde treatment and compared this with the effects of hydrogen peroxide (H2O2) or heat treatment. One- and two-dimensional SDS-PAGE were used to assess the effects. Formaldehyde treatment induced the synthesis of 70- and 72-kD stress-like proteins in rat PMC. Pretreatment of PMC with 50 microM H2O2 and heat (45 degrees C) also induced proteins with the same molecular weight. Two-dimensional SDS-PAGE analysis established that formaldehyde-induced 70-kD proteins had the same pI values as 70-kD heat shock proteins previously observed in mammalian cells. These results suggest that formaldehyde, H2O2 and heat shock induce stress proteins in rat PMC. It will be important to establish whether or not these stress proteins are responsible for the functional alterations observed in the mast cells.

Animals↗

Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells.

To elucidate the cellular mechanism of endothelin-1 biosynthesis induced by angiotensin and vasopressin, we first cloned and sequenced full-length bovine preproendothelin-1 complementary DNA (cDNA) from a cultured bovine carotid artery endothelial cell cDNA library. The predicted bovine preproendothelin-1 consists of 202 amino acid residues and has a high percentage of homology to human, porcine, and rat preproendothelin-1 (70%, 81%, and 77%, respectively). Big endothelin-1, an intermediate form, consists of 39 residues differing only at position Val28 from porcine (Ile28) and His27 from rat (Arg27). The predicted 21-residue mature endothelin-1 is identical to human, porcine, rat, canine, and mouse endothelin-1. Northern blot analysis with the cloned cDNA as a probe demonstrated that a single 2.3-kb preproendothelin-1 messenger RNA (mRNA) is expressed not only in endothelial cells, but also in various bovine tissues, including lung, brain, heart, intestine, kidney, ovary, and urinary bladder. Angiotensin II and arginine vasopressin immediately and dose-dependently induced expression of preproendothelin-1 mRNA, whose effects were abolished by specific receptor antagonists. These findings suggest that stimulation of endothelin-1 secretion from endothelial cells by both agonists may be principally due to induction of preproendothelin-1 mRNA.

Amino Acid Sequence↗

Synthesis and release of endothelin-1 by human decidual cells.

We have studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from human decidual cells in early pregnancy, and whether ET-1 acts directly on their own cells. It was observed that ET-1-like immunoreactivity (ET-1-LI) was released from cultured decidual, but not villous, cells, as a function of time. Reverse-phase high-pressure liquid chromatography of the conditioned media from the decidual cells revealed a major peak of ET-1-LI coeluting with standard ET-1. Phorbol myristate acetate, a protein kinase C activator, dose-dependently increased the release of ET-1-LI from the decidual cells, while a protein kinase C inhibitor, H7, significantly attenuated the stimulatory effect of phorbol myristate acetate on ET-1-LI release. Northern blot analysis demonstrated the expression of messenger RNA for prepro-ET-1 in the decidual tissue, but no such messenger RNA was observed in the villous tissue. The human decidual tissue contained a noninteracting, single class of binding sites demonstrating higher affinity for ET-1 and ET-2 than ET-3. This would be most consistent with the ETA receptor subtype. An ET-1-induced, dose-dependent accumulation of total inositol phosphates was also observed in human decidual cells prelabeled with myo-[3H]inositol. The present results demonstrate for the first time that human decidual cells in early pregnancy can synthesize and release ET-1. These cells also possess specific functional receptors for ET-1 which are coupled to phosphoinositide hydrolysis. Thus our data suggest a possible role for ET-1 in autocrine and/or paracrine function in human decidual cells.

Binding, Competitive↗

Enantioselective oral bioavailability of 0-isovaleryl propranolol as a potential prodrug of propranolol.

The enantioselective oral bioavailability of propranolol (PL) from 0-isovaleryl-PL was determined and compared with parent PL in beagle dogs. The bioavailability of the individual enantiomer from the prodrug increased about 2 fold. The AUC ratio between the S(-)- and R(+)-isomer posed at 0.89 which was statistically not different from that obtained after administration of PL alone. These features indicate that 0-isovaleryl-PL promises to be a potential prodrug of PL from the pharmacokinetic and pharmacodynamic point of view.

Administration, Oral↗

Study of interaction of pranoprofen with human serum albumin: binding properties of enantiomers and metabolite.

The interaction of pranoprofen, pranoprofen glucuronide and pranoprofen methylester with human serum albumin (HSA), was investigated by equilibrium dialysis and spectroscopic techniques. The binding affinities of pranoprofen glucuronide and pranoprofen methylester to HSA were found to be almost the same, although they were remarkably small as compared to that of the parent compound, pranoprofen. Pranoprofen and pranoprofen methylester showed stereoselective affinities to HSA. It was found from the competitive displacement experiments using the fluorescent probes that the specific binding site for pranoprofen was site II, the diazepam site, and that the binding sites of pranoprofen glucuronide and pranoprofen methylester were site I, the warfarin site. In addition, from the binding data with modified HSA, it seemed that tyrosine-411 was specifically involved in the pranoprofen binding. The absorption spectral changes which accompanied the binding of pranoprofen and pranoprofen methylester to HSA or detergents implied that the HSA binding site of pranoprofen consisted of a cationic site on the surface of the albumin molecule with a hydrophobic region to accommodate the aromatic ring and that the binding site for pranoprofen methylester seemed to occupy a wide hydrophobic area. These limited data indicated differences in the location and microenvironments of binding sites for pranoprofen and its glucuronide on the HSA molecule.

Anti-Inflammatory Agents, Non-Steroidal↗

[The effects of long-term intake of a low concentration of sodium fluoride on bone loss in the growing senescence-accelerated mouse (SAM-P/6)].

The long-term effects of low concentrations of sodium fluoride (0, 1 and 5 mg/l) in drinking water on bone metabolism were examined in the growing senescence accelerated mouse (SAM-P/6) as a spontaneous experimental model of senile osteoporosis. In 4 and 8 months of age respectively, there were almost no differences in body weight, and serum calcium, phosphorus and alkaline phosphatase levels between controls and fluoride groups. Calcium contents per dry weight of femoral bone were higher in fluoride groups than in controls. The bone mass of the trabecular was not affected by the low-concentration sodium fluoride intake. However, sodium fluoride decreased the rate of bone mass loss associated with aging in the cortical bone in SAM-P/6 compared with the control. The results of this study suggest that, in growing SAM-P/6 mice, a long-term low-concentration sodium fluoride intake affects the skeletal metabolism.

Animals↗

Combined dose ratios of dopamine and dobutamine and right ventricular performance after cardiac surgery.

The effect of combined administration of different dose ratios of dobutamine (DB) and dopamine (DA) (DB/DA ratio of 1:1; 1.5:0.5; 2:0; 0.5:1.5; and 0:2), with the added dose kept constant (10 micrograms/kg/min-20 micrograms/kg/min), on right ventricular function (measured by the thermal washout method with the aid of a rapid-response thermistor) was determined in ten patients after cardiac surgery (between 12 and 24 h after surgery). The following values represent the mean +/- SD of DB only and of the DB/DA-equal combination vs DA only. The DB/DA-equal or DB-dominant combination increased the right ventricular ejection fraction vs DA only (0.39 +/- 0.12 [p less than 0.01] and 0.37 +/- 0.11 [p less than 0.05], respectively, vs 0.32 +/- 0.12) and the stroke volume index (43 +/- 12 ml/m2 [p less than 0.01] and 41 +/- 15 ml/m2, respectively, vs 38 +/- 14 ml/m2) and decreased right ventricular end-diastolic pressure (RVEDP) (10 +/- 4 mm Hg [p less than 0.01] and 11 +/- 4 mm Hg [p less than 0.05], respectively, vs 13 +/- 5 mm Hg) and pulmonary capillary wedge pressure (10 +/- 4 mm Hg [p less than 0.01] and 12 +/- 5 mm Hg [p less than 0.05], respectively, vs 14 +/- 6 mm Hg) to the same degree as DB alone. The DB/DA-equal or DB-dominant combination did not induce tachycardia (heart rate, 105 +/- 11 [p less than 0.05] and 95 +/- 14 beats per minute, respectively, vs 90 +/- 17 beats per minute) or have any effect on the right ventricular end-diastolic volume index (RVEDVI) (115 +/- 30 ml/m2 and 117 +/- 33 ml/m2, respectively, vs 127 +/- 42 ml/m2). Moreover, the diastolic parameters of the right ventricle (the ratio of RVEDVI/RVEDP: 15 +/- 8 [p less than 0.05] and 13 +/- 7, ml/mm Hg/m2, respectively, 11 +/- 5 ml/mm Hg/m2) decreased as the ratio of DA increased. This change in the diastolic properties of the right ventricle might have been caused by release of norepinephrine in the myocardium by DA or by improved coronary perfusion with DB. The DB/DA-equal and DB-dominant combinations were superior to DB or DA alone and to the DA-dominant combination in obtaining enhanced right ventricular performance.

Adult↗

ACTH increases expression of c-fos, c-jun and beta-actin genes in the dexamethasone-treated rat adrenals.

Our recent finding that ACTH increases c-fos mRNA in the adrenal gland of hypophysectomized rats indicates that the gene product FOS may play an important role(s) in mediating the action of ACTH. However, hypophysectomy employed in that study causes the disappearance of trophic hormones other than ACTH and may modify the effect of ACTH. Thus, in the present investigation, dexamethasone-treated rats were used. Since FOS functions only when it dimerizes with JUN (the product of c-jun gene), the changes in the levels of c-fos and c-jun mRNAs were studied together with that of beta-actin mRNA which is also affected by ACTH. Northern blot analysis was employed to determine the mRNA levels. It was demonstrated that ACTH increases the mRNAs coding c-fos and c-jun in the adrenal glands of dexamethasone-treated, ACTH-suppressed rats. The c-fos mRNA was not detectable before ACTH administration. After ACTH administration, the mRNA levels were transiently increased, the maximum level being observed at 30 min after ACTH. At 180 min post ACTH, the level returned to the unstimulated level. The mRNA coding c-jun was detectable before ACTH administration and it also increased rapidly after ACTH with maximal stimulation at 30 min. However, the mRNA level at 180 min post ACTH was still higher than the unstimulated level. The changes in beta-actin mRNA were approximately the same as those of c-jun mRNA. These results suggest that increased expression of c-fos, c-jun and beta-actin genes by ACTH may play an important role in mediating its action on the adrenals.

Actins↗

[Intraoperative blood recovery in transurethral resection of prostate (TURP)].

Blood collected from irrigating fluid in TURP was studied if it was appropriate blood as autologous transfusion or not. TURP was performed aided by continuous irrigation through suprapubic cystostomy. The cystostomy tube was connected to the Shiley STAT or Haemonetics Cell Saver in 15 patients. The average weight of resected adenoma was 36 g per patient. The product of washed blood gave an average yield of 440 ml per patient with an average RBC count of 469 x 10(3)/mm3, hemoglobin of 14.6 g/dl, hematocrit of 44.8%, platelets of 15400/mm3. The half-life of collected red blood cells tagged with 55Cr was 22 days. The urine in 10 patients (67%) were contaminated with bacteria before TURP, and 3 of collected blood were contaminated with bacteria (20%). As for carcinoma cells, cultured urinary bladder carcinoma cells (T24) and renal carcinoma cells (ACHN) were completely eliminated after filtration through leukocyte removal filter Sepacell or Pall RC. As results, the intraoperatively collected blood from irrigating fluid in TURP was useful and safe as autologous blood transfusion.

Blood Transfusion, Autologous↗

[Autologous blood retransfusion in transurethral resection of prostate (TURP)].

UNLABELLED: Blood collected from the irrigation fluid used during TURP was retransfused in 17 patients. Of the 17 patients, 8 cases were also transfused preoperatively reserved blood. The weight of resected adenoma (g), resection time (minutes), the volume of salvaged blood (ml) of 9 cases who were transfused only salvaged autologous blood were 30.6 g, 63 min. and 355 ml, respectively, and those of 8 patients who were given both salvaged and preoperatively reserved autologous blood were 46.1 g, 78 min. and 703 ml, respectively. No patient was transfused homologous blood. Preoperative urine cultures showed contamination of bacteria in 12 cases (70.6%), and the blood concentrated from irrigated fluid was positive for bacteria in 2 cases (11.8%). Blood count (RBC, Hb, Ht) just after TURP, after blood retransfusion, at the next and the 7th day after the operation were compared to those of just before TURP (Blood Count Ratio). The ratio of the 9 cases who received only salvaged blood were 83.5%, 96.8%, 90.9%, 85.2% each and the ratio of the 8 cases who were transfused both salvaged and preserved blood were 86.9%, 102.6%, 101.4%, 97.5% each. There were no adverse effects due to the autologous blood retransfusion. CONCLUSION: Retransfusion of salvaged autologous blood from the irrigating fluid of TURP was clinically safe and effective. No homologous blood was transfused in TURP when salvaged autologous blood with or without preserved blood was retransfused to the patient.

Blood Transfusion, Autologous↗