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Biomedical subjects

K Takano

Publications and source records attributed to K Takano.

At least 145 records · Page 8Linked to original sources

Effect of genetic background on establishment of mouse embryonic stem cells.

We established 13 embryonic stem (ES) cell lines from 542 embryos crossed between various strains of mice: 10 lines from 129/Sv-ter embryos (10/48, 20.8%) and 3 lines out of other 9 combinations of intra- or inter-strain matings (1 from intracross of C57BL/6CrSlc, 1 from B6D2F1 x C57BL/6CrSlc, 1 from Yok:ddY x Slc:ICR). No ES cell line from 129/Sv-ter x Slc:ICR embryos suggests that ICR strain might have inhibitory genetic factor(s) for the ES cell formation. Some ES cell lines could be obtained from hybrids even if none or few lines from their parental strains, suggesting a heterosis effect can be expected for establishing ES cell lines in mice.

Animals↗

Serum biochemical values in two inbred strains of mastomys (Praomys coucha).

Serum samples collected from 119 (72 male and 47 female) mastomys (Praomys coucha) of 2 specific-pathogen-free inbred strains (RI4 and RI7) were analyzed for 12 serum biochemical parameters. Sex-related differences (p < 0.01) were noted in alkaline phosphatase and glucose; the both higher in females than in males. Age-related changes (p < 0.01) were observed in total protein, albumin, total cholesterol, and alkaline phosphatase, with higher values for the first three parameters in the older group (200-250 days of age) than in the younger group (90-140 days of age). Four out of 12 parameters showed strain-related differences (p < 0.01), consistent with the large amount of genetic heterogeneity reported in this species. These serum biochemical reference values should provide information for the use of mastomys in laboratory research.

Animals↗

The structure and function of folliculo-stellate cells in the anterior pituitary gland.

The folliculo-stellate cells (FS cells) in the anterior pituitary gland are characterized by their star-like appearance and their ability to form follicles. Although FS cells do not produce any pituitary hormones, their special tendency to surrounding endocrine cells with their long cytoplasmic processes suggests that they regulate endocrine cells by intercellular communication. In spite of many morphological and cytophysiological studies recently performed, a precise understanding of the major functions of FS cells in the pituitary gland remains obscure. We review here the morphological characteristics of FS cells and their suspected functions in the anterior pituitary gland. It is well established that the FS cell produces many kinds of growth factors, i.e., fibroblast growth factor, vascular endothelial cell growth factor and interleukin 6. The biological significances of these growth factors in the anterior pituitary gland are also discussed in this paper. The origin and differentiation of FS cells, especially the possibility that the FS cell is a kind of stem cell which has the potential to differentiate into endocrine cells, is also presented.

Animals↗

Normal development of the pituitary gland: assessment with three-dimensional MR volumetry.

BACKGROUND AND PURPOSE: Currently available data on pituitary volume have been based on indirect methods of measurement and are mostly limited to adult populations. The purpose of this study was to determine the normal development of pituitary volume by means of direct measurements made on thin-section 3D MR acquisitions. METHODS: The volume of the normal pituitary gland in children and adolescents was measured by using 3D MR sequences with a section thickness of 0.6 to 0.75 mm. The clinical study group consisted of 199 pediatric patients with clinically normal pituitary function and no abnormal findings on routine MR studies. The volume of the posterior pituitary was also measured in all the subjects. RESULTS: A phantom study revealed measurement errors within 25%. In the clinical study, the measured pituitary volumes showed a growth spurt during puberty, which was more prominent in girls. Posterior pituitary volumes showed gradual growth without such a spurt. Among 5- to 9-year-olds, the posterior pituitary volumes were significantly larger for boys than for girls. CONCLUSION: Normal development of the pituitary gland and posterior pituitary was determined by means of 3D MR volumetry. With this technique, we found a gender difference in the volume of the posterior pituitary.

Adolescent↗

[Preventive effect of prostaglandin E1 on cisplatin-induced nephrotoxicity].

In order to prevent the nephrotoxicity induced by cisplatin (CDDP), prostaglandin E1 (PGE1) was administered intravenously after anticancer chemotherapy to six patients with lung cancer. All patients underwent two courses of multi-drug chemotherapy with the same regimen including a single administration of 80 mg/m2 CDDP. From the 7th day of the 2nd course of chemotherapy, 120 micrograms PGE1 had been administered for five days. During the two courses of chemotherapy, serum creatinine, blood urea nitrogen, creatinine clearance (Ccr), 24-h excretions of beta 2-microglobulin (beta 2-MG) and N-acetylglucosaminidase (NAG) in urine were measured every week in all patients. The mean value of Ccr was higher in the 2nd course than in the control course (65 ml/min vs. 74 ml/min). The 24-h excretions of beta 2-MG and NAG were also reduced in the 2nd course. Out of six patients, only one was complicated by mild phlebitis at the PGE1 infusion site. From these results it was suggested that PGE1 was effective for prevention of CDDP nephrotoxicity.

Aged↗

[A case of paraneoplastic cerebellar degeneration associated with small cell lung cancer].

Paraneoplastic cerebellar degeneration (PCD) is a clinical syndrome and known to be occasionally associated with small cell carcinoma of the lung (SCLC). PCD usually affects patients before the cancer is evident. The disorder evolves subacutely, and causes severe pancerebellar dysfunction. In this paper, we report a case of PCD associated with SCLC. A 65-year-old man presenting with 2 weeks of progressive vertigo, gait ataxia, and speech disturbance, was readmitted to our hospital. He had earlier been given a diagnosis of SCLC, oat cell carcinoma, and had undergone high-dose chemotherapy with peripheral blood stem cell transplantation during his first admission. Following that treatment regimen, the tumor disappeared completely and the patient had been in remission. Based on neurological findings and the presence of anti-neuronal antibodies a diagnosis of PCD was made. Although cyclophosphamide (500 mg/m2) was administered, the patient experienced no relief of his cerebellar ataxia. Six months afer readmission, he died of cardiac tamponade due to malignant pericarditis. A histological examination at autopsy found few Purkinje cells and a proliferation of Bergmann's astrocytes in the cerebellar cortex. These findings were consistent with the diagnosis of PCD.

Aged↗

Development of the temporal lobe in infants and children: analysis by MR-based volumetry.

BACKGROUND AND PURPOSE: Recent advances in data-processing techniques have allowed more accurate MR-based volumetric measurement than was possible in the past. The purpose of this study was to use this technique to evaluate the development of the temporal lobes in childhood. METHODS: The study group consisted of 42 subjects aged 3 weeks to 14 years (mean age, 5 years), all with normal findings on a routine MR study and none with a history of epilepsy. MR images were acquired on a 1.0-T system using a T1-weighted 3D ultrafast gradient-echo sequence. The volumes of the hippocampal formations and temporal lobes were measured by using a workstation, and the percentage of hippocampal formations in the temporal lobes was calculated. Myelination in the limbic system and related structures was also evaluated. RESULTS: The volume of the hippocampal formations increased sharply until the age of 2 years, and continued to increase slowly thereafter. However, the percentage of hippocampal formations in the temporal lobes showed a negative correlation with age. The hippocampal formations on the right side were larger than those on the left in 38 cases (91%), and the anterior temporal lobes on the right were larger than those on the left in 32 cases (76%). This right-left asymmetry of the hippocampal formations and anterior temporal lobes was observed from early infancy, and these differences were statistically significant. A longitudinal fasciculus of high signal intensity was seen in the white matter beneath the subiculum by about 3 months of age. CONCLUSION: MR-based volumetry established developmental characteristics of the temporal lobe, such as a hippocampal growth spurt, a growth difference between the hippocampal formation and the rest of the temporal lobe, and right-left asymmetry. Knowledge of these characteristics may aid in the understanding of hippocampal and temporal lobe abnormalities in children.

Adolescent↗

[A case of symptomatic interhemispheric arachnoid cyst in the elderly].

The incidence of interhemispheric cyst is rare. There have been only 12 cases reported in adults since the advent of CT. We encountered a case of an interhemispheric arachnoid cyst in a 54-year-old patient who had developed paraparesis. Excision of the cystic wall produced a satisfactory result. The CT and MRI scans were not contributory to histological differentiation of the lesions. According to the literature, however, it is highly likely that these patients are suffering from an arachnoid cyst, when the interhemispheric cyst without agenesis of the corpus callosum occurs in adults.

Arachnoid Cysts↗

[A case of recurrent breast cancer successfully treated with docetaxel].

A 53-year-old female underwent mastectomy for left breast cancer in April, 1993. She was given oral tamoxifen but this had to be discontinued due to its side effects. In March, 1998, she developed bone and lung metastases, in spite of treatment with combination chemotherapy (CEF). We thus treated here with docetaxel 90 mg three times and 40 mg six times. After the chemotherapy, she achieved complete remissions of the lung metastases and a decrease in serum CEA, CA 15-3, NCC-ST439, and BCA225. Adverse reactions to docetaxel were grade 2 alopecia, grade 4 neutropenia, dysgeusia, and fluid retention. All were tolerable. This new agent may play an important future role in chemotherapy for recurrent breast cancer.

Antineoplastic Agents, Phytogenic↗

[Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter with SPECT (I): Biodistribution and absorbed dose].

A Phase 1 clinical study of 123I-FP-CIT, N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I), developed for evaluation of dopamine transporter (DA-T) by single photon emission computed tomography (SPECT), was performed in 12 healthy male volunteers. No adverse reactions to 123I-FP-CIT (167 MBq) injection were observed. In sequential whole-body images after intravenous injection, the radioactivity was distributed mainly in the liver, abdomen, lungs and brain, and it decreased gradually with time. The radioactivity was excreted mainly in the urine and no prolonged retention of radioactivity was observed in any organs at 2 days post-injection. The radiation absorbed dose of 123I-FP-CIT, calculated on the basis of the pharmacokinetics, was equal to or less than those of other brain diagnostic imaging agents. These results suggest that i.v. injection of 123I-FP-CIT causes no significant problems in terms of its safety, biodistribution or absorbed dose.

Adult↗

[Metabolism of 123I-FP-CIT in humans].

The metabolism of N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-FP-CIT) in healthy humans was studied. Plasma and urine samples, obtained after i.v. administration of 123I-FP-CIT, were analyzed using the two-dimensional thin-layer chromatography technique. Eleven radiochemical components were detected in both plasma and urine, and four of them were the parent 123I-FP-CIT and its metabolites, N-(3-fluoropropyl)-2 beta-carboxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-acid), 2 beta-carboxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-nor-acid) and 2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I) (123I-nor-CIT). These four identified radiochemical components occupied about 80% or more in ratio of the radiochemical components in the plasma and urine. In the metabolites of 123I-FP-CIT, the high polar metabolites--123I-acid and 123I-nor-acid--were found to be the major components, while lipophilic 123I-nor-CIT was a minor component. Free iodide (123I-) was not found in the plasma or urine. Thus, the main metabolic reactions which 123I-FP-CIT undergoes in humans seem to be hydrolysis of the ester bond and N-dealkylation. In vivo deiodination of 123I-FP-CIT was found to be minimum. Current results suggest that the metabolites of 123I-FP-CIT hardly influence evaluation of the dopamine transporter in the human brain.

Adult↗

[The possibility of acute inflammatory reaction affects the development of pressure ulcers in bedridden elderly patients].

To test the hypothesis that acute inflammatory reaction associates with the development of pressure ulcers in bedridden elderly patients, 40 hospitalized elderly patients suffering from bacterial pneumonia, cerebrovascular disease, and femoral bone fracture were enrolled in this study. All of them were divided into two groups with pressure ulcers (group P; 17 patients) and without one (group N; 23 patients). The blood samples were taken from them within 5 days after the patients being bedridden. Although no significant difference exist in pressure ulcer risk factors (age, gender, Braden scale, underlying diseases, blood pressure, and heart rate) between the two groups, white blood cell, plasma C-reactive protein and fibrinogen in group P increased significantly as compared with those in group N. Besides number of platelets and maximum platelet aggregation rate were significantly higher in group P than in group N. Serum albumin and hemoglobin of both groups decreased after being bedridden, especially hemoglobin in group P was significantly lower than that in group N. While the concentration of serum IL-6 did not indicate a significant difference between both the groups, serum IL-1 beta increased significantly in group P. In conclusion, we suggested that acute inflammatory reaction releasing proinflammatory cytokines affected the development of pressure ulcer in bedridden elderly patients.

Aged↗

[Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter by SPECT (II): Tracer kinetics in the brain].

The kinetics of 123I-FP-CIT in the brain for healthy subjects were studied. Twelve dynamic SPECT data sets (0- to 6-hr after an intravenous injection) from a Phase 1 clinical trial of 123I-FP-CIT were analyzed. Tracer concentrations in the striatum, midbrain, cerebellum and cerebral cortex were measured on the SPECT images co-registered with the corresponding MR images. High tracer accumulation was observed in the striatum, which peaked at 60 min post-injection, followed by slow elimination (3%/hr). The kinetics were similar both in the cerebellum and in the cerebral cortex, which peaked at 15 min post-injection, followed by rapid elimination. Tracer accumulation in the midbrain was higher than in the cerebellum and cerebral cortex. The striatal specific/nonspecific binding ratio ((striatal-occipital)/occipital concentration ratio) was stable at 3-hr post-injection and later at a value of 3, suggesting that the specific binding of 123I-FP-CIT could be evaluated from a single SPECT image at 3- to 6-hr post-injection. The specific/nonspecific binding ratio at 4-hr post-injection showed a negative correlation with aging (r = -0.70, p = 0.01), with a decrease rate of 11%/decade (95% confidence interval: 3%-19%/decade).

Adult↗

Prognostic and Therapeutic Implications of the MIB-1 Labeling Index in Breast Cancer.

BACKGROUND: Assessment of tumor proliferative activity is considered to be the most powerful prognostic factor aside from axillary lymph node status. The purpose of this study is to assess the clinical value of measurement of proliferative activity using the MIB-1 labeling index in patients with breast cancer. METHODS: Surgical specimens from 36 patients with benign breast disorders and146 patients with breast cancer were investigated. The MIB-1 labeling index wasdetermined on the specimens stained by immunohistochemical methods as much as possible. Clinical factors associated with the MIB-1 labeling index were reviewed. RESULTS: The MIB-1 labeling index for non-proliferative disorders, proliferative disorders, and breast cancer was 3.4 +/-1.9%, 8.9 +/-6.2% and 20+/-12%, respectively. The MIB-1 labeling index and tumor size, lymph node metastasis status, and clinical stage according to the TNM classification correlated significantly. Survival rate was inversely correlated with the MIB-1 labeling index. No patientwith an MIB-1 labeling index of less than 10% had lymph node metastases, and all are alive without recurrence. Patients with an MIB-1 labeling index of over 30% had an extremely poor prognosis. CONCLUSION: The MIB-1 labeling index is very useful for predicting both either extremely good or extremely poor prognosis, and axillary lymph node metastasis

Journal Article↗

A general rule for the relationship between hydrophobic effect and conformational stability of a protein: stability and structure of a series of hydrophobic mutants of human lysozyme.

To get a general rule for the relationship between hydrophobic effect and conformational stability, five Ile to Val and nine Val to Ala mutants (3SS mutants) from 3SS (C77A/C95A) human lysozyme were constructed. As known from previous studies, the 3SS protein lacking a disulfide bond between Cys77 and Cys95 is destabilized by enthalpic factors, as revealed by a decrease of about 20 kJ/mol in the denaturation Gibbs energy change (DeltaG) value, as compared to the wild-type protein, which has four disulfide bonds. In this study, the stabilities and structures of the 3SS mutants were determined by differential scanning calorimetry and X-ray crystal analysis, respectively, and compared with those of the mutants (4SS mutants) from the wild-type (4SS) protein published previously. The stabilities of all the 3SS mutants, except for V110A-3SS were decreased as compared with that of the 3SS protein, coinciding with the results for the 4SS mutants. The change in the denaturation Gibbs energy change (DeltaDeltaG) values of the 3SS mutants relative to the 3SS protein at the denaturation temperature (49.2 degreesC) of the 3SS protein at pH 2.7 were similar to those of the equivalent 4SS mutants relative to the wild-type at 64.9 degreesC. The Delta DeltaG values of the 3SS mutants correlated with the changes in hydrophobic surface area exposed upon denaturation (Delta DeltaASAHP) for all of the hydrophobic residues when the effects of the secondary structure propensity were considered. This correlation is identical with that previously found for the 4SS mutants. The linear relation between Delta DeltaG and Delta DeltaASAHP for all of the hydrophobic residues with the same slope was found also for the mutants of T4 lysozyme already reported, indicating that this is a general relationship between changes in conformational stability and changes in ASA values of hydrophobic residues due to mutations.

Calorimetry↗

Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants.

The contribution of hydrogen bonds to the conformational stability of human lysozyme was investigated by the combination of calorimetric and X-ray analyses of six Tyr --> Phe mutants. Unfolding Delta G and unfolding Delta H values of the Tyr --> Phe mutant proteins were changed by from +0.3 to -4.0 kJ/mol and from 0 to -16 kJ/mol, respectively, compared to those of the wild-type protein. The net contribution of a hydrogen bond at a specific site to stability (Delta Gwild/HB), considering factors affected by substitutions, was evaluated on the basis of X-ray structures of the mutant proteins. In the present study, one of six mutant proteins was suitable for evaluating the strength of the hydrogen bond. Delta Gwild/HB for the intramolecular hydrogen bond at Tyr124 was evaluated to be 7.5 kJ/mol. Results of the analysis of other mutants also suggest that hydrogen bonds of the hydroxyl group of Tyr, including the hydrogen bond with a water molecule, contribute to the stabilization of the human lysozyme.

Calorimetry, Differential Scanning↗