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Biomedical subjects

M Konishi

Publications and source records attributed to M Konishi.

At least 19 recordsLinked to original sources

Importance of intra-individual variation in tumour volume of hepatic colorectal metastases.

AIMS: The efficacy of surgical resection for multiple colorectal hepatic metastases (MCHM) has been controversial. We examined the survival of patients who received surgery for MCHM and examined the factors associated with survival. METHODS: A retrospective analysis was performed of 50 consecutive patients who received hepatic resections for MCHM, defined as four or more metastatic lesions of colorectal cancer. RESULTS: Overall survival after hepatic resection for MCHM was 48% at 3years and 43% at 5years (median survival, 22.3months). Multivariate analyses revealed that a coefficient of variation (CV) in volume of hepatic metastases in each individual patient above 1.8 (P=0.01, HR=4.08, 95% CI=1.33-12.5) was the only poor prognostic factor after resection of MCHM. CONCLUSIONS: A CV in volume of hepatic metastases in each individual patient above 1.8 predicts poor survival after hepatectomy of MCHM. Thus, the CV in volume of hepatic metastases in each individual patient might be useful in planning the therapeutic strategy for patients with MCHM.

Adenocarcinoma↗

Behavioral guides for sensory neurophysiology.

The study of natural behavior is important for understanding the coding schemes of sensory systems. The jamming avoidance response of the weakly electric fish Eigenmannia is an excellent example of a bottom-up approach, in which behavioral analyses guided neurophysiological studies. These studies started from the electroreceptive sense organs to the motor output consisting of pacemaker neurons. Going in the opposite direction, from the central nervous system to lower centers, is the characteristic of the top-down approach. Although this approach is perhaps more difficult than the bottom-up approach, it was successfully employed in the neuroethological analysis of sound localization in the barn owl. In the latter studies, high-order neurons selective for complex natural stimuli led to the discovery of neural pathways and networks responsible for the genesis of the stimulus selectivity. Comparison of Eigenmannia and barn owls, and their neural systems, has revealed similarities in network designs, such as parallel pathways and their convergence to produce stimulus selectivity necessary for detection of natural stimuli.

Animals↗

Hepatitis C virus free-virion and immune-complex dynamics during interferon therapy with and without ribavirin in genotype-1b chronic hepatitis C patients.

The Synergistic effect of interferon (IFN) and ribavirin for patients with chronic hepatitis C has been demonstrated, but ribavirin has no apparent direct antiviral effect against hepatitis C virus (HCV) when used as monotherapy. To elucidate the mechanism of ribavirin on enhanced HCV eradication when used in combination therapy, we investigated the serum HCV dynamics of free-virions (FV) and immune-complexes (IC) in genotype-1b infected patients treated with IFN-alpha2b alone (n = 11) or in combination with ribavirin (n = 15). Serum FV- and IC-HCV RNA were separated by immunoprecipitation using anti-human immunoglobulin and quantified serially using real-time detection polymerase chain reaction. At the first phase (day 0-2), the decline of FV- and IC-HCV RNA was similar between the two treatment groups. At the second phase (day 2-28), the decline of IC was significantly faster in patients treated with IFN plus ribavirin compared with IFN alone [exponential decay slope = 0.079 +/- 0.036 vs 0.048 +/- 0.027 log10/day, P = 0.0248; half-life = 81.1 +/- 21.4 vs 135.1 +/- 61.4 h, P = 0.0053], although the second phase FV-decline was not significantly different between the two treatment groups. The fast second phase decline of IC was associated with sustained virological response to therapy. These results suggest that ribavirin may modulate the humoral immune response against HCV and trigger a favourable response to IFN. In conclusion, analysis of early IC-HCV dynamics is useful for predicting the response to therapy and for understanding the mechanism of action of antiviral drugs in chronic hepatitis C patients.

Adult↗

Effects of bezafibrate in patients with chronic hepatitis C virus infection: combination with interferon and ribavirin.

An association of hepatitis C virus (HCV) with low-density lipoproteins (LDL) in serum of patients with chronic hepatitis C (CHC) has been suggested. We conducted a prospective study in CHC patients complicated with hyperlipidaemia, to examine whether bezafibrate, which is commonly used for treatment of hyperlipidaemia, reduces serum HCV-RNA titre and improves liver dysfunction. Fifteen patients received daily oral bezafibrate treatment (400 mg/day) for 8 weeks, and its effects on serum lipids, transaminases, HCV-RNA titres, and HCV-RNA titres bound to LDL were evaluated. Fifteen untreated patients with CHC and hyperlipidaemia were used as controls. The mean serum alanine aminotransferase levels and HCV-RNA titres significantly decreased at the end of bezafibrate therapy in the treated group (105 +/- 34 to 80 +/- 32 IU/L, P = 0.02 and 2.23 +/- 2.71 to 1.78 +/- 2.38 x 10(7) copies/mL, P < 0.01 respectively), but no changes were observed in the control group. Serum HCV-RNA titres bound to LDL, as quantified by immunoprecipitation using anti-LDL antibody, also decreased in all 15 treated patients [5.55 +/- 6.59 to 1.07 +/- 1.58 x 10(6) copies/ml, P < 0.01 (mean reduction rate was -78.5 +/- 17.0%)]. Sucrose density-gradient ultracentrifugation study revealed that HCV-RNA-decreased density fractions after the bezafibrate were identical to LDL-density fractions (1.015-1.062 g/mL). Eight CHC patients were treated with bezafibrate, interferon, and ribavirin triple therapy for 32 weeks, and four patients achieved sustained virological response to therapy. This pilot study provides further evidence of an association between HCV and LDL in serum and suggests the potential usefulness of bezafibrate as an anti-HCV reagent for the treatment of CHC patients.

Adult↗

Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter.

The hypothalamus, especially the preoptic area, plays a crucial role in thermoregulation, and our previous studies showed that the periaqueductal gray matter is important for transmitting efferent signals to thermoregulatory effectors in rats. Neurons responsible for skin vasodilation are located in the lateral portion of the rostral periaqueductal gray matter, and neurons that mediate non-shivering thermogenesis are located in the ventrolateral part of the caudal periaqueductal gray matter. We investigated the distribution of neurons in the rat hypothalamus that are activated by exposure to neutral (26 degrees C), warm (33 degrees C), or cold (10 degrees C) ambient temperature and project to the rostral periaqueductal gray matter or caudal periaqueductal gray matter, by using the immunohistochemical analysis of Fos and a retrograde tracer, cholera toxin-b. When cholera toxin-b was injected into the rostral periaqueductal gray matter, many double-labeled cells were observed in the median preoptic nucleus in warm-exposed rats, but few were seen in cold-exposed rats. On the other hand, when cholera toxin-b was injected into the caudal periaqueductal gray matter, many double-labeled cells were seen in a cell group extending from the dorsomedial nucleus through the dorsal hypothalamic area in cold-exposed rats but few were seen in warm-exposed rats. These results suggest that the rostral periaqueductal gray matter receives input from the median preoptic nucleus neurons activated by warm exposure, and the caudal periaqueductal gray matter receives input from neurons in the dorsomedial nucleus/dorsal hypothalamic area region activated by cold exposure. These efferent pathways provide a substrate for thermoregulatory skin vasomotor response and non-shivering thermogenesis, respectively.

Animals↗

Distribution and superinfection of bovine leukemia virus genotypes in Japan.

A study to investigate the types and distribution of bovine leukemia virus (BLV) was conducted on about eight hundred cattle drawn from 53 farms found in 16 prefectures in Japan. Agar gel immunodiffusion (AGID) tests of serum samples and nested-PCR to detect BLV provirus, in peripheral blood leukocytes were performed. To identify genotypes, restriction fragment length polymorphism (RFLP) was performed with a PCR-amplified 444 bp fragment of the env gene using endonucleases. Three genotypes (1, 3, and 5) were dominant in Japan, and were found in 48.3%, 32.7%, and 16.9% of PCR positive cattle, respectively. Of the cattle infected with genotype 1, 84.7% were strongly positive in the AGID test. Similarly, in cattle with genotype 3, 78.9% were strongly positive. However, only 59.1% of cattle with genotype 5 were strong positive. Three cattle showed unusual RFLP patterns and they were found to be infected with more than one genotype. These results suggest that some BLV infected cattle can not induce effective immune reactions and suffer from superinfection by BLV in the field.

Animals↗

The role of craniofacial growth in leptin deficient (ob/ob) mice.

OBJECTIVES: To elucidate the role of leptin on maxillo-facial morphological growth using hereditary obesity model ob/ob mice, and to examine the presence of the leptin receptor gene expression in the mouse condylar head cartilage. DESIGN: Leptin was intraperitoneally administered once a day in 10 C57BL/6J (lean) and 10 C57BL/6J-ob (ob/ob) mice (leptin administration group), and phosphate-buffered saline (PBS) in 10 lean and 10 ob/ob mice (PBS administration group), between the fifth and 11th week after birth. The amount of fat, the body amount without fat, the rate of body fat, and the width of the condylar cervical area were measured during the 11th week, and roentgenographic cephalometric analysis was performed at the fifth, eighth, and 11th week. Furthermore, the condylar head cartilage in C57BL/6J mice was stereoscopically excised to extract total RNA, and RT-PCR method was performed regarding the leptin receptor gene. RESULTS: The body fat amount in ob/ob mice with leptin production insufficiency was greater than that in lean mice, and significant differences were noted in every measurement item regarding maxillo-facial morphology. Recovery of bone length was noted in ob/ob mice by administering leptin. Furthermore, the expression of the leptin receptor gene in the condylar head cartilage was confirmed. CONCLUSION: Exogenous leptin administration leads to significant increases in craniofacial dimensions; and leptin receptors are expressed in mandibular condylar cartilage. These results indicate an important role for leptin in craniofacial growth and morphology. We speculate that leptin's direct peripheral effect on bone and cartilage is closely involved in this role.

Adipose Tissue↗

Cochlear and neural delays for coincidence detection in owls.

The auditory system uses delay lines and coincidence detection to measure the interaural time difference (ITD). Both axons and the cochlea could provide such delays. The stereausis theory assumes that differences in wave propagation time along the basilar membrane can provide the necessary delays, if the coincidence detectors receive input from fibers innervating different loci on the left and right basilar membranes. If this hypothesis were true, the left and right inputs to coincidence detectors should differ in their frequency tuning. The owl's nucleus laminaris contains coincidence detector neurons that receive input from the left and right cochlear nuclei. Monaural frequency-tuning curves of nucleus laminaris neurons showed small interaural differences. In addition, their preferred ITDs were not correlated with the interaural frequency mismatches. Instead, the preferred ITD of the neuron agrees with that predicted from the distribution of axonal delays. Thus, there is no need to invoke mechanisms other than neural delays to explain the detection of ITDs by the barn owl's laminaris neurons.

Acoustic Stimulation↗

Dynamic control of auditory activity during sleep: correlation between song response and EEG.

The song nucleus high vocal center (HVC) sends neural signals for song production and receives auditory input. By using electroencephalography (EEG) to objectively identify wake/sleep state, we show that HVC auditory responses change with physiological states. Comparison of EEG and HVC records revealed that HVC response to auditory stimuli is greatest during slow-wave sleep. During slow-wave sleep, HVC neurons responded preferentially to the bird's own song. Strikingly, both spontaneous and forced waking during sleep caused HVC auditory responses to cease within milliseconds of an EEG-measured state change. State-dependent phenomena in downstream nuclei, such as robustus archistriatalis, are likely to be derivatives of those in HVC.

Animals↗

Evaluation and application of liquid chromatographic columns coated with 'intelligent' ligands: (I) acylcarnitine column.

Unique stationary phases of octadecylsilica (ODS) coated with acylcarnitines have been developed for liquid chromatographic columns. The ODS column coated with acylcarnitine was readily prepared by recycling the solution containing acylcarnitine through an ODS column in a closed loop. Acylcarnitine was adsorbed on the ODS surfaces by hydrophobic interaction between the acyl group of acylcarnitine and the octadecyl group of the ODS phases. The ODS column coated with stearoylcarnitine (CN-18 column) was the most stable among the four columns coated with acylcarnitines of various acyl chain lengths (decanoylcarnitine, lauroylcarnitine, myristoylcarnitine, and stearoylcarnitine) under the condition of delivery of the mobile phase, indicating that adsorption of acylcarnitine on the ODS surfaces depended on the length of acyl chains. The CN-18 column was usable for delivering the mobile phase contained less than 20% (v/v) acetonitrile, retaining almost the same separation efficiency as the intact ODS column. The retention behavior of ionic solutes on the CN-18 column could be explained by both ionic and electrostatic interactions between the solutes and the stationary phase. The CN-18 column enabled efficient separation of inorganic anions, nicotinic acids, amino acids, and nucleotides. The chiral ODS column coated with enantiomer of stearoylcarnitine, L-stearoylcarnitine (L-CN-18 column) could achieve direct enantiomeric separation of DL-tryptophan, alpha-methyl-DL-tryptophan and DL-3-indolelactic acid using 100% water as the mobile phase. The L-CN-18 column could also separate enantiomers of amino acids and alpha-hydroxycarboxylic acids by ligand-exchange chromatographic mode using a mobile phase containing copper(II) ion. The chiral recognition is discussed for enantiomeric separation on the L-CN-18 column.

Carnitine↗

A monoclonal antibody specific to a song system nuclear antigen in estrildine finches.

This paper describes a monoclonal antibody that recognizes a molecule whose expression is mostly restricted to some of the forebrain areas that control singing behavior in adult estrildine species studied, including the zebra, Bengalese, and spice finches. When the song system displays extreme sexual dimorphism, as in these species, antibody staining occurs only in the male's song nuclei. However, protein expression is identical in both sexes of estrildine finches, in which females also have a well-developed song system. Canaries appear to lack the protein, but it can be induced in female zebra finches by early estrogen treatment. Antibody staining patterns in the zebra finch show that the protein's expression is developmentally regulated to coincide with the abrupt increase in the volume and cell size of the male's or the estrogen-treated female's song system.

Animals↗

Auditory spatial receptive fields created by multiplication.

Examples of multiplication by neurons or neural circuits are scarce, although many computational models use this basic operation. The owl's auditory system computes interaural time (ITD) and level (ILD) differences to create a two-dimensional map of auditory space. Space-specific neurons are selective for combinations of ITD and ILD, which define, respectively, the horizontal and vertical dimensions of their receptive fields. A multiplication of separate postsynaptic potentials tuned to ITD and ILD, rather than an addition, can account for the subthreshold responses of these neurons to ITD-ILD pairs. Other nonlinear processes improve the spatial tuning of the spike output and reduce the fit to the multiplicative model.

Acoustic Stimulation↗

Intracellular calibration of the fluorescent Mg2+ indicator furaptra in rat ventricular myocytes.

Single ventricular myocytes enzymatically isolated from rat hearts were loaded with the Mg2+ indicator furaptra, and the relationship between the fluorescence ratio signal (R) and the intracellular free concentration of Mg2+ ([Mg2+]i) was studied in situ at 25 degrees C. After the application of ionophores (ionomycin, monensin, nigericin and valinomycin), an immediate change in furaptra R was noted, followed by a slow change in R that reached a steady level in 2-4 h. The direction of the early change in R that accompanied rigor contraction was independent of the extracellular Mg2+ concentration ([Mg2+]o), and was consistent with the breakdown of ATP and release of bound Mg2+. The intracellular calibration curve was constructed from the steady levels of R obtained at various [Mg2+]o between 0 and 47 mM. The dissociation constant of intracellular furaptra was estimated to be 5.3 mM, which was 44% higher than that determined in salt solutions (3.7 mM). The basal [Mg2+]i of rat ventricular myocytes calculated with the intracellular curve averaged 0.91 mM.

Adenosine Triphosphate↗

Phase II study of sequential high-dose methotrexate and fluorouracil combined with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer.

BACKGROUND: The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer. METHODS: Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m2, day 1) fluorouracil (1.5 g/m2, day 1), leucovorin (15 mg/m2, days 2-4), and doxorubicin (30 mg/m2, day 15), repeated at a 28-day interval, and followed by radical surgery. RESULTS: A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls. CONCLUSIONS: Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate.

Adenocarcinoma, Scirrhous↗

Spatial assessment by magnetic resonance cholangiopancreatography for preoperative imaging in partial pancreatic head resection.

BACKGROUND: Partial pancreatic head resection has been recommended for intraductal papillary mucinous tumor (IPMT). We report the usefulness of preoperative assessment by magnetic resonance cholangiopancreatography (MRCP) compared with endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We studied 12 cases of surgically resected IPMT in the pancreatic head. The MRCP and ERCP images were interpreted, and we examined the detection rate of each imaging technique for the Wirsung duct, the Santorini duct, the entire cystic tumor, and the communication between the tumor and the ducts. RESULTS: In all cases MRCP correctly identified the entire cystic tumor, and the communication between the tumor and the pancreatic ducts was seen in 64% of cases. In contrast, the detection rate by ERCP of the entire cystic tumor and of the communication between the cystic tumor and the ducts was only 8% and 18%, respectively. CONCLUSION: MRCP clearly showed the relationship of the cystic tumor and the pancreatic ducts and was very useful for preoperative imaging for partial pancreatic head resection.

Aged↗

Nuclear transfer of blastomeres expressing EGFP-reporter gene may improve the efficiency of transgenic cattle.

The effect of timing of microinjection of DNA constructs on the efficiency of transgenic embryo production and improved efficiency and quality through combining EGFP as a reporter gene with nuclear transfer techniques were examined. From 12 to 24 h after insemination, constructs of pCXNeo-EGFP were microinjected into a pronucleus of bovine IVM-IVF zygotes. Due to the difficulty in visualizing pronuclei, the incidence of successful injection of linear DNA was higher when zygotes were injected between 20 and 24 h, as compared with an early period between 12 and 16 h after insemination. However, developmental competence of DNA-injected zygotes and the EGFP expression rate were not affected by the injection time. A majority of the embryos expressing EGFP signal were mosaic. Following nuclear transfer of blastomeres expressing EGFP, 4.5% of morulae that developed from the NT eggs had a strong EGFP signal in all live blastomeres. In other embryos, EGFP signal had been lost. When cells derived from the EGFP-positive NT morulae were subcultured, all the cells expressed strong EGFP signal at the second passage and demonstrated neomycin resistance. These results show that transient expression of nonintegrated EGFP appears frequently in EGFP-positive bovine embryos and that additional selection of EGFP-positive morulae after nuclear transfer of EGFP-positive blastomeres would facilitate selection of transgenic embryos.

Animals↗

Orthostatic hypotension in elderly persons during passive standing: a comparison with young persons.

BACKGROUND: The present study was aimed at clarifying the mechanism of orthostatic hypotension (OH) that occurs in elderly persons and at investigating assisting methods to prevent OH by evaluating changes in autonomic nervous system (ANS) activity and cerebral circulation of elderly persons when engaged in passive standing. METHODS: Eight elderly volunteers and 9 young volunteers gave informed consent to participate in the study. Two experimental conditions were established: (i) "active standing," in which the subjects stood on their own with guidance from an assistant, and (ii) "passive standing," in which the subjects were placed in a standing position completely by an assistant. ANS was determined before and after standing by measuring the heart rate variability. The reaction of the ANS was evaluated on the basis of low-frequency power (LF: 0.05--0.15 Hz) and high-frequency power (HF: 0.15--0.4 Hz), which were separated from the R-R interval data by power spectral analysis using the fast Fourier transformation. Cerebral perfusion was measured over the right frontal region using a near-infrared spectroscopy cerebral oxygen monitor. RESULTS: The main findings were: (i) Transient decreases in blood pressure occurred immediately after standing in both the young and elderly subjects. (ii) The LF:HF ratio increased significantly ( p <.05) immediately after active standing in the young subjects, whereas this ratio increased in the elderly subjects after some delay. (iii) The LF:HF ratio increased significantly ( p <.01) immediately after passive standing in the young subjects, whereas this ratio decreased significantly ( p <.05) in the elderly subjects. (iv) In the elderly subjects, the total hemoglobin (HbT) and oxyhemoglobin showed the greatest decrease during the 15-second period after standing. The maximum changes in the HbT with passive standing differed significantly ( p <.01) from those observed during active standing. CONCLUSIONS: Our findings emphasize the need to devise bioengineered means that allow elderly persons to exert themselves, to maintain or improve muscle contractility and ANS function, while providing minimum assistance for standing.

Adult↗