Search PubMed⌕ Search

Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 595 records · Page 33Linked to original sources
PubMed1995

Structural elucidation of aculeximycin. IV. Absolute structure of aculeximycin, belonging to a new class of macrolide antibiotics.

Aculeximycin (1) produced by Streptosporangium albidum possesses a 30-membered polyhydroxy macrocyclic lactone and five sugars including aculexitriose. We have described the determination of the planar structure of N-diacetylated aculeximycin (2) using degradation products, which were obtained by DBU-methanol treatment, ozonolysis and periodative oxidation. In order to determine the relative and absolute configurations of aculeximycin, first, the relative and absolute configurations of the degradation products 10, 11, 12 and 13 were determined. Rychnovsky's method was very useful to determine the relative configurations of these degradation products, and CD exciton chirality and the modified Mosher's methods were applied to determine their absolute configurations. From these results, fourteen out of the twenty asymmetric centers in aculeximycin were determined to be 5S, 17R, 20S, 21R, 23R, 24R, 29S, 30R, 31S, 34R, 35S, 36S and 37R. The absolute configurations at C-14 and C-15 on the hemiketal ring were confirmed using 12 obtained by the partial glycol bond cleavage of 9. Absolute configurations of the remaining asymmetric centers were determined by spectral analysis of 15 and NOE experiment on 1. From these results, the absolute configuration of 1 was determined to be 5S, 7R, 10S, 11R, 14R, 15S, 17R, 19R, 20S, 21R, 23R, 24R, 25S, 29S, 30R, 31S, 34R, 35S, 36S and 37R.

Anti-Bacterial Agents↗
PubMed1995

[Metabolic fate of porphyrin and its precursors in porphyria and porphyrinuria].

The metabolic fate of porphyrins and its precursors in porphyria and porphyrinuria is discussed to understand their excretion into the feces or urine. Eight enzymes play important roles in the porphyrin pathway. An enzymatic defect at each step of heme synthesis will induce each typical form of porphyria with the exception of the first enzyme. Each porphyria is described according to the enzyme in the heme biosynthetic sequence. Lead, which disturbs two enzymes involved in the heme biosynthesis, is one of typical chemicals inducing porphyrinuria. Lead porphyrinuria is also described according to the enzymes in the pathway. The figure of porphyrin pathway, drawn in details in the present chapter, will make it easier to understand the heme biosynthetic pathway related to porphyria or porphyrinuria.

Aminolevulinic Acid↗
PubMed1995

[Effectiveness of haloperidol in the treatment of chorea minor].

Chorea minor is the most curious manifestation of rheumatic fever, first described by Sydenham in 1686. Subsequent evidence showed that chorea could be a late manifestation of rheumatic fever, often occurring several months after a streptococcal infection in contrast to other major manifestations. During the ten-year period between 1984 and 1993, 11 children with rheumatic fever were seen at our hospital, two cases of these being accompanied with chorea minor. Case 1, a male aged 12, presented with involuntary movements. He was diagnosed as having rheumatic fever because of chorea and systolic ejection murmur at the apex of the heart. Plain cranial CT was normal. However, positron emission computed tomography revealed an increased 11C-glucose uptake in the caudate nucleus as compared with the cerebral cortex. Case 2, a female aged 14, presented with involuntary movements. Plain cranial CT was normal, but single photon emission CT showed a difference between the right and left brain. These two patients were given penicillin G (PCG), predonisolone (PSL) and haloperidol. Haloperidol was administered, because PCG and PSL had no effect to improve the clinical manifestations. After administer decreased to a half with a clinical improvement, but the level of GABA did not change. Haloperidol seemed to be an effective and useful agent for motor manifestations of the disease.

Adolescent↗
PubMed1995

Death in head-down position: an autopsy report with reference to physiological mechanism.

A 74-year-old man was found dead in the head-down position in a hole in a pile of trash at his home. There was severe congestion and hemorrhage in the head and neck regions, and bronchial petechiae. Head-down tilt is a well-known model in studying the effects of weightlessness during space flight. By comparing our case with the physiological studies on head-down tilt, we determined that the head-down posture would increase cardiac output, and systemic and intracranial pressure, while it would suppress respiration by a central or peripheral mechanism.

Aged↗
PubMed1995

[Orbital varix presenting orbital apex syndrome].

On 7 July 1993, a 61 year-old female presented a seven-day history of double vision and retro-ocular pain. Neurological examination on admission demonstrated right oculomotor palsy and pain in the right frontal nerve. Routine CT scan and MRI disclosed no abnormalities. Her symptoms deteriorated progressively and increased in severity, resulting in complete ptosis and visual disturbance in the right eye, for which she was hospitalized. Angiography also failed to demonstrate any lesion. Herrical CT scan demonstrated a small mass lesion at the right orbital apex. A frontotemporal extradural approach operation was performed on July 6, 1993. The anterior clinoid process and minor wing of the sphenoid were drilled to expose the optic canal and the superior orbital fissure. When the periorbita just beside the optic sheath was opened, a large vein was observed to be impinging on the optic nerve and nerves which pass through the superior orbital fissure. This vein was carefully dissected, coagulated and removed. The postoperative course was uneventful. Her severe retro-ocular pain completely disappeared immediately after the operation. Although complete remission of ptosis and return of eye movements to normal were noted, her visual acuity is at present limited to hand movement. Orbital varix is a common cause of unilateral intermittent proptosis. However, there has been no report in the literature of orbital varix with orbital apex syndrome as the initial clinical appearance. In this type of patient with orbital varix and retrobulbar hemorrhage or impairment of intraorbital nerves, surgical intervention using a transcranial approach to the lesion should be undertaken.

Cranial Nerve Diseases↗
PubMed1995

[Antitumor effect of intra-arterial tumor necrosis factor-alpha in rats with transplanted intracerebral glioma and its evaluation by MRI].

Recombinant human TNF-alpha was administrated intra-arterially to rats with transplanted intracerebral glioma. 1 x 10(6) of T9 rat glioma cells were transplanted into Fisher 344 rat brain stereotaxically and 1000 units of TNF-alpha was administrated at a rate of 100 microl/min. via an internal carotid artery 1 or 3 weeks after the transplantation. The effects of TNF-alpha were evaluated by MRI and histopathological examinations. Neurological symptoms, i.e. hemiparesis, appeared after 9.0 +/- 0.63 days and all rats died of tumor overloading 14.5 +/- 0.84 days after the transplantation. Single injection of TNF-alpha on 7th day after the transplantation induced regression of the tumor size in one of six rats. The tumors were detected 3 days after transplantation by MRI and they were revealed as low/iso intensity mass in T1WI, iso/high intensity in T2WI, and were enhanced by Gd-DTPA heterogeneously. On 7/14 days after the transplantation, the tumor grew approximately 7/10 mm in diameter. The single 1000 units of TNF-alpha were administrated via an internal carotid artery. 3 days after the administration of TNF-alpha, regression of the tumor size was seen in one of six rats and decrease of peritumoral edema was seen in three. These effects of TNF-alpha were, however, transient and they were not demonstrated on day 7. Single injection of TNF-alpha was not effective for large tumors more than 10 mm in diameter seen 14 days after the transplantation. These data suggest that intra-arterial TNF-alpha should be administrated at an early stage of the tumor growth and several injections are needed to cause regression in the size of the gliomas.

Animals↗
PubMed1994

Regulation of low density lipoprotein receptor activity in Chinese hamster ovary cells transfected with the c-fms gene.

Chinese hamster ovary (CHO) cells were transfected with the human c-fms gene, which encodes the receptor for macrophage colony-stimulating factor, to examine the effects on the low density lipoprotein (LDL) receptor activity. Degradation of [125I]LDL was significantly reduced in the transfected CHO cells as compared to non-transfected cells when incubated in lipoprotein-deficient serum. Quantitative analysis of LDL receptor mRNA using a competitive PCR method demonstrated that LDL receptor suppression occurred at transcription. These findings suggest that expression of the c-fms gene is involved in the regulation of LDL receptors on macrophages.

Animals↗
PubMed1994

Changes in the volume and performance of the left ventricle in the early neonatal period.

To evaluate the effect of changes in preload on left ventricular (LV) performance, we used echocardiography to measure end-diastolic dimension, end-systolic dimension, and stroke volume in newborns at 2, 12, 24, and 120 h of age. The stroke volume was calculated by the pulsed Doppler technique. The stroke volume showed the highest level at 2 h of age. The size of the ductus arteriosus correlated with the stroke volume. These results indicated that the increase in stroke volume was related to the increase in LV preload due to the shunt flow volume through the patent ductus arteriosus. M-mode echocardiographic indexes such as end-diastolic dimension, LV end-diastolic volume, and LV ejection fraction did not show any significant changes from 2 to 120 h of age. We conclude that M-mode echocardiographic evaluation of LV performance is unreliable in the early neonatal period. Our data also provide a useful basis for the interpretation of abnormal left ventricular systolic function in the early neonatal period.

Blood Pressure↗
PubMed1994

Two significant aspects of microcystin-LR: specific binding and liver specificity.

Microcystin-LR is a unique and potent liver tumor promoter, belonging to the okadaic acid class compounds. Although microcystin-LR is a potent inhibitor of protein phosphatases 1 and 2A, as is okadaic acid, microcystin-LR has liver specificity dominance. Two significant aspects, specific binding and liver specificity of [3H]dihydromicrocystin-LR, a reduced form of microcystin-LR, were studied and compared with those of [3H]okadaic acid. [3H]-Dihydromicrocystin-LR had higher affinity for the receptors in both the particulate and cytosolic fractions of rat liver and various tissues than had [3H]okadaic acid. Intraperitoneal administration of [3H]dihydromicrocystin-LR into mice resulted in the highest uptake into the liver, 71.5 +/- 6.9% of the total administered radioactivity, whereas p.o. administration resulted in less than 1% uptake into the liver, suggesting that the mechanisms of the incorporation of microcystin-LR into the liver by i.p. and p.o. administrations are greatly different. The presence of associated forms of [3H]dihydromicrocystin-LR with macromolecules in the liver indicates a need for further investigation.

Animals↗
PubMed1994

Identification of unlawful food dyes by thin-layer chromatography-fast atom bombardment mass spectrometry.

A thin-layer chromatographic-fast atom bombardment mass spectrometric (TLC-FAB-MS) method incorporating an analyte condensation technique was established for the identification of the 27 food dyes consisting the twelve dyes permitted for use in foods and the fifteen unlawful dyes in Japan. The use of magic bullet [1,4-dithiothreitol-1,4-dithioerythritol (3:1)] as a matrix allowed the measurement of the FAB mass spectra of the food dyes except for Food Blue No. 2 (Indigo Carmine). The separation was performed on a C18-modified silica gel TLC plate using the following two solvent systems: methanol-acetonitrile-5% aqueous sodium sulphate solution (3:3:10) and methyl ethyl ketone-methanol-5% aqueous sodium sulphate solution (1:1:1). The condensation technique for concentration of a diffuse sample spot on the TLC plate improved the detection limit 4-20-fold with good reproducibility. The method was successfully applied to the identification of unlawful dyes in imported foods.

Chromatography, Thin Layer↗
PubMed1994

Metabolism of chylomicron remnants in transgenic mice expressing apolipoprotein E in the intestine.

Apolipoprotein E (apoE) has high affinity for the cell surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma chylomicron clearance, a transgenic mouse line which overexpresses apoE in the intestine was established. Immunohistochemistry demonstrated that considerable amounts of apoE were localized to mucosal cells of the intestine. In an oral retinyl palmitate challenge test, both the peak height and area under the curve in transgenic mice were less than 25% of those in controls. We speculate that the apoE molecules produced in the intestine of transgenic mice were incorporated onto newly synthesized chylomicron particles before their secretion into the plasma and thereby contributed to rapid plasma clearance of chylomicron remnants. Gene expression of apoE in the intestine would be a promising way to control postprandial hyperlipemia.

Administration, Oral↗
PubMed1994

Structure elucidation of glykenin glycosidic antibiotics from Basidiomycetes sp. V. High-performance liquid chromatographic separation of components of glykenin.

The glycosidic antibiotics of the glykenin (GK) family produced by Basidiomycetes sp. were separated into nine components (GK-I-VII and DG) by normal-phase chromatography. It was found that these components differ in the number and location of the acetyl groups in the sugar moiety. Each component (GK-I-VII and DG) was further separated into three isomers (A, B and C), which possess different aglycones, by reversed-phase chromatography on an ODS column with methanol-acetonitrile as eluent. The best composition of the eluent was found to be methanol-acetonitrile-1% trifluoroacetic acid (4:3.5:2.5). The profile analysis of GK-III-VII and DG was also carried out using a modified mobile phase. The combination of normal- and reversed-phase chromatography separated all components of the GK mixture except GK-I and II. The relationship between structure and separation behaviour of GK is discussed.

Aminoglycosides↗
PubMed1994

Simultaneous racemization and isomerization at specific aspartic acid residues in alpha B-crystallin from the aged human lens.

We provide evidence that the racemization and isomerization of aspartyl(Asp) residues occur simultaneously in the alpha B-crystallin in the lens of aged (mean age: 80 years) and young (age: 11 months) humans. We purified alpha B-crystallin and subjected it to tryptic digestion. The resulting peptides were separated by reverse-phase high-performance chromatography (RP-HPLC) and were characterized by amino-acid composition, sequence analysis and mass spectrometry. Two specific sites, Asp-36 (D/L of Asp: 0.92) and Asp-62(D/L of Asp: 0.57), among 13 Asp/asparginyl (Asn) residues in aged alpha B-crystallin, were found to be highly racemized and isomerized to form beta-Asp residues. The beta-Asp-containing peptides were clearly distinguished from normal Asp-containing (alpha-Asp) peptides by RP-HPLC. The racemization and isomerization of Asp residues in aged alpha B-crystallin may occur via a succinimide intermediate. In young alpha B-crystallin, we observed neither racemization nor isomerization. We also found that Met-68 was oxidized to form Met sulfoxide to a greater extent in aged alpha B-crystallin than in young alpha B-crystallin. We concluded that racemization, isomerization, and oxidation of alpha B-crystallin occur spontaneously in the aging process.

Aged↗