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Biomedical subjects

T Ichikawa

Publications and source records attributed to T Ichikawa.

At least 415 records · Page 23Linked to original sources

Dose-dependent pharmacokinetics of glycyrrhizin in rats.

The dose-dependent pharmacokinetics of glycyrrhizin (GLZ) was investigated by measuring drug disappearance from plasma and biliary excretion in rats. The decline in plasma concentration was biexponential after an i.v. dose of 5, 10, 20, or 50 mg/kg. Dosage, however, had a marked effect on the pharmacokinetics, with a greater-than-proportional increase in area under the plasma concentration curve (AUC) at doses of 20 and 50 mg/kg, even though the increase was proportional at doses of 5 and 10 mg/kg. There was also a significant increase of the steady-state distribution volume (Vdss), as well as significant decreases in total body (CLtot) and biliary (CLB) clearances, at 20 and 50 mg/kg from those at 5-10 and 5-20 mg/kg, respectively. The AUC, Vdss, and renal clearance (CLR) at a given dose showed no significant difference between rats with and without bile fistulas. The plasma unbound fraction (fp) (0.006-0.026) increased with increasing plasma GLZ concentration over the observed range (2-900 micrograms/ml). No significant change in Vdss for unbound GLZ was observed between the doses, indicating that the distribution of GLZ into tissues is not changed by an increase in dose. On the other hand, a dose dependency in CLtot for unbound GLZ was observed and confirmed to be attributed to dose dependency in CLB for unbound GLZ since there was no significant difference in CLR or metabolic clearance for unbound GLZ between the doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glycyrrhizin binding site on human serum albumin.

The binding site of glycyrrhizin (GLZ) on human serum albumin was detected through competitive displacement experiments with GLZ and ibuprofen (IBU) (diazepam site), warfarin (WAR), salicylate (SAL) (digitoxin site), or deoxycholic acid (DCA) by means of an ultrafiltration technique. The specific binding of GLZ was subject to competitive inhibition by IBU, WAR, SAL, or DCA (1 or 4 mM). The extent of displacement was in the order of: DCA greater than IBU greater than WAR greater than SAL. Conversely, the specific bindings of WAR and DCA and the low-affinity bindings of IBU and SAL were subject to competitive inhibition by GLZ (1 or 4 mM). The extent of inhibition by GLZ was in the order of DCA greater than IBU greater than WAR not equal to SAL. In addition, the low-affinity IBU binding and the specific DCA binding showed mutual competitive inhibition at 4 mM, with almost identical displacements. It was concluded that the specific GLZ binding site on human serum albumin may be located mostly within the low-affinity IBU binding site area (probably the same as the specific DCA binding site area) and partially within the specific WAR binding site area and the low-affinity SAL binding site area.

Binding Sites↗

Recombinant mouse prolactin: expression in Escherichia coli, purification and biological activity.

Transformation of Escherichia coli cells with a recombinant plasmid containing modified mouse prolactin (mPRL) cDNA and a pKK223-3 vector resulted in efficient expression of mPRL protein. Cloned mPRL cDNA was modified by removing the 5' non-translating sequence as well as the sequence which encoded the signal peptide of preprolactin for recombination. In addition, approximately 100 nucleotides of the 5'-terminal region of the cDNA, which include the ATG initiation codon and the following 31 codons of mature mPRL, were replaced by a chemically synthesized oligonucleotide duplex. The sequence of this duplex was chosen to be rich in AT without changing the amino acid sequence of the protein. The modified cDNA was finally inserted into the multicopy plasmid, pUC19, before high-level expression of mPRL in E. coli cells was obtained. Western blotting analysis of total protein from transformed E. coli cells showed that both 23 and 16 kDa peptides were recognized by specific mPRL antisera. The purified and refolded 23 kDa protein exhibited a growth-stimulating effect on rat Nb 2 Node lymphoma cells, and was very similar to that of natural pituitary PRL.

Amino Acid Sequence↗

Clinical evaluation of pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2.

We have previously described the purification and partial characterization of a new pancreatic cancer-associated antigen, a pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. This study describes the clinical evaluation of various assay systems for this antigen which depend on measuring respective serum levels. Elevated levels of antigen were detected in the sera from both patients with malignant and non-malignant diseases. However, elevated serum levels of CA19-9 and Lewisa and Lewisb epitopes on moieties were restricted to pancreatic and biliary tract cancers, although adequate sensitivity was not attained. Coordinate evaluation of these three markers improved the sensitivity to some extent without loss of specificity for the diagnosis of pancreatic and biliary tract cancers, because of the heterogeneity of the coexpression of these epitopes. We developed additional assay systems with a combination of this antigen and two lectins (Bauhinia purpurea (BPA) and Vicia villosa (VVA)). Elevated levels of BPA- and VVA-reactive antigens were detected in 41% and 31%, respectively, of pancreatic cancer sera samples. Few patients with chronic pancreatitis had an elevated serum level of either antigen, and higher elevated levels of these markers were restricted to the sera of patients with malignancies. Our results suggest that this antigen is found in the sera of patients with various conditions and in the sera of normal subjects but that antigens bearing CA19-9 or Lewisa or Lewisb epitopes and an altered carbohydrate structure recognized by BPA and VVA lectins are preferentially present in the sera of patients with pancreatic and other malignancies.

Antigens, Neoplasm↗

Simultaneous determination of hydrogen, methane and carbon dioxide of breath using gas-solid chromatography.

The analysis of respiratory hydrogen and methane was estimated as a useful index of intestinal fermentation of undigestible carbohydrate. A simultaneous and precious analysis of these gases as well as carbon dioxide was studied. A gas-impermeable multi-laminated film bag metalized by aluminum vapor was fitted to use as a storage bag; its impermeability was verified by measuring the residual rate of hydrogen after 3 months' storage. Hydrogen, methane and carbon dioxide of the breath gas even at 1 ppm could be determined simultaneously by using a gas-solid chromatography installed with a photoionization detector and active carbon column. To observe the genesis of hydrogen and methane after carbohydrate ingestion, pectin, a typical water-soluble dietary fiber, was fed to healthy volunteers. Increasing excretion of pulmonary hydrogen or methane showed the sign of intestinal fermentation as the results of carbohydrate malabsorption.

Adult↗

[Brainstem glioma with supratentorial meningeal dissemination--a case report].

We present a very rare case of 7 year-old-girl who had a pontine glioma with supratentorial meningeal involvement. She complained severe headache with meningeal irritation. She showed fluctuating cranial nerve impairment of the both abducens and glosopharyngeal nerves but no signs of weakness or facial paresis. She also reported two episodes of generalized convulsion with unconsciousness during admission. MRI disclosed a hypointensity intrinsic brainstem mass with an enhancing exophytic component in the prepontine cistern and a sharp contrast uptake is disclosed in the left-meninges of the supratentrial structures. An open biopsy was performed and diagnosed as a high grade astrocytoma.

Astrocytoma↗

[A case of pre-Cushing's syndrome].

A 66-year-old female was admitted to Chiba University Hospital for the evaluation of a left adrenal mass which was incidentally discovered by computerized tomography. The patient had no clinical signs of Cushing's syndrome. Although the plasma ACTH level was suppressed, serum cortisol and urinary 17-OHCS levels were normal. Serum cortisol was not suppressed by dexamethasone and loss of diurnal rhythm of cortisol was observed. Uptake of 131I-aldosterone in the left adrenal gland was noted, but no accumulation was observed in the right one. Left adrenalectomy was performed. The tumor resected was 20 x 22 x 26 mm in size. Pathological diagnosis was adreno-cortical adenoma. Whether slight abnormality of adrenocortical function without clinical symptoms observed in the present case would develop into a clinically typical Cushing's syndrome remains to be solved.

Adenoma↗

[Two familial cases with exertion-induced heat stroke--relationship to malignant hyperthermia].

Two patients in a family of exertion-induced heat stroke were reported. Case 1: A 23-year-old male, paternal cousin of case 2, was admitted to our hospital because of loss of consciousness during running under a burning sun. On physical and neurological examinations, he was deeply comatose with high fever, tachycardia, and increased deep tendon reflexes. Laboratory findings disclosed rhabdomyolysis, acute renal failure, disseminated intravascular coagulation, liver injury, and brain edema. He recovered after intensive cooling, some antibiotics, glycerol and sodium dantrolene administration. Case 2: A 19-year-old male experienced loss of consciousness and high fever during playing soccer at 15 years of age, and was admitted to a hospital. On admission, he had high fever of 38.7 degrees C, and increased serum CK level. He recovered two weeks after admission. He was readmitted to our hospital to evaluate the predisposition for malignant hyperthermia. His physical and neurological examinations showed no abnormalities. Routine laboratory findings were within normal limits. Muscle biopsy findings of cases 1 and 2 were mildly increased number of fibers with centrally placed nuclei. Caffeine test on skinned muscle fibers from the biopsies showed normal response in both type 1 and 2 fibers. The present patients were diagnosed as having exertion-induced heat stroke, but with no increased muscle fiber sensitivity to caffeine, suggesting that the pathomechanism differs from that of malignant hyperthermia induced by malfunction of sarcoplasmic reticulum.

Adult↗

[An experimental study on repair and recovery of lacerated muscles--histological and histochemical observations].

A histological and histochemical study of the repairing process of skeletal muscle after transection and immediate suture was conducted using the gastrocnemius muscle of hamsters. The muscles were examined from one hour to twelve weeks after operation and were prepared as specimens for either transverse or longitudinal sections. During the first two days, necrotic fibers were scavenged by macrophages. Early regenerating fibers appeared at the extent of about 1-2 mm on both sides of the cut ends by the fourth day. After one week, myotubes identified as type 2C were abundant. By the fourth week regenerating fibers had grown longitudinally and bridged the injury site between the proximal and distal muscle fiber segments. After six weeks, they had almost matured histochemically. After eight weeks, there was substantial repair of the injury site with scarce fibrous tissue. This study has clearly demonstrated the histological and histochemical findings of repairing process of the skeletal muscle after transection.

Animals↗

[A comparative study of histopathological findings and CT images related to pancreatic carcinomas. An attempt at diagnosis in tissue characterization by CT].

From January 1980 to February 1991, computed tomography (CT) images of 39 patients with pancreatic carcinoma who had undergone surgery at the National Cancer Center Hospital were reviewed retrospectively. The average age of the patients was 63.0 years (the range was from 45 to 78), with 19 males and 20 females. The histopathological diagnosis was tubular adenocarcinoma in 35 cases, papillary adenocarcinoma in 2 and other diagnoses in 2. The tumor was located at the head of the pancreas in 25 cases and at the body and/or tail in 12. In the remaining 2 cases, the tumor was at the head and body in one, and at the whole pancreas in the other. The CT images were compared with the histopathological findings, and four parameters were determined to establish the histological characterization of pancreatic carcinomas in CT: density (plain CT, CE-CT) characteristics, margin of the tumor, and delayed contrast enhancement. CT findings such as irregular margin and heterogeneous characteristics of the tumor were associated with the macroscopic type of cut surface and INF. The infiltrative cancerous extension was especially reflective of the margin irregularity of the tumor on CE-CT. On the delayed CT scan performed on 9 patients, the low density tumor on early contrast enhanced CT became isodense with the surrounding parenchyma. According to these findings, the possibility exists that delayed contrast enhancement relate to fibrous tissue. In conclusion, there was a good correlation between CT images and histopathological findings related to pancreatic carcinomas.

Adenocarcinoma↗

[A novel model of autoimmune uveo-retinitis in nude mice grafted with embryonic rat thymuses].

When the T cell functions of congenitally athymic nude (nu/nu) mice were reconstituted by implantation of embryonic rat thymi (thymus grafted nude mice), uveoretinitis histologically characterized by complete loss of photoreceptor layer was found to develop spontaneously in 4.0, 18.2, 42. 9 and 70.4% of the mice at 3, 5, 7 and 12 months of age, respectively. In mice with uveoretinitis serum IgG antibody reacted with the retinal photoreceptor layer, and with interphotoreceptor retinoid-binding protein, but not with retinal S-antigen by immunoblot analysis and ELISA. The lesions could be transferred to syngeneic nude mice by splenic CD4+ T cells. This suggest that an autoimmune response to IRBP induced the uveoretinitis in thymus grafted nude mice.

Animals↗

[Hepatoblastoma: clinico-radiological study of fifteen cases].

From January 1976 to October 1989, 15 patients with hepatoblastoma who underwent surgery at the National Cancer Center Hospital were evaluated by clinico-radiological techniques. Eight patients were boys and seven were girls; their average age was 3 years and 5 months. Abdominal mass or distention was initially noted in 12 patients. Alpha-fetoprotein level was extremely high (average, 327 micrograms/ml) in all cases but one. Hepatitis B surface antigen was negative in all cases. Tumors occupied mainly the right lobe of the liver in 67% of patients, and the mean tumor diameter was 11.1 cm. Of 15 hepatoblastomas, 10 were grossly classified as massive type and five as multinodular. Histopathological diagnosis was well differentiated (fetal type) hepatoblastoma in 10 patients and poorly differentiated (embryonal type) hepatoblastoma in five. Fibrous capsule was also recognized in eight. The noncancerous liver was normal in all cases. Ultrasonography (US) (n = 7 patients) demonstrated an inhomogeneous internal echo with well demarcated margin in five cases and without such margin in two. Nonenhanced CT (n = 6) showed an isodense or low density mass in all cases. Drip infusion CT (n = 5) revealed isodensity in the early phase. Dynamic CT performed in one patient showed a well enhanced mass that appeared hypervascular on angiography. Preoperative chemotherapy and radiation therapy provoked histological changes such as necrosis, fibrosis and calcifications. These changes were reflected on CT images. Both US and CT demonstrated the characteristic internal structure and gross appearance of hepatoblastoma.

Adolescent↗

Production of an antiserum using a fusion protein produced by a cDNA for rat choline acetyltransferase.

A fusion protein produced by a cDNA for rat choline acetyltransferase (ChAT) inserted into a translation vector was used for immunization of rabbits. An antiserum was obtained that could recognize a single protein band in immunoblot analysis of a partially purified enzyme preparation of the rat brain. The antiserum revealed ChAT immunoreactivity in the motoneurons and terminal-like structures in the neuropil of the ventral horn in cryostat sections of the cervical spinal cord of the rat. This antiserum may be of particular use to study the development of the cholinergic neuron.

Animals↗

[Imaging diagnosis of small hepatocellular carcinoma by CT during arterial portography and Lipiodol-CT].

To evaluate the rates of detection for CT during arterial portography (CTAP) and Lipiodol-CT in small hepatocellular carcinoma (HCC), including early stage HCC, a comparative prospective study was performed in 24 candidates for surgery with 39 histopathologically proved lesions: eight lesions of early HCC, four of early advanced HCC and 27 of advanced HCC. The following results were obtained. 1) Ten of 24 patients had multiple primary HCC foci, 70% of which were, moreover, located in different segments. 2) Detection rates for digital subtraction angiography (DSA), CTAP and Lipiodol-CT were 67%, 87% and 72%, respectively. For 13 lesions undetected by DSA, the detection rates for CTAP and Lipiodol-CT were 62% and 31%. 3) For small HCC (n = 16) of less than 2 cm in diameter, CTAP (75%) tended to be superior to Lipiodol-CT (44%). 4) For early HCC (n = 8), CTAP (63%) showed a significantly higher detection rate than Lipiodol-CT (25%). 5) In contrast, detection rates for small (less than or equal to 2 cm) early advanced (n = 3) and advanced HCCs (n = 5) were almost the same: 67% and 100% by CTAP and 67% and 80% by Lipiodol-CT, respectively. To diagnose multiple primary HCCs in a candidate for surgery, CTAP is imperative following angiography.

Aged↗

[Depiction of the normal adrenal gland evaluation with 0.5 tesla MRI].

MR studies of the abdomen in 128 patients were reviewed in order to evaluate the normal adrenal glands. The studies were performed on a 0.5-Tesla superconducting unit. T1-weighted spin-echo (T1WI), T2-weighted spin-echo (T2WI) and T2*-weighted gradient-echo (T2*-WI) images were obtained. T1WI demonstrated the normal adrenal glands in 90% of the patients. T2*WI identified the glands in 86%, a higher rate than the 73% for T2WI. On both T1WI and T2WI, the right adrenal gland was demonstrated of a lower rate than the left adrenal gland, because the right retroperitoneal fat layer was narrow in patients with hepatic tumors. T2*WI depicted both adrenal glands equally, because the intensity of the left adrenal gland was the same as that of collateral veins from portal hypertension. It is suggested that both T1WI and T2WI with a gradient echo pulse sequence are more useful in depicting the adrenal glands than both T1WI and T2WI.

Adrenal Glands↗

[Clinical application of helical scanning CT of upper abdomen].

The helical scanning CT unit, in which an X-ray tube continuously rotates at the rate of one revolution per second with constant movement of the table on which the patient is placed, was clinically tested in scanning of upper abdomen. Quality of the images obtained was equal to that of conventional CT. The images were particularly good at an X-ray beam width of 5 mm and table movement of 5 mm/sec with scan parameters of 120 kvp, 200 mA. Because of limitation of the X-ray tube capacity. X-ray beam width of 5 mm and table movement of 10 mm/sec with scan parameters of 120 kvp, 150 m, would be the most appropriate clinically. Application of the helical scanning CT will result in examination times shorter than in the case of conventional high-resolution CT and be obtained images at early vascular enhancement phase through the whole scanning area, so that it can be expected to be extremely useful in clinical diagnosis involving upper abdomen.

Adult↗

[Serum osteocalcin concentration in a patient with pseudohypoparathyroidism type Ib].

A seventeen-year-old youth was presented with muscle cramps and convulsions. A brain CT scan showed calcification in the region of the ganglia, and a diagnosis of brain tumor was thus made and an anticonvulsant given for two years. At age nineteen, the patient developed pseudohypoparathyroidism owing to low serum calcium and high serum PTH levels. However, serum alkaline phosphatase and serum osteocalcin levels were high, lesion was detected in the femur neck. These data indicated that the bone remodeling response to PTH had remained intact in this patient. Serum osteocalcin is known to increase in primary hyperparathyroidism. However, unlike patients with hyperparathyroidism, those with pseudohypoparathyroidism show no increase in serum 1,25(OH)2D. The present case was thus useful for examining the direct effect of PTH on serum osteocalcin. The patient was administered 1 alpha (OH)D, and his condition monitored for two years. During this period, osteocalcin and PTH levels decreased while that of 1,25(OH)2D increased. Osteocalcin and PTH levels were found to be closely correlated (r = 0.68, p less than 0.01). The present results indicate the possibility that PTH may increase serum osteocalcin independent of Vitamin D.

Adolescent↗

Genetic factors and suppression of metastatic ability of prostatic cancer.

Progression of prostatic cancer from nonmetastatic to high metastatic ability may involve the loss of a metastasis suppressor gene. To test this possibility, nonmetastatic and highly metastatic Dunning rat prostatic cancer cells were fused. Hybrid clones were isolated which conserved the chromosomes from their parental cells. When these hybrids were injected into animals, none developed distant metastases. When these nonmetastatic primary tumors were passaged in vivo, occasional animals developed distant metastases. Cytogenetic analysis of eight of these metastatic revertants demonstrated a consistent loss of a copy of a normal chromosome 2. Although previous studies have demonstrated that specific chromosomes can inhibit tumorigenicity in cell fusion experiments, this is the first study to show that prostatic cancer metastasis is associated with the loss of a specific chromosome. Furthermore, these studies suggest that a metastasis suppressor gene for rat prostatic cancer is located on chromosome 2.

Animals↗