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Biomedical subjects

T Koizumi

Publications and source records attributed to T Koizumi.

At least 145 records · Page 8Linked to original sources
PubMed1998

Molecular heterogeneity of hCGbeta--related glycoproteins and the clinical relevance in trophoblastic and non-trophoblastic tumors.

We analyzed immunoreactive hCG/hCGbeta (IR-beta) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free hCGbeta were contained in both serum and urine, the beta-CF could be detected only in the urine of the patients. The relative contribution of the beta-CF to the total urinary IR-beta accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggested that the ratios of intact hCG, free hCGbeta, and beta-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-beta. The chromatographic study indicated that these urinary IR-beta were essentially attributed to beta-CF, leading to the evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG beta by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when beta -CF is measured in urine of the patients.

Antibodies, Monoclonal↗
PubMed1998

[A case of relapsed thymic carcinoma that responded remarkably to chemotherapy with CPT-11].

A chemotherapeutic protocol for advanced thymic carcinoma has not been established as yet. We described a case of advanced and relapsed thymic carcinoma that responded remarkably to subsequent chemotherapy with CPT-11. A 61-year-old man was admitted to our hospital because of facial edema and general fatigue. Chest X-ray and CT scan showed anterior mediastinal tumor which involved large vessels and pericardium. CT guided needle biopsy yielded a diagnosis of squamous cell type of thymic carcinoma. The patient was initially treated with ADOC (ADM, CDDP, VCR, CPA) chemotherapy and had successfully controlled for six months. However, the mediastinal tumor recurred and radiotherapy and nedaplatin plus ETP therapy were not effective. Then, CPT-11 chemotherapy (80 mg/m2, 2 weeks) was performed. The patient showed a partial response after two courses of CPT-11 chemotherapy. This case suggests that CPT-11 is a useful chemotherapeutic agent for advanced thymic carcinoma.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Pharmacokinetic characteristics of the novel anticancer agent CPT-11 and its active metabolite in plasma and lung lymph fluid following intravenous administration to sheep.

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT-11, 100286-90-6) is one of the most promising novel anticancer agents, especially for lung cancer. 7-Ethyl-10-hydroxycamptothecin (SN-38), an active metabolic of CPT-11, has much stronger cytotoxicity than CPT-11. The present study was designed to evaluate the distribution and behavior of CPT-11 and SN-38 in lung lymph circulation following intravenous infusion. Awake sheep with chronically instrumented lung lymph fistulas were prepared. The concentrations of CPT-11 and SN-38 in plasma and lung lymph fluid were measured after intravenous infusion of 100 mg/body of CPT-11 for 90 min. SN-38 constantly showed higher lymph to plasma concentration ratios than those of CPT-11, and the % area under the curve (AUC) ratio of SN-38/CPT-11 in lymph fluid was significantly higher than that in plasma. These data indicated that SN-38 distributed in lung tissue moved more easily into lung lymph fluid than CPT-11, and might be more rapidly metabolized in lung tissue than plasma. CPT-11 may have favorable therapeutic effects on intrathoracic malignancies such as lung cancer and lymph metastasis.

Animals↗
PubMed1997

Direct action of nitric oxide on osteoblastic differentiation.

The effect of nitric oxide (NO) on osteoblastic differentiation was examined in cultured mouse osteoblasts. Interleukin-1beta and tumor necrosis factor-alpha expressed inducible NO synthase gene with little effect on constitutive NO synthase gene. These cytokines increased NO production, which was inhibited by L-NMMA pretreatment, and decreased alkaline phosphatase (AIPase) activity, which was not restored by L-NMMA. Furthermore, NO donors, sodium nitroprusside and NONOate dose-dependently elevated AIPase activity and expression of osteocalcin gene. These results suggest that NO directly facilitates osteoblastic differentiation and the cytokine-induced inhibition of AIPase activity is mediated via mechanism other than NO.

Alkaline Phosphatase↗
PubMed1997

Alpha-1 adrenoceptor subtypes (high, low) in human benign prostatic hypertrophy tissue according to the affinities for prazosin.

BACKGROUND: A novel classification of alpha-1 adrenoceptor subtypes (High, Low) was applied to human benign prostatic hypertrophy (BPH) tissue. METHODS: Human BPH specimens were examined by a radioligand binding assay method using 3H-prazosin, and those data were compared with preoperative therapies. RESULTS: (1) Scatchard analysis showed a high-affinity site (Kd:27.18 +/- 6.41 pM; Bmax:9.29 +/- 0.98 fM/mg protein; mean +/- SE) as alpha 1H, and a low-affinity site (Kd: 4088.0 +/- 744.34 pM, Bmax: 140.81 +/- 19.98 fM/mg protein) as alpha 1L subtype, for prazosin. (2) The Kd and Bmax were not different in the nontreated group (n = 5), alpha 1 blocker group (n = 5), and antiandrogen group (n = 5), in either alpha 1-high affinity or alpha 1-low affinity subtype. (3) Phenoxybenzamine had different pKi values for the above two adrenoceptor subtypes. Scatchard analysis showed that alpha 1-high affinity binding site disappeared in the presence of 1 microM of phenoxybenzamine, and the Kd and Bmax values in the presence of 1 microM of phenoxybenzamine were almost identical to the alpha 1-low affinity site of the two subtypes. CONCLUSIONS: Human BPH tissue possesses both alpha 1H- and alpha 1L-adrenoceptor subtypes according to the affinities for prazosin, and only the alpha 1H subtype can be completely inhibited by some concentration of phenoxybenzamine. Treatment by alpha 1 blocker may not change the conditions of alpha 1-adrenoceptors in prostatic tissue.

Adrenergic alpha-Antagonists↗
PubMed1997

Expression of alpha and beta genes of human chorionic gonadotropin in lung cancer.

To confirm the ectopic production of human chorionic gonadotropin (hCG) in lung cancer, we attempted to detect the presence of mRNA transcripts of the alpha and beta genes for hCG in lung cancer tissues obtained from surgical operations. Although we were able to show the presence of hCG beta mRNA transcripts in lung cancer tissue by Northern blot, the sensitivity of the assay was too low for a precise analysis of hCG beta mRNA transcripts in most lung cancers. Using reverse transcription PCR (RT-PCR) and Southern blot analysis, however, various amounts of mRNA transcripts of hCG beta genes 3, 5, 7 and 8 were demonstrated in 9 of the 14 lung cancer tissues examined, while no mRNA transcripts were detectable in 12 normal lung tissues from the same patients. Our results are consistent with a clear difference in serum and urinary hCG beta levels observed between normal subjects and lung cancer patients. The expression of the hCG alpha gene, however, was detected in normal lung tissues more frequently than in lung cancer tissues using RT-PCR Southern blot. Our results strongly suggest the production of hCG beta as being part of the phenotype of malignantly transformed lung cells and further strengthen its superior specificity over intact hCG or hCG alpha as a tumor marker for lung cancers.

Aged↗
PubMed1997

Overexpression of c-fos inhibits down-regulation of a cyclin-dependent kinase-2 inhibitor p27Kip1 in splenic B cells activated by surface Ig cross-linking.

Splenic B cells activated by surface Ig (sIg) cross-linking transiently express the c-fos gene within 0.5 h and then enter into S phase of the cell cycle within 48 h. To investigate a role of c-fos in cell cycle progression, we used splenic B cells from IFN-alphabeta-inducible c-fos transgenic mice (Mx-c-fos). In the absence of IFN, the cell cycle progression of Mx-c-fos B cells stimulated with anti-IgM Ab was similar to that in control B cells. The cell cycle was arrested in G1 phase when we added IFN to the culture within 12 h after anti-IgM Ab stimulation, suggesting that overexpression of c-fos until mid-G1 phase perturbs activation of the cell cycle regulatory machinery. In control B cells, cyclin E and cdk2 were induced within 24 to 48 h after stimulation, and this induction was accompanied by down-regulation of a cdk2 inhibitor p27Kip1. As a consequence of these activation processes, cdk2 kinase activity was induced in B cells in the late G1 phase. However, kinase activity was not detected in Mx-c-fos B cells, presumably because the down-regulation of p27 was perturbed. These data suggest that c-Fos can negatively control cell cycle regulatory machinery in sIg-stimulated B cells.

Animals↗
PubMed1997

Cloning of the cDNA encoding rat Presenilin-1.

We isolated rat presenilin-1 (PS-1; also called S182 previously) cDNA from total brain RNA by using a reverse transcription-polymerase chain reaction (RT-PCR) technique with primers homologous to the conserved sequences of human and mouse PS-1. Rat PS-1 cDNA encoded 468 amino acids (aa) and the deduced aa sequence was highly homologous to those of the human (88.4%) and mouse (92.7%). Northern blot analysis of the rat PS-1 cDNA revealed two mRNA species in rat neurotypic pheochromocytoma and glioma cell lines (PC-12 and C6, respectively) that migrated at rates corresponding to approximately 3.0 and 7.5 kb.

Alzheimer Disease↗
PubMed1997

Characterization of a potent uveitopathogenic site derived from rat phosducin.

Phosducin is a retinal and pineal phosphoprotein assumed to play an important role in visual phototransduction. Phosducin is also a uveitopathogenic retinal antigen, but its potency has been reported to be mild. During the course of studies aimed at identifying uveitopathogenic sites in phosducin, we found that rat phosducin possessed a potent uveitopathogenic site. In this study, we characterize the potent uveitopathogenic site by using synthetic peptides. Several synthetic peptides from this region plus adjuvants were injected into Lewis rats, and the uveitopathogenic core sequence was defined. We also determined the pivotal amino acid residues by using synthetic peptides with single residue substitution. Immunization with PDC(R)65-96 (amino acid residues 65 through 96 derived from rat phosducin) at doses of 0.83 nmol or more induced severe experimental autoimmune uveitis (EAU) in all rats within 12 days. Experimental autoimmune pinealitis (EAP) was also observed in all rats after immunization with 0.83 nmol or higher doses of the peptide. The lowest dose of the peptide to induce EAU and EAP was 0.24 nmol. The smallest peptide that induced EAU as severe as PDC(R)65-96 was PDC(R)77-87, which consisted of 11 amino acid residues (YELIHQDKEDE). The core sequence within the uveitopathogenic site was a pentapeptide (LIHQD), amino acid residues from 79 to 83. To determine the role of individual residues within PDC(R)77-87, we tested the uveitopathogenicity of analogues of PDC(R)75-85 and PDC(R)77-89, respectively, in which each of the residues from 77 to 87 was replaced by alanine (A). Analogous peptides bearing a single residue substitution at 80 (I-->A) and 82 (Q-->A), respectively, were not uveitopathogenic. Our findings demonstrated the presence of a potent uveitopathogenic site in PDC(R)65-96 whose potency in Lewis rats was comparable to that of S-antigen. The pivotal amino acid residues for uveitopathogenicity were the residues at 80 (I) and 82 (Q). The clinical and histological features of this EAU closely resembled those of the EAU induced by S-antigen and recoverin.

Adoptive Transfer↗
PubMed1997

Endothelin receptors and their cellular signal transduction mechanism in human cultured prostatic smooth muscle cells.

1. Endothelin (ET) receptors, and their cellular signal transduction mechanism, were characterized in a primary culture of human prostatic smooth muscle cells (HP cell). 2. [125I]-ET-1 and [125I]-ET-3 binding studies revealed that both ETA and ETB receptors were present in the HP cells, and the ratio of ETA to ETB receptors was 1.4:1. 3. Analysis of ET receptor mRNA by reverse transcription-polymerase chain reaction also demonstrated that HP cells express both ETA and ETB receptors. 4. ET-1 and ET-3 increased intracellular free Ca2+ concentration ([Ca2+]i) in the HP cells in a concentration-dependent manner. Use of subtype selective antagonists BQ-123 and BQ-788, indicated that both ETA and ETB receptors were coupled to an increase in [Ca2+]i. 5. Pretreatment of the cells with pertussis toxin resulted in a significant but partial attenuation of the [Ca2+]i increase mediated through the ETA and ETB receptors. However, sensitivity to pertussis toxin (PTX) was significantly different between them. 6. In conclusion, HP cells possess ETA and ETB receptors. Further, these two endothelin receptor subtypes evoke an increase in [Ca2+]i possibly via the action of different GTP-binding proteins.

Calcium↗
PubMed1997

Percutaneous central venous catheterization via the great saphenous vein in neonates.

In 44 neonates (mean birthweight 1207 g and mean gestational age 30.0 weeks), very small central venous catheters were percutaneously inserted via the great saphenous vein on 46 occasions. Catheter-related complications such as catheter blockages in 17 (37%), edema in a unilateral leg in three (6%), and mechanical disruption in two (4%) were noted. Although two of the neonates were found to have bacteremia and five neonates died, none were catheter related. The optimal length of catheter insertion (Y) from the great saphenous vein at the level of the medial maleollus to the inferior vena cava at T9 and L3 was calculated by regression equations utilizing total body length (X). Radiographs taken with extended and flexed leg postures revealed that the catheter tips were retracted with extension of the lower extremities and the degree of displacement ranged from 1 to 4 (mean 2.7) vertebral levels. Because this movement might cause migration into veins that connect to the inferior vena cava, the catheter tip should be located between T9 and L3, except at the renal vein junction. Percutaneous central venous catheterization via the great saphenous vein is safe and useful. Regression equations provided for rapid estimation of the optimal length of insertion.

Catheterization, Central Venous↗
PubMed1997

The effect of aerosolized furosemide in infants with chronic lung disease.

To investigate whether aerosolized furosemide would improve pulmonary function in premature infants with chronic lung disease, we enrolled eight preterm ventilator-dependent infants in a cross-over, double-blind, placebo-controlled trial. Either aerosolized furosemide (2 mg/kg) or placebo (0.9% saline) was administered, and serial pulmonary function tests were performed before and at 1 and 2 h after each inhalation. After furosemide inhalation, static respiratory compliance increased significantly by 24.3% and 23.2% as percentage change from the baseline value at 1 and 2 h (p = 0.014 and 0.022, respectively). Also, tidal volume increased significantly by 33.8% and 28.7% at 1 and 2 h, respectively (p = 0.004 and 0.009). In contrast, no changes were observed in them after placebo inhalation. Total respiratory resistance was unchanged after both furosemide and placebo inhalation. There were no differences in urine volume in two groups. These data suggested that aerosolized furosemide improved pulmonary function in infants with chronic lung disease without excessive diuresis.

Administration, Inhalation↗
PubMed1997

Study on baths with crude drug. III. The effect of ligustici chuanxiong rhizoma extract on the percutaneous absorption of some natural compounds.

To investigate the permeability of natural compounds through hairless mouse skin, compounds having a range of lipophilicity, i.e., ginsenoside-Re (1), baicalein (2), glycyrrhizin (3), baicalein (4), wogonin (5), honokiol (6), magnolol (7), bergapten (8), shikonin (9) and sinomenine (10) were used. These compounds permeated through the skin a little, however, they were generally accumulated into the skin. The uptake amount into the skin of each compound related to their lipophilicities in the in vitro experiment. Furthermore, Ligustici Chuanxiong Rhizoma (Senkyu) ether extract (SEE) enhanced their permeability into the skin; especially, it exhibited an effect on the skin permeability of moderately lipophilic compounds such as 4, 8. The effect of SEE in vivo was similar to that obtained in the in vitro experiment. From these results, it was clarified that natural compounds having high lipophilicity sufficiently permeated into the hairless mouse skin owing to their accumulative property, and SEE enhanced the permeability of the moderately lipophilic compounds into the skin.

Animals↗
PubMed1997

Enantioselective fluorination of organic molecules. I. Synthetic studies of the agents for electrophilic, enantioselective fluorination of carbanions.

In order to develop novel methods for electrophilic and enantioselective fluorination of active methine compounds, preliminary experiments were carried out. The N-tosyl derivative 5 obtained from D-phenylglycine was fluorinated with FClO3 or diluted F2 gas to give the N-fluoro-N-tosyl derivative 6. N-tosyl- or N-mesyl-(S)-alpha-phenethylamine 7 or 8 was subjected to FClO3 fluorination to produce the corresponding N-fluoro derivative, 10 or 11, respectively. Enantioselective fluorination of some methine compounds was attempted employing the above N-fluoro agents. Best result was obtained when 2-benzyl-1-tetralone/KHMDS was treated with 10 to produce the fluorinated tetralone 17 in 53% yield with enantiomeric excess (ee) of 48%.

Anions↗
PubMed1997

Diffuse pulmonary amyloidosis with monoclonal IgG-kappa gammopathy.

A 62-year-old female with diffuse pulmonary amyloidosis developed abnormal radiographic findings while under observation for hyperimmunoglobulinemia over a ten-year period. Serum immunoglobulin G (IgG) was elevated (4,620 mg/dl), and associated with monoclonal gammopathy (M protein) of the kappa type, but no evident abnormalities were apparent in bone marrow. Chest radiograph and computed tomography showed a diffuse reticulonodular shadow in the bilateral lung. Thoracoscopic lung biopsy specimen revealed depositions of amyloid in the bronchus and pulmonary vessel. We emphasize that diffuse pulmonary amyloidosis should be considered a possible diagnosis in the presence of monoclonal immunoglobulin.

Amyloidosis↗
PubMed1997

[The pharmacokinetics of D-lactate, L-lactate and acetate in humans].

In this study, the pharmacokinetics of D-lactate, L-lactate and acetate were investigated in 36 adult surgical patients. After induction of general anaesthesia, the subjects received intravenous injection of either 5 mmoles of D-lactate and 5 mmoles of L-lactate simultaneously (Group DL), 10 mmoles of L-lactate (Group L), or 10 mmoles of acetate (Group A). Serial arterial blood samples were obtained before the injection, and 3, 5, 7, 9 and 11 minutes after the infusion of each preparation. Plasma concentrations of D-lactate, L-lactate and acetate were measured by high performance liquid chromatography, enzymatic analysis and spectrophotometry. The pharmacokinetic parameters; distribution volume (Vd) and half-life (t1/2) were calculated with a one-compartment model from the incremental plasma concentration decay curve after administration. In Group DL, there were no differences between D-lactate and L-lactate in Vd and t1/2. Also, between L-lactate in Group DL and that in Group L, there were no differences in Vd and t1/2. The Vd and T1/2 of acetate, however, were smaller than those of L-lactate in Group L. We conclude that the pharmacokinetics of D-lactate is similar to those of L-lactate, and that acetate may be metabolized more rapidly than L-lactate.

Acetic Acid↗
PubMed1997

[Tumor lysis syndrome after treatment for mediastinal non-Hodgkin's lymphoma].

An 18-year man was admitted to the hospital because of acute dyspnea. Roentgenological examination revealed a large anterior mediastinal tumor. Histologic examination of a specimen from a cervical lymph node yielded a diagnosis of non-Hodgkin's lymphoma of, diffuse, large, T-cell type. Acute respiratory failure and a massive pleural effusion developed, and mechanical ventilation was begun. Chemotherapy with adriamycin, vincristine, cyclophosphamide, and prednisolone resulted in rapid shrinking of the mass. Acute renal failure developed because of hypoperfusion of the kidney caused by acute circulatory failure and the tumor lysis syndrome, and rapid increases in the concentrations of lactate dehydrogenase, creatine phosphokinase, and uric acid in serum after the tumor collapsed. Mediastinal malignant lymphoma often forms a bulky mass, and effective chemotherapy, while it can prolong survival, may also cause the tumor lysis syndrome.

Acute Disease↗