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Biomedical subjects

J Konishi

Publications and source records attributed to J Konishi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Monoclonal antibody-dendrimer conjugates enable radiolabeling of antibody with markedly high specific activity with minimal loss of immunoreactivity.

For the purpose of radioimmunotherapy, labelling of monoclonal antibody with high specific activity is often necessary, especially when using a radionuclide with a shorter half-life. Polyamine dendrimers (PAMAM) are novel synthetic polymeric molecules with large numbers of amine residues on their spherical surface. In order to bind large numbers of radiometals to single antibody molecules, the generation-4 PAMAM (G4), which has 64 amines, was conjugated with 43 molecules of 2-(p-isothiocyanatobenzyl)-6-methyl-diethylene triamine penta-acetic acid (1B4M), a derivative of DTPA. This product [G4-(1B4M)43] was then conjugated with OST7, a murine monoclonal IgG1. We evaluated the achievable specific activity for 111In labeling, immunoreactivity, biodistribution, and tumor targeting in mice of the 111In- or 153Gd-OST7-G4-(1B4M)43 as compared with radiolabeled OST7-1B4M or 56C-1B4M. The maximum specific activity of 111In-OST7-G4-(1B4M)43 and 111In-OST7-1B4M was 470 and 8.7 GBq/mg (12,700 and 263 mCi/mg), respectively. Immunoreactivity of radiolabeled OST7-G4-(1B4M)43 and OST7-1B4M, as determined by the binding to KT005 cells expressing the antigen, was respectively 91% and 84% of that of 125I-labelled OST7. Biodistribution studies for preparations with maximum specific activity in normal mice 3 h after injection showed that 111In- or 153Gd-OST7-G4-(1B4M)43 cleared faster from the blood and accumulated more in the liver than did 111In- or 153Gd-OST7-1B4M. The dendrimer 1B4M [G4-(1B4M)64] itself showed similar saturation effects with metals. The radioactivity in all the other organs reflected the rapid clearance of radioactivity from the blood. 153Gd-OST7-G4-(1B4M)43 showed specific accumulation in the KT005 tumor. In conclusion, we could successfully bind 49 times as many metal atoms to an antibody molecule as is possible with conventional metal labeling for indium and gadolinium, and did so with minimal loss of immunoreactivity. When we achieved radiolabeling with maximum specific activity, Gd conjugate showed better biodistribution than In conjugate.

Animals↗
PubMed2000

Significant regional heterogeneity of coronary flow reserve in paediatric hypertrophic cardiomyopathy.

Previous studies have indicated that cardiac events in young patients with hypertrophic cardiomyopathy (HCM) are related to ischaemia rather than to arrhythmia. We measured coronary flow reserve in paediatric HCM and compared the values with those in adult HCM. We studied 12 patients with HCM including six paediatric (<20 years old; mean 13 years) and six adult patients (>20 years old: mean 62 years), and six healthy young adults (mean 29 years) as controls. Every patient underwent magnetic resonance imaging (MRI) for anatomical assessment. Myocardial blood flow at rest and after dipyridamole infusion was measured with dynamic nitrogen-13 ammonia positron emission tomography (PET). Partial volume effect was corrected for using the anatomical data obtained with MRI. In adult patients with HCM, coronary flow reserve in the hypertrophied septal region was not significantly different from that in the non-hypertrophied lateral wall (1.38+/-0.29 vs 1.77+/-0.39, respectively). In the paediatric patients, coronary flow reserve in the hypertrophied septal region was significantly lower than in the non-hypertrophied lateral wall (0.84+/-0.33 vs 2.74+/-0.90, respectively, P<0.01). In addition, coronary flow reserve in adult patients was lower than in control subjects both in the septal wall (1.38+/-0.29 vs 2.94+/-0.35, respectively, P<0.0001) and in the lateral wall (1.77+/-0.39 vs 2.85+/-0.69, respectively, P<0.05). In contrast, coronary flow reserve in paediatric patients was not significantly different from that in control subjects in the lateral wall (2.74+/-0.90 vs 2.85+/-0.69, respectively), while absolute reduction of myocardial blood flow was noted after pharmacological vasodilatation in the hypertrophied septal region. In conclusion, significant regional differences of coronary flow reserve were present in the paediatric patients with HCM. These results suggest that paediatric patients with HCM intrinsically have the potential to experience significant regional ischaemia even in the absence of coronary stenosis.

Adolescent↗
PubMed2000

FDG-PET of autoimmune-related pancreatitis: preliminary results.

The purpose of this retrospective study was to elucidate the fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings in autoimmune-related pancreatitis (AIP), which is a reversible chronic pancreatitis with an autoimmune cause. The study group comprised six patients with clinically diagnosed AIP. After 370 MBq (10 mCi) of FDG had been injected intravenously, the abdomen and/or the whole body was scanned at 1 h post injection in all patients, and scanning was repeated at 2 h in four patients. PET findings were evaluated visually and/or semiquantitatively using the standardized uptake value (SUV). In four of the six patients, PET demonstrated intense uptake in the whole pancreas, which appeared swollen on computed tomography, and the accumulation increased with time in three patients. In one patient, intense focal uptake in the pancreatic head was observed, and the accumulation decreased over time. In the remaining patient, no abnormal accumulation in the pancreas was observed. Follow-up PET scanning after steroid therapy was performed in three patients, and intense FDG uptake was no longer observed. Our preliminary data show that AIP can cause intense FDG uptake in the pancreas. This fact, and the benign status of the condition, should be kept in mind when making a diagnosis with FDG-PET in patients with pancreatic disorders.

Cell Survival↗
PubMed2000

Curative resection of microgastrinomas based on the intraoperative secretin test.

The intravenous secretin injection test (secretin test) has been used for the differential diagnosis of gastrinoma. In this study we report that the intraoperative secretin test (IOS test) is also useful for determining the extent of curability in patients with Zollinger-Ellison syndrome (ZES). Twelve patients with ZES underwent surgical exploration and the IOS test. The results of the IOS test were obtained by rapid radioimmunoassay of the serum gastrin level (IRG) within 60 minutes. The test was diagnosed as negative when the maximum increase of serum IRG was less than 80 pg/ml and also less than 20% of the basal serum IRG level. Three of the twelve patients underwent pancreatoduodenectomy (PD), and two patients underwent distal pancreatectomy. Extirpation of duodenal tumors with dissection of regional lymph nodes was performed in seven patients. In two of the seven patients the IOS test remained positive after extirpation of the duodenal tumors and the dissection of regional lymph nodes. In one patient PD was performed on the basis of the positive results, and the IOS test became negative after PD. In the other patient, two tiny metastatic liver tumors were identified and were resected, but the IOS test did not become negative. We closed the abdomen in 11 patients when we obtained negative results from the IOS test. The results of the IOS test were almost identical to the data obtained by the standard assay postoperatively. The serum IRG levels of all but one patient fell to the normal level, and the secretin test became negative postoperatively. The IOS test is thus useful and indispensable for curative resection of microgastrinomas in patients with ZES.

Adult↗
PubMed2000

Adnexal torsion: MR imaging findings of viable ovary.

We report a case of torsed ovarian cystic tumor, in which contrast-enhanced high-resolution MR images accurately contributed to the diagnosis of torsion despite the lack of symptoms and to the preoperative evaluation of viability of the edematous ovary. Accurate preoperative assessment by MR images and prompt conservative surgical approach succeeded in salvaging the involved ovary.

Adult↗
PubMed2000

Different influence of macrophage migration inhibitory factor (MIF) in signal transduction pathway of various T cell subsets.

It has been shown that macrophage migration inhibitory factor (MIF) modulates not only macrophage functions, but also T cell functions. However, detailed analysis of the MIF function on responses of various T cell subpopulations remained to be elucidated. In this report, using a neutralizing anti-MIF monoclonal antibody (mAb) we examined MIF functions on various T cell lineages. It was shown that anti-MIF mAb inhibited antigen-specific responses of both IFN-gamma producing and IL-4 producing T cells. The inhibition appeared to be related to blockade of the signal pathway via T cell receptor (TCR) but not that via IL-2 receptor (IL-2R). However, the anti-MIF mAb showed no inhibitory effect on NK-T cell responses stimulated through TCR. These results suggest that MIF is involved in the signal pathway via TCR in mainstream T cells but not in NK-T cells.

Amino Acid Sequence↗
PubMed2000

Functional differentiation of the auditory association area in prelingually deaf subjects.

BACKGROUND: it is believed that the number of neurons of the human cortex increases rapidly in the first postnatal year, and then decreases gradually towards adult level as their functions are revised up to 11 years of age ('synaptic revision'). It is also confirmed that regional cerebral blood flow (rCBF) at rest represents the density of the neurons and decreases in accordance with the synaptic revision in process. If synaptic revision does not occur, rCBF remains at high level. Thus, we can evaluate whether functional differentiation has occurred in the human cortex by measuring rCBF at resting state. OBJECTIVE: to examine functional differentiation of the auditory association area (A2) in prelingually deaf subjects. METHODS: six postlingually and six prelingually deaf subjects who had undergone cochlear implant (CI) were involved in the current study. All prelingually deaf subjects underwent CI over 8 years old. The rCBF in A2 was examined during resting and listening to speech sounds using positron emission tomography (PET) and H2(15)O intravenous injection. Twelve normal subjects' rCBFs were also measured as control. Furthermore, three prelingually deaf subjects underwent follow up PET studies in which cortical activities in A2 for listening and lipreading were examined. RESULTS: in the examination of rCBF at rest, rCBFs of prelingually deaf subjects in A2 showed significantly higher than those of either the postlingually deaf subjects or normal subjects. During listening, rCBFs in A2 increased in postlingually deaf subjects and normal subjects, while there was no significant rCBF increase in the prelingually deaf. High rCBF level in A2 at rest observed in prelingually deaf subjects implied a lack of synaptic revision, and it was suggested that the functional differentiation for auditory processing was little in the A2 of prelingually deaf subjects. In the follow up study for three prelingually deaf subjects, activation of A2 was observed during lipreading but not during listening in two cases, who had developed the skill of lipreading while speech recognition was not improved by CI. In contrast, the other case had not used any visual clues in daily communication prior to CI, and the hearing acuity was well improved by CI. This case demonstrated an activity in A2 during listening, while lipreading induced no activation. CONCLUSION: it is suggested that functional differentiation of A2 should differ according to which of visual and auditory clue is chiefly used during critical periods for speech acquisition. The findings are thought to be important for us to schedule the education and treatment for prelingually deaf children.

Adolescent↗
PubMed2000

Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors.

The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions.

Animals↗
PubMed2000

Essential role of the right superior parietal cortex in Japanese kana mirror reading: An fMRI study.

Functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates responsible for Japanese kana mirror reading. Japanese kana words, arranged vertically from top to bottom, were used in the mirror reading task in 10 normal right-handed Japanese adults. Since both mirror-reversed and normally oriented kana items are read in the same (top to bottom) direction, it was possible to minimize the oculomotor effects which often occur in the process of mirror reading of alphabetical language. By using the SPM96 random effect analysis method, a significant increase in the blood oxygen level-dependent signal during mirror reading relative to normal reading was detected in multiple brain regions, including the bilateral superior occipital gyri, bilateral middle occipital gyri corresponding to Brodmann area (BA) 18/19, bilateral lingual gyri (BA 19), left inferior occipital gyrus (BA 18), left inferior temporal cortex (BA 37), bilateral fusiform gyri (BA 19), right superior parietal cortex (SPC) (BA 7), left inferior frontal gyrus (BA 44/45) and an inferior part of the left BA 6. In addition to these cortical regions, the right caudate nucleus and right cerebellum were also activated. The activation found in the right SPC and the left inferior temporal region is consistent with the hypothesis that mirror reading involves both the dorsal visuospatial and ventral object recognition pathways. In particular, a significant correlation was found between the fMRI signal change in the right SPC and the behavioural performance (error index) in the task. This may reflect increased demand on the right SPC for the spatial transformation which is required for the accurate recognition of mirror-reversed kana items. This relationship between the haemodynamic response in a specific brain area and the behavioural data provides new evidence for the essential role of the right SPC in Japanese kana mirror reading.

Adult↗
PubMed2000

Participation of the left posterior inferior temporal cortex in writing and mental recall of kanji orthography: A functional MRI study.

To examine the neuropsychological mechanisms involved in writing kanji (morphograms), we used functional MRI (fMRI) in 10 normal volunteers, all right-handed, native Japanese speakers. The experimental paradigms consisted of kana-to-kanji transcription, mental recall of kanji orthography and oral reading and semantic judgement of kana words. The first two tasks require manual and mental transcription of visually presented kana words into kanji, respectively, whereas the last two tasks involve language processing of the same set of stimulus words without recall of kanji. The transcription and mental recall tasks yielded lateralized activation of the left posterior inferior temporal cortex (PITC). By contrast, neither oral reading nor semantic judgement produced similar activation of the area. These results, in good accordance with lesion data, provide converging evidence that the left PITC plays an important role in writing kanji through retrieval of their visual graphic images, and suggest language-specific cerebral organization of writing. The set of fMRI experiments also provides new neuroimaging data on the cortical localization of basic language functions in people using a non-alphabetical language.

Adult↗
PubMed2000

Evaluation of pancreatic islet cell tumors by fluorine-18 fluorodeoxyglucose positron emission tomography: comparison with other modalities.

PURPOSE: Pancreatic islet cell tumors are potentially malignant tumors and are often difficult to detect with current imaging modalities. Positron emission tomography (PET) using fluorine-18-labeled fluorodeoxyglucose (FDG) is an imaging technique with high sensitivity for malignant tumors. The aim of this study was to assess the feasibility of FDG PET to detect pancreatic islet cell tumors. METHODS: Nineteen lesions of histologically proved islet cell tumors were evaluated in 12 patients (5 men, 7 women; ages 22 to 77 years). FDG uptake was analyzed semiquantitatively as a standardized uptake value. The diagnostic accuracy of PET was compared with that of US, CT, and MRI. RESULTS: Of 19 lesions, 8 showed positive PET results (standardized uptake value > 2.3), and localization was indicated in 2 lesions. In nine tumors that were not detected by PET, seven were small tumors ranging from 1.5 to 8 mm in diameter and were not identified by other imaging methods. The sensitivity rate of PET was 53%, whereas those of US, CT, and MRI were 53%, 50%, and 53%, respectively. CONCLUSION: Our data suggest that FDG PET has a limitation in that it does not detect some small-sized islet cell tumors, mainly depending on their size, but it has potential utility as a complementary modality for other imaging techniques.

Adenoma, Islet Cell↗
PubMed2000

Avidin chase can reduce myelotoxicity associated with radioimmunotherapy of experimental liver micrometastases in mice.

Myelotoxicity is the main factor which decides the maximum tolerated dose (MTD) in radioimmunotherapy (RIT). Since bone marrow is mostly irradiated from blood radioactivity, enhancing the clearance of unbound circulating radiolabeled antibody is important to reduce myelotoxicity and to increase the MTD. We applied the avidin chase method, which was devised to obtain high tumor-to-background ratios in tumor-targeting, to RIT of experimental liver micrometastases and evaluated its influence on the side effects and therapeutic outcome. Seven days after intrasplenic injection of human colon cancer LS174T cells, nude mice were intravenously injected with biotinylated (131)I-labeled anti-CEA monoclonal antibody (MAb) (24 - 38 microg, 11.1 MBq). Mice of the chase group then received an intravenous injection of avidin twice (24 and 30 h, 72 - 115 microg each). Biodistribution, side effects (white blood cell counts and body weight change), and short- and long-term therapeutic effects were determined. Avidin chase markedly accelerated the clearance of radiolabeled MAb from the blood (P < 0.0001) and normal tissues, resulting in milder leukocytopenia and body weight loss, both of which recovered earlier than in the non-chase group (P < 0.01). The tumor uptake of radiolabeled MAb was also decreased by avidin chase, but the metastases-to-background ratios were increased. Avidin chase gave the therapeutic gain ratio of 1.89. Treated groups with and without avidin chase showed significant therapeutic effects compared to the non-treated group. There was no significant difference in the therapeutic effects between the two treated groups. Avidin chase effectively reduced the side effects of RIT and should increase the MTD.

Animals↗
PubMed2000

Atrophy of the corpus callosum associated with a decrease in cortical benzodiazepine receptor in large cerebral arterial occlusive diseases.

OBJECTIVES: It remains controversial whether selective neuronal ischaemic change develops in patients with occlusion of the large cerebral arteries. Previous studies have shown atrophy of the corpus callosum with reduced cortical oxygen metabolism in large cerebral arterial occlusive diseases, which might be indirect evidence of loss of the neurons in cortical layer 3. Recent studies of patients with ischaemic cerebrovascular diseases have demonstrated reduced central benzodiazepine receptor (BZR) binding in the normal appearing cortical areas, which might be more direct evidence of changes of the neurons. Although pathophysiology of the decreased BZR is unclear, a decrease in the cortical BZR binding with neuronal loss would cause atrophy of the corpus callosum. The purpose of this study was to determine whether atrophy of the corpus callosum is associated with a decrease in cortical BZR binding in large cerebral arterial occlusive diseases. METHODS: Seven patients with occlusive diseases of the middle cerebral or internal carotid artery and only minor subcortical infarctions were studied. Single photon emission tomographic images of (123)I labelled iomazenil (IMZ) obtained 180 minutes after injection were analysed for BZR binding. The midsagittal corpus callosum area/skull area ratio (on T1 weighted magnetic resonance images) was compared with the cerebral IMZ uptake/cerebellar IMZ uptake ratio. RESULTS: Compared with 23 age and sex matched control subjects, the patients had significantly decreased callosal area/skull area ratio. The degree of corpus callosum atrophy was significantly and strongly (rho=0.99, p<0.02) correlated with that of the decreases in the mean cerebral cortical IMZ uptake ratio. CONCLUSION: Corpus callosum atrophy may occur in association with a decrease in cortical BZR binding in large cerebral arterial occlusive diseases. Corpus callosum atrophy with decreased cortical BZR binding might reflect cortical neuronal damage in large cerebral arterial occlusive diseases.

Aged↗
PubMed2000

Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease.

OBJECTIVES: The loss of the neurons in layer 3, one of the groups of cortical neurons most vulnerable in various degenerative brain diseases, results in axonal degeneration leading to atrophy of the corpus callosum. Previous studies showed callosal atrophy in three degenerative dementias: frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD). However, it is unclear whether a characteristic pattern of atrophy is present in each. The objective of this study was to investigate whether the pattern of the callosal atrophy was different among patients with FTD, PSP, or early onset AD. METHODS: Eleven patients with FTD, nine patients with PSP, 16 patients with early onset AD, and 23 normal controls, all age and sex matched, were studied using MRI. The ratios of midsagittal corpus callosum areas to the midline internal skull surface area on T1 weighted images were analyzed. The corpus callosum was divided into quarters: the anterior, middle-anterior, middle-posterior, and posterior portions. RESULTS: Compared with controls, all three patient groups had significantly decreased total callosal/skull area ratio. An analysis of covariance adjusted for the total callosal area/skull area ratio showed that the anterior quarter callosal/skull area ratio in FTD, the middle-anterior quarter area ratio in PSP, and the posterior quarter area ratio in AD were significantly smaller than those in the other three groups. CONCLUSION: Although atrophy of the corpus callosum is not specific to any degenerative dementia, the patterns of the atrophy are different among patients with FTD, PSP, or early onset AD. Differential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia.

Aged↗
PubMed2000

Cloning and expression of the gene encoding the thermophilic NAD(P)H-FMN oxidoreductase coupling with the desulfurization enzymes from Paenibacillus sp. A11-2.

The gene encoding the NAD(P)H-flavin oxidoreductase (flavin reductase) which couples with the thermophilic dibenzothiophene (DBT)-desulfurizing monooxygenases of Paenibacillus sp. A11-2 was cloned in Escherichia coli and designated tdsD. Nucleotide sequence analysis suggested that the gene product consisted of 200 amino acids and showed about 30%, 27% and 26% amino acid sequence similarity to the major flavin reductase of Vibrio fischeri, the NADH dehydrogenase of Thermus thermophilus and several oxygen-insensitive NAD(P)H nitroreductases in the Enterobacteriaceae family, respectively. Both the growing and resting recombinant E. coli, in which tdsD was coexpressed with a set of desulfurizing genes, showed a rate of DBT removal about 5 times higher than the recombinants lacking tdsD. Maximal desulfurization was observed close to 45 degrees C and 55 degrees C in the resting cells and in the cell-free extraction reaction with the tdsD-coexpressing recombinants, respectively. In an organic/aqueous biphasic system, the coexpression of tdsD also markedly enhanced the rate of DBT removal.

Journal Article↗
PubMed2000

Purification and characterization of dibenzothiophene sulfone monooxygenase and FMN-dependent NADH oxidoreductase from the thermophilic bacterium Paenibacillus sp. strain A11-2.

A dibenzothiophene (DBT) sulfone monooxygenase (TdsA), which catalyses the oxidative CS bond cleavage of DBT sulfone to produce 2-(2-hydroxyphenyl)benzenesulfinate (HPBS) was purified from the thermophilic DBT desulfurizing bacterium Paenibacillus sp. strain A11-2 by multistep chromatography. The molecular mass of the purified enzyme was determined to be 120 kDa by gel filtration and the subunit molecular mass was calculated to be 48 kDa by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) indicating a dimeric structure. The N-terminal amino acid sequence of the purified TdsA was determined to be MRQMHLAGFFAAGNTHH, which revealed no significant similarity to any other known amino acid sequences. The purified TdsA absolutely required an oxidoreductase for its activity. This oxidoreductase (TdsD) was also purified to homogeneity, and its molecular size was calculated to be 50 kDa and 25 kDa by gel filtration and SDS-PAGE, respectively. TdsD was completely FMN-dependent, and FAD could not act as a cofactor. The N-terminal amino acid sequence of the purified TdsD was determined to be TSQTAEQSIAPIVAQYRHPEQPISALFVNR, which showed significant similarity to kinesin-like protein (44% identity). The optimal temperatures for the activity of TdsA and TdsD were 45 degrees C and 55 degrees C, respectively. Both enzymes showed optimal activity at pH 5.5. TdsA was slightly inhibited by sulfate, but not by 2-hydroxybiphenyl (2-HBP), which is another end product of DBT. TdsA showed higher activity toward bulkier substrates than its mesophilic counterpart, DszA. These properties suggest the applicability of biodesulfurization to the processing of actual petroleum fractions.

Journal Article↗