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Biomedical subjects

H Seto

Publications and source records attributed to H Seto.

At least 127 records · Page 7Linked to original sources

Studies on the biosynthesis of bialaphos. Biochemical mechanism of C-P bond formation: discovery of phosphonopyruvate decarboxylase which catalyzes the formation of phosphonoacetaldehyde from phosphonopyruvate.

The biosynthetic step following the phosphoenolpyruvate (PEP) phosphomutase reaction which forms a C-P bond of bialaphos was proven by the identification of phosphonopyruvate (PnPy) and phosphonoacetaldehyde (PnAA) as intermediates in the culture broth of Streptomyces hygroscopicus, a producing organism of bialaphos, and by detection of enzymatic decarboxylation of PnPy to PnAA. Purified PnPy decarboxylase turned out to require thiamine diphosphate and Mg2+ as cofactors. PnPy decarboxylase drives the unfavorable forward reaction to form PnPy catalyzed by PEP phosphomutase and is suggested to be essential to C-P compound biosynthesis.

Acetaldehyde↗

Studies on the biosynthesis of bialaphos. Biochemical mechanism of C-P bond formation: discovery of phosphonopyruvate decarboxylase which catalyzes the formation of phosphonoacetaldehyde from phosphonopyruvate

The biosynthetic step following the phosphoenolpyruvate (PEP) phosphomutase reaction which forms a C-P bond of bialaphos was proven by the identification of phosphonopyruvate (PnPy) and phosphonoacetaldehyde (PnAA) as intermediates in the culture broth of Streptomyces hygroscopicus, a producing organism of bialaphos, and by detection of enzymatic decarboxylation of PnPy to PnAA. Purified PnPy decarboxylase turned out to require thiamine diphosphate and Mg2+ as cofactors. PnPy decarboxylase drives the unfavorable forward reaction to form PnPy catalyzed by PEP phosphomutase and is suggested to be essential to C-P compound biosynthesis.

Journal Article↗

Fatty acids selectively inhibit eukaryotic DNA polymerase activities in vitro.

The in vitro relationship between eukaryotic DNA polymerases and fatty acids was investigated. Some fatty acids strongly inhibited the activities of DNA polymerase alpha and/or beta in vitro. The kinetics of inhibition by linoleic acid showed that DNA polymerase alpha was non-competitively inhibited with respect to the DNA template and substrate (dTTP), while DNA polymerase beta was inhibited competitively with both DNA and substrate.

Animals↗

Characteristics of 45Ca2+ release induced by quinolidomicin A1, a 60-membered macrolide from skeletal muscle sarcoplasmic reticulum.

Quinolidomicin A1, a 60-membered macrolide purified from an actinomycete Micromonospora sp. markedly induced 45Ca2+ release from the heavy fraction of skeletal muscle sarcoplasmic reticulum (HSR), but induced only slightly from the light fraction of sarcoplasmic reticulum (LSR), showing a lack of the ionophoretic activity even at a high concentration (300 microM). This was also confirmed by measuring the 45Ca2+ transport activity of quinolidomicin A1 across an organic solvent barrier. Quinolidomicin A1 (3-300 microM) increased 45Ca2+ release from HSR with an EC50 value of approx. 20 microM. The potency of quinolidomicin A1 was approx. 100-fold higher than that of caffeine. The bell-shaped profile of Ca2+ dependence for quinolidomicin A1 was different from that for caffeine. Blockers of Ca2+ release channels such as Mg2+ (10 mM), procaine (10 mM) and ruthenium red (10 microM) partially blocked quinolidomicin A1 (30 microM)-induced 45Ca2+ release from HSR. At 0 degrees C, quinolidomicin A1-induced 45Ca2+ release was ascertained not to be due to the inhibition of Ca2+ ATPase by the ATPase assay. Quinolidomicin A1 potentiated [3H]ryanodine binding to HSR with a decrease in KD but without a change in Bmax. These results suggest that quinolidomicin A1-induced Ca2+ release from HSR is consisted of two components, which are both sensitive and insensitive to blockers of Ca2+ release channels, and that the former component is associated with the ryanodine receptor.

Actinomycetales↗

Extensive soft-tissue involvement of dermatomyositis detected by whole-body scintigraphy with 99mTc-MDP and 201TL-chloride.

The authors present a case of extensive soft-tissue radioactivity visualized on both 99mTc-MDP and 201Tl-chloride scintigrams in a patient with dermatomyositis and colon cancer. Incidentally, diffuse and intense uptake of 99mTc-MDP was observed in the shoulder girdles, anterior chest wall, psoas muscles, both proximal thighs and right lower limb, corresponding to the sites of symptomatic muscles, even though skin lesions were limited and no calcification was detected on radiographs. Moreover, 201Tl-chloride was also intensely accumulated in nearly the same sites as the symptomatic muscles as shown on the 99mTc-MDP bone scintigrams. Whole-body scintigraphy with 99mTc-MDP and 201Tl-chloride is a useful tool to detect occult muscle lesions with dystrophic calcification and hyperemia in dermatomyositis.

Calcinosis↗

Brain SPECT of Creutzfeldt-Jakob disease.

SPECT imaging with I-123 IMP or Tc-99m HMPAO was performed in two patients with Creutzfeldt-Jakob disease to evaluate abnormalities in brain perfusion. In the first patient, there was decreased perfusion of the left frontal, parietal, and temporal lobes. CT and MRI were negative. In the second patient, there was patchy perfusion and slightly decreased perfusion of the right hemisphere. MRI revealed slight brain atrophy and bilateral high intensity areas in the basal ganglia on T2 weighted images. Subsequent SPECT imaging revealed severely decreased perfusion of the entire brain. Subsequent MRI demonstrated severe brain atrophy.

Aged↗

Scintigraphic study of malignant melanoma with 123I-iodoamphetamine.

N-isopropyl-p-I-123-iodoamphetamine (123I-IMP) is extracted by the brain in proportion to regional blood flow. It is particularly useful in the clinical assessment of various pathological conditions related to altered cerebral flow. Moreover, it has been reported that 123I-IMP is avidly incorporated into melanin and melanotic melanoma. We evaluated 123I-IMP scintigraphy using either planar or single photon emission tomography (SPET) studies in 10 patients with malignant melanoma. The patients were classified into two groups according to the tumour site: Group A, six patients with primary or metastatic cutaneous malignant melanoma of the extremity with planar scintigraphy; Group B, four patients with primary malignant melanoma of other organs with planar scintigraphy and SPET. In Group A, tumour uptake was demonstrated in four of six patients; in Group B, three of four patients had tumour accumulation on SPET and planar scintigraphy. SPET revealed the exact tumour localization, even in the case of a tumour located in the lung. These results suggest that planar scintigraphy using 123I-IMP is useful in the detection of malignant melanoma. Furthermore, more clear tumour localization is possible with SPET, even in the case of a tumour located in the lung.

Aged↗

Simultaneous assessment of regional adrenergic activity and perfusion with 123I-MIBG and 201Tl in congestive heart failure.

Simultaneous assessment of regional adrenergic activity and perfusion with 123I-meta-iodobenzylguanidine (123I-MIBG) and 201Tl in various organs was performed in 13 patients with congestive heart failure (CHF) and 13 subjects without heart failure. In order to reduce the crosstalk of 201Tl to the 123I energy window to less than 5%, a dose of 123I-MIBG more than five times greater than that of 201Tl was administered following 201Tl scintigraphy. Regional uptake of 201Tl (%dose) was significantly increased in the heart (left ventricle) and lung (both P < 0.01) in the patients with CHF. The increased global cardiac uptake could have been related to the enlarged left ventricle. The patterns of regional uptake of 123I-MIBG (% dose) at 15 min were similar to those of 201Tl, suggesting that early 123I-MIBG uptake could in part depend on regional perfusion in both groups. At 3 h, regional uptake of 123I-MIBG was significantly increased in the heart, lung and kidney (all P < 0.01) in the patients with CHF. The delayed 123I-MIBG uptake indicates the degree of neuronal accumulation of the tracer, and therefore reflects adrenergic activity. Interestingly, the cardiac 123I-MIBG (adrenergic activity) to 201Tl (unit of perfusion) ratio decreased significantly in the heart (P < 0.01) but increased significantly in the kidney (P < 0.01) in the patients with CHF compared with the control group. Cardiac 123I-MIBG washout was also significantly increased in the CHF patients. Moreover, the cardiac 123I-MIBG:201Tl ratio was negatively correlated with plasma norepinephrine concentration (r = -0.74, P < 0.01), but positively correlated with LVEF (r = 0.60, P < 0.01). These data suggest that there may be impairment of both the neuronal uptake function and the vesicular storage function in the failing heart, and an increment in neuronal uptake function in the kidneys in patients with CHF. We suggest that dual-tracer scintigraphy is a useful non-invasive method for the simultaneous assessment of adrenergic activity and perfusion in various organs in patients with heart failure.

3-Iodobenzylguanidine↗

Studies on cochleamycins, novel antitumor antibiotics. III. Biosyntheses of cochleamycins: incorporation of 13C- and 2H-labeled compounds into cochleamycins.

Biosynthetic studies using 13C- and 2H-labeled compounds revealed that the carbon skeletons of cochleamycins A and B were derived from eight acetic acid units and one propionic acid unit with the introduction of an acetoxy group at C-10, which was replaced by an isobutyryl residue derived from valine in cochleamycins A2 and B2.

Antibiotics, Antineoplastic↗