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Biomedical subjects

T Nakanishi

Publications and source records attributed to T Nakanishi.

At least 19 recordsLinked to original sources

Purification, gene cloning, and gene disruption of the transcription elongation factor S-II in Saccharomyces cerevisiae.

Saccharomyces cerevisiae S-II was purified to near homogeneity as a protein stimulating RNA polymerase II. Four of seven lysyl endopeptidase-digested fragments of S-II were located in the PPR2 sequence reported previously. Analysis of a genomic clone of S-II revealed that S-II and PPR2 are the same protein consisting of 309 amino acid residues, and frame shifts were found in the sequence of PPR2 gene reported previously. Yeast S-II and mouse S-II showed high similarity in their amino acid sequences, especially in their amino-terminal and carboxyl-terminal regions. A gene disruption experiment showed that an S-II null mutant was not lethal under usual growth conditions, indicating that S-II is not essential for the growth of yeast.

Amino Acid Sequence

[Growth rate of abdominal aortic aneurysms as measured by Computerized tomography].

To evaluate the growth rate of abdominal aortic aneurysms, sequential computed tomography (CT) examinations were performed on 125 nonoperated patients (M/F 101/24, mean age 67 +/- 8 years, 129 lesions) at intervals of at least 6 months. Growth rates of aneurysms were obtained by subtracting the first from the last diameter and adjusting for examination interval. Mean growth rate was 0.28 +/- 0.26 cm/year. Aneurysms with an initial diameter exceeding 4 or 5 cm showed significantly faster growth than smaller aneurysms. There was no significant correlation between growth rate and atherosclerogenic factors, but systolic blood pressure was significantly higher in patients whose aneurysms ruptured. Our study showed quantitatively that aneurysms with a large diameter have a rapid growth rate, the growth rate of infrarenal aneurysms is significantly faster than that of suprarenal aneurysms, and blood pressure control is important to prevent rupture.

Adult

[Potential usefulness of computer-aided diagnosis (CAD) in a mass survey for lung cancer using photo-fluorographic films].

We investigated the potential usefulness of computer-aided diagnosis (CAD) in a mass survey for lung cancer. When the sensitivity of the computer output was adjusted nearly equal to that of the mass survey in our database which contained 198 photofluorographic films, some shadows detected by the computer output were different from those detected by human observers. Therefore, the best estimated sensitivity of an observer using the computer output was equal to or greater than the sensitivity of double reading. It is expected that CAD may have a role in a mass survey for lung cancer using photofluorographic films.

Diagnosis, Computer-Assisted

Identification of a shark sequence resembling the major histocompatibility complex class I alpha 3 domain.

Elasmobranchs (sharks and rays) branched off from the vertebrate line leading to the mammals more than 400 million years ago. They do not exhibit acute allograft rejection, and so far no report has pointed to the presence of major histocompatibility complex (MHC) antigen-like molecules in elasmobranchs. Here we demonstrate the existence of a gene in the shark (Triakis scyllia) genome with a sequence that resembles the MHC class I alpha 3 domains of other vertebrates. Several amino acids considered to be important for the interaction of the T-cell coreceptor CD8 with the MHC class I alpha 3 domain are conserved in the shark sequence.

Amino Acid Sequence

Effect of tumor size on the enhancement by gamma interferon of the localization of radiolabeled F(ab')2 fragments of anti-intercellular adhesion molecule-1 monoclonal antibodies in human colon carcinoma cells grafted in nude mice.

Because tumor size has been shown to influence the specific accumulation of radiolabeled anti-tumor-associated antigen monoclonal antibodies (mAb), the present study has investigated the effect of the tumor size on the enhancement by gamma interferon (IFN-gamma) of the accumulation of radiolabeled mAb in malignant lesions. Intercellular adhesion molecule-1 (ICAM-1) has been used as a marker because of its high susceptibility to modulation by IFN-gamma. F(ab')2 fragments of anti-ICAM-1 mAb CL207.14 have been selected to visualize malignant lesions, because they had been shown to be more sensitive probes for our experiments than whole IgG. Administration of IFN-gamma to human colon carcinoma-bearing nude mice increased the expression of ICAM-1 in the xenografts and the specific accumulation of 125I-F(ab')2 fragments of anti-ICAM-1 mAb CL207.14. The latter effect is influenced by the size of the lesions, because it was observed only in tumors with an approximate diameter of 8 mm and an approximate weight of 250 mg. If these results obtained in an animal model system are applicable to patients with malignant diseases, the present investigation suggests that administration of IFN-gamma enhances the sensitivity of immunoscintigraphy and the efficacy of immunotherapy with radiolabeled mAb which recognize tumor-associated antigens that are susceptible to modulation by IFN-gamma. However, the effect of IFN-gamma is not a general phenomenon but is influenced by the size of the malignant lesions.

Animals

[Detection of intrahepatic lipids by 1H-MRS--studies by breath-holding & 1 cm3 VOI].

The authors performed 1H-MR spectroscopy (MRS) to depict lipids in the liver of 10 healthy volunteers. Spectra were obtained by a 1.5 T-MR unit, with STEAM from 1 x 1 x 1 cm3 VOI. Lipid peaks were depicted in 7 of the 10 volunteers by breath-holding 1H-MRS study, while in only 4 on normal breathing. The existence of lipids could not be depicted through chemical shift imaging adopting in-phase & opposed images. This suggests a clinical utility of 1H-MRS, particularly through breath-holding studies, in depicting lipids from 1 x 1 x 1 cm3 VOI in the liver in vivo.

Humans

Changes of plasma des-gamma-carboxy prothrombin levels in patients with hepatocellular carcinoma in response to vitamin K.

The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half-life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K-deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK-4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects.

Aged

Distribution of oocysts, sporocysts and sporozoites of Eimeria tenella and Eimeria maxima in the digestive tract of chicken.

The distribution of oocysts, sporocysts and sporozoites of Eimeria tenella and Eimeria maxima in the digestive tract of chicken and in excreta was investigated. At 1 h after the oral inoculation of E. tenella oocysts, the number of sporocysts in the cecum was 3.4 x 10(6) and decreased gradually thereafter, and the number of sporozoites in the cecum increased and remained at a high level until 12 h after the inoculation. Small numbers of sporocysts and sporozoites of E. tenella were found in other intestinal sites. A great number of E. maxima sporozoites was found, especially in the jejunum, 2 h after the inoculation. The findings that the largest populations of sporozoites of E. tenella and E. maxima were found in the cecum and the jejunum, respectively, indicate that the site specificity of sporozoite invasion for each species is determined before the invasion takes place.

Animals

Intravascular stent prosthesis for right ventricular outflow obstruction.

OBJECTIVES: This study was designed to assess the impact of implantation of balloon-expandable stents on right ventricular outflow obstruction in children with congenital heart disease. BACKGROUND: Intravascular stenting has been established as a useful treatment in adults with coronary and peripheral vascular disease. Its application in the treatment of infants and children with pulmonary, systemic and right ventricular conduit obstruction resistant to balloon angioplasty is limited. METHODS: A total of 24 stainless steel stents were implanted in 17 patients. Five stents were placed within right ventricular to pulmonary artery conduits, 17 in branch pulmonary arteries and 1 in an aortopulmonary collateral vessel. Follow-up time has ranged from 1 to 14 months, with 6 patients having hemodynamic and angiographic studies greater than 1 year after stent placement. The mean age at implantation was 7.4 +/- 5.6 years and the mean weight 33 +/- 16 kg. RESULTS: Optimal stent position was obtained in 22 of 24 implantations. In one patient the stent slipped from the delivery balloon and was left positioned in the inferior vena cava. No embolization or thrombotic event has been documented. Among patients with right ventricular to pulmonary artery conduit obstruction, the gradient was immediately reduced from 85 +/- 30 mm Hg to 35 +/- 20 mm Hg after stent implantation; however, three patients required conduit replacement because of persistent obstruction with elevated right ventricular pressures (82 +/- 16 mm Hg). In 10 of 11 patients with pulmonary artery stenosis, clinical improvement was noted in association with enlargement of vessel diameter by 92% +/- 90% (range 17% to 355%) and the gradient reduction of 22 +/- 24 mm Hg to 3 +/- 4 mm Hg. CONCLUSIONS: These data support the view that intravascular stenting will become an important adjunct in the management of children with congenital heart disease.

Child

Effects of interleukin-1 beta on blood pressure, sympathetic nerve activity, and pituitary endocrine functions in anesthetized rats.

The effects of interleukin-1 beta (IL-1), an endogenous pyrogen, on both the central and peripheral endocrine, sympathetic, and cardiovascular systems were investigated by injecting it intracisternally (IC) and intravenously (IV). Intracisternal injections of IL-1 caused dose-dependent vasopressor responses, which were accompanied by corresponding increases in the abdominal sympathetic discharge. Blood pressure increased gradually, and attained a peak response at 20 to 30 min. Heart rate also increased dose-dependently. Intracerebroventricular pretreatments with indomethacin abolished both the pressor responses and tachycardia. The IV injections similarly elicited vasopressor responses with gradual onset, which were also accompanied by corresponding increases in the abdominal sympathetic firings. However, IL-1 did not constrict the peripheral vasculature in the perfused hindlimb preparation. Both IC and IV injections of IL-1 increased plasma vasopressin and corticotropin dose-dependently after 30 min. These results indicate that IL-1 of both central and peripheral origin may cause vasopressor responses. These may be partly mediated by the release of vasopressor pituitary hormones. The site of action could be a similar region in the central nervous system.

Adrenocorticotropic Hormone

Similarity, in molecular structure and function, between the plant toxin purothionin and the mammalian pore-forming proteins.

Many proteins containing domains of a cysteine-rich repeated motif, such as epidermal growth factor (EGF), have been reported. Here we report strong similarity between the amino acid sequence of a plant toxin--i.e., purothionin and its homologues--and with those of a domain found in mammalian pore-forming cytoplasmic proteins: components of complement and perforin of cytotoxic T-lymphocytes or natural killer-like cytotoxic cells. These similar sequences were found to be identical to the so-called EGF-like cysteine-rich repeated motif itself. Electron-microscopic observations indicated that, like complement and perforin, purothionin forms pores in the cytoplasmic membrane of target cells, resulting in their death within a few hours. On the basis of these sequence comparisons and physiological functions, we propose a scheme for the evolution of proteins containing modules of the cysteine-rich repeat motif.

3T3 Cells

Scintigraphic analysis of hemodynamics in a patient with a single large pulmonary arteriovenous fistula.

A pulmonary perfusion study was performed on a 54-year-old man with a single large pulmonary arteriovenous fistula (aneurysmal type) using Tc-99m MAA. On the static imaging, a defect corresponding to the location of the mass and right-to-left shunt was clearly documented. Decreased uptake of Tc-99m MAA in the lung field surrounding the lesion was observed and was thought to reflect a "steal" of blood flow by the fistula. One advantage of using radionuclide angiography with Tc-99m MAA rather than with Tc-99m pertechnetate was that it more easily provided a time-activity curve that added useful quantitative information about the altered pulmonary hemodynamics.

Arteriovenous Fistula

Bone and gallium scintigraphy in sacral chordoma. Report of four cases.

Bone scintigraphy with Tc-99m HMDP and gallium scintigraphy were evaluated in four patients with a primary sacrococcygeal chordoma. All lesions showed a photon-deficient or cold lesion corresponding to the tumor on bone scintigraphy, with no abnormal accumulation clearly observed on gallium scintigraphy. These findings led the authors to conclude that a midline sacrococcygeal tumor showing reduced uptake or a cold lesion on bone scintigraphy and no increased accumulation on gallium scintigraphy could be a chordoma rather than the malignant neoplasm suspected in this region.

Adult

Potential usefulness of computerized nodule detection in screening programs for lung cancer.

RATIONALE AND OBJECTIVE: To alert radiologists to possible nodule locations and subsequently to reduce the number of false-negative diagnoses, the authors are developing a computer-aided diagnostic (CAD) scheme for the detection of lung nodules in digital chest images. METHODS: A computer-vision scheme was applied to photofluorographic films obtained in a mass survey for detection of asymptomatic lung cancer in Japan. Ninety-five patients with abnormal test results who had primary and metastatic lung cancers and 103 patients with normal test results were included. RESULTS: The sensitivity of the computer output was comparable with that of physicians in this mass survey (62%). The computer detected approximately 40% of all nodules missed in the mass survey, but missed 17 true-positive results identified in the mass survey. The CAD scheme produced an average of 15 false-positive findings per image. CONCLUSION: If the number of false-positive results can be significantly reduced, computer-vision schemes such as this may have a role in lung cancer screening programs.

False Positive Reactions

Effects of endothelin-1 and inhibition of nitric oxide production with NG-monomethyl-L-arginine on arterial pressure and regional blood flow in anesthetized rats.

Regional hemodynamic responses to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, were compared with those to endothelin (ET) using tracer microspheres with a reference sample method in anesthetized rats. Intravenous injections of these agents (16 and 160 mmol/kg of L-NMMA and 0.1 or 0.5 nmol/kg of ET-1) dose-dependently increased the blood pressure to the similar level. The cardiac index markedly decreased with ET-1, but was not greatly influenced by L-NMMA. Coronary and cerebral blood flow were not affected by these agents. ET-1 increased the bronchial arterial flow, and markedly decreased the flow in the other organs and tissues examined. L-NMMA almost homogeneously increased the regional vascular resistance to the lesser extent compared to ET-1. Although both ET-1 and nitric oxide are produced in the same cells and exhibit interrelationships, the present results indicate that the regional vascular effects of these agents are different: (a) ET-1 preferentially constricts arteries in all organs and tissues except the lung (where it increases flow) and the heart and brain where it has no wasted effects, leading to reduction in cardiac output, and (b) nitric oxide dilates arteries predominantly in the kidneys, muscle, and white adipose tissues.

Amino Acid Oxidoreductases

Measurements of serum levels of nitrate ions in men and women: implications of endothelium-derived relaxing factor in blood pressure regulation and atherosclerosis.

As endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitric ions, we measured serum levels of nitrate (NO3-) concentrations as an index of endothelium-derived NO, to assess its role in blood pressure regulation. Because serum NO3- levels in men were significantly elevated compared to those in women, data from these two groups were analyzed separately. In men, multiple regression analysis revealed that NO3- significantly correlated with age, systolic blood pressure, body mass index (BMI), and total cholesterol. Blood pressure correlated with age, BMI, and NO3- with multivariate analysis. In women, NO3- significantly correlated with age, systolic blood pressure, and total cholesterol with a simple correlation. With multiple regression analysis, serum NO3- highly correlated with serum levels of triglyceride and total cholesterol and age. The blood pressure correlated with four parameters, i.e., total cholesterol, age, BMI, and NO3-. In summary, serum NO3- levels seem to relate to serum lipids and glucose levels and blood pressure, which strongly suggests that production of endothelium-derived NO is increased in the atherosclerotic process.

Adult

Clinical and experimental studies on the mechanism of abnormal accumulation in lung scanning with 123I-IMP.

To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter-induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion.

Aged

Altered kinetics of 123I-IMP in irradiated rabbit lungs.

Radiation-induced alteration of intrapulmonary kinetics of 123I-IMP was investigated in 11 rabbits receiving a 50 Gy dose of radiation to one lung. In all 13 examinations of these rabbits, 3-17 weeks following radiation, the delayed images of 123I-IMP lung scintigrams showed abnormal accumulation in the irradiated lungs. The time-activity curves of the irradiated lung following injection of 123I-IMP had shallower downslopes of both the initial fast phase and the following slow phase than those of the non-irradiated lung. Finally the radioactivity of the irradiated lung exceeded that of the normal lung. The altered intrapulmonary kinetics of 123I-IMP in the irradiated lung was clearly confirmed. 99Tcm-MAA lung perfusion scintigrams showed reduced uptake in the irradiated lungs; the uptake decreased with time following radiation. Pulmonary arterial perfusion was considered to influence the distribution and kinetics of 123I-IMP, however, those of 123I-IMP did not reflect only the pulmonary arterial perfusion observed by 99Tcm-MAA scintigrams. Chest radiography and histological studies revealed a relatively slight change or injury of the irradiated lung in these rabbits. These results indicate that this agent could be useful in detecting and assessing early lung injury induced by radiation, and will give us pathological information in addition to lung perfusion in the peripheral area where the large 99Tcm-MAA molecule cannot reach.

Amphetamines