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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 811 records · Page 45Linked to original sources

Synthetic dipeptide, N-stearoyl-D-Ser-L-Pro-OEt, induces release of tissue-type plasminogen activator in cultured cells and in experimental animals.

The tissue-type plasminogen activator (t-PA)-releasing action of synthetic dipeptides containing Gly, Ser or Pro was investigated. Among 10 dipeptides, Boc-L-Ser-L-Pro-OH and H-L-Ser-L-Pro-OH induced t-PA release in vitro, but the others were inactive. Since Boc-L-Ser-L-Pro-OH was more effective than H-L-Ser-L-Pro-OH, 7 related dipeptides with N-acylation were synthesized. Five of them enhanced the release of t-PA; N-stearoyl-L-Ser-L-Pro-OH (FK-5) had the greatest effect. Four compounds were further examined for activity to enhance the release of t-PA in rats. FK-5 produced a two-fold increase in fibrinolytic activity, and N-palmitoyl-L-Ser-L-Pro-OH (FK-4) also markedly enhanced the release of t-PA. Since FK-5 caused severe hemolysis, 7 analogues of FK-5 were synthesized. All of them enhanced the release of t-PA from melanoma (Bowes) cells. In rats, FK-5, N-stearoyl-D-Ser-L-Pro-OH (FK-8) and N-stearoyl-D-Ser-L-Pro-OEt (FK-10) enhanced the fibrinolytic activity two-fold. FK-5 and FK-8 also exhibited strong hemolytic activity, but FK-10 did not induce hemolysis. Therefore, FK-10 was examined in rabbits. After the injection of this compound, the fibrinolytic activity in the euglobulin fraction was markedly enhanced without accompanying hemolysis. Thus, FK-10 potently enhances fibrinolytic activity both in vitro and in vivo.

Amino Acid Sequence↗

Opposite changes in serum sodium and potassium in patients in diabetic coma.

We studied the changes in serum sodium (Na) and potassium (K) levels in seventeen patients in diabetic ketoacidosis and nine patients in non-ketotic hyperosmolar coma, who had marked hyperglycemia (707.4 +/- 75.6 mg/dl, mean +/- SEM) and dehydration. The disorder characterized two types of alteration. The one group was hyponatremia with hyperkalemia in 17 patients in diabetic ketoacidosis (132.9 +/- 2.0 and 5.7 +/- 0.2 mEq/l), and 4 patients in non-ketotic hyperosmolar coma (125.8 +/- 4.3 and 5.2 +/- 0.5 mEq/l). The other was hypernatremia (162.5 +/- 1.8 mEq/l) with hypokalemia (3.4 +/- 0.2 mEq/l) in 5 patients in non-ketotic hyperosmolar coma. Intensive therapy with insulin and fluid administration improved the diabetic hyperglycemia and associated abnormalities. The vectors showing the normalization of serum Na and K levels was in quite opposite directions between the patients with hyponatremia with hyperkalemia and those with hypernatremia with hypokalemia. The amounts of loss of circulatory blood volume exceeded 20% in three groups of patients, a loss greater in the hypernatremic patients than in the hyponatremic ones. These results indicate that serious body water depletion produces hypernatremia instead of hyponatremia in patients in diabetic coma. The disorder may be caused by the altered distribution of electrolytes between the intra- and extra-cellular spaces.

Adult↗

In vivo diuretic effect of a new non-peptide arginine vasopressin antagonist, OPC-31260, in conscious rats.

The present study was undertaken to determine whether a non-peptide arginine vasopressin (AVP) antagonist (5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetra hydro-1H- benzazepine; OPC-31260) antagonizes the antidiuretic action of endogenous and exogenous AVP in conscious rats. OPC-31260, given orally at a dose of 5 mg/kg or higher, increased urinary volume (UV) and reduced urinary osmolality (Uosm) in a dose-dependent manner, in rats acutely denied access to water. Minimal Uosm was obtained 1-2 h after oral administration of OPC-31260. OPC-31260 caused sustained water diuresis for more than 12 h when water was available ad libitum since OPC-31260 (30 mg/kg) reduced Uosm to less than 230 mOsmol/kg H2O, significantly less than the control value of 600 mOsmol/kg H2O. Water deprivation for 24 h increased plasma AVP levels to 7.2 pmol/l and increased Uosm to 2160 mOsmol/kg H2O. In such water-deprived rats, oral administration of OPC-31260 at 100 mg/kg was diuretic; it markedly increased free water clearance and decreased Uosm to 202 mOsmol/kg H2O. In homozygous Brattleboro rats (with inherited AVP deficiency), given free access to water, subcutaneous infusion of the V2 agonist 1-deamino-8-D-AVP (dDAVP) at a rate of 1 ng/h markedly decreased UV to 12.6 from 148.7 ml/day and increased Uosm to 1762 from 231 mOsmol/kg H2O. OPC-31260 (30 mg/kg) promptly increased UV and reduced Uosm to levels similar to those before the administration of dDAVP; repeated OPC-31260 treatment had sustained effects. These results indicate that OPC-31260 is an orally effective non-peptide AVP antagonist to the antidiuretic action of AVP in the conscious rat.

Animals↗

Parosteal osteosarcoma. A clinicopathological study.

The records of 226 patients (sixty-seven who were managed at our institution and 159 who were identified from the consultation files) who had had a parosteal osteosarcoma were reviewed. The criteria for diagnosis were that, roentgenographically, the lesion had arisen from the surface of the bone and that, histologically, the tumor was well differentiated (Grade 1 or 2); it was characterized by well formed osteoid within a spindle-cell stroma; and, when there was medullary involvement, less than 25 per cent of the medullary cavity was affected. Dedifferentiation was more common (16 per cent of the patients) than previously reported and was associated with a poor prognosis. Cross-sectional imaging studies demonstrated medullary involvement in 22 per cent of the patients, an unmineralized soft-tissue mass peripheral to the mineral component in 51 per cent, and adjacent soft-tissue invasion in 46 per cent. In contrast to the findings in our previous studies, medullary involvement was not a poor prognostic factor. At an average of thirteen years (range, two to forty-one years), eleven of the sixty-seven patients who were managed at our institution died of the tumor; ten of these patients had a dedifferentiated tumor. Statistical analysis of the thirty-nine patients who had had the primary treatment at our institution revealed that incomplete resection was associated with an increased risk of local recurrence and that dedifferentiation markedly increased the risk of metastasis.

Adolescent↗

Effects of endothelin-1 on intraocular pressure and aqueous humor dynamics in the rabbit eye.

The effects of endothelin-1 (ET-1) on intraocular pressure (IOP) and aqueous humor dynamics were studied in the rabbit eye. The intravitreal injection of 10(-5) M ET-1 (20 microliters) produced a biphasic IOP response consisting of an initial rise of 1 to 2 hours in duration, and a subsequent prolonged reduction lasting for more than 96 hours. Aqueous humor dynamics were determined 24 hours after the 10(-5) M ET-1 injection. Aqueous humor formation, measured fluorophotometrically, was decreased by 58%. Total outflow facility increased by 94%, according to measurement by two-level constant pressure perfusion. The change of uveoscleral outflow determined by fluorescein-dextran perfusion was not significant. The decrease in aqueous flow and the increase in total facility accounted for most of the IOP reduction after the ET-1 injection. Endothelin, which is endogenously present in the eye, may play a role in the regulation of intraocular pressure.

Animals↗

[Prospective study on the influence of social activity on development of dementia in the neurologically normal elderly].

We investigated the rate of development of dementia in 84 neurologically normal elderly subjects living in an old-age home (30 subjects, mean 77.2 years) or their own home 954, 73.7) prospectively. We examined cerebral blood flow (CBF), Hasegawa's scale (HS) and Kohs' block design test 6 to 9 years before this study (1991). HS and Kohs' IQ were significantly lower in the old-age home group than that in their own home group at that time. However, there were no demented subjects. Mortality was 21%, and we confirmed 9 dementia and 6 stroke cases during the period of observation. Twenty-seven percent of the old-age home group showed dementia in 1991. This rate was significantly higher than that for the elderly living in their own home (6.7%). Occurrence of stroke was also significantly higher in the former group than in the latter group. The subjects who developed stroke during observation showed a high incidence of dementia. Mean CBF measured on the first examination was significantly lower in dementia cases with stroke than in dementia cases without it. We performed MRI in 4 demented cases in 1991 (Fig. 1). Two cases showed no significant lesions and the other cases showed cerebral infarction which could cause dementia. These results indicate that life style and social environment may have significant effect on aging of the brain and on development of dementia in the elderly.

Aged↗

[Thoracoscopic observation and diagnosis in cases of pleural, mediastinal, and pulmonary lesions].

Thoracoscopy was performed in a total of 424 patients at our institute from January 1970 to December 1993. The indications for thoracoscopy were pneumothorax (121 cases), primary lung cancer (98 cases), mediastinal tumor (45 cases), metastatic lung tumor (23 cases), pleuritis (35 cases), diffuse lung disease (38 cases), tuberculosis (20 cases), benign lung tumor (10 cases), and other (34 cases). By 1990, diagnostic thoracoscopy had been performed in 383 patients. Since 1991, thoracoscopy has been used therapeutically for spontaneous pneumothorax (24 cases), mediastinal and chest wall tumors (9 cases), pulmonary nodules (2 cases), and others (8 cases). Findings useful for diagnosis were obtained in 326 cases and biopsy was performed in 173 cases. Thoracoscopy was especially useful in the diagnosis of diffuse lung disease, pleuritis, and small pulmonary nodules. Recent advances in endoscopic equipment and refinement of thoracoscopic techniques have expanded the application of this procedure. Our experience indicates a markedly expanded role for thoracoscopy in the diagnosis and treatment of thoracic diseases, with less postoperative morbidity.

Humans↗

Retinal detachment with tear in the posterior fundus following ocular contusion.

Two unusual cases of rhegmatogenous retinal detachment following contusion to the eyeball showed retinal tears at the posterior fundus close to the optic disc and the large retinal blood vessels. In both cases, the tears were not detected immediately after the injury due to a coexisting vitreous hemorrhage. Both patients were successfully treated by pars plana vitrectomy, air-fluid exchange, and endolaser photocoagulation. During vitrectomies, an adhesion of the vitreous to the flap or the operculum of the tear was observed, with detachment of the remainder of the posterior vitreous from the retina. Vitrectomy allowed a more complete resolution of posterior tractional forces than scleral buckling, and eliminated the vitreous hemorrhage.

Adult↗

[Two cases of membranous glomerulonephritis associated with hepatitis C virus infection].

Although the occasional occurrence of glomerulonephritis associated with hepatitis C virus (HCV) infection has been reported recently in the literature, the type described has been mainly membranoproliferative glomerulonephritis (MPGN); membranous glomerulonephritis (MGN) is very rare. In this paper, two cases of MGN associated with HCV infection are reported. Case 1 was a 56-year-old male who had positive HCV Ab and HCV RNA. The diagnosis of chronic active hepatitis was verified by liver biopsy. Laboratory data showed proteinuria (5g per day), hematuria and hypocomplementemia by hemolytic assay. Renal biopsy led to the diagnosis of MGN in stage II. The patient was treated with interferon alpha for 6 months, resulting in improvement of hypocomplementemia, transient reduction of GOT and GPT during the course of treatment. The GOT and GPT were aggravated again after the completion of therapy. No improvement was seen in proteinuria and hematuria, and HCV Ab remained positive. Case 2 was a 69-year-old male who had positive HCV Ab and HCV RNA, and had normal liver function. Subsequently, his GOT value was slightly elevated. Proteinuria (2g per day) was demonstrated. The diagnosis of MGN in stage II was made on the basis of renal biopsy. The clinical characteristics of these two cases suggest that MGN is a type of glomerulonephritis associated with HCV infection.

Aged↗

[A case of thoracic empyema extended into the abdominal cavity].

A case of thoracic empyema after artificial pneumothorax for lung tuberculosis was presented, which extended into the abdominal cavity. 65 years old man, who was operated on for lung tuberculosis about 30 years ago, took the routine physical examination and the abdominal mass was picked up on examination. Echogram and CT showed huge homogeneous mass in the right thorax and the right upper abdominal cavity. The operative finding showed that thoracic empyema extended into the abdominal cavity and formed a huge mass. Decortication and extirpation of thoracic empyema and abdominal mass was performed with a combined partial resection of the lung, diaphragma, and thoracic wall. The histopathology of the abdominal mass showed chronic empyema and hematoma.

Abdomen↗

An autopsy case of licorice-induced hypokalemic rhabdomyolysis associated with acute renal failure: special reference to profound calcium deposition in skeletal and cardiac muscle.

A 78-year-old man was hospitalized because of muscular weakness and acute renal failure. He had been taking glycyrrhizin (280 mg/day) for the last 7 years. Hypertension was noted in his history. Serum potassium was 1.9 mEq/l with metabolic alkalosis. There was hyporeninemic hypoaldosteronism. Serum enzymes, including GOT, LDH and CPK were markedly elevated. In addition, serum myoglobin was as high as 46 micrograms/ml with massive myoglobinuria. Oliguria occurred and blood urea nitrogen and serum creatinine rapidly elevated from 20.9 to 87 mg/dl and from 1.3 to 6.7 mg/dl, respectively. Profound calcium deposition was found in the damaged skeletal muscles, including the quadriceps femoris, axillar, neck, and cardiac muscles. These results indicate that licorice-induced pseudoaldosteronism produces hypokalemic rhabdomyolysis, resulting in acute renal failure and profound deposition of calcium into the damaged skeletal and cardiac muscles.

Acute Kidney Injury↗

[Anterior segment of the eye and cranial nervous (II, III, VI, VII) infiltration in relapsing acute lymphoblastic leukemia (L1)].

A 42-year-old male was admitted with nasal bleeding. On admission he showed no abnormal neurological sign. A diagnosis of acute lymphoblastic leukemia (ALL) (L1) was made, and modified L-10M protocol was performed. During consolidation chemotherapy, the bone marrow was in remission but he showed left facial palsy. Four days after the onset of left facial palsy, the patient developed bilateral facial palsy followed by left oculomotor and abducens nerve palsy. At this time, bilateral ocular fundus showed papilloedema, exudate, bleeding, Roth's spot and leukemic infiltration to the anterior segment of the eye. Systemic chemotherapy with intrathecal injection of anti-leukemic drugs and whole brain irradiation was partially successful against cranial nervous system (CNS) complaints, but the patient relapsed. Seven month later hypopyon and secondary glaucoma developed and trabeculectomy was performed. The bone marrow revealed an increase of leukemic blasts. Chemotherapy consisting of various drugs was not effective, and he died of pneumonia. In this case, although intrathecal chemotherapy and whole brain irradiation were attempted, leukemia evolved CNS, retina and uvea despite the fact that the bone marrow was in complete remission, allowing various cranial nerve signs and ocular manifestations to occur.

Abducens Nerve↗

[Evaluation of medicinal lymph node dissection in advanced gastric cancer].

In order to improve the results of surgical treatment in advanced gastric cancer, we performed preoperative targeted chemotherapy for metastatic lymph nodes. The solution which contained aclarubicin adsorbed on activated carbon was submucously injected around gastric tumor under endoscopic observation 2-7 days prior to the operation. We termed this method medicinal lymph node dissection (MLD). Our standard surgical treatment (SST) for gastric cancer consists of gastrectomy and extended lymph node dissection (N1 and N2 lymph nodes). Patients of curative resection with histologically positive lymph node metastasis were enrolled, as the subjects. We compared the cumulative survival rate in 47 patients treated with SST+MLD (MLD group) with that in 125 patients treated with SST only (control group). Five year survival rates in the MLD and control groups were 60% and 48%, respectively. The MLD group showed significantly higher survival rate in patients with N3, N4 and infrapyloric lymph node metastasis. A significant difference of the survival rate suggests the efficacy of SST+MLD against micrometastasis in N3 and para-aortic lymph nodes. The SST+MLD therapy is recommended to the advanced gastric cancer, especially in the lower third of the stomach.

Aclarubicin↗

Staphylococcal neutral phosphatase. A highly cationic molecule with binding properties for immunoglobulin.

Staphylococcal neutral phosphatase (NPtase) was purified from two Staphylococcus aureus strains by sequential high salt extraction, ultracentrifugation and ion exchange chromatography. The enzyme showed maximum phosphatase activity at neutral pH, appeared as two bands in SDS-PAGE (31 and 32 kDa), and the isoelectric point was > 10. No close similarity between NPtase and other known bacterial proteins in respect of their N-terminal amino acid sequences was found. Purified NPtase bound rat and human polyclonal IgG [intact and F(ab')2 fragments], IgM, IgA, intact myeloma immunoglobulins, myeloma light chains, gamma heavy chain and, with a much lower affinity, Fc fragments. Furthermore, NPtase can bind serum albumin. Heparin, a highly negatively charged molecule, significantly inhibited NPtase binding to immunoglobulins and HSA, but did not inhibit the binding of specific antibodies to NPtase; this indicates that charge interactions are important. The newly characterized staphylococcal phosphatase with binding properties for immunoglobulin is an interesting bacterial protein that could be involved in post-infectious sequelae.

Amino Acid Sequence↗

Computerized tomography of two patients with morning glory syndrome.

Morning glory syndrome (MGS), an uncommon optic disc anomaly, is characterized by a funnel-shaped, excavated optic disc surrounded by chorioretinal pigmentary disturbance. Generally, it is an isolated ocular abnormality. The authors describe two patients in whom MGS developed in association with brain abnormalities. In both cases, there was enlargement of the optic nerve that showed increased radiodensity similar to that of sclera and cavum vergae in the brain cavity present in computerized tomography (CT). To our knowledge, the coexistence of MGS, cavum vergae and an enlarged retrobulbar optic nerve showing increased radiodensity have not been previously reported. The findings suggest that MGS may be based on a developmental anomaly involving the brain, and the enlarged optic nerve may be associated with sclera because of the isodensity in CT.

Adult↗

[Atrial pacing with the A-V paceport pulmonary artery catheter].

Atrial pacing is often necessary during cardiac surgery. A total of 20 patients undergoing cardiac surgery were atrially paced with either a multipurpose pulmonary artery catheter (PAC) or an A-V paceport PAC (n = 10 each). Atrial pacing was successful in all the patients before cardiopulmonary bypass. The output threshold was 4.2 +/- 0.7 mA for a multipurpose PAC and 3.8 +/- 0.7 mA for A-V paceport PAC. Atrial pacing with both PAC's was readily performed and useful during cardiac surgery.

Catheterization↗

Evaluation of laboratory parameters reflecting activity of lupus nephritis in children: indicators of severe renal lesions.

Assessment of activity of lupus nephritis is critical in the management and ultimate prognosis of patients. Clinical and laboratory data of 18 children with lupus nephritis were examined to determine what factors reflect activity of renal lesions. Using a histologic scoring system with an activity index (AI) and a chronicity index (CI), correlations between histologic scores and laboratory parameters were analyzed. Serum total protein, albumin and complement at the time of renal biopsy inversely correlated with the AI, but not parameters correlated with the CI. Serum complement levels correlated inversely with the amount of glomerular immune deposits, while the AI and CI correlated with the amount of immune deposits. These results suggest that hypoalbuminemia and hypocomplementemia are indicators of severe, active lupus nephritis, pointing to the need for early renal biopsy and intensive therapy.

Adolescent↗