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Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 829 records · Page 46Linked to original sources

Giant cell glioblastoma in the frontal cortex of a dog.

A dark gray mass 3 cm in diameter replacing the right frontal cortex was found in the brain of a 5-year-old male Doberman Pinscher dog at necropsy. Microscopic studies revealed that the mass consisted of a proliferation of pleomorphic tumor cells: large bizarre or plump eosinophilic cells, multinucleated giant cells, and small lymphocytic cells. These neoplastic cells at the margin of the necrotic area had a psuedopalisade arrangement and tended to proliferate around blood vessels. Immunohistochemically, the tumor cells reacted intensely with the antibody for vimentin and moderately with those for S-100 and glial fibrillary acidic protein. This canine tumor is placed in the category of glioblastoma or undifferentiated astrocytoma, which is analogous to human giant cell glioblastoma.

Animals↗

Solution-phase synthesis of an anti-human immunodeficiency virus peptide, T22 ([Tyr5,12,Lys7]-polyphemusin II), and the modification of Trp by the p-methoxybenzyl group of Cys during trimethylsilyl trifluoromethanesulfonate deprotection.

T22 ([Tyr5,12,Lys7]-polyphemusin II) was previously synthesized by a solid-phase method and was found to have a strong anti-human immunodeficiency virus (HIV) activity, comparable to that of 3'-azido-2',3'-dideoxy-thymidine (AZT). In the present study, the solution-phase synthesis of T22 was attempted in order to produce this peptide on a large scale. An 18-residue peptide amide corresponding to the entire amino acid sequence of T22 was synthesized by assembling four peptide fragments and two amino acid derivatives, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf) in trifluoroacetic acid followed by air-oxidation. During this deprotection, a significant by-product derived from the transfer of the p-methoxybenzyl (MBzI) group from the sulfhydryl group of the cysteine residue to the side chain of the tryptophan residue was formed. This side reaction was found to be efficiently suppressed by adopting a two-step deprotection procedure using silver trifluoromethanesulfonate (AgOTf)-TMSOTf or trimethylsilyl bromide (TMSBr)-TMSOTf.

Amino Acid Sequence↗

Medicinal foodstuffs. I. Hypoglycemic constituents from a garnish foodstuff "taranome," the young shoot of Aralia elata SEEM.: elatosides G, H, I, J, and K.

Five new saponins named elatosides G, H, I, J, and K were isolated from a garnish foodstuff "Taranome," the young shoot of Aralia elata SEEM., together with hederagenin-3-O-glucuronopyranoside and elatoside C. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. Elatosides G, H, and I were found to exhibit potent hypoglycemic activity in the oral glucose tolerance test in rats.

Analysis of Variance↗

Bioactive saponins and glycosides. I. Senegae radix. (1): E-senegasaponins a and b and Z-senegasaponins a and b, their inhibitory effect on alcohol absorption and hypoglycemic activity.

E-Senegasaponins a, b, and c were isolated from Senegae Radix, the root of Polygala senega L. var. latifolia TORREY et GRAY, together with their Z-isomers of the 4"-methoxycinnamoyl moiety, Z-senegasaponins a, b, and c. The structures of E-senegasaponins a and b and Z-senegasaponins a and b have been elucidated on the basis of chemical and physicochemical evidence, and the geometrical isomeric structure of the 4"-methoxycinnamoyl group in each saponin was found to show tautomer-like behavior in methanol solution or under irradiation with fluorescent lamps. E and Z-Senegasaponins a and b were found to exhibit potent inhibitory effects on alcohol absorption and hypoglycemic activity in the oral D-glucose tolerance tests in rats, and some structure-activity relationships of the acylated bisdesmoside-type saponins were clarified.

Animals↗

E-senegasaponins A and B, Z-senegasaponins A and B, Z-senegins II and III, new type inhibitors of ethanol absorption in rats from senegae radix, the roots of Polygala senega L. var latifolia Torrey et Gray.

New inhibitors of ethanol absorption, E-senegasaponins a and b, Z-senegasaponins a and b, Z-senegins II and III, were isolated from Senegae Radix, the roots of Polygala senega L. var latifolia Torrey et Gray, together with senegins II and III. Their chemical structures have been elucidated on the basis of chemical and physicochemical evidence, and the geometrical isomeric structures of methoxycinnamoyl moiety in each saponin were found to show tautomer-like behavior. The inhibitory effects of senegasaponins, senegins, and their related compounds have been examined, and some structure-activity relationship have been found.

Animals↗

Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity.

All disulfide analogs (types I, II and III) of protegrin (PG)-1, an 18-residue antimicrobial peptide having two intramolecular disulfide bonds, were synthesized using regioselective disulfide bond formation. Random air-oxidation of the fully reduced PG-1 formed the type III PG-1. In addition, a type III analog containing an amidated carboxy-terminal residue was also prepared. Each analog showed significant and different antibacterial and anti-human immunodeficiency virus (HIV) activity. Deletion of two disulfide bridges caused a significant decrease in activity.

Amino Acid Sequence↗

[Examination of toxin production from environmental Bacillus cereus and Bacillus thuringiensis].

Emetic toxin- and entero toxin-producing activities were examined for 524 strains of Bacillus cereus and 90 strains of Bacillus thuringiensis to determine the distribution and contamination in natural environment, including foods, vegetable, soil and etc. Emetic toxin was assayed by the production of acid from HEp-2 cells induced by the culture supernatants of Bacillus, which was developed as an improved method for the detection of B. cereus heat-stable emetic-toxin by us. In the 524 strains of B. cereus tested, 11 out of 60 strains obtained from bean paste and 5 out of 20 strains obtained from peach produced emetic toxin which was detected by the HEp-2 cell method. All these emetic toxin-producing isolate strains were classified into H1 serotype. The 90 strains of B. thuringiensis did not produce emetic toxin, but the 47 strains produced entero toxin.

Bacillus cereus↗

Prediction of stroke lesions in stroke-prone spontaneously hypertensive rats by glutathione peroxidase in erythrocytes.

The incipient timing of cerebral strokes in the stroke-prone spontaneously hypertensive rats (SHRSP) was biochemically determined by investigating the relationship between the glutathione peroxidase (GSH-Px) activity in erythrocytes and the extent of stroke lesions. When the blood pressure of SHRSPs was maintained at over 240 mmHg, the GSH-Px activity fell, and the body weight also decreased. In SHRSP whose GSH-Px activity in erythrocytes had dropped below 23 units/ml of blood, the incidence of cerebral strokes was 98% (n = 88/90). The hematocrit level did not change even after the GSH-Px activity had dropped to 23 units/ml of blood. The reduced GSH-Px activity in erythrocytes observed during continued hypertension was found to be due to a decrease in GSH-Px protein, and not to any inactivation of the enzyme, as evident from immunochemical titration. At the moment when the GSH-Px activity had dropped to 23 units/ml of blood, and the control diet was changed to one based on fish or a hydralazine treatment given, the activity recovered, and an increase in body weight and prolongation of the life-span were observed. It was deduced from these findings that tracing the GSH-Px activity in erythrocytes in SHRSP would serve as an indicator for predicting and prognosing stroke lesions.

Animals↗

Mechanism of hypertension induced by chronic inhibition of nitric oxide in rats.

In order to clarify the mechanism of hypertension induced by a nitric oxide (NO) synthase inhibitor, L-NG-nitro-L-arginine (LNNA), metabolites of NO, catecholamines, and hemodynamic parameters were measured during 7 days of oral administration of LNNA in rats. Control rats received either L-arginine (L-Arg) or the vehicle. systolic blood pressure, measured by the tall-cuff method was elevated throughout the period of LNNA administration, but that in the two control groups was not influenced by treatment. Heart rate decreased on the second day only in LNNA-treated rats. Although L-Arg treatment had no influence, LNNA markedly decreased the plasma level and the urinary excretion of nitrate ions (NO-3). Urinary excretion of noradrenaline was significantly decreased on the second day of LNNA administration and returned to the control level thereafter. When hemodynamic changes were measured by using radioactive microspheres, LNNA was found to increase blood pressure by markedly increasing total peripheral resistance. Cardiac output was decreased by LNNA. L-Arg, again, did not influence the hemodynamic variables as compared with the vehicle control group. The regional vascular resistance index was increased by LNNA in many tissues and organs, except the brain and the heart. Regional blood flow, on the other hand, was significantly decreased only in the liver and skin by LNNA. The marked reduction in NO3- in urine by LNNA-treatments may indicate that the measured NO3- is exclusively of endogenous origin, and that inhibition of NO production causes elevation of blood pressure by constricting peripheral arteries. Sympatholytic responses by the baroreceptor reflex were thereby evident only on the second and the third days, which was indicated by bradycardia and suppression of noradrenaline excretion into urine. These results indicate that the inhibition of NO synthase actually decreases production of endogenous NO, and that the hypertension caused by decreases in NO production is due to elevation of total peripheral vascular resistance.

Animals↗

Effect of glycemic control on calcium and phosphorus handling and parathyroid hormone level in patients with non-insulin-dependent diabetes mellitus.

The present study was undertaken to determine whether improvement of hyperglycemia alters calcium and phosphorus handling, parathyroid hormone (PTH) secretion and bone turnover in patients with non-insulin-dependent diabetes mellitus (NIDDM). We measured serum and urinary mineral levels, serum intact PTH and osteocalcin on admission and at discharge (38 +/- 3 days later, Means +/- SEM) in 28 patients with poorly-controlled NIDDM (63 +/- 2 years old, 13 males and 15 females). During the hospitalization period, glycemic control was markedly improved. Serum calcium levels remained unchanged, but serum phosphorus increased. Urinary calcium and phosphorus excretion decreased. Serum intact PTH decreased from mid-normal (30.0 +/- 2.2 ng/l) to low normal values (24.0 +/- 1.3 ng/l) (P < 0.01, normal values: 10-65 ng/l). Serum osteocalcin increased from 4.14 +/- 0.35 to 4.92 +/- 0.40 micrograms/l (P < 0.01, normal values: 2.5-13 micrograms/l). On admission, urinary calcium and phosphorus excretion showed a positive correlation with urinary glucose excretion. Serum calcium levels showed a negative correlation with serum intact PTH (r = -0.46, P < 0.05). Moreover, the change in serum calcium during the hospitalization was negatively correlated to the change in serum intact-PTH (r = -0.45, P < 0.05). Serum phosphorus concentrations showed a positive correlation with the renal threshold for phosphorus excretion on admission (r = 0.86, P < 0.01). These results indicate that hyperglycemia causes excess urinary calcium and phosphorus excretion in patients with NIDDM. In response to urinary calcium loss, PTH secretion is mildly stimulated. Bone formation seems to be suppressed in the hyperglycemic state in spite of increased PTH secretion.

Adult↗

Effect of transforming growth factor beta-1 on the intracellular calcium in cardiac fibroblasts.

We attempted to determine the effects of transforming growth factor beta-1 on intracellular Ca2+ concentration changes in the presence of isoproterenol in cardiac fibroblasts. Transforming growth factor beta-1 inhibited the increase of intracellular Ca2+ concentration in the presence of isoproterenol in fibroblasts. It also inhibited the production of cyclic-AMP in fibroblasts in the presence of isoproterenol. Islet-activating protein did not block these reactions of transforming growth factor beta-1. Forskolin did not affect the intracellular calcium concentration change resulting from treatment with transforming growth factor beta-1. Binding of [3H]CGP-12177 was decreased to 47% of control preincubated for 24 hours with transforming growth factor beta-1 in fibroblasts. Scatchard plots suggested a decrease in beta-adrenergic receptor number without specific change in receptor affinity. These results suggested that transforming growth factor beta-1 modulates the signal transduction through beta-adrenergic receptor and intracellular Ca2+ concentration by regulating the number of receptors in fibroblasts.

Animals↗

Neurons with perineuronal sulfated proteoglycans in the human visual cortex, with special reference to their reactions to lectins.

The human visual cortex, especially its ganglionic lamina, was found to contain many neurons with perineuronal sulfated proteoglycans which were stained with cationic iron colloid and aldehyde fuchsin. It also contained many neurons with surface glycoproteins labeled with lectin Vicia villosa agglutinin (VVA) or Glycine max agglutinin (SBA). Double staining frequently showed that the neurons stained with cationic iron colloid were not labeled with lectin VVA or SBA. Hyaluronidase and chondroitinase ABC/heparitinase/keratanase digestions eliminated the perineuronal cationic iron colloid reaction, but never interfered with the cell surface lectin labeling. These findings indicate that the cell surface glycoproteins reactive to lectin VVA or SBA are neither structural elements nor adhesive molecules of the proteoglycans. Double staining further demonstrated that in some neurons with perineuronal sulfated proteoglycans, the cytoplasm was labeled with lectin Arachis hypogaea agglutinin (PNA). It was further noticed that the lectin VVA-labeled neurons were not always identical with the neurons labeled with lectin SBA or with lectin PNA.

Colloids↗

Strongly anionic sites in peripheral axons of the rat sciatic nerve: light and electron microscopic detection using cationic colloidal iron.

Anionic sites in the rat sciatic nerve were studied by light and electron microscopy using a fine-granular cationic colloidal iron staining method (Murakami et al., 1986). The axon, as well as the endoneurium, the epineurium and the basement membrane of Schwann cells, were all confirmed to react strongly to the cationic colloidal iron even at a pH value of 1.0-2.0. Prior hyaluronidase digestion decreased the colloidal strain of the epineurium; chondroitinase ABC weakened that of the endoneurium and the basement membrane of Schwann cells. However, as axons retained stainability with cationic colloidal iron even after combined digestion with hyaluronidase, chondroitinase ABC, heparitinase and keratanase, the authors consider sulfated glycoconjugates and not those substances which are digestible with such common enzymes. The acid groups ionized at pH 1.0 are most likely sulfate groups. Methylation deprived the axon of the reactivity to cationic colloidal iron staining, and even subsequent saponification could not recover this reactivity to its full extent. In the axon, electron microscopy revealed a deposition of colloidal iron on the external surfaces of microtubules and neurofilaments in the axoplasm and of very fine filaments connecting them. This highly negatively charged intra-axonal network could also serve toward a supportive function in maintaining the spatial distribution of microtubules either mechanically or through electrostatic repulsion or, possibly, serve as an intra-axona cation exchange reservoir.

Animals↗

Perineuronal sulfated proteoglycans and dark neurons in the brain and spinal cord: a histochemical and electron microscopic study of newborn and adult mice.

Neurons of intracerebellar nuclei in the mouse brain were demonstrated to possess a marked surface coat, formed 3-4 weeks after birth, which was stainable with cationic iron colloid or aldehyde fuchsin. Neurons with a similar surface coat were noted as relay or local interneurons in rather restricted areas such as the occipital cortex, retrosplenial cortex, zona incerta, hippocampal subiculum and spinal posterior horn. Dark neurons with condensed cytoplasm were also shown to be covered with the surface coat. The surface coat was stained doubly with cationic iron colloid and aldehyde fuchsin. Digestion with hyaluronidase eliminated the stainability of the surface coat to both agents. Combined digestion with chondroitinase ABC, heparitinase and keratanase eliminated the cationic iron colloid staining of the surface coat, but did not interfere with the aldehyde fuchsin staining of the surface coat. Electron microscopy of ultrathin sections revealed that the iron particles indicating sulfated proteoglycans were preferentially deposited in the perineuronal tissue spaces. Many neurons in the hippocampal subiculum possessed cell surface glycoproteins which were labeled with lectin Vicia villosa or soybean agglutinin and formed 1-2 weeks after birth. Double staining revealed that these lectin-labeled neurons were identical in part with the neurons reactive to the cationic iron colloid. Dark neurons began to appear 3-4 weeks after birth. The formation of perineuronal sulfated proteoglycans and the appearance of dark neurons, both occurring during the weaning period, may reflect the morphological and physiological completion of the brain. Dark neurons are suggested to be exhausted cells that are restored to light or normal neurons after sleep.

Aging↗

Localization of the glycosaminoglycans in the synovial tissues from osteoarthritic knees.

Localization of the glycosaminoglycans (GAG) was examined in the synovial membranes of patients with osteoarthritis under light microscopy using a fine cationic colloidal iron staining method combined with enzymatic digestion. Our staining method was very useful for demonstrating the difference in the localization of GAG in regions of the inflammatory site in the osteoarthritic synovial membrane. Hyaluronic acid was mainly located in connective tissues in the surface intercellular and perivascular spaces, chondroitin sulfate A/C in the highly fibrous part of and connective tissue around blood vessels, dermatan sulfate (chondroitin sulfate B) in the subsurface interstitium and vascular endothelial cells and heparan sulfate in part of vascular endothelial cells. No keratan sulfate was detected. GAG is reported to have an important role in cell movement, adherence and aggregation in the inflammatory sites. These findings should be useful for understanding the role of GAG in physiological and pathologic processes of secondary synovitis.

Adult↗

Mechanical left ventricular support in patients with Marfan's syndrome: a report of two cases.

Left ventricular assist device (LVAD) was utilized for the treatment of postcardiotomy heart failure in two patients with Marfan's syndrome. Patient 1 (a 22-year-old) with annuloaortic ectasia (AAE) and DeBakey type II dissection had been supported by LVAD for 87h after composite graft replacement of the ascending aorta and aortic valve. Patient 2 (a 52-year-old) with AAE and DeBakey type I dissection had been supported by LVAD for 91 h after aortic valve replacement. During the assist, both patients complicated bleeding from the fragile left atria near the sites of cannulation. Patient 1 died of multiple organ failure on the 62nd postoperative day, but patient 2 returned to work after surgery.

Adult↗

Male reproductive toxicity of ethinylestradiol associated with 4 weeks daily dosing prior to mating in rats.

Parameters of male reproductive toxicity of ethinylestradiol were assessed by conducting a mating test, sperm assay, organ weight determination and histopathological examination. Male Sprague Dawley rats were orally administered 0.1, 0.3, 3 or 10 mg/kg/day ethinylestradiol for 4 weeks prior to mating. Body weight gain and food consumption were suppressed in all treated groups. Reproductive ability of the 3 and 10 mg/kg/day males disappeared. Slightly low copulation indices were observed in the 0.1 and 0.3 mg/kg/day groups, although fertility indices were not affected. Sperm could hardly be found in the epididymis of 3 and 10 mg/kg/day males. Sperm counts were also decreased in the other treated groups, but sperm motility was not affected. Decreased absolute and/or relative weights of testes, epididymides, prostate and seminal vesicles were observed in all treated groups along with testis, epididymis, seminal vesicle and prostate atrophy, and degenerative changes of spermatocytes, spermatids, Sertoli cells and Leydig cells. These results suggest that sperm quantification and histopathological assessment are more appropriate for assessing male reproductive toxicity of ethinylestradiol than performance of copulation and fertility tests.

Animals↗

A case of nonmetastatic trophoblastic disease followed by magnetic resonance imaging.

The consecutive findings of the magnetic resonance (MR) imaging in a patient with nonmetastatic trophoblastic disease are reported. On MR image, there are noted two kinds of MR findings which suggest the existence of trophoblastic disease; one was a typical hypervascular mass of heterogeneous signal intensity within myometrium, and the other was the increase in myometrial and parametrial flow void. The former finding appeared only for a short period while the disease was highly active. The latter finding well paralleled the serum human chorionic gonadotropin (hCG) level, and the remarkable flow void, indicating dilatated blood vessels, disappeared with the complete remission of the disease. These findings suggest that MR imaging may be useful for diagnosing and following gestational trophoblastic disease.

Adult↗