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Biomedical subjects

T Ohara

Publications and source records attributed to T Ohara.

At least 109 records · Page 6Linked to original sources
PubMed1996

Zero flow pressure in human coronary circulation.

UNLABELLED: Coronary pressure flow (P/F) relationship has been investigated mainly from the viewpoint of coronary resistance. However, recent experimental evidence suggests that the zero flow pressure intercept (Pzf) provides important characteristics of coronary circulation. Although Pzf is likely to provide meaningful information about characteristics of coronary circulation, no data are available about Pzf in humans. The authors attempted to determine Pzf in humans by analyzing P/F relationship during long cardiac pause. This relationship, provoked by intracoronary adenosine triphosphate (ATP) infusion, was analyzed in 9 patients (8 men, 1 woman) with coronary heart disease (ages: fifty-six +/- six years). After the diagnostic cardiac catheterization, ATP, 0.6 mg/3 mL, was administrated by bolus intracoronary injection during measurements of coronary blood flow velocity. Coronary blood flow velocity in the left anterior descending artery was measured with a 0.018-inch Doppler angioplasty guide wire (FloWire, Cariometrics, Inc., Mountain View, Calif.). The dynamic P/F relationship was obtained by correlation of the instantaneous aortic pressure and flow velocity with each other at constant intervals. The least square linear regression analysis was applied to the P/F data to yield the extrapolated Pzf axis. Immediately after intracoronary injection of ATP, long pause (5320 +/- 1498 msec) appeared and coronary blood flow velocity decreased to 11 +/- 8 cm/sec. Pzf calculated with P/F relationship was 14 +/- 7 mmHg. CONCLUSIONS: Thus, the results clearly demonstrate that Pzf is higher than right atrial and left ventricular end-diastolic pressure in humans, indicating the complexity of the determinants of the Pzf.

Adenosine Triphosphate↗
PubMed1996

A case of hypertensive-diabetic cardiomyopathy demonstrating left ventricular wall motion abnormality.

We report a case of hypertensive-diabetic cardiomyopathy demonstrating left ventricular regional wall motion abnormality, with a normal coronary artery documented on coronary arteriography. Dipyridamole-infusion 201Tl scintigraphy demonstrated transient perfusion defects in the infero-posterior wall of the left ventricle, where reduced wall motion was demonstrated on contrast left ventriculography. Myocardial SPECT (single photon emission tomography) imaging with [123I] beta-methyliodophenylpentadecanoic acid (BMIPP) and 201Tl demonstrated reduced [123I]BMIPP uptake compared with 201Tl uptake in the infero-posterior wall of left ventricle. These results suggest that the impairment of myocardial free fatty acid metabolism is an etiologic or contributory factor for regional wall motion abnormality, together with small-vessel coronary artery disease, in this patient.

Cardiomyopathies↗
PubMed1996

Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs.

We have expressed and biologically characterized recombinant human growth/differentiation factor 5 (huGDF5). This protein is composed of a mature homodimer consisting of 15 kD subunits. Using recombinant expressed protein, we have demonstrated that huGDF5 in vitro stimulated mesenchyme aggregation and chondrogenesis in rat limb bud cells. In vivo, partially purified huGDF5 induced cartilage and bone formation in muscular tissues of rodents. However, in contrast to the effects of other BMPs, as for example BMP-2, the osteoblastic MC3T3-E1 cells did not respond to huGDF5 as measured by alkaline phosphatase activity. These results suggest that the action of GDF5 may be relatively specific for chondrogenesis during the entire process of the endochondral bone formation. GDF5 may control the morphogenesis of cartilaginous tissue, including joints, in the skeletal development of limbs.

Alkaline Phosphatase↗
PubMed1996

[A case of bronchiolo-alveolar carcinoma with high production of carbohydrate antigen (CA19-9)].

A 75-year-old female had loss of appetite, left hypochondrial and back pain. An X-ray and a computed tomogram of both lungs showed multiple small granular shadows. By Tc-labelled bone scintigram, multiple uptakes were found. Since high serum CA19-9 was obtained, pancreatic or bile duct cancer with multiple lung and bone metastasis was suspected. The autopsy revealed, small nodules in both lungs were well-differentiated adenocarcinoma, bronchiolo-alveolar type, and immunohistologically, tumor cells were stained positively for CA19-9. Since CA19-9 exists in normal bronchial glands and bronchiole, high level of serum CA19-9 in our patient may be derived from the neoplastic bronchiolar epithelium.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1996

Hereditary nephritis associated with low-tone sensorineural hearing difficulty: a case report.

The proband was a 14-year-old girl with hematuria and proteinuria. Many members of her maternal pedigree had hematuria and proteinuria. Her mother, younger brother (age 12 years) and younger sister (age 9 years) had microscopic hematuria and proteinuria with normal renal function. Her mother had nephrotic syndrome during pregnancy and a renal biopsy was performed. Light microscopic findings of the renal biopsy specimen revealed mild mesangial proliferation and irregularity of glomerular basement membrane. The pedigree showed no chronic renal failure and no deafness. The proband had experienced microscopic hematuria and occasionally macroscopic hematuria since 3 years of age. Proteinuria increased steadily and at the age of 14 years, she had nephrotic syndrome and renal dysfunction (creatinine clearance of 57.9 ml/min/1.48 m2). Renal biopsy was performed and light microscopic findings showed segmental mesangial cell proliferation and numerous interstitial foam cells without significant findings by immunofluorescent study. Electron microscopic examination showed splitting into many layers and thinning of the glomerular basement membrane. She had no complaint of hearing. However, audiological studies detected bilateral low-tone (from 125 Hz to 1000 Hz) sensorineural hearing difficulty, ranging from 30 to 40 dB. High scores on the short increment sensitivity index (SISI) test suggested inner ear hearing difficulty. Audiogram of her brother revealed also low-tone sensorineural hearing loss. Hereditary nephritis with the characteristic lesion of the glomerular basement membrane and sensorineural hearing difficulty has been known as Alport syndrome. Alport syndrome associated with familial low-tone hearing difficulty has not been reported previously.

Adolescent↗
PubMed1995

Capillary electrophoresis/frontal analysis for microanalysis of enantioselective protein binding of a basic drug.

A new HPCE method was developed for the enantioselective determination of the unbound concentration of a basic drug under plasma protein binding equilibrium. The racemic basic drug verapamil (VER) and human serum albumin mixed solution was used as a model sample solution. The sample solution was introduced into a fused-silica capillary hydrodynamically or electrokinetically. During the electrophoresis following hydrodynamic injection, the unbound drug zone migrated apart from the sample zone and was separated into two zonal peaks with a plateau due to enantiomers by a chiral selector (trimethyl-beta-cyclodextrin) dissolved in the acidic running buffer solution (pH 2.5). By the electrokinetic introduction of the same sample solution from the anodic end, only the unbound drug entered the capillary and was separated into the enantiomers, which also gave the zonal peaks with plateau. The unbound concentration of each enantiomer was determined from the plateau peak height. The results obtained by the different methods for sample introduction agreed well with those determined by conventional ultrafiltration-chiral HPLC, which was employed as a reference method. The unbound concentration of (S)-VER was 1.7 times higher than that of the antipode. The sample size used in the present method was approximately 200 nL, which is about one-thousandth of that in the reference method. The electrokinetic introduction gave a better peak shape than the hydrodynamic introduction.

Electrophoresis, Capillary↗
PubMed1995

Role of [Ca2+]i in lethal oxidative injury in rat cultured inner medullary collecting duct cells.

Reactive oxygen metabolites have been implicated in the pathogenesis of toxic, ischaemic and immunologically mediated renal injury. An increase in the cytosolic free Ca2+ concentration ([Ca2+]i) has been proposed as a mechanism of oxidative stress-induced cell injury. We used a fluorescence spectrometer and a fluorescence probe to measure the [Ca2+]i and viability of rat primary cultured inner medullary collecting duct (IMCD) cells during oxidative stress induced by 5 mM tert-butyl hydroperoxide (TBHP). Initially, this oxidative stress evoked a small increase in [Ca2+]i which was followed by a slower sustained increase from the resting level of 170.8 +/- 38.8 nM to 1490.5 +/- 301.7 nM after 60 min, and this preceded the loss of plasma membrane integrity, measured by the propidium iodide fluorescence method. The elimination of extracellular Ca2+ from the culture medium prevented the TBHP-induced [Ca2+]i increase and improved cell viability. Restoration of extracellular Ca2+ resulted in an immediate and large increase in [Ca2+]i and extensive cell death. Verapamil, a Ca2+ channel blocker, inhibited the [Ca2+]i increase and afforded significant protection against cellular injury following exposure to TBHP-induced oxidative stress. Extracellular acidosis also prevented the increase in [Ca2+]i and cell death caused by this oxidative stress. These results are consistent with the hypothesis that oxidative stress-induced IMCD cellular injury may be the result of increased [Ca2+]i caused, in part, by activation of voltage-dependent Ca2+ channels.

Animals↗
PubMed1995

Overproduction, purification, and diagnostic use of the recombinant HIV-1 Gag proteins, the precursor protein p55 and the processed products p17, p24, and p15.

HIV-1 Gag protein precursor p55, and its processed products, p17, p24, and p15 were overproduced in Escherichia coli and purified to near homogeneity. To study the antigenic properties and the potentiality as the diagnostic and prognostic reagents, varying amounts of the purified Gag proteins were dotted onto the polyvinylidene difluoride membrane and reacted with 40 sera of HIV-1-infected individuals (35 AC, 1 ARC, and 4 AIDS patients) and 10 sera of normal healthy donors. p55 reacted with 40 (100%) sera of HIV-1 carriers, while p17, p24, and p15 reacted with 37 (92.5%), 35 (87.5%) and 34 (85%) of the 40 sera of HIV-1 carriers, respectively. On the whole, the reaction of p55 was especially strong and that of p15 was the weakest. p55 showed the strongest reaction among the four Gag proteins with all specimens, and it showed a positive reaction with a carrier serum with which none of the processed Gag proteins showed a positive reaction. Therefore, p55 is the most useful antigen among the four Gag proteins for detection of the Gag antibodies and may even be one of the most useful antigens for the diagnosis of HIV-1 infection.

Chromatography, Gel↗
PubMed1995

Angiotensin-converting enzyme polymorphism and development of diabetic nephropathy in non-insulin-dependent diabetes mellitus.

We determined the distribution frequency of angiotensin-converting enzyme insertion/deletion (I/D) polymorphism in 111 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) of at least 10 years duration (80 patients with diabetic nephropathy and 31 patients without nephropathy) and 76 healthy Japanese controls. Patients with diabetic nephropathy showed an excess of the ID genotype compared with patients without nephropathy (p < 0.02) and less of the II genotype compared with healthy controls (p < 0.01) and patients without nephropathy (p < 0.01). NIDDM patients with the II genotype have a decreased risk for the development of diabetic nephropathy.

Adult↗
PubMed1995

[Clinical efficacy of the Porges Urospiral, a reversible intraprostatic spiral stent, in patients with benign prostatic hypertrophy].

The Porges Urospiral, a urethral spiral stent made of stainless steel wire, is designed for patients with benign prostatic hypertrophy. To evaluate the safety and efficacy of the stent, a prospective uncontrolled study was performed on 60 patients who complained of urinary retention (48 patients) or severe dysuria (12 patients) due to prostatic hypertrophy. Four patients had neurogenic disorders resulting in bladder dysfunction. The average age of the patients was 77.4 years old, ranging from 61 to 91 years old. In 48 patients, the stent was used instead of transurethral resection of the prostate (TUR-P) because of the patients poor general conditions, while in 12 patients the stent was transiently used until TUR-P. Subjective symptoms, according to an original scoring system, and objective signs, uroflowmetry measurements and residual urine volume, before and 3 months after stent insertion were compared. The stent was indwelt for more than 3 months in 40 of the 57 patients in whom the stent could be inserted. Out of 37 evaluable patients, subjective symptoms improved in all the patients and objective symptoms improved in 26 patients (70.3%). Complications included urinary incontinence, urination pain, urethral pain, gross hematuria or migration of the stent. Although these complications disappeared in a few days after the insertion of the stent in a majority of the patients, the stent was removed in 17 patients due to complications within 3 months after insertion. The overall clinical efficacy of this stent was 56% in 50 evaluable patients who had no neurogenic disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

A chorioretinal lesion in a patient with Kimura's disease.

A 47-year-old male patient with Kimura's disease showed a white and slightly elevated choroidal lesion surrounded by serous retinal detachment in his left eye. Serological examination revealed esinophilia. Swelling in his left cheek had been increasing during a period of 20 years, and diagnosis of Kimura's disease had been made earlier by biopsy. Fluorescein angiography suggested disturbance of choroidal circulation and dysfunction of retinal pigment epithelium. After corticosteroid therapy, improvement was seen in the fundus findings, the swelling in the cheek and eosinophilia.

Angiolymphoid Hyperplasia with Eosinophilia↗
PubMed1994

Intratumoral injection of a streptococcal preparation, OK-432, before surgery for gastric cancer. A randomized trial. Cooperative Study Group of Preoperative Intratumoral Immunotherapy for Cancer.

BACKGROUND: The preoperative intratumoral injection with OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo, Japan), an immunomodulatory agent prepared from an attenuated strain of streptococcus pyogenes, activates the regional immune system and causes degeneration of cancer tissue in carcinoma of the stomach. METHODS: A multi-institutional randomized trial of OK-432 to determine its clinical usefulness was conducted. Three hundred and ninety-five patients with gastric cancer were assigned randomly either to receive or not to receive a preoperative intratumoral injection of OK-432. Among them, 277 patients with advanced cancer were treated by common postoperative chemoimmunotherapy consisting of mitomycin C, tegafur, and OK-432. All patients were followed for at least 5 years. RESULTS: The adverse effects of OK-432 injected intratumorally predominantly were mild fever, anorexia, and abdominal pain, however, no treatment was required for these symptoms. Overall, there were no differences in outcome between the OK-432 and control groups. However, analysis based on stage showed that a preoperative intratumoral injection of OK-432 significantly improved the 5-year survival rate of patients with Stage III cancer (P = 0.0229), at 47.7% for the OK-432 group and 27.5% for the control group. In subset analysis, when the 5-year survival of patients with and without tumor infiltrating lymphocytes (TIL) was compared, OK-432 injected intratumorally had a significant positive effect on the group showing a moderate to marked number of TIL (P = 0.0438). CONCLUSION: These results showed that the intratumoral injection of OK-432 may improve survival of patients with Stage III gastric cancer. Cancer 1994;3097-3103.

Adjuvants, Immunologic↗
PubMed1994

Increase in 3-deoxyglucosone levels in diabetic rat plasma. Specific in vivo determination of intermediate in advanced Maillard reaction.

A specific assay of 3-deoxyglucosone (3-DG) was developed in our laboratory to help elucidate the relationship between advanced Maillard reaction and diabetic complications. 3-DG is known as a highly reactive intermediate of the reaction in vitro and a precursor of advanced glycosylation end products such as pyrraline and pentosidine, which have been previously detected in vivo. 3-DG was converted to a stable compound, 2-(2,3,4-trihydroxybutyl)-benzo[g]quinoxaline, by reacting with 2,3-diaminonaphthalene. Since the derivative had a characteristic UV spectrum, it was determined at 268 nm by high performance liquid chromatography. This method was sensitive enough to detect 10 ng/ml (61.7 nM) of 3-DG in vitro. A slight modification to this method allowed in vivo detection of small amounts of 3-DG. Plasma free 3-DG levels were significantly higher in streptozotocin-induced diabetic rats compared with controls (918 +/- 134 nM versus 379 +/- 69 nM, p < 0.001) and were suppressed with the administration of aminoguanidine, an inhibitor of Maillard reaction. Plasma pyrraline levels in diabetic rats also increased in parallel with elevated 3-DG levels but were only marginally suppressed by administration of aminoguanidine. Our results indicate that 3-DG is present in vivo under normal conditions and that its level increases in diabetic subjects. Determination of 3-DG represents a good tool to predict development and progression of diabetic complications and to assess the efficiency of inhibitors to Maillard reaction.

2-Naphthylamine↗
PubMed1994

Identification of three catalytic triad constituents and Asp-225 essential for function of lysine-specific serine protease, Achromobacter protease I.

Achromobacter protease I is a lysine-specific serine protease that Achromobacter lyticus M497-1 extracellularly secretes. The structural aspects necessary for the protease to function were investigated by means of site-directed mutagenesis to identify the constituents of the catalytic triad and the amino acid residue responsible for lysine specificity. The precursor molecules, which were produced by substitution of His-57, Asp-113, or Ser-194 for alanine, could not be converted to the mature form. In contrast, a precursor of a mutant in which either His-56 or Ser-193 is converted to alanine was perfectly processed autocatalytically and attained full protease activity. Substitution of Glu-190, one of the two candidates for determining lysine specificity, to glutamine, aspartic acid, or leucine had no or little effect on both proteolytic activity and substrate specificity. However, the kinetic parameters were subtly different from one another, depending on the nature of substituents in these mutants. The substitution of the other candidate, Asp-225, for asparagine or leucine resulted in the failure of maturation to the active forms. However, the precursor of the D225E mutant slowly matured and was essentially inactive. The observed reduction of protease activity is largely due to a decrease in the affinity of lysine to the protease. These results suggest that His-57, Asp-113, and Ser-194 are the three constituents of the catalytic triad in Achromobacter protease I and that Asp-225 plays a critical role in restricted substrate specificity as a lysyl endopeptidase.

Alcaligenes↗
PubMed1994

A technique for changing a PTCA balloon catheter over a regular-length guidewire.

In 100 patients who underwent coronary angioplasty with more than one balloon catheter for a lesion, these over-the-wire balloon catheters were changed by using a regular-length guidewire. In order to change to another balloon, the inflation device was connected to the central guide wire lumen of the catheter after pulling back the catheter until the proximal end of the regular length guide wire disappeared. By pulling back the balloon catheter from the guiding catheter by applying a pressure with the inflation device, the balloon was taken out of the guiding catheter leaving the wire in the coronary artery. One hundred forty-nine of 163 attempted procedures were completed successfully. Our technique helped in performing a fast, safe, and reliable changing procedure compared to the procedure with an extended guidewire.

Adult↗
PubMed1994

High-performance capillary electrophoresis/frontal analysis for the study of protein binding of a basic drug.

A simple high-performance capillary electrophoresis (HPCE) method based on the principle of frontal analysis was applied to the determination of the concentration of unbound basic drug in protein binding equilibrium. A small volume of sample solution (approximately 80 nL) containing 113-340 microM of verapamil (VER) and 100-550 microM of human serum albumin was introduced into the fused silica capillary (effective length, 22 cm; 50-microns i.d.) by suction. Because the silanol groups on the inner surface of the capillary were bound with linear polyacrylamide through Si-C bonds, electroosmotic flow was not generated even at pH 7.4 with an applied voltage of +10 kV. The unbound drug bearing positive charge migrated electrophoretically from the drug-protein mixed zone toward the detection end, whereas human serum albumin did not co-migrate because of its negative charge. The bound drug migrated after it was released from the protein. As a result of an 80-nL injection of the sample solution, VER was eluted as a zonal peak with a plateau region. The VER concentration calculated from the plateau height agreed well with the unbound VER concentration determined by the conventional ultrafiltration-HPLC method, with good reproducibility (CV, < 6.23%, n = 15). The present HPCE/FA system was applied to the Scatchard analysis of VER and alpha 1-acid glycoprotein binding, and the estimated binding parameters agreed well with literature values.

Blood Proteins↗