[The mouse model and human disease (sequel)].
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Animals↗
Biomedical subjects
H F Kung
Publications and source records attributed to H F Kung.
Selective in vitro and in vivo binding of [(125)I]ADAM to serotonin transporters in rat brain.
An improved iodinated tracer, ADAM (2-((2-((dimethylamino)methyl)- phenyl)thio)-5-iodophenylamine) for imaging serotonin transporters (SERT) with single photon emission computerized tomography (SPECT), was prepared and characterized. Scatchard analysis of saturation binding of [(125)I]ADAM to rat frontal cortical membrane homogenates gave a K(d) value of 0.15 +/- 0.03 nM and a B(max) value of 194 +/- 65 fmol/mg protein. Biodistribution of [(125)I]ADAM in rat brain after an iv injection showed a high specific binding in the regions of hypothalamus, cortex, striatum, and hippocampus, where SERT are concentrated and the specific binding peaked at 120-240 min postinjection [(hypothalamus-cerebellum)/cerebellum = 4.3 at 120 min post-iv injection]. Moreover, the specific hypothalamic uptake was blocked by pretreatment with SERT selective competing drugs, such as paroxetine and (+)McN5652, while other noncompeting drugs, such as ketanserin, raclopride, and methylphenidate, showed no effect. The radioactive material recovered from rat brain homogenates at 120 min after [(125)I]ADAM injection showed primarily the original compound (>90%), a good indication of in vivo stability in the brain tissues. Both male and female rats showed similar and comparable organ distribution pattern and regional brain uptakes. Ex vivo autoradiograms of rat brain sections (120 min after iv injection of [(125)I]ADAM) showed intense labeling in several regions (olfactory tubercle, lateral septal nucleus, hypothalamic and thalamic nuclei, globus pallidus, central gray, superior colliculus, substantia nigra, interpeduncular nucleus, dorsal and median raphes, and locus coerulus), which parallel known SERT density. These results strongly suggest that the novel tracer ADAM is superior to the congers (i.e., IDAM) reported previously. When labeled with I-123, ADAM will be an improved and useful SPECT imaging agent for SERT in the brain.
Animals↗
Coiled-coil motif as a structural basis for the interaction of HTLV type 1 Tax with cellular cofactors.
Human T lymphotropic virus type 1 (HTLV-1) Tax is a multifunctional protein centrally involved in transcriptional regulation, cell cycle control, and viral transformation. The regulatory functions of Tax are thought to be mediated through protein-protein interaction with cellular cofactors. Previously we have identified several novel binding partners for Tax, including human mitotic checkpoint protein MAD1 (TXBP181), G-protein pathway suppressor GPS2 (TXBP31), and IkappaB kinase regulatory subunit IKK-gamma. Here we described two additional Tax partners, TXBP151 and TXBP121. A closer examination of the sequences of eight independent cellular Tax-binding proteins identified by us and others revealed that all of them share a single characteristic, a highly structured coiled-coil domain. We also noted that Tax and the Tax-binding coiled-coil proteins can homodimerize. Additionally, the same domain in Tax is responsible for interaction with different coiled-coil proteins. Taken together, our findings point to a particular coiled-coil structure as one of the Tax-recognition motifs. The interaction of Tax with a particular subgroup of cellular coiled-coil proteins represents one mechanism by which Tax dysregulates cell growth and proliferation.
Amino Acid Motifs↗
Maternal cold inducible RNA binding protein is required for embryonic kidney formation in Xenopus laevis.
We cloned a major isoform of Xenopus homologue of cold inducible RNA binding protein (CIRP), XCIRP-1. XCIRP-1 was neither cold inducible nor essential for cell division during early embryonic development. Suppression of XCIRP-1 dose dependently produced tailbuds with deformations of the brain and internal organs. The defects were XCIRP-1 specific as they could be rescued by sense transcript. Suppression of XCIRP-1 also disrupted the morphogenetic migration of the C3 blastomeres (lineaged to become the embryonic kidney, the pronephros). In animal cap explants, depletion of XCIRP-1 inhibited activin/retinoic acid induced expressions of pronephros related Xlim-1 and WT1 genes. These results suggest that XCIRP-1 is required for the specification and morphogenetic lineage migration of the pronephros.
Abnormalities, Multiple↗
Molecular basis for differing antineurogenic effects of GATA-1a and GATA-1b in Xenopus.
The erythroid transcription factor GATA-1 in Xenopus has been cloned as a pair of presumably duplicated genes designated as xGATA-1a and xGATA-1b. Although both xGATA-1a and xGATA-1b are able to stimulate erythropoiesis, only xGATA-1b is capable of inhibiting neurogenesis in Xenopus embryos. Chimeras of these two genes were constructed by permuting coding and untranslated regions (UTR) on both ends of these two xGATA-1, and their neurogenesis-inhibitory effects were studied. These results reveal that (1) sequence variations between the coding regions alone do not account for the neurogenesis effect; (2) 3' UTR of xGATA-1a causes the loss of the neurogenesis inhibition of xGATA-1b; (3) 3' UTR of xGATA-1b is essential to inhibit neurogenesis. In addition, the presence of either UTR does not affect the stability of the mRNA in vitro. These observations suggest the influence of 3' UTR in xGATA-1 on the inhibition of neurogenesis.
3' Untranslated Regions↗
In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease.
Strategies for treating Alzheimer's disease (AD) include therapies designed to decrease senile plaque (SP) formation and/or promote clearance of SPs, but clinical trials of these treatments are limited by the lack of effective methods to monitor changes in plaque burden in the brains of living AD patients. However, because SPs are extracellular deposits of amyloid-beta peptides (Abeta), it may be possible to eventually develop radioligands that cross the blood-brain barrier (BBB) and label SPs so they can be visualized by current imaging methods. As a first step toward the generation of such a radioligand, we developed a probe, [(trans,trans)-1-bromo-2, 5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB)], and we report here that BSB has the following properties essential for a probe that can detect SPs in vivo. First, BSB sensitively labels SPs in AD brain sections. Second, BSB permeates living cells in culture and binds specifically to intracellular Abeta aggregates. Third, after intracerebral injection in living transgenic mouse models of AD amyloidosis, BSB labels SPs composed of human Abeta with high sensitivity and specificity. Fourth, BSB crosses the BBB and labels numerous AD-like SPs throughout the brain of the transgenic mice after i.v. injection. Thus, we conclude that BSB is an appropriate starting point for future efforts to generate an antemortem diagnostic for AD.
Alzheimer Disease↗
Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: effects of methylphenidate as measured by single photon emission computed tomography.
Ten previously untreated adults with attention deficit hyperactivity disorder (ADHD) were investigated before and after 4 weeks of treatment with a dose of 3x5 mg methylphenidate/d by single photon emission computed tomography (SPECT) with [Tc-99m]TRODAT-1, the first Tc-99m labelled SPECT ligand specifically binding to the dopamine transporter (DAT). For semiquantitative evaluation of the DAT, specific binding ([STR-BKG]/BKG) was calculated in the striatum (STR) with the cerebellum used as background (BKG). The patients with ADHD presented with increased specific binding of Tc-99m-TRODAT-1 to the DAT as compared with age and sex matched controls ([STR-BKG]/BKG 1.43+/-0.18 vs. 1.22+/-0.05, P<0.001). After treatment with methylphenidate specific binding decreased in all patients ([STR-BKG]/BKG 1.02+/-0.23, P<0.001). Thus, for the first time it could be demonstrated using SPECT that methylphenidate lowers increased striatal DAT availability in adults suffering from ADHD.
Adult↗
Histone acetylation is a checkpoint in FGF-stimulated mesoderm induction.
We have previously demonstrated that the transcription factor, AP-1 (c-jun/c-fos heterodimer), mediates fibroblast growth factor (FGF) signaling during mesoderm induction in Xenopus embryo. In the present studies, we show that histone acetylation is involved in FGF-mediated signaling leading to mesoderm induction. Histone acetylation is a dynamic process regulated by the activities of two histone-modifying enzymes, the histone acetyltransferase(s) and histone deacetylase(s) (HDACs). We found that basal and FGF-regulated activator protein 1 (AP-1) activity in Xenopus embryo is markedly reduced by treatment of trichostatin A (TSA), a specific inhibitor of HDAC. However, activity of another transcription factor, NFkappaB, is enhanced by TSA treatment. AP-1-mediated mesoderm induction in the animal caps is dramatically suppressed by TSA at a dose-dependent manner. This suppression can be rescued by ectopic expression of HDAC3 at early stage. Finally, we found that histone acetylation in animal caps is inhibited by FGF whereas enhanced by TSA (as a control). Therefore, we propose that histone acetylation is a checkpoint for transduction of the FGF/AP-1 signals to induce mesoderm. Published 2000 Wiley-Liss, Inc.
Acetylation↗
Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment.
Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [99mTc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3x5 mg/day). All subjects were injected with 800 MBq [99mTc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semiquantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background [(STR-BKG)/BKG]. Data were compared with an age-matched control group. It was found that untreated patients presented with a significantly increased specific binding of [99mTc]TRODAT-1 to the DAT as compared with normal controls [(STR-BKG)/BKG: 1.43+/-0.18 vs 1.22+/-0.06, P<0.001]. Under treatment with methylphenidate, specific binding decreased significantly in all patients [(STR-BKG)/BKG: 1.00+/-0.14, P<0.001]. Our findings suggest that the number of DAT binding sites is higher in drug-naive patients suffering from ADHD than in normal controls. The decrease in available DAT binding sites under treatment with methylphenidate correlates well with the improvement in clinical symptoms. The data of this study help to elucidate the complex dysregulation of the dopaminergic neurotransmitter system in patients suffering from ADHD and the effect of treatment with psychoactive drugs.
Adult↗
Simplified quantification of dopamine transporters in humans using [99mTc]TRODAT-1 and single-photon emission tomography.
Quantification of dopamine transporters (DAT) using [99mTc]TRODAT-1 and single-photon emission tomography (SPET) requires full kinetic modeling of the data, using complex and invasive arterial blood sampling to provide an input function to the model. We have shown previously that a simpler reference tissue model provides accurate quantitative results, using a reference region devoid of DAT as the input to the model and thereby obviating the need for blood sampling. We now extend this work into humans, and develop further simplifications to make the imaging protocol much more practical as a routine procedure. Fourteen healthy subjects (age 29.8 +/- 8.4 years, range 18.7-45.5 years) underwent dynamic SPET for 6 h following injection of 752 +/- 28 MBq [99mTc]TRODAT-1. The kinetic data were analyzed using nonlinear regression analysis (NLRA) and Logan-Patlak graphical analysis. In addition, simple average ratios of striatal-to-background counts were obtained for three 1-h periods (3-4 h, 4-5 h, 5-6 h), and compared against the kinetic models. All methods gave an index of specific binding, proportional to the binding potential, known as the distribution volume ratio (DVR). The reference tissue NLRA gave mean values of k3=0.013 +/- 0.003 min(-1), k4=0.011 +/- 0.002 min(-1), and DVR=2.29 +/- 0.17. Graphical analysis gave a value of DVR=2.28 +/- 0. 16, and the three ratio values of DVR were: 3-4 h, 2.18 +/- 0.15; 4-5 h, 2.34 +/- 0.13; and 5-6 h, 2.46 +/- 0.19. Graphical analysis was highly correlated with NLRA (R2=0.91, slope=0.90 +/- 0.08). The ratio methods correlated well with NLRA (3-4 h, R2=0.71, slope= 0.73 +/- 0.13; 4-5 h, R2=0.86, slope=0.73 +/- 0.09; 5-6 h, R2=0.80, slope=1.00 +/- 0.15), and also with graphical analysis (3-4 h, R2=0.65, slope=0.74 +/- 0.16; 4-5 h, R2=0.85, slope=0.78 +/- 0.09; 5-6 h, R2=0.88, slope=1.11 +/- 0.12). The optimum equilibrium time point for obtaining a simple ratio was approximately 4.5-5.5 h. In conclusion, the simple ratio techniques for obtaining a quantitative measure of specific binding correlated well with the reference tissue kinetic models, using both NLRA and graphical analysis. The optimum time for obtaining a ratio appeared to be in the range 4.5-5.5 h. Earlier time points, while still relatively accurate, had a lower sensitivity and may not be optimized for measuring small changes in DAT concentrations.
Adolescent↗
Induction of oocyte maturation by jun-N-terminal kinase (JNK) on the oncogenic ras-p21 pathway is dependent on the raf-MEK signal transduction pathway.
PURPOSE: We have previously found that microinjection of activated MEK (mitogen activated kinase kinase) and ERK (mitogen-activated protein; MAP kinase) fails to induce oocyte maturation, but that maturation, induced by oncogenic ras-p21 and insulin-activated cell ras-p21, is blocked by peptides from the ras-binding domain of raf. We also found that jun kinase (JNK), on the stress-activated protein (SAP) pathway, which is critical to the oncogenic ras-p21 signal transduction pathway, is a strong inducer of oocyte maturation. Our purpose in this study was to determine the role of the raf-MEK-MAP kinase pathway in oocyte maturation and how it interacts with JNK from the SAP pathway. METHODS: We microinjected raf dominant negative mutant mRNA (DN-raf) and the MEK-specific phosphatase, MKP-T4, either together with oncogenic p21 or c-raf mRNA, into oocytes or into oocytes incubated with insulin to determine the effects of these raf-MEK-MAP kinase pathway inhibitors. RESULTS: We found that oocyte maturation induced by both oncogenic and activated normal p21 is inhibited by both DN-raf and by MKP-T4. The latter more strongly blocks the oncogenic pathway. Also an mRNA encoding a constitutively activated MEK strongly induces oocyte maturation that is not inhibited by DN-raf or by MKP-T4. Surprisingly, we found that oocyte maturation induced by JNK is blocked both by DN-raf and MKP-T4. Furthermore, we discovered that c-raf induces oocyte maturation that is inhibited by glutathione-S-transferase (GST), which we have found to be a potent and selective inhibitor of JNK. CONCLUSION: We conclude that there is a strong reciprocal interaction between the SAP pathway involving JNK and the raf-MEK-MAP kinase pathway and that oncogenic ras-p21 can be preferentially inhibited by MEK inhibitors. The results imply that blockade of both MEK and JNK-oncogenic ras-p21 interactions may constitute selective synergistic combination chemotherapy against oncogenic ras-induced tumors.
Animals↗
2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM): an improved serotonin transporter ligand.
Serotonin transporters (SERT) are target-sites for commonly used antidepressants, such as fluoxetine, paroxetine, sertraline, and so on. Imaging of these sites in the living human brain may provide an important tool to evaluate the mechanisms of action as well as to monitor the treatment of depressed patients. Synthesis and characterization of an improved SERT imaging agent, ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine)(7) was achieved. The new compound, ADAM(7), displayed an extremely potent binding affinity toward SERT ( K(i)=0.013 nM, in membrane preparations of LLC-PK(1)-cloned cell lines expressing the specific monoamine transporter). ADAM(7) also showed more than 1,000-fold selectivity for SERT over norepinephrine transporter (NET) and dopamine transporter (DAT) ( K(i)=699 and 840 nM, for NET and DAT, respectively). The radiolabeled compound [(125)I]ADAM(7) showed an excellent brain uptake in rats (1.41% dose at 2 min post intravenous [IV] injection), and consistently displayed the highest uptake (between 60-240 min post IV injection) in hypothalamus, a region with the highest density of SERT. The specific uptake of [(125)I]ADAM(7) in the hypothalamus exhibited the highest target-to-nontarget ratio ([hypothalamus - cerebellum]/cerebellum was 3.97 at 120 min post IV injection). The preliminary imaging study of [(123)I]ADAM in the brain of a baboon by single photon emission computed tomography (SPECT) at 180-240 min post IV injection indicated a specific uptake in midbrain region rich in SERT. These data suggest that the new ligand [(123)I]ADAM(7) may be useful for SPECT imaging of SERT binding sites in the human brain.
Animals↗
A novel serotonin transporter ligand: (5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol.
The serotonin transporters (SERT) are the primary binding sites for selective serotonin reuptake inhibitors, commonly used antidepressants such as fluoxetine, sertraline, and paroxetine. Imaging of SERT with positron emission tomography and single photon emission computed tomography in humans would provide a useful tool for understanding how alterations of this system are related to depressive illnesses and other psychiatric disorders. In this article the synthesis and characterization of [(125)I]ODAM [(5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol, 9)] as an imaging agent in the evaluation of central nervous system SERT are reported. A new reaction scheme was developed for the preparation of compound 9, ODAM, and the corresponding tri-n-butyltin derivative 10. Upon reacting 10 with hydrogen peroxide and sodium[(125)I]iodide, the radiolabeled [(125)95%). In an initial binding study using cortical membrane homogenates of rat brain, ODAM displayed a good binding affinity with a value of K(i) = 2.8 +/- 0.88 nM. Using LLC-PK(1) cells specifically expressing the individual transporter (i.e. dopamine [DAT], norepinephrine [NET], and SERT, respectively), ODAM showed a strong inhibition on SERT (K(i) = 0.12 +/- 0.02 nM). Inhibition constants for the other two transporters were lower (K(i) = 3.9 +/- 0.7 microM and 20.0 +/- 1.9 nM for DAT and NET, respectively). Initial biodistribution study in rats after an intravenous (IV) injection of [(125)I]ODAM showed a rapid brain uptake and washout (2.03, 1.49, 0.79, 0.27, and 0.07% dose/organ at 2, 30, 60, 120, and 240 min, respectively). The hypothalamus region where the serotonin neurons are located exhibited a high specific uptake. Ratios of hypothalamus-cerebellum/cerebellum based on percent dose per gram of these two regions showed values of 0.35, 0. 86, 0.86, 0.63, and 0.34 at 2, 30, 60, 120, and 240 min, post-IV injection, respectively. The specific uptake in hypothalamus can be effectively blocked by pretreatment of known SERT ligands. The results suggest that this novel ligand displays desirable in vitro and in vivo properties as a potential SERT imaging agent.
Animals↗
Characterization of human and mouse peroxiredoxin IV: evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species.
The aim of this study was to identify and characterize human and mouse Prx-IV. We identified mouse peroxiredoxin IV (Prx-IV) by virtue of sequence homology to its human ortholog previously called AOE372. Mouse Prx-IV conserves an amino-terminal presequence coding for signal peptide. The amino acid sequences of mature mouse and human Prx-IV share 97.5% identity. Phylogenetic analysis demonstrates that Prx-IV is more closely related to Prx-I/-II/-III than to Prx-V/-VI. Previously, we mapped the mouse Prx-IV gene to chromosome X by analyzing two sets of multiloci genetic crosses. Here we performed further comparative analysis of mouse and human Prx-IV genomic loci. Consistent with the mouse results, human Prx-IV gene localized to chromosome Xp22.135-136, in close proximity to SAT and DXS7178. A bacterial artificial chromosome (BAC) clone containing the complete human Prx-IV locus was identified. The size of 7 exons and the sequences of the splice junctions were confirmed by PCR analysis. We conclude that mouse Prx-IV is abundantly expressed in many tissues. However, we could not detect Prx-IV in the conditioned media of NIH-3T3 and Jurkat cells. Mouse Prx-IV was specifically found in the nucleus-excluded region of cultured mouse cells. Intracellularly, overexpression of mouse Prx-IV prevented the production of reactive oxygen species induced by epidermal growth factor or p53. Taken together, mouse Prx-IV is likely a cytoplasmic or organellar peroxiredoxin involved in intracellular redox signaling.
3T3 Cells↗
Glutathione-S-Transferase as a selective inhibitor of oncogenic ras-p21-induced mitogenic signaling through blockade of activation of jun by jun-N-terminal kinase.
We have identified the intracellular detoxification enzyme, glutathione-S-transferase (GST), as a potent inhibitor of the activation of jun by its kinase, jun-N-terminal kinase (JNK), in vitro. All three major isozymes (alpha, mu, and pi) bind to JNK-jun complexes and inhibit activation of jun by JNK. We now find that GST inhibits JNK-induced oocyte maturation in vivo and strongly inhibits oocyte maturation induced by oncogenic ras-p21 protein, but not by insulin-activated normal cellular p21 protein. These results correlate with the finding that oncogenic, but not insulin-activated normal, p21 induces high levels of activated JNK. GST also strongly blocks induction of oocyte maturation by protein kinase C (PKC) which is a critical downstream target of oncogenic but not normal ras-p21. Thus, we have established a new function for GST as a potent physiological inhibitor of the ras-JNK-jun pathway.
Animals↗
Regulation of extracellular concentrations of 5-hydroxytryptamine (5-HT) in mouse striatum by 5-HT(1A) and 5-HT(1B) receptors.
The ability of selective serotonin (5-HT) receptor agonists to reduce the extracellular concentration of 5-HT was examined in the striatum of awake, unrestrained mice by in vivo microdialysis. Systemic administration of either 8-OH-PIPAT (R-(+)-trans-8-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)] aminotetralin), a novel 5-HT(1A) receptor agonist, or CP 94,253, a selective 5-HT(1B) receptor agonist, resulted in significant dose-related reductions of striatal 5-HT. The effect of 8-OH-PIPAT (1.0 mg/kg) was blocked by pretreatment with WAY 100635 (0.1 mg/kg), a selective 5-HT(1A) receptor antagonist, but it was not blocked by pretreatment with GR 127935 (0.056 mg/kg), a selective 5-HT(1B/1D) receptor antagonist. The effect of CP 94,253 (1.0 mg/kg) was blocked by pretreatment with GR 127935 (0.056 mg/kg) but was not blocked by pretreatment with WAY 100635 (0.1 mg/kg). Neither WAY 100635 nor GR 127935 altered extracellular 5-HT levels at the doses that were able to completely block the effects of either 8-OH-PIPAT or CP 94,253. The present findings suggest that, on systemic administration, both 8-OH-PIPAT and CP 94,253 are potent and selective agonists at the somatodendritic 5-HT(1A) autoreceptor and terminal 5-HT(1B/1D) autoreceptor, respectively, and are each able to cause decreases in extracellular levels of 5-HT in the mouse striatum by activating a distinct set of receptors.
Animals↗
Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson's disease and in healthy volunteers.
UNLABELLED: [99mTc]TRODAT-1 is a radiolabeled tropane that binds dopamine transporters. The primary goal of this study was to determine whether its regional cerebral distribution could differentiate between patients with Parkinson's disease and healthy human volunteers. METHODS: The sample consisted of 42 patients with Parkinson's disease, 23 age-matched controls, and 38 healthy adults younger than 40 y old. SPECT scans of the brain were acquired on a triple-head gamma camera 3-4 h after the intravenous injection of 740 MBq (20 mCi) [99mTc]TRODAT-1. Mean counts per pixel were measured manually in subregions of the basal ganglia and normalized to the mean background counts to give specific uptake values ([SUVs] approximately k3/k4). Patient and control groups were also compared with automated statistical parametric mapping techniques. Logistic discriminant analyses were performed to determine the optimum uptake values for differentiating patients from age-matched controls. RESULTS: Quantitative image analysis showed that the group mean SUVs in patients were less than the mean values in controls for all regions (all Ps < 0.000001). There was overlap in the caudate as well as in the anterior-most portion of the putamen, but not in the posterior putamen, even when the asymptomatic sides of 5 patients with clinically defined hemi-Parkinson's disease were factored in. CONCLUSION: The findings indicate that Parkinson's disease can be detected with [99mTc]TRODAT by simply inspecting the images for uptake in the posterior putamen. Appropriate asymmetries seem to be visible with quantification in patients with clinically defined hemi-Parkinson's disease, even though changes in the putamen contralateral to the clinically unaffected side in these patients appear to precede the development of symptoms.
Adult↗
Sulfur metabolism in Escherichia coli and related bacteria: facts and fiction.
Living organisms are composed of macromolecules made of hydrogen, carbon, nitrogen, oxygen, phosphorus and sulfur. Much work has been devoted to the metabolism of the first five elements, but much remains to be understood about sulfur metabolism. We review here the situation in Escherichia coli and related bacteria, where more than one hundred genes involved in sulfur metabolism have already been discovered in this organism. Examination of the genome suggests that many more will be found, especially genes involved in regulation, scavenging of sulfur containing molecules and synthesis of coenzymes or prosthetic groups. Furthermore, the involvement of methionine as the universal start of proteins as well as that of its derivative S-adenosylmethionine in a vast variety of cell processes argue in favour of a major importance of sulfur metabolism in all organisms.
Amino Acid Sequence↗