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Biomedical subjects

K Nakanishi

Publications and source records attributed to K Nakanishi.

At least 19 recordsLinked to original sources

[MR imaging evaluation of plica synoviallis mediopatellaris of the knee joint].

To evaluate the diagnostic ability of MR imaging for plica synoviallis mediopatellaris (PSM), we retrospectively reviewed the MR imaging findings of patellofemoral space in 20 knee joints of 11 patients. In all 20 knee joints, arthroscopy and MR imaging were available. MR imaging was performed with a 1.5 Tesla Magnetom (Siemens) using a round surface coil. Pulse sequences were SE (TR 600 ms/TE 26 ms), SE (TR 200 ms/TE 26, 70 ms) and FLASH (TR 450 ms/TE 15 ms/FA 90 degrees). In six of the 20 knees with PSM proved by arthroscopy, a low intensity band was shown above the medial condyle of the femur on both T1- and T2-weighted MR images, and on FLASH images this band was shown as intermediate intensity. In the other 14 knees with no PSM observed by arthroscopy, the low intensity band was not shown on MR imaging. In all 20 knees, a similar low intensity band was shown about 1 cm cranial to the medial condyle of the femur. This should not be diagnosed as PSM. The low intensity band seen on T1- and T2-weighted MR images and its anatomical relation to the medial condyle are important in diagnosing PSM.

Adolescent

Diversion of the sign of phototaxis in a Chlamydomonas reinhardtii mutant incorporated with retinal and its analogs.

The blind mutant FN68 of the unicellular flagellate green alga Chlamydomonas reinhardtii is negatively phototactic in the presence of the native chromophore all-trans retinal. In contrast, analog chromophores such as a ring-acyclic retinal and those in which trans/cis isomerization about the C11 = C12 double bond was blocked induced predominantly positive phototaxis in the same strain under the same experimental conditions. These observations can be interpreted by assuming that the negative and the positive phototaxis is mediated distinctively by two rhodopsin species which differ in their affinities with the exogenous chromophores. However, a more reasonable explanation, which requires fewer assumptions, is that the sign of phototaxis depends on a delay in intracellular photosignal transduction. This novel view was deduced directly from the widely accepted hypothesis [1980, Microbiol. Rev. 44, 572-630] on phototaxis mechanisms.

Animals

Structure and activity studies of pardaxin and analogues using model membranes of phosphatidylcholine.

Thirteen synthetic pardaxin analogues were assayed for their ability to interact with model membranes of phosphatidylcholine. The results suggested the following: An amphipathic alpha-helix from isoleucine-14 to leucine-26 is responsible for most of the membrane perturbing properties of pardaxin. A hydrophobic N-terminal region enhances the activity of the isoleucine-14 to leucine-26 alpha-helix by binding the pardaxin molecule to the lipid bilayer. A bend centered around 12Ser-13Pro appears to create overall amphipathicity for the two different helical regions of pardaxin, but this contributes only slightly to potency. The C-terminal amino acids are unimportant for membrane perturbing activity and may be present only to enhance transportation in an aqueous environment prior to membrane binding in the native system.

Amino Acid Sequence

Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and platelet-derived endothelial cell growth factor.

Gliostatin is a polypeptide growth inhibitor of apparent M(r) = 100,000 with a homodimeric structure comprising two 50-kDa subunits, acting on astrocyte as well as astrocytoma cells (Asai, K., Hirano, T., Kaneko, S., Moriyama, A., Nakanishi, K., Isobe, I., Eksioglu, Y.Z., and Kato, T. (1992) J. Neurochem., 59, 307-317). The amino acid sequences of 13 tryptic peptides including the amino terminus were completely identical to those of platelet-derived endothelial cell growth factor (PD-ECGF) (Ishikawa, F., Miyazono, K., Hellman, U., Drexler, H., Wernstedt, C., Hagiwara, K., Usuki, K., Takaku, F., Risau, W., and Heldin, C.-H. (1989) Nature 338, 557-562). Gliostatin and PD-ECGF, purified from human placenta, shared growth inhibition on glial cells and growth promotion on endothelial cells, and exhibited similar values for half-maximal dose of glial growth inhibition (ID50 = 1.3 nM) and the half-maximal concentration of endothelial growth promotion (EC50 = 1.0 nM), suggesting that both factors evoke the biological actions through an identical receptor on each cell surface. We have further demonstrated evidence of a novel neurotrophic action of gliostatin/PD-ECGF toward embryonic rat cortical neurons in culture. The half-maximal concentration of gliostatin/PD-ECGF for neurotrophic action was 0.3 nM. All actions on glial, endothelial, and neuronal cells, were abolished by a monoclonal antibody against gliostatin. These data indicate that gliostatin/PD-ECGF may play important roles on development and regeneration of the central nervous system and may also involve the induction of angiogenesis for the formation of blood brain barrier.

Amino Acid Sequence

[Dynamic 3DFT FISP MR imaging of hepatocellular carcinoma].

Dynamic 3 dimensional Fourier transformation (3DFT) FISP MR imaging was performed in 5 patients with hepatocellular carcinoma before partial hepatectomy. Immediately after 0.1 mmol/kg of Gd-DTPA was administered intravenously, 3DFT FISP images (TR/TE/flip angle/slice thickness, 20 msec/8 msec/30 degrees/2-4 mm) were obtained every 30 seconds until 150 sec. We correlated dynamic MR images of the 5 patients with gross and microscopic findings. Some regions in the tumor corresponding to viable cells showed high intensity enhancement and other regions corresponding to necrotic regions showed no enhancement on the early phase images. We concluded that dynamic 3DFT FISP MR imaging which had good spatial resolution was useful in evaluating the vascularity of the tumor.

Aged

[Differentiation between hepatoma and hemangioma by inversion recovery snapshot FLASH MR imaging with variable TIs].

To differentiate hepatoma from hemangioma, MR studies were performed for 18 patients with 21 untreated liver tumors (hepatoma 10, hemangioma 11). We obtained inversion recovery snapshot FLASH images of liver tumors with variable TIs (50, 100, 150, 200, 250, 300, 400, and 500 msec). 8 hemangiomas showed higher intensity than liver parenchyma on the images at 150 msec and less of TI, and lower intensity at 200 msec or more TI. In 7, signal intensity of hepatoma became low at 150 msec or less of TI or remained high with prolonged TI. Inversion recovery snapshot FLASH imaging with variable TIs will be useful for differentiating between hepatoma and hemangioma.

Adult

High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/tumor necrosis factor.

Patients with high level of serum endotoxin did not necessarily develop into lethal shock, whereas some patients died of septic shock even when their serum endotoxin levels were low. These results indicate that limiting factor which determines the host to be endotoxin shock principally depends on the host susceptibility to endotoxin instead of serum endotoxin level. To understand this susceptible status of the host to endotoxin, we used Propionibacterium acnes primed mouse endotoxin shock model. We found that P. acnes-primed mice responded to low dose of LPS by enhanced production of IL-1 and TNF. And such mice were highly susceptible to the lethal shock inducing effect of IL-1 and/or TNF, which also induced high level of serum IL-6 in these mice. Therefore, measurement of serum IL-6 level provides us with the information of the preceding exposure of the host to either LPS or IL-1 and/or TNF and the highly susceptible status of the host to these stimuli. Based on these results obtained from animal model, we investigated the relationship between serum IL-6 levels and serum endotoxin levels in the patients with malignant hematologic disorders. We found that these patients fell into two groups; an endotoxin susceptible group, equivalent to P. acnes-primed mice, showing high level of serum IL-6 with low level of serum endotoxin, and a nonendotoxin susceptible group, equivalent to P. acnes-nonprimed mice, showing low or undetectable level of serum IL-6 with high level of serum endotoxin. We propose that the measurement of serum IL-6 level in the patients positive for endotoxin is a useful tool in evaluating diagnosis and prognosis of endotoxin shock.

Adolescent

In vivo incorporation of 14C-phenylalanine into ascidian tunichrome.

Ascidia ceratodes exposed to 14C-phenylalanine in the surrounding seawater incorporates the radiolabel into newly biosynthesized tunichrome molecules. Radioactivity can be detected in tunichrome extracted from circulating blood cells within one day following initial exposure to the radiolabel; weak activity (less than or equal to 4 microCi/mol tunichrome = 22 nmol phenylalanine/mol tunichrome) is detected in 1 to 10 days; significantly higher amounts of radiolabel (57 microCi/mol tunichrome = 318 nmol phenylalanine/mol tunichrome) appear 20 days after seawater exposure. Therefore, phenylalanine can function as a precursor in the biosynthesis of tunichrome.

Animals

Role and regulation of interleukin (IL)-2 receptor alpha and beta chains in IL-2-driven B-cell growth.

Substantial proportions of resting B cells constitutively express low levels of IL-2 receptor (IL-2R) alpha and/or beta chains. The expression of these chains is differentially regulated by anti-IgM and IL-2/IL-4. The anti-IgM induces IL-2R alpha chain expression, whereas each of the two cytokines induces IL-2R beta chain expression in a dose-dependent manner. Moreover, IL-2 induces the growth of B cells, when the cells were pretreated with IL-2 or IL-4 for 24 h. The magnitude of this IL-2-driven B-cell growth depends upon the level of IL-2R beta chain expression. Costimulation of the B cells with IL-2 and anti-IgM shifts the dose-response curve, and the cells proliferate at an IL-2 concentration as low as 40 pM. These results indicate that the levels of anti-IgM-induced IL-2R alpha chain and IL-2-induced IL-2R beta chain determine the sensitivity of the cells to IL-2.

Animals

Isolation and structure of an intrastrand cross-link adduct of mitomycin C and DNA.

A new covalent mitomycin C-DNA adduct (4) was isolated from DNA exposed to reductively activated mitomycin C (MC) in vitro. The MC-treated DNA was hydrolyzed enzymatically under certain conditions, and the new adduct was isolated from the hydrolysate by HPLC. Its structure was determined by ultraviolet and circular dichroism spectroscopy and chemical and enzymatic transformations conducted on microscale. In the structure, a single 2" beta, 7"-diaminomitosene residue is linked bifunctionally to two guanines in the dinucleoside phosphate d(GpG). The guanines are linked at their N2 atoms to the C1" and C10" positions of the mitosene, respectively. A key to the structure was a finding that removal of the mitosene from the adduct by hot piperidine yielded d(GpG); another was that the adduct was slowly converted to the known interstrand cross-link adduct 3 by snake venom diesterase and alkaline phosphatase. Adduct 4 represents an intrastrand cross-link in DNA formed by MC. Of the two possible strand-polarity isomers of 4, 4a in which the mitosene 1"-position is linked to the 3'-guanine of d(GpG) is designated as the proper structure, on the basis of the mechanism of the cross-linking reaction. The same adduct 4 was isolated from poly(dG).poly(dC), synthetic oligonucleotides containing the GpG sequence, and Micrococcus luteus and calf thymus DNAs. The relative yields of interstrand and intrastrand cross-links (3 and 4) were determined under first-order kinetic conditions; an average 3.6-fold preference for the formation of 3 over that of 4 was observed. An explanation for this preference is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation

Identification of immuno-reactive lipocortin 1-like molecules in serum and plasma by an enzyme immunoassay for lipocortin 1.

A two-site enzyme immunoassay for lipocortin 1 (LC1) has been developed. The detection limit of LC1 was 0.2 ng/tube and the optimal assay range was 1 to 100 ng/tube. The assay system enabled us to identify immunoreactive lipocortin 1-like molecules (IR-LC1) in human serum and plasma. Normal human serum and plasma IR-LC1 concentrations were 44.6 ng/ml for males and 43.1 ng/ml for females with no significant difference between both sexes. The age-related analysis among nine age groups from newborn to 69 years old revealed that the serum or plasma level was high in infants (77.5 ng/ml for newborn and 75.6 ng/ml for 1 month-1 year group), and the 40-year-old (52.2 ng/ml) and 50-year-old (51.3 ng/ml) groups. The major population of plasma IR-LC1 was of 70 kDa in size corresponding to that of the LC1 homodimer. The present enzyme immunoassay system is sufficiently sensitive for the clinical study of LC1 in human body fluids, tissues and organs.

Adolescent

Intrahepatic venous and portal venous aneurysms examined by color Doppler flow imaging.

Thirteen cases with liver cystic lesions, which were suspected to communicate with intrahepatic vessels on the basis of ordinary sonography, were examined by color Doppler flow imaging. By this method, blood flow within the cystic lesion was detected in 5 of these cases, and the communication to the intrahepatic vessel confirmed. Information about the hemodynamics of aneurysms was obtained. Two of these lesions were diagnosed as an aneurysmal porta-hepatic venous fistula, another 2 as a portal venous aneurysm, and the remaining 1 as a hepatic venous aneurysm.

Aneurysm

Past and present studies with ponasterones, the first insect molting hormones from plants.

The search for antitumor compounds from Southeast Asian plants led to ponasterones, the first phytoecdysteroids, just a year after structure determination of ecdysone and 20-hydroxyecdysone. An independent study of Chinese herb constituents by Takemoto et al. at Tohoku University led to the simultaneous and totally independent discovery of phytoecdysteroids. These findings greatly facilitated research in insect and crustacean physiology. The original structural studies on various phytoecdysteroids have led to interdisciplinary bioorganic studies in the area related to ecdysone receptor, ecdysone biosynthetic precursor (or its storage form), crustacean molt inhibitory factors, and so on.

Animals

Islet amyloid polypeptide (IAPP) gene analysis in a Japanese diabetic with marked islet amyloid deposition.

Islet amyloid polypeptide (IAPP) is a major constituent of pancreatic amyloid deposits in many patients with non-insulin-dependent diabetes mellitus (NIDDM). We analyzed the IAPP gene in a Japanese diabetic with marked islet amyloid deposition. Pancreatic specimens were obtained from an 87-year-old NIDDM patient who had had diabetes for 37 years. All islets (100/100) in his pancreas had IAPP-positive amyloid deposition, and 70% of the area of the islet was replaced by amyloid. We amplified the coding regions as well as the upstream region of the IAPP gene by polymerase chain reaction (PCR). The products of PCR were sequenced, and the sequences of the coding regions were identical to the Caucasian ones. However, the nucleotides of two positions of 5'-upstream and one position of intron 2 were different from the Caucasian data: the upstream region of the IAPP gene in the patient had cytosine substituted for thymine at -259, and had two alleles including cytosine and adenine at -229, respectively. The nucleotide of position 539, that is guanine, was deleted. A possible difference in the IAPP promoting region between the Japanese and Caucasian population was suggested.

Aged

Insulin administration induces capillary growth in brown adipose tissue of heat-exposed rats.

1. An apparent effect of insulin administration on enlargement of interscapular brown adipose tissue (BAT) was found in heat-exposed rats, but not in warm-adapted or cold-acclimated rats. 2. BAT extracts from the heat-acclimated/insulin-treated (HI) rats notably increased the capillary growth in an in vitro angiogenesis model in which microvascular fragments and myofibroblastic (Mf) cells isolated from lipid tissues were grown in co-culture, although a direct effect of insulin was not high. 3. BAT extracts from the HI rats stimulated the production of endothelial cell growth factor and collagen by Mf cells. 4. It is probable that an increased angiogenic activity contributes to the capillary growth and tissue growth in BAT of HI rats.

Acclimatization

A novel microbial sensor using luminous bacteria.

A novel microbial sensor system that uses luminous bacteria was developed for the determination of both glucose and toxic compounds. The sensor system consisted of a membrane with luminous bacteria immobilized upon it and a photomultiplier. Measurements were based on the in vivo intensity of the light emitted by the bacteria, as this is affected by their environment. A linear relationship was observed between increased luminescence and concentrations of glucose between 0.05 mM and 0.55 mM. The relative standard deviation was 10% for 0.55 mM glucose (n = 10). Toxic compounds such as benzalkonium chloride, sodium dodecyl sulphate and chromium(VI) were also detected by measuring the decrease in luminescence in their presence.

Bacteria

Intermittent intensive combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (cyclic PAC chemotherapy) for ovarian cancer.

Despite high primary response rates with cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancer remains unsatisfactory. This prompted us to design a new systematic approach using a combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide (PAC), namely, cyclic PAC chemotherapy. This is a 3-step chemotherapy with 3 courses of the PAC regimen in each step. It was administered for 18 months to patients with clinical Stage Ic-IV ovarian cancer, after cytoreductive surgery. In the present study, the cyclic PAC, brief PAC, and FAM (5-Fu, an alkylating agent, and mitomycin C) groups included 27 cases, 34 cases, and 38 cases, respectively. Treatment of Stage Ic-IV disease by cyclic PAC improved the outcome (57% estimated 5-year survival rate) compared to brief-PAC and FAM (20% and 32%, respectively). The outcome for patients with Stage III or IV ovarian cancer was also superior for the cyclic-PAC group compared to the brief-PAC and FAM groups (cyclic-PAC 44%, brief-PAC 9%, and FAM 0% estimated 5-year survival rates). Cyclic PAC chemotherapy was thus found to be capable of dramatically improving the long-term survival rate of ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols