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K Nakada

Publications and source records attributed to K Nakada.

At least 37 records · Page 2Linked to original sources

Inter-mitochondrial complementation: Mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA.

Here we investigated the pathogenesis of deletion mutant mitochondrial (mt)DNA by generating mice with mutant mtDNA carrying a 4696-basepair deletion (DeltamtDNA4696), and by using cytochrome c oxidase (COX) electron micrographs to identify COX activity at the individual mitochondrial level. All mitochondria in tissues with DeltamtDNA4696 showed normal COX activity until DeltamtDNA4696 accumulated predominantly; this prevented mice from expressing disease phenotypes. Moreover, we did not observe coexistence of COX-positive and -negative mitochondria within single cells. These results indicate the occurrence of inter-mitochondrial complementation through exchange of genetic contents between exogenously introduced mitochondria with DeltamtDNA4696 and host mitochondria with normal mtDNA. This complementation shows a mitochondria-specific mechanism for avoiding expression of deletion-mutant mtDNA, and opens the possibility of a gene therapy in which mitochondria possessing full-length DNA are introduced.

Animals↗

Endocrine profiles and embryo quality in Japanese black cattle superovulated with human menopausal gonadotrophin and porcine follicle stimulating hormone.

Induction of superovulation using human menopausal gonadotriphin (hMG) in Japanese Black cattle can result in the recovery of a higher percentage of high quality embryos compared with that using porcine follicle stimulating hormone (FSH). In order to clarify the endocrinological mechanism involved in this discrepancy, 30 superovulation sessions of 17 Japanese Black cattle were studied. Fifteen cattle were super-stimulated with hMG (total 600 IU), and the remaining 15 cattle were given FSH (total 20 mg). The plasma profiles of LH, estradiol-17beta (E2) and progesterone (P4) were correlated, and the embryo quality was investigated. The total number of ova recovered and the number of transferable embryos tended to be larger in the hMG-treated group than in the FSH-treated group. The percentage of excellent embryos tended to be higher in the hMG-treated group than in the FSH-treated group (54.3 and 28.7%, respectively, p < 0.10). The E2 level increased during the first 3 days after the initial administration of either hMG or FSH and was higher in the hMG-treated group than in the FSH-treated group (p < 0.05). During this period, the E2 level could be categorized into one of the following three types according to whether it increased or decreased and according to the degree of increase or decrease: (1) increase by a factor of 1.2 or more (quick increase type) (2) slight increase by a factor less than 1.2 (slow increase type), and (3) no increase (unstable increase type). In the group treated with hMG, 66.7% of the animals (10 of 15 cattle) showed a quick increase in the E2 level. However, in the FSH-treated group, 40% (six of 15) of the animals showed a slow increase in the E2 level. The plasma LH level increased dramatically 8 h prior to the peak level in both the hMG- and FSH-treated groups, and then it returned to the basal level 12 h later. After the administration of prostaglandin (PG)F2alpha, the LH peak level was attained within 44 h in 80% of the animals in the hMG-treated group, whereas in the FSH-treated group, the LH peak level tended to be reached later. The P4 level did not increase during the period of hMG or FSH treatment and decreased drastically following administration of PGF2alpha. After the onset of oestrus, the P4 level was higher in the hMG group than in the FSH group, and 5 to 7 days after oestrus, the level remained higher in the hMG group than in the FSH group (p < 0.05). After the first 3 days of hMG administration, the E2/P4 ratio was higher than that after FSH administration. Furthermore, on the day following PGF2alpha administration, the ratio was significantly higher in the hMG group than in the FSH group (p < 0.05). These results indicate that superovulation in cattle given hMG results in a significant increase in plasma E2 during the first 3 days and that the increase in the plasma P4 level is larger a few days after oestrus and thereafter compared with FSH-induced superovulation. Therefore, such plasma level profiles may be related to the increased recovery rate of high quality embryos.

Animals↗

Different phenotypes of dysplastic kidney in obstructive uropathy in fetal lambs.

PURPOSE: The cause of cyst production in renal dysplasia is uncertain. The authors hypothesized that different patterns of renal dysplasia result from variations in the timing and site of the urinary tract obstruction. METHODS: The authors operated on fetal lambs at 50 and 60 days' gestation. Male lambs underwent urethral and urachal ligation and female lambs unilateral ureteric ligation. They were delivered by cesarean section at 145 days' gestation and killed. RESULTS: Of 12 lambs operated on at 50 days' gestation, 4 survived. Of 26 lambs operated on at 60 days, 21 survived. The authors identified 3 types of dysplastic kidneys. Type A, fibrotic kidneys (2.2 g) with no cysts and interstitial fibrosis. There were reduced numbers of proximal tubules, but distal tubules and collecting ducts persisted. (50-day obstruction, n = 5 kidneys); type B, Sponge-like kidneys (37g): these had large cysts with minimal interstitial fibrosis. (87% of 60-day uretheral and urachal ligation model n = 12 kidneys); Type C, Small kidneys (4.8 g) with no large cysts (60-day Ureteric ligation model n = 7 kidneys). CONCLUSION: The authors produced 3 different types of renal dysplasia by creating urinary tract obstruction at different sites and gestational ages.

Animals↗

Liver regeneration on chicken chorioallantoic membrane.

To explore how the liver regenerates, liver pieces from 15-day-old chicken embryos were grafted onto the chorioallantoic membrane (CAM) of 9-day-old chicken embryos and cultured for 11 days at the longest. The cultured liver pieces were examined histologically. The liver implants were gradually engulfed into the CAM and underwent necrosis of hepatocytes, except in their peripheral areas, during the first 1-4 days after grafting. Surviving cells in the peripheral areas began to proliferate 4 days after grafting. Thereafter, the cells were assembled into normal liver tissues and represented almost all the areas of the implants 9 days after grafting. Only after penetration of blood vessels from CAM did the liver implants enter a phase of rapid regeneration to form well-organized liver tissues. At the early stage of regeneration, the cells at the peripheral areas did not produce albumin, but reproduced it in the regenerated liver tissues, implying that hepatocytes restored their functions that were temporarily lost in the process of regeneration. Thus, we concluded that the liver pieces from 15-day-old chicken embryos had the ability to form normal liver tissues on CAM and that the blood supply played an important role in liver regeneration.

Albumins↗

Pituitary chromophobe carcinoma with a low level of serum gonadotropin and an aspermatogenesis in a dog.

A 5-year-old male Shiba dog with progressive neurologic signs was examined by computed tomography (CT). A CT image of the brain disclosed a large, spherical high-density lesion in the thalamus and diencephalon. Serum LH, FSH and testosterone levels were all low. Macroscopically the large mass was connected with the sella turcia, and it was histopathologically diagnosed as a pituitary chromophobe carcinoma. An aspermatogenesis was observed in the testes. Therefore, it was suggested that the low levels of gonadotropin secretion from the pituitary gland due to the pituitary tumor resulted in the failure of maturation of spermatozoa and spermatids.

Adenocarcinoma↗

Immunohistochemical detection of inhibin-alpha, -betaB, and -betaA chains and 3beta-hydroxysteroid dehydrogenase in canine testicular tumors and normal testes.

Immunohistochemical detection of inhibin-alpha, -betaA and -betaB chains and 3beta-hydroxysteroid dehydrogenase (HSD) was carried out on primary testicular tumors from 15 dogs and normal testes from three adult dogs. Histopathologically, the tumors were composed of three types: Leydig cell tumors in five dogs, Sertoli cell tumors in five dogs, and seminoma in five dogs. In normal testes, immunostaining against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD revealed positive reactivity in the cytoplasm of Leydig cells. In testicular tumors, immunoreactive cells against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD were localized in all Leydig cell tumors but not in any Sertoli cell tumors or seminomas. The results of radioimmunoassay for plasma inhibin in dogs with Leydig cell tumors showed higher concentrations than those in dogs with Sertoli cell tumors and seminomas and those in normal dogs. The concentration of inhibin in the plasma was markedly decreased by the surgical removal of the Leydig cell tumor in one dog. Our findings suggest that inhibin is synthesized by normal and neoplastic Leydig cells in the canine testis, and the secreted inhibin may be inhibin A and inhibin B.

3-Hydroxysteroid Dehydrogenases↗

Comparison of (18)F-FDG, (131)I-Na, and (201)Tl in diagnosis of recurrent or metastatic thyroid carcinoma.

UNLABELLED: There are several reports about the usefulness of (18)F-FDG PET in thyroid cancer. However, few studies have compared FDG PET with (131)I and (201)Tl scintigraphy. The aim of this study was to evaluate the clinical significance of whole-body FDG PET in differentiated thyroid cancer and to compare the results with those obtained from (131)I and (201)Tl scintigraphy. METHODS: Whole-body FDG PET was performed on 32 patients (10 men, 22 women; age range, 30-77 y; mean age, 54 y) with differentiated thyroid cancer (5 cases of follicular cancer and 27 of papillary cancer) after total thyroidectomy. An overall clinical evaluation was performed, including cytology, thyroglobulin level, sonography, MRI, and CT, to allow a comparison with functional imaging results for each patient. Metastatic regions were divided into five areas: neck, lung, mediastinum, bone, and other. Multiple lesions in one area were defined as one lesion. The tumor-to-background ratio (TBR) was measured for the lesions that were positive for both (201)Tl uptake and FDG PET uptake. RESULTS: The number of lesions totaled 47. Forty-one (87%) were detected by all scintigraphic methods. FDG uptake was concordant with (131)I uptake in only 18 lesions (38%). FDG uptake was concordant with (201)Tl uptake in 44 lesions (94%). Only one lesion was negative for FDG uptake and positive for (201)Tl uptake, and two lesions were positive for FDG uptake and negative for (201)Tl uptake. A significant correlation was seen between the TBR of (201)Tl and that of FDG (r = 0.69; P<0.05). CONCLUSION: These data indicate that for detecting metastatic lesions, FDG PET and (131)I scintigraphy may provide complementary information, whereas FDG PET may provide results similar to those of (201)Tl scintigraphy. Thus, the combination of (131)I scintigraphy and FDG PET (or (201)Tl scintigraphy) is the method of choice for detecting metastatic thyroid cancer after total thyroidectomy.

Adenocarcinoma, Follicular↗

Appearance and number of follicles and change in the concentration of serum FSH in female bovine fetuses.

The aim of this study was to determine the relationships between early follicular development, the time at which follicles appear in early stages of follicular development, and changes in the serum concentrations of FSH in the female bovine fetus. Thirty-five female bovine fetuses aged between 59 and 285 days, as estimated from the crown-rump length, were obtained from dams at an abattoir. Serum samples were separated from fetal blood obtained from the heart. Fetal ovaries were removed and weighed. The content of oestradiol in one of the fetal ovaries and the serum concentrations of FSH and oestradiol were determined using radioimmunoassay. Sections of the other ovary were examined histologically for the appearance and number of follicles. The follicles were divided into four stages: primordial, primary, secondary and early antral. The appearance of primordial, primary, secondary and early antral follicles was observed at day 74, day 91, day 120 and day 150, respectively. Serum concentrations of FSH in female bovine fetuses increased between day 120 and day 150 of gestation. Fetal serum concentrations of oestradiol increased from day 120. The number of early antral follicles increased from day 180 together with an increase in the fetal ovarian content of oestradiol. These findings indicate that, in the female bovine fetus as well as in adult cows, the number of follicles and stages of follicular development are associated with changes in the concentration of FSH.

Animals↗

Anisotropic optical spectra of PrBa2Cu4O8: possible Tomonaga-Luttinger liquid response of the quasi-one-dimensional metallic CuO double chains.

The optical spectra of PrBa2Cu4O8 show large in-plane anisotropy. For the a polarization (E perpendicular chain), the spectrum is characterized by a gap of 1.4 eV, indicating the charge-transfer insulating nature of the CuO2 planes. For the metallic chain direction (E // b), the spectrum deviates from a simple Drude response; reflectivity R(b)(omega) shows a sharp edge at approximately 1 eV but it also shows a dip at approximately 15 meV, which splits the conductivity spectrum into two parts--a zero-energy mode with small weight and a pronounced 40 meV mode. These features are discussed in terms of a Tomonaga-Luttinger liquid in a doped 1D Mott insulator and compared with 1D Bechgaard salts.

Journal Article↗

The role of LH pulse frequency in ACTH-induced ovarian follicular cysts in heifers.

The aim of the present study was to induce ovarian cysts experimentally in cattle using ACTH and to closely examine the role of LH pulse frequency in ovarian cyst formation. Five regularly cycling Holstein-Friesian heifers (15-18-month-old) were used. Ovaries were scanned daily using an ultrasound scanner with a 7.5 MHz rectal transducer. Daily blood samples were obtained via tail venepuncture for hormone analyses. Additional blood samples (for FSH and LH pulses) were obtained through an indwelling jugular vein catheters every 15 min for 8 h on Days 2 (early luteal phase; ELP), 12 (mid-luteal phase; MLP) and 19 (follicular phase; FP) of control estrous cycle and on alternate days during follicular cyst (FC) formation and persistence. Cysts were induced using subcutaneous injections of ACTH (Cortrosyn) Z; 1 mg) every 12 h for 7 days beginning on Day 15 of the subsequent estrous cycle. Plasma concentrations of progesterone (P4), estradiol-17beta, FSH and LH were determined by double antibody radioimmunoassay while cortisol concentration was determined by enzyme immunoassay (EIA). Ovarian follicular and endocrine dynamics were normal during the control estrous cycles. Ovarian follicular cysts were induced in four of the five heifers. Mean maximum size of cysts was larger (P<0.05) than that of ovulatory follicles (26.78+/-3.65 versus 14.1+/-0.90 mm), respectively. Cortisol levels were increased during ACTH treatment. High concentrations of estradiol and low progesterone were observed after cyst formation. LH pulse frequency was significantly reduced (P<0.05) during cyst formation and persistence compared to ELP (7.5+/-0.75) and FP (6.5+/-0.58), but was not significantly (P=0.23) different from MLP (2.8+/-0.29) pulses. Mean LH pulse amplitude and concentrations were not different. Similarly, the mean pulse frequency, amplitude and concentration of FSH were not different between control study and cystic heifers. These results suggest that the LH pulse frequency observed following ACTH treatment may interact with high estradiol concentration to induce ovarian cyst formation in heifers.

Adrenocorticotropic Hormone↗

Novel tissue culture method: skeletal muscle implantation under gizzard serous membrane of a chick.

A novel method for a long-term culture of skeletal muscle is described. Skeletal muscle pieces from young chicks were implanted under the gizzard serous membrane of the same chicks. Following muscle degeneration, new well-grouped muscle fibers were formed by the fusion of myocytes that differentiated from surviving satellite cells, and the regenerated muscle tissues were maintained in position for longer than 60 days. The implants were in the vital circulatory system, receiving trophic and oxygen supplies, and are completely free from motor nerve innervation and cell contamination with exogenous muscle cells, not as in intra-muscular implantation. Therefore, this tissue culture method should be useful for studying skeletal muscle regeneration and maturation over a long period. Furthermore, osteogenesis and feather development were also found in the implants of embryonic limbs by using the same method. These observations showed that not only skeletal muscle tissues but also other tissues could be cultured under the gizzard serous membrane.

Actins↗

Renal salvage procedure for synchronous bilateral Wilms' tumor.

This report describes a renal salvage procedure performed in a 2-year-old girl with bilateral renal tumors comprising a multilocular, cystic tumor of the right kidney and a solid and cystic nephroblastoma of the left kidney after chemotherapy. Surgery was performed because the right kidney became hydronephrotic due to compression by the enlarged cysts, while the left tumor showed only minimal shrinkage even after three courses of chemotherapy. The right-sided cysts were simply unroofed and the left-sided tumor was extirpated by partial nephrectomy. Her postoperative course was uneventful with considerable recovery of the function of each kidney. This procedure should be considered if the pathological features of the tumor are relatively favourable.

Child, Preschool↗

Immunohistochemical studies on regulation of alternative splicing of fast skeletal muscle troponin T: non-uniform distribution of the exon x3 epitope in a single muscle fiber.

Troponin T (TnT) isoforms of chicken fast skeletal muscle are classified into two types, breast-muscle-type (B-type) and leg-muscle-type (L-type) isoforms. These isoforms are produced from a single gene by differential alternative splicing of pre-mRNA. We investigated immunohistochemically the distribution of B-type TnT isoforms in chicken leg muscle (musculus biceps femoris), using anti-exon x3 that was raised against a synthetic peptide corresponding to exon x3 and recognized B-type, but not the L-type, TnT isoforms. Mosaic patterns of immunostaining showing locally different expression of B-type TnT isoforms in a single fiber were observed among fibers, and the non-uniform distribution of the isoforms was also detected in sectioned fibers and myofibrils from the muscle. The results indicated that regulation of pre-mRNA splicing of fast skeletal muscle TnT was different not only among the muscle fibers but also within a single fiber, suggesting that heterogeneous myonuclei in regulation of alternative splicings occur in a single muscle fiber.

Alternative Splicing↗

Changes in concentrations of plasma immunoreactive follicle-stimulating hormone, luteinizing hormone, estradiol-17beta, testosterone, progesterone, and inhibin in heifers from birth to puberty.

This study was designed to clarify the characteristics of changes in plasma concentrations of reproductive hormones in heifers from birth to puberty. Weekly or daily hormonal changes were observed in 39 heifers. Daily changes in the concentration of follicle-stimulating hormone (FSH) demonstrated a consistent cycle of hormone changes over a 7- to 8-day period in heifers from approximately 10 days to 9 months old. Weekly changes in reproductive hormones showed that there were three brief periods in heifers between birth and puberty in which dramatic changes occur. The first period was the first week after birth, during which a reciprocal relationship between steroid hormones and gonadotropins was observed. At birth, the concentrations of steroid hormones were higher than those at any other age. These hormone levels rapidly decreased within the first week after birth. Gonadotropin levels, however, increased from birth to 1 week of age. The second period of major change was at approximately 4 weeks of age when there was an increase in the concentrations of luteinizing hormone (LH), estradiol-17beta, testosterone, and immunoreactive inhibin. The third period was the last 5 weeks before the first ovulation, when there was an increase in the concentrations of estradiol-17beta followed by an increase in (LH). These results suggest that regular hormone changes start from 10 days after birth and that the periods from birth to 4 weeks of age and the last 5 weeks before the first ovulation in heifers are important to the development of reproductive functions before puberty.

Animals↗

Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes.

Mice carrying mitochondrial DNA (mtDNA) with pathogenic mutations would provide a system in which to study how mutant mtDNAs are transmitted and distributed in tissues, resulting in expression of mitochondrial diseases. However, no effective procedures are available for the generation of these mice. Isolation of mouse cells without mtDNA (rho0) enabled us to trap mutant mtDNA that had accumulated in somatic tissues into rho0 cells repopulated with mtDNA (cybrids). We isolated respiration-deficient cybrids with mtDNA carrying a deletion and introduced this mtDNA into fertilized eggs. The mutant mtDNA was transmitted maternally, and its accumulation induced mitochondrial dysfunction in various tissues. Moreover, most of these mice died because of renal failure, suggesting the involvement of mtDNA mutations in the pathogeneses of new diseases.

Animals↗

Early fetal obstructive uropathy produces Potter's syndrome in the lamb.

BACKGROUND: If creating an obstructive uropathy early in glomerulogenesis produces MCDK (Multicystic Dysplastic Kidney), then a very early obstruction may produce Potter's Syndrome (PS) with oligohydramnios. METHODS: Fetal lambs at 50 days' gestation underwent urethral and urachal ligation using fine SILASTIC (Dow Corning, Midland, MI) tubing and were delivered by cesarean section at 145 days' gestation. At the time of death, kidney weight, length, and lung volumes were measured. These samples were examined histologically. Urinary sodium, chloride, potassium, and osmolarity also were measured. These were compared with normal-term fetuses. RESULTS: One ewe miscarried. Two of 3 of 50-day obstructive uropathy lambs survived. The 2 survivors had dysplastic kidneys. One with large gastroschisis did not have PS but the other had renal, pulmonary, and chest wall hypoplasia. Both male lambs had undescended testes with a large bladder. Kidney weights were 2 g in the PS lamb and 16 g in controls. Lung volume was 84 mL in the PS lamb and 340 mL in controls. The lamb's face was compressed and the fetus was hydropic. Urine sodium, potassium, and osmolarity levels were higher than that of controls. CONCLUSIONS: This is the first successful model ligating the penile urethra and urachus in a 50-day lamb. The authors' previous 60-day model did not have PS, but an earlier obstructive uropathy caused MCDK with PS.

Abnormalities, Multiple↗

Glomerular size in renal dysplasia secondary to obstructive uropathy: a further exploration of the fetal lamb model.

BACKGROUND/PURPOSE: Creating an obstructive uropathy early in glomerulogenesis would produce multicystic dysplastic kidneys (MCDK). Measuring the mean planar area of the glomeruli (GMPA) may clarify the pathogenesis of MCDK. METHODS: Fetal lambs at 60 days' gestation had their left ureter ligated and were delivered by cesarian section at 145 days' gestation. Kidney weight and length were recorded. GMPA in 3 zones (outer, middle, inner) of the sectioned kidney was measured using a computerized planimeter. The obstructed kidneys were compared with contralateral unobstructed kidneys. The unpaired Student's t test was used to determine significance. RESULTS: One ewe miscarried. Four of 5 (80%) 60-day lambs survived. All had dysplastic kidneys. Mean kidney weights were 4.3 +/- 0.84 g in MCDK and 16.8 +/- 3.6 g in controls (P< .05). The GMPA of the outer, middle, and inner zones of the MCDK were 2.7 x 10(-3) mm2, 3.2 x 10(-3) mm2, and 4.0 x 10(-3) mm2, respectively. Controls were 2.8 x 10(-3) mm2, 4.4 x 10(-3) mm2, and 6.0 x 10(-3) mm2. The glomeruli of 60-day fetal kidneys were 3.0 x 10(-3) mm2, 6.1 x 10(-3) mm2, and 11.0 x 10(-3) mm2. MCDK had smaller glomeruli in the inner and middle zones than controls. CONCLUSION: Fetal glomeruli appear to grow from the inner zone of the kidney. Early urinary tract obstruction stops this growth.

Animals↗