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Biomedical subjects

Y Nakano

Publications and source records attributed to Y Nakano.

At least 271 records · Page 15Linked to original sources

Implications of heat shock/stress proteins for medicine and disease.

Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. The HSP70 family functions as molecular chaperones and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to the chaperoning activities, HSP70 has been suggested to exert its protective action by protecting mitochondria and by interfering with the stress-induced apoptotic program. The biochemical and functional properties of HSPs observed in cultured cells may be relevant to organs and tissues in whole animals. The activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nerve system elicits the stress response in selected peripheral tissues; the HSP70 expression in the vasculature and stomach increases resistance against hemodynamic stress and stress-induced mucosal damage, respectively. Gastric mucosa pretreated with mild irritants acquires a tolerance against subsequent mucosal-damaging insults. This phenomenon is known as "adaptive cytoprotection". Transient ischemia also induces ischemic tolerance in the brain and heart, which is called "ischemic preconditioning". The heat shock response is believed to contribute to the acquisition of the tolerance. The therapeutic applications of chaperone inducers that induce HSPs without any toxic effect are also introduced.

Animals↗

Transaxillary endoscopic partial mastectomy for comparatively early-stage breast cancer. An early experience.

For optimal cosmetic results in breast cancer surgery, we developed an alternative operation using endoscopy to remove tumors through a small single incision remote from the breast itself. The tumor is endoscopically resected with electrocautery and low constant suction through a short incision in the axilla, 5 cm long, after which axillary dissection is performed through the same wound in the usual manner, under visualization by the naked eye. Primary reconstruction of the breast is performed with the remaining mammary gland and a subcutaneous fat flap on the serratus muscle. Seven patients underwent this surgery. The postoperative shape of the breasts was judged to be cosmetically satisfactory, and the surgical wounds were not visible from the front in all cases. This operation has the same therapeutic oncological effect as a standard lumpectomy and, in addition, offers a greater cosmetic advantage in cases of early breast cancer.

Adult↗

[Evaluation of intra-arterial infusion chemotherapy for advanced gastric cancer].

We evaluated the therapeutic efficacy of intraarterial infusion chemotherapy in advanced gastric cancer, its side effect and patient prognosis, in comparison with systemic infusion. Of 125 cases of advanced gastric cancer, 41 cases received intraarterial chemotherapy (A group) and the rest were given systemic infusion (S group). Protocols of chemotherapy were 5-FU + MTX in 49 cases, 5-FU + cisplatin in 62, and 5-FU + MMC in 14. Location of the disease was the peritoneum in 69 cases, nodes in 59, liver in 38, and other sites, 33. The response rate of A group was significantly higher than that of S group, at 31% and 13% respectively. Although 41% of cases showed side effects (> or = grade 2), there was no significant difference between the 2 groups. The median survival period and 1-year survival rate were 8.4 months and 35%, respectively, and there was no significant difference between the 2 groups. In cases with liver metastasis, the prognosis of A group was better than that of S group. The results suggest that intra-arterial infusion chemotherapy is an effective treatment for liver metastasis from gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Liver metastases from breast cancer--clinical features and treatment].

Between 1986 and 1997, we treated 55 patients with liver metastases of breast cancer. In this study, the clinical features and effects of systemic or intra-arterial chemo-endocrine therapy for these patients were reviewed to clarify the characteristics of liver metastases and establish the optimum therapy. One of the 55 patients underwent hepatectomy, 25 were treated with systemic chemo-endocrine therapy [A] and 10 were treated with one-shot intra-arterial chemoembolization through hepatic artery [B] while the other 19 were given hepatic arterial infusion chemotherapy [C]. The response rate in the group [B] and [C] were better than in group [A], whereas there was no significant difference in survival time among the three groups. There were 14 cases (25.5%) among them showing metastasis in the thoracico-abdominal lymph nodes. In these patients, liver metastases seemed to have occurred through the lymphogenic route. In the intra-arterial chemotherapy ([B] + [C]) group, the survival time of patients with metastasis in the thoracico-abdominal lymph nodes was significantly shorter than that of patients without metastasis (p = 0.01). This study suggests that intra-arterial chemotherapy combined with MPA should be effective and useful for advanced breast cancer patients with liver metastases. And for lymphogenic liver metastases, it should be necessary to be combined with more intensive systemic chemo-endocrine therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Size comparison of the male and female human corpus callosum from autopsy samples.

161 cases of human-brain autopsies (93 Male, 68 Female) were collected from three samples in the Kinai district of Japan. From photographs of the midsagittal plane of each brain, surface areas of the corpus callosum (CC in mm2) and of the medial view of the cerebrum (H in mm2) were measured. The absolute H and CC values from each of the three samples were larger in males than in females, with full overlapping of the male and female ranges for both H and CC values. However, the relative values of CC corrected for H (CC/H) were almost equal between sexes. The relative values for the posterior one-fifth (splenium) of the CC, which were divided by CC or H, were slightly higher in females than in males in each of the three samples, but without statistical significance. This trend was also found in the relative values for the posterior one-third of the CC and in the relative values for region, meaning the posterior one-fifth of the CC subtracted from the posterior one-third of the CC (isthmus), but not in the relative values for the anterior one-fifth (genu) of the CC.

Aged↗

Development and characterization of cationic liposomes conjugated with HVJ (Sendai virus): reciprocal effect of cationic lipid for in vitro and in vivo gene transfer.

Today, nonviral gene transfer vectors attract more attention as a therapeutic strategy for human diseases, because viral vectors such as adenoviral and herpes viral vectors have been proven to have problems, especially in immunogenicity and cytotoxicity. However, the main limitation of nonviral vectors has been low efficiency of gene expression. To overcome this defect, we have developed a new class of transfection vehicles, HVJ-cationic liposomes. The use of the cationic lipid DC-cholesterol facilitates efficient entrapment of negatively charged macromolecules (plasmid DNA, oligodeoxynucleotides, and proteins) and efficient interaction with negatively charged plasma membranes of cultured cells in vitro. Moreover, the fusogenic envelope proteins of hemagglutinating virus of Japan (HVJ) enhance delivery of the enclosed materials into cells. Using firefly luciferase as a marker, we optimized the liposome formula. As a result, we have succeeded in obtaining 100-800 times higher gene expression in vitro than with the conventional HVJ-anionic liposomes. However, in vivo gene transfer experiments have revealed that the use of cationic lipid instead of anionic lipid reduced the transgene expression dramatically in organs such as muscle and liver. We further discovered that the use of anionic liposomes with a viral-mimic king lipid composition increased transfection efficiency by several times in vivo. We conclude that the alternative usage of transfer vectors, for example, HVJ-anionic liposomes for in vivo delivery to extended areas of organs and HVJ-cationic liposomes for in vitro delivery (and possibly for in vivo delivery to a restricted area of organs), is of significance.

Animals↗

Electron paramagnetic resonance and mutational analyses revealed the involvement of photosystem II-L subunit in the oxidation step of Tyr-Z by P680+ to form the Tyr-Z+P680Pheo- state in photosystem II.

To reveal the molecular mechanism of involvement of photosystem II (PSII)-L protein in the electron transfer in PSII, effects of mutations in PSII-L on the photochemistry of PSII were investigated by means of electron paramagnetic resonance (EPR) and flash photolysis. Wild type and a series of mutant versions of PSII-L were overproduced in Escherichia coliand chromatographically purified. Plastoquinone 9 (PQ-9) depleted PSII reaction center core complex consisting of CP47/D1/D2/Cytb-559/PSII-I/PSII-W was prepared and reconstituted with the wild type and each mutant version of PSII-L together with or without PQ-9. EPR signal indicating the formation of Tyr-Z+P680Pheo- state upon room-temperature illumination disappeared in CP47/D1/D2/Cytb-559/PSII-I/PSII-W, and it was recovered when the complex was reconstituted with the wild-type PSII-L. Mutation of a few amino acid residues in the carboxyl-terminal region of PSII-L, such as substitution of a triad of Tyr34, Phe35, and Phe36 by Leu, selectively resulted in the loss of the capability of PSII-L to recover the light-induced formation of Tyr-Z+P680Pheo- state in the reconstituted complex. Hydropathy profile of PSII-L suggests that it spans the membrane once by a hydrophobic stretch of the carboxyl-terminal side as its carboxyl end to face to the lumen. If this is the case, the amino acid residues essential for PSII-L to function are expected to be located close to the donor side of P680, suggesting the interaction of PSII-L with Tyr-Z (and/or Tyr-D) or P680 to facilitate the oxidation of Tyr-Z by P680+ to form Tyr-Z+P680Pheo- state in PSII. Evidence against PSII-L being involved in the electron transfer from Pheo- to QA was obtained by the flash photolysis experiments.

Amino Acid Sequence↗

Lack of effect of transmembrane gradient of magnesium and sodium on regulation of cytosolic free magnesium concentration in rat lymphocytes.

The regulation of the intracellular concentration of Mg2+ ([Mg2+]i) is not fully understood. The level of Mg in lymphocytes is a good predictor of total body Mg status. We measured [Mg2+]i and total Mg in rat lymphocytes by using, respectively, the fluorescent Mg2+ indicator mag-fura-2 and atomic absorption spectrophotometry. The basal [Mg2+]i in rat lymphocytes was 328 +/- 23 micromol/l. An elevation to 5 mmol/l or the removal of extracellular Mg2+ did not affect [Mg2+]i. A reduction in extracellular Na+ did not influence [Mg2+]i for 60 min. The total Mg concentration in lymphocytes also remained stable. Results suggest that the permeability of the plasma membrane to Mg2+ is very low, and that Na+/Mg2+ exchange is not involved in the regulation of [Mg2+]i in rat lymphocytes.

Animals↗

Oscillation of ADP-ribosyl cyclase activity during the cell cycle and function of cyclic ADP-ribose in a unicellular organism, Euglena gracilis.

In Euglena gracilis, the activity of ADP-ribosyl cyclase, which produces cyclic ADP-ribose, oscillated during the cell cycle in a synchronous culture induced by a light-dark cycle, and a marked increase in the activity was observed in the G2 phase. Similarly, the ADP-ribosyl cyclase activity rose extremely immediately before cell division started, when synchronous cell division was induced by adding cobalamin (which is an essential growth factor and participates in DNA synthesis in this organism) to its deficient culture. Further, cADPR in these cells showed a maximum level immediately before cell division started. A dose-dependent Ca2+ release was observed when microsomes were incubated with cADPR.

ADP-ribosyl Cyclase↗

The gnd gene encoding a novel 6-phosphogluconate dehydrogenase and its adjacent region of Actinobacillus actinomycetemcomitans chromosomal DNA.

A 10-kb DNA fragment containing the gnd gene from Actinobacillus actinomy-cetemcomitans Y4 was isolated and sequenced. The structural gnd gene codes for 6-phosphogluconate dehydrogenase that consists of 484 amino acids. In contrast to the gnd gene in Escherichia coli, Salmonella typhimurium, or Klebsiella pneumoniae, the gnd gene of A. actinomycetemcomitans was not located in the rfb or cps operon. The zwf gene encoding glucose 6-phosphate dehydrogenase, which is another enzyme consisting of pentose-phosphate pathway, sided at 3.8-kb upstream from the gnd gene. A phylogenetic tree based on sequence analyses showed higher homology of 6-phospho-gluconate dehydrogenase of A. actinomycetemcomitans with the eucaryotic enzymes rather than with bacterial enzymes.

Actinobacillus↗

Expressions of a calcium-binding protein (spot35/calbindin-D28K) in mouse olfactory cells: possible relationship to neuronal differentiation.

We used immunohistochemistry to investigate the expression of spot35/calbindin-D28k (calbindin) in mouse olfactory epithelium during development. Cell stages of immunopositive olfactory cells were determined by comparing the levels of proliferating cell nuclear antigen (PCNA). Calbindin-positive cells were abundant in the middle layer of the epithelium of animals before 2 weeks of age and gradually diminished during development. Only low levels were detectable near the basement membrane in the adult. Changes of calbindin-positive cells in terms of number and distribution were apparently compatible with localization changes of premature olfactory cells. PCNA overlapped calbindin in the nasal mucosa at lower magnifications on stained serial sections and immunohistochemical double staining revealed that calbindin-immunoreactive cells were located mainly just above PCNA-immunoreactive cells in the basal layer of the epithelium. This indicated that calbindin is expressed postmitotically in immature olfactory cells and is lost by mature cells. These findings suggest that calbindin might support the maturation of the olfactory cells, such as the projection of the neuronal processes, by stabilizing intracellular calcium ions in immature cells.

Aging↗

An improved computer method to prepare 3D magnetic resonance images of thoracic structures.

The mediastinal and cardiovascular anatomy is complex. We have developed a three-dimensional (3D) reconstruction system for the major mediastinal structures using magnetic resonance imaging data on a NeXT workstation. The program uses a combination of automatic and manual procedures to determine the contours of the cardiac structures. The geometric centers of the contours are connected by a 3D space curve, and the central axis of each cardiac structures is determined. The contours are projected on the perpendicular plane to the central axis and semiautomatically processed until the contours of one pixel are obtained. Then the surface rendering with transparency is performed. Compositing combines two images so that both appear in the composite, superimposed on each other. Demonstration of the various mediastinal lines and cardiovascular diseases by the composits of the partly transparent 3D images has promoted a better understanding of the complex mediastinal and cardiovascular anatomy and diseases.

Heart↗

Synovial sarcoma of the hand.

We report on a 23-year-old woman with a poorly differentiated synovial sarcoma on the palm of her hand which presented as a painless nodule. The MRI findings are presented along with the clinical and pathologic features. Because of similar morphological features, these tumors can be confused with benign lesions such as aggressive fibromatosis or ganglion cysts, especially when very small. The possibility of a synovial sarcoma mimicking a benign lesion needs to be considered when the mass does not have an unequivocal benign diagnosis on MR imaging. Following wide resection and reconstruction, our patient has been disease free with good function for 28 months.

Adult↗