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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 469 records · Page 26Linked to original sources

Corticotropin-releasing factor up-regulates its own receptor gene expression in corticotropic adenoma cells in vitro.

To investigate the expression of CRF receptor (CRF-R) in human corticotropic adenoma (hCA) cells, we analyzed messenger RNA (mRNA) levels of type-1 CRF-R (CRF-R1). Adenomas were obtained from 10 patients with Cushing's disease. Northern blot analysis using a rat CRF-R1 complementary RNA probe revealed a main hybridization band of 2.7 kilobases in all the hCAs. The CRF-R1 mRNA level significantly increased after 1 h, reached 15-fold the basal level at 8 h, and remained elevated 24 h after the addition of 10 nmol/L CRF in vitro. Dose dependency of the stimulatory effect of CRF was also demonstrated in hCA cells, whereas CRF down-regulated CRF-R1 mRNA levels in rat anterior pituitary (AP) cells. Treatment with dexamethasone or vasopressin decreased the CRF-R1 mRNA level in hCA cells, as observed in rat AP cells. In conclusion, we detected CRF-R1 mRNA in all hCAs tested. The CRF-R1 mRNA level was up-regulated by CRF itself in cultured hCA cells, in contrast to the down-regulation in rat AP cells.

Adenoma↗

Effects of hyperosmotic NaCl and glycerol stress on stress response of human HeLa cells.

The maintenance of intracellular osmotic pressure is of fundamental importance for cell survival. Since osmoregulatory processes are important to all living organisms, large fluctuations in environmental osmolarity may elicit or modulate stress responses. We examined whether hyperosmotic stress induced or modulated stress responses in human HeLa cells. When HeLa cells were incubated in medium supplemented with 50-150 mM NaCl or 0.2-1.0 M glycerol for 3-27 h, the stress response, analyzed at the levels of HSP70 synthesis, HSP70 mRNA accumulation, and heat shock transcription factor (HSF) activation, was not induced by either hyperosmotic stress. In hyperosmotic 150 mM NaCl or 1.0 M glycerol medium, the stress response to heat shock was inhibited at the levels of HSF activation, HSP70 mRNA accumulation, and HSP70 synthesis. In vitro activation of HSF showed that inhibition of this activation by hyperosmotic NaCl or glycerol stress was not irreversible. Furthermore, addition of the physiological osmolyte betaine to medium reversed the inhibition of heat-induced HSP70 synthesis under hyperosmotic NaCl stress but not under hyperosmotic glycerol stress. The effect of betaine against hyperosmotic NaCl stress was observed mainly at the translation level, and betaine seemed to enable cells to translate HSP70 mRNA specifically under heat shock conditions by restoring protein synthetic ability.

Betaine↗

Effects of various doses of intracoronary verapamil on coronary resistance vessels in humans.

To investigate the vasodilatory effect of various doses of intracoronary verapamil on coronary resistance vessels, we studied 13 patients with normal angiograms. A coronary Doppler guide wire was inserted into the left anterior descending coronary artery, and coronary blood flow velocity (CBFV) was measured. Verapamil was injected into the left coronary artery at doses of 0.1 mg, 0.5 mg, 1.0 mg, and 2.0 mg at 10-min intervals. Nitroglycerin was also injected into the same artery to avoid changes in cross-sectional area. As a measure of coronary vascular resistance, coronary vascular resistance index (CVRI) was calculated as the quotient of mean aortic pressure/CBFV. An injection of verapamil produced a dose-dependent increase in CBFV: 79 +/- 38% with 0.1 mg, 131 +/- 56% with 0.5 mg, 143 +/- 46% with 1.0 mg, and 128 +/- 47% with 2.0 mg of verapamil. The percent peak decreases in CVRI were dose dependent: -42 +/- 13% with 0.1 mg, -50 +/- 17% with 0.5 mg, -62 +/- 14% with 1.0 mg, and -60 +/- 9% with 2.0 mg of verapamil. Thus, intracoronary verapamil produces a dose-dependent dilation of coronary resistance vessels, and the optimal effect is produced with an injection of verapamil at a dose of 1.0 mg into the left coronary artery. At this dose, verapamil did not affect atrioventricular conduction.

Adult↗

Profiles of insulin-like growth factor binding proteins and the protease activity in the maternal circulation and its local regulation between placenta and decidua.

Insulin-like growth factors (IGF) and their specific binding proteins (IGFBPs) are believed to be important regulators of fetal growth. IGFBP protease which proteolyzes IGFBPs and changes the biochemical properties of IGFBPs is also presumed to be involved in fetal growth. The aim of this study is to elucidate the physiological significance of IGFBP protease in fetal growth and regulators of protease in placenta and decidua. The intact IGFBP-3 was proteolyzed into fragments when pregnant serum was incubated with 125I-IGFBP-3. IGFBP-3 protease activity showed a marked increase at 5 weeks of gestation and reached a plateau in maternal circulation at 15 weeks of gestation. These changes in protease activity correlated with the profiles of IGFBPs in the maternal circulation analyzed by Western ligand blot, where the IGFBP-1 is only the dominant IGFBP. The intact IGFBP-3 was proteolyzed when culture media of decidual cells were incubated with 125I-IGFBP-3, but was not proteolyzed when culture media of trophoblast cells were incubated with 125I-IGFBP-3. Decidual protease activity was slightly increased by IGF-I and completely inhibited by progesterone. The protease activity was more increased in the mothers with growth retarded infant than in those in the mothers with normal growth infants, suggesting that the protease activity is elevated in compensation for the impaired fetal growth. These results suggest that increased protease activity in maternal blood may be involved in the fetal growth indirectly by reducing the binding activity of IGFBP-3 to IGF-I, and that protease activity in maternal blood may be derived from decidua that is regulated by placental hormones.

Adult↗

Desmopressin stimulation test for diagnosis of ACTH-dependent Cushing's syndrome.

We evaluated the usefulness of a desmopressin (DDAVP) test in the diagnosis of ACTH-dependent Cushing's syndrome. After an intravenous injection of 5 microg DDAVP, plasma ACTH levels increased to more than 200% of the basal levels in 10 of 10 patients with Cushing's disease, but remained less than 150% in all of 11 normal subjects, 3 patients with Addison's disease, 5 cases of Cushing's disease in remission, and 3 patients with ectopic ACTH syndrome. Peak levels of plasma cortisol after the DDAVP stimulation were 159 +/- 14% in the patients with Cushing's disease, and less than 150% of the basal levels in the other 5 groups. We also found a case of Cushing's disease with periodicity which responded to DDAVP only in the active stage. In vitro studies revealed that DDAVP directly stimulates ACTH release from corticotropic adenoma cells through V1b but not V2 vasopressin receptors. In conclusion, the DDAVP stimulation test, i.e., determination of plasma ACTH levels after 5 microg DDAVP injection, seems useful for discriminating Cushing's disease from normality, and may serve to facilitate the differentiation between Cushing's disease and ectopic ACTH syndrome.

Adenoma↗

Distal acinar emphysema and interstitial pneumonia in a patient with von Recklinghausen's disease: five-year observation following quitting smoking.

Cystic lesion, malignancy and interstitial pneumonia are well-known as pulmonary complications of patients with von Recklinghausen's disease. We report herein an unusual patient with distal acinar emphysema and interstitial pneumonia of prominent hypercellularity demonstrated by transbronchial biopsy and broncho-alveolar lavage fluid (BALF). Six months after quitting smoking, the total cell count of BALF was remarkably reduced. This patient remains stable under 5-year observation in terms of symptoms and findings of both BALF and pulmonary function tests. Quitting smoking may have facilitated a favorable prognosis for the particular lung disease complicated in this patient.

Bronchoalveolar Lavage Fluid↗

Sinus pericranii associated with a cerebellar venous angioma--case report.

A 64-year-old male presented with sinus pericranii associated with a venous angioma draining through a large venous lake. Increased venous pressure and flow in the dural venous lake in contact with the venous sinus may have developed the sinus pericranii. Three-dimensional computed tomography was very useful in determining the site of the transcranial venous anastomotic channels, and magnetic resonance imaging was also very useful in detecting the intracranial vascular anomalies.

Cerebral Veins↗

Stromal invasion by carcinoma of the cervix: assessment with dynamic MR imaging.

OBJECTIVE: The purpose of this study was to evaluate dynamic MR imaging in assessing the depth of stromal invasion by carcinoma of the cervix and to compare dynamic MR imaging with T2-weighted and contrast-enhanced T1-weighted MR imaging. SUBJECTS AND METHODS: Forty-one patients with carcinoma that was clinically considered to be confined to the cervix were examined with T2-weighted, dynamic, and contrast-enhanced T1-weighted MR imaging before surgery. We evaluated enhancement patterns of the cervix and tumor and assessed the degree of stromal invasion with MR imaging. The degree of stromal invasion was divided into two groups: superficial disease (no stromal invasion or invasion of < or = 3 mm) and deep invasion (> 3 mm of stromal invasion). Then we compared these MR findings with histologic results for the depth of stromal invasion. RESULTS: With dynamic MR imaging, cervical carcinoma with deep invasion was seen as a focal enhanced area in the early dynamic phase. The cervical epithelium and stroma enhanced less vividly. In distinguishing deep invasion from superficial disease, we found the accuracy of T2-weighted MR images, dynamic MR images, and contrast-enhanced T1-weighted MR images to be 76%, 98%, and 63%, respectively. In particular, the detectability of 3.1-5.0 mm of stromal invasion with dynamic MR images was significantly higher than that with the other techniques: with T2-weighted MR images, we saw 3.1-5.0 mm of stromal invasion in 23% of patients; with dynamic MR images, in 92%; and with contrast-enhanced T1-weighted MR images, in none. Superficial disease was not revealed with any of the three MR techniques. CONCLUSION: We believe that dynamic MR imaging is superior to T2-weighted MR imaging and contrast-enhanced T1-weighted MR imaging when assessing the depth of invasion of cervical carcinoma.

Adenocarcinoma↗

[The effects of preventive regimens for the prophylaxis of infection after bone marrow transplantation].

The effects of regimens on the prevention of infection in 42 adult leukemia patients receiving bone marrow transplantation was analyzed. Standard risk patients (transplantation in 1st remission of acute leukemia and chronic phase of chronic myelogeneous leukemia received marrow from HLA compatible sibling or autologous marrow) showed shorter febrile days than high risk patients (transplantation in more advanced stage of leukemia and transplantation from unrelated donor), 1.33 mean days vs. 4.93 mean days respectively. Poorer intake of non-absorved antibiotics resulted in higher rate of bacterial colonization in stool after transplantation. And that, the degree of gut sterilization correlated with the duration of febrile days during the period of less than 100/microliter peripheral neutrophil count in high risk patients. Thus, prophylactic regimens of infection in bone marrow transplantation should be considered according to the risk of patient, that is, more practical and complete prophylaxis in risk patients and more conventional one in standard risk patients.

Adult↗

Followup study of renal function in children with reflux nephropathy after resolution of vesicoureteral reflux.

PURPOSE: We evaluated data collected for 10 years on children with reflux nephropathy to identify a means of predicting the prognosis. MATERIALS AND METHODS: A total of 15 boys and 13 girls were enrolled in this study at least 2 years after surgical and spontaneous resolution of vesicoureteral reflux in 25 and 3 patients, respectively. They were followed for more than 10 years and renal function was periodically evaluated. Urinary beta 2-microglobulin, alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, microalbumin and 99mtechnetium dimercapto-succinic acid uptake were measured. RESULTS: Of the 28 patients 12 had high levels of urinary alpha 1-microglobulin during followup, including all 7 in whom renal function deteriorated. In 3 children with elevated alpha 1-microglobulin urinary microalbumin gradually increased after puberty. Although elevated levels of urinary beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase and microalbumin were also observed, they were less predictive of renal function than alpha 1-microglobulin. CONCLUSIONS: These results suggest that elevated urinary levels of alpha 1-microglobulin may predict the risk of abnormal renal function in children with reflux nephropathy even before the appearance of significant proteinuria.

Acetylglucosaminidase↗

Large vestibular aqueduct syndrome with high CT density and high MR signal intensity.

We report a case of large vestibular aqueduct syndrome with a markedly dilated endolymphatic sac bilaterally. The density and signal intensity of the extraosseous portion of the sac were higher than those of cerebrospinal fluid on CT and MR studies. The findings may represent protein-rich and hyperosmolar fluid within the endolymphatic sac.

Adult↗

[Histological findings of specimens obtained by directional coronary atherectomy from patients with acute myocardial infarction].

The histological characteristics of acute myocardial infarction were examined in specimens obtained from infarct-related coronary artery lesions (20 left anterior descending artery, 2 left circumflex artery, 8 right coronary artery) in 30 patients with initial acute myocardial infarction who underwent directional coronary atherectomy following intracoronary thrombolysis within 6 hours after the onset of chest pain. Resected tissues were fixed in 10% buffered formalin and embedded in paraffin, and the 4 microns-thick paraffin sections were stained with hematoxylin-eosin and examined by light microscopy. Thrombus and/ or intramural hemorrhage were present in all samples. There were high incidences of cholesterol cleft in 19 (63%), foam cell in 21 (70%), calcium deposit in 19 (63%) and intimal proliferation in 16 (53%). These data suggest that thrombus and/or intramural hemorrhage are important in the onset of acute myocardial infarction.

Aged↗

Urinary excretion of epidermal growth factor in children with reflux nephropathy.

PURPOSE: We determined urinary levels of epidermal growth factor in children with reflux nephropathy to evaluate the clinical significance of urinary epidermal growth factor. MATERIALS AND METHODS: We studied 59 boys and 41 girls 3 to 15 years old with reflux nephropathy, and 64 boys and 36 girls 3 to 15 years old who were healthy. Levels of urinary epidermal growth factor were determined by sandwich enzyme immunoassay using spot urine samples. We also determined the levels of serum creatinine, urinary alpha 1-microglobulin and urinary microalbumin. Absolute values of function of the left and right kidneys were assessed by 99mtechnetium dimercapto-succinic acid (DMSA) uptake. RESULTS: Levels of urinary epidermal growth factor gradually decreased with age in healthy children. There were low levels of urinary epidermal growth factor in 20 of the 44 patients (45%) with unilateral low DMSA uptake and 18 of the 19 (95%) with low total DMSA uptake (right and left uptakes). Urinary epidermal growth factor significantly correlated with serum creatinine (R = -0.702, p < 0.0001), urinary alpha 1-microglobulin (R = -0.606, p < 0.0001), urinary microalbumin (R = -0.708, p < 0.0001) and total DMSA uptake (R = 0.744, p < 0.0001). CONCLUSIONS: These results suggest that urinary epidermal growth factor may be a useful clinical tool to monitor functional nephron mass in children with reflux nephropathy.

Adolescent↗

Comparison between urea removal in hemodialysis and continuous ambulatory peritoneal dialysis using a mathematical kinetic model.

Urea removal by continuous ambulatory peritoneal dialysis (CAPD) was compared with that by hemodialysis (HD) using a mathematical kinetic model. The time-averaged urea-nitrogen concentration (TAC) in the blood of a patient on maintenance HD was calculated by the model. Clearance with HD giving a TAC value equal to the constant urea-nitrogen concentration in the blood of a patient on CAPD was obtained, leading to the relation of equivalent clearances between HD and CAPD on the assumption that the urea-generation rate of the patient on CAPD was equal to that of the patient on HD.

Blood Urea Nitrogen↗

[Somatotopical mapping of the human somatosensory cortex with echo-planar MRI].

The somatotopical organization of the somatosensory cortex was analyzed. Echo-planar imaging was used to obtain functional images, and magnetic field strength was 1.5T. Natural stimulation at a frequency of 3 Hz (scrubbing or tapping) was applied to one of the three cutaneous areas: toes, fingertips, and tongue tip. The focal bands which show the significant signal increases were located on the contralateral post-central gyrus, and these changes of signal intensity originate from the cortical parenchyma because there were no major veins in the central sulcus. The focal bands which respond to each stimulation sites were anatomically distinct and located medially-to-laterally in the order of toes, fingertips, and tongue tip.

Adult↗

Pharmacological properties of the new centrally acting muscle relaxant (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride.

The pharmacological properties of (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride (CAS 144576-50-1, MS-322), a new centrally acting muscle relaxant, were investigated and compared with those of eperisone-HCl (CAS 56839-43-1) in experimental animals. MS-322 (1.5-6 mg/kg i.v.) reduced both anemic and intercollicular decerebration-induced rigidity in rats. Similar doses were required for these effects. The activity of MS-322 (200 mg/kg p.o.) against intercollicular decerebration-induced rigidity was greater and longer lasting than that of the same dose of eperisone-HCl. MS-322 (0.75-6 mg/ kg i.v.) inhibited the flexor reflex in anesthetized cats in a dose-dependent manner and more strongly than eperisone-HCl. MS-322 had no effect on the neuromuscular junction in anesthetized rats. The muscle relaxant activity of MS-322 in mice, demonstrated by the traction and rota-rod tests was stronger than that of eperisone-HCl, whereas MS-322 affected spontaneous motor activity in mice less than eperisone-HCl. The results of this study suggest that MS-322 is a potent centrally acting muscle relaxant with relatively weak depressant activity at other central nervous system pathways.

Animals↗

[Surgical result of left ventricular free wall rupture complicating acute myocardial infarction].

From 1980 to 1995, we experienced 20 cases of surgical repair for left ventricular free wall rupture complicating acute myocardial infarction. These were divided into three types based on their clinical symptoms; 10 of the sudden blowout type, 4 of the rapid blowout type and 6 of the oozing type. In the rapid type, unconsciousness following the onset of the blowout rupture was restored by cardiopulmonary resuscitation (CPR) or pericardiocentesis. Seven out 20 cases (35%) survived. In the sudden blowout type, only one case treated by using the pericardial patch gluing technique without cardiopulmonary bypass survived. Three out of 4 cases (75%) of the rapid blow out type survived. Three out 6 cases (50%) of the oozing type survived. The causes of death were classified as table death for 5 cases, LOS for 1 case, and cerebral death for 3 cases of the 9 fatal cases of the sudden blowout type. Hemostasis was very difficult in 1 case of the rapid type. The 3 cases of the oozing type died respectively of LOS, cerebral death and pneumonia after surgery. Pericardiocentesis or subxyphoid drainage was performed preceding the repair of the rupture in 4 cases of the rapid blowout, and in 5 cases of the oozing type. However, re-rupture occurred in 2 cases of the rapid type and in 2 cases of the oozing type. In 7 cases in whom pericardial patch gluing technique was applied, a procedure in use since 1990, all cases were safely weaned from CPB, with 4 cases out of 7 (57%) surviving. Meanwhile, in 13 cases in which infarctectomy and myocardiography was carried out, 5 cases (38%) could not be weaned from CPB. Three cases (23%) survived after infarctectomy and myocardiography. Even some cases of blowout rupture were able to survive as long as blood pressure was elevated and consciousness was restored by CPR or pericardiocentesis as in cases of the rapid type. The pericardial patch gluing technique at the infarct site proved to be an effective procedure.

Aged↗