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Biomedical subjects

T Kamitani

Publications and source records attributed to T Kamitani.

At least 37 records · Page 2Linked to original sources

Analysis of IL-18 bioactivity and IL-18 mRNA in three patients with adult T-cell leukaemia, acute mixed lineage leukaemia, and acute lymphocytic leukaemia accompanied with high serum IL-18 levels.

Interleukin-18 (IL-18) bioactivity in sera and IL-18 mRNA expression in leukaemia cells of three patients with adult T-cell leukaemia (ATL), acute mixed lineage leukaemia (AMLL) and acute lymphocytic leukaemia (ALL) accompanied with high serum IL-18 levels have been analysed. There was little serum IL-18 bioactivity in the three patients with ATL, AMLL and ALL, while IL-18 mRNA expression was detected in leukaemia cells of all three patients.

Acute Disease↗

Urinary trypsin inhibitor levels in the urine of patients with haematological malignancies.

The urinary trypsin inhibitor (UTI) levels in the urine of patients with various haematological malignancies were determined, using automated latex agglutination immunoturbidimetry. The mean UTI levels in urine in acute non-lymphocytic leukaemia, myelodysplastic syndrome, non-Hodgkin's lymphoma, and multiple myeloma groups were significantly elevated, compared with the normal control group. It was found that the UTI level in urine changed from an elevated value to a normal value with haematological improvement by chemotherapy in a patient with myelodysplastic syndrome included in a previous study. These results suggest tha

Antineoplastic Agents↗

Do P1 and N1 evoked by the ERP task reflect primary visual processing in Parkinson's disease?

OBJECTIVES: To evaluate whether P1 and N1 evoked by ERP tasks could appropriately reflect primary visual processing in Parkinson's disease (PD). METHODS: We recorded ERPs in 13 PD patients with duration of illness less than 5 years and 18 age-matched normal control subjects. P1 and N1 from Oz were evoked by a visual oddball and a delayed matching S1-S2 task. The effect of different events on P1 and N1 was studied. All patients were given an ECD-SPECT examination, and the SPECT images were overlaid on the 3D-MRI. The correlation of P1 or N1 to the regional cerebral blood flow (rCBF) was studied. RESULTS: P1 was not influenced by different events. There was no significant P1 differences between the PD and the normal group. N1 was significantly shorter and smaller in the patients than that in the normal group. N1 amplitude after the waveform subtraction (target-frequent) in the PD group did not show significant difference with that in the normal controls, nor with the N1 before the subtraction. Nd, the subcomponent of N1 after the subtraction in the patients was significantly earlier and smaller than that in the normal controls. P1 only weakly correlated with the rCBF in the occipital lobe. N1 was correlated with the rCBF in a global region. CONCLUSIONS: The results provided some evidence that P1 might reflect the primary visual processing, and N1 might be involved in both primary and cognitive visual processing. The altered N1 in the PD patients might be due to the deformed Nd.

Aged↗

The hemispherical laterality of the visual evoked potentials during simple dot stimulus in normal human subjects.

We studied scalp visual evoked potentials (VEPs) during a simple visual attention paradigm using a dot stimulus, which was presented every 1600 ms, at the center of a screen. The visual attention paradigm consisted of three tasks: task R, task L and task N. The subjects were instructed to press a button either with the right hand (task R) or with the left hand (task L) after seeing the dot. They were also instructed just to look at a dot, without pressing the button (task N). We defined N1 as a negative wave with a latency of 50-130 ms, P1 as a positive wave with a latency of 110-150 ms and N2 as a negative wave with a latency of 130-210 ms. During task R, P1-N2 amplitude at T6 was significantly greater than that at T5. The N1-P1 and N2 amplitudes at O2 were significantly greater than those at O1. During task L, the waveforms at T6 and O2 were more clearly detected than those at T5 and O1. We conclude that there is a functional dominance of the right cerebral hemisphere in our simple visual reaction tasks.

Adult↗

A dominant-negative UBC12 mutant sequesters NEDD8 and inhibits NEDD8 conjugation in vivo.

NEDD8, a novel ubiquitin-like protein, has been shown to conjugate to proteins in a manner analogous to ubiquitination and sentrinization. Recently, human UBC12 was identified as a putative NEDD8 conjugation enzyme (E2). While investigating the in vivo function of UBC12, we found that the point mutant, UBC12(C111S), showed a dominant-negative effect on NEDD8 conjugation. This mutant, with a single Cys-to-Ser substitution at the conserved Cys residue in the E2 family, could specifically inhibit NEDD8 conjugation. We observed the dominant-negative effect on NEDD8 conjugation to substrates, including the C-terminal fragment of cullin-2 (Cul-2-DeltaN), full-length cullin-1, and also other uncharacterized target proteins. Interestingly, UBC12(C111S) formed a heterodimeric conjugate with NEDD8. This conjugate was stable under stringent conditions, including 6 m guanidine HCl, 8 m urea, 2% SDS, or 5% beta-mercaptoethanol. Our results are consistent with the hypothesis that UBC12(C111S) sequesters the NEDD8 monomer by forming a UBC12(C111S)-NEDD8 conjugate and, in turn, inhibits the subsequent transfer of NEDD8 to its targets. To examine the biological role of NEDD8 conjugation, this dominant-negative form of UBC12 was applied to a cell growth assay. Overexpression of UBC12(C111S) led to inhibition of growth in U2OS and HEK293 cells. Thus, this dominant-negative form of UBC12 could be useful in defining the role of NEDD8 modification in other biological systems.

Amino Acid Sequence↗

Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins.

Covalent conjugation of proteins by ubiquitin or ubiquitin-like molecules is an important form of post-translational modification and plays a critical role in many cellular processes. Similar to the concept of phosphorylation and dephosphorylation, these conjugates are regulated by a large number of deconjugating enzymes. Here, we report the cloning of a 2,141-base pair DNA fragment from human placenta cDNA library by a strategy that involves expressed sequence tag data base searching, polymerase chain reaction, and rapid amplification of cDNA ends. Nucleotide sequence analysis revealed that the cloned cDNA contains an open reading frame of 1,143 base pairs encoding a novel protease, USP21, which is composed of 381 residues with a calculated molecular mass of 43 kDa. The human USP21 gene is located on chromosome 1q21 and encodes a member of the ubiquitin-specific protease family with highly conserved Cys and His domains. The activity and specificity of USP21 were determined by using a COS cell expression system in vivo. We showed that USP21 is capable of removing ubiquitin from ubiquitinated proteins as expected. Furthermore, USP21 is capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates. As expected from its biochemical activity, overexpression of USP21 has a profound growth inhibitory effect on U2OS cells. Thus, USP21 is the first ubiquitin-specific protease shown to have dual specificity for both ubiquitin and NEDD8 and may play an important role in the regulation of cell growth.

Amino Acid Sequence↗

Ubiquitin-like proteins: new wines in new bottles.

Ubiquitin is a small polypeptide that covalently modifies other cellular proteins and targets them to the proteasome for degradation. In recent years, ubiquitin-dependent proteolysis has been demonstrated to play a critical role in the regulation of many cellular processes, such as cell cycle progression, cell signaling, and immune recognition. The recent discovery of three new ubiquitin-like proteins, NEDD8, Sentrin/SUMO, and Apg12, has further broadened the horizon of this type of post-translational protein modification. This review will focus on the biology and biochemistry of the Sentrin/SUMO and NEDD8 modification pathways, which are clearly distinct from the ubiquitination pathway and have unique biological functions.

Amino Acid Sequence↗

The correlation between P300 alterations and regional cerebral blood flow in non-demented Parkinson's disease.

P300 was evoked by a visual oddball and an S1-S2 task in 22 non-demented Parkinson's disease (PD) patients (13 in the early stage, nine in the late stage) and 18 normal controls. Reaction time was also measured. All patients undertook the (99)Tc-ECD SPECT examination. Quantitative regional cerebral blood flow (rCBF) was obtained by overlying SPECT image on the 3D-magnetic resonance image. In the PD patients in the late stage, P300 latency to S2-same and reaction time were significantly prolonged, while rCBF at bilateral frontal, temporal, and the right parietal lobes was decreased. P300 latency to S2-same was significantly correlated with the rCBF at bilateral temporal lobes. Reaction time was significantly correlated with the rCBF at the right frontal and parietal lobes, as well as the temporal and occipital lobes. The results suggest that P300 changes in non-demented PD in the late stage could be related to the temporal lobe dysfunction.

Aged↗

Visual event-related potentials in progressive supranuclear palsy, corticobasal degeneration, striatonigral degeneration, and Parkinson's disease.

To determine whether there are characteristic changes in event-related potentials (ERPs) in parkinsonian syndromes we studied 8 patients with progressive supranuclear palsy (PSP), 10 patients with corticobasal degeneration (CBD), 9 patients with striatonigral degeneration (SND), and 16 patients with idiopathic Parkinson's disease (PD) with a mean duration of illness shorter than 5 years in each group. A visual oddball paradigm was employed to elicit P300. P300 to the rare target and rare nontarget stimuli and reaction time (RT) to rare target stimuli in each group were compared with those in the corresponding age-matched normal control group and to each other after age correction. The correlation of P300 and RT to motor disability score was also studied. In PSP P300 amplitude was markedly reduced while in CBD P300 latency was prolonged. P300 amplitude to rare nontargets in SND and PD was attenuated. The mean RT in the PSP and the CBD group was significantly longer than in the other two groups. The mean RT in PD and P300 amplitude to rare nontargets in both CBD and PD showed significant correlation with the severity of motor disability. Simultaneous measurement of P300 and RT may yield useful supplementary information in facilitating diagnosis of parkinsonian syndromes in addition to clinical criteria.

Aged↗