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Biomedical subjects

B C Chu

Publications and source records attributed to B C Chu.

At least 19 recordsLinked to original sources

Inhibition of oligo(glutamine) precipitation by glutamine-containing peptides.

When a solution of glutamine is added to solid 1,1'-carbonyldiimidazole, a mixture of oligo(glutamine)s up to about the 11-mer is formed rapidly. On standing overnight, the solution deposits a precipitate that does not easily redissolve. We have studied the inhibition of this precipitation by glutamine-containing peptides. We find that the alternating peptides (arg.gln)(4) and (arg.gln)(8) are efficient inhibitors of precipitation while arg(5), (glu.gln)(4), and a nonalternating octapeptide of the same composition as (arg.gln)(4) do not inhibit precipitation even though all the arg-containing peptides readily adsorb to oligo(glutamine) precipitates. A possible structural basis for this difference is discussed.

Adsorption↗

Intramedullary schwannoma of the spinal cord: report of two cases.

We report magnetic resonance findings in the intramedullary schwannoma of the cervical spinal cord in two patients. In both cases, the solid portions of the tumours enhanced intensely after administration of Gd-DTPA and the enhanced border was sharply delineated from the adjacent spinal cord. Schwannomas should be considered in the differential diagnosis of intramedullary tumours when magnetic resonance images show a strongly enhancing mass with sharply delineated borders.

Adolescent↗

MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging.

We assessed the utility of fluid-attenuated inversion-recovery (FLAIR) and diffusion-weighted (DWI) images in investigation of tacrolimus (FK-506) encephalopathy, and to see whether we could predict its cause from clinical and imaging data. In seven patients with presumed FK-506 toxicity the areas involved on MRI were similar to those in cyclosporin A (CsA) toxicity. The abnormal signal was most evident on FLAIR in all cases. In three of four patients who underwent DWI, no diffusion abnormalities were detected; in the remaining patient, increased diffusion was seen in the deep white matter bilaterally on the apparent diffusion coefficient map, consistent with the findings on T2-weighted spin-echo and FLAIR images. Five of the six patients for whom we had clinical data showed sudden changes in electrolyte or fluid equilibrium due to diarrhoea, a polyuria or oliguria one day before or on the day of onset of the central nervous system disturbances. We speculate that FK-506 encephalopathy is triggered by the disturbance of the electrolyte and/or fluid equilibrium, given a certain serum level of FK-506.

Adolescent↗

Diffusion-weighted MR findings in a reversible case of acute Wernicke encephalopathy.

We report a case of acute Wernicke encephalopathy (WE) in which apparent diffusion coefficient maps showed areas of increased diffusion in the bilateral medial thalami that corresponded to the hyperintense lesions on T2-weighted imaging. The hyperintense lesions on T2-weighted imaging disappeared with full recovery from symptoms. These findings suggest that the hyperintense lesions of the acute changes of WE include reversible vasogenic edema and are not caused by acute ischemia.

Anemia, Aplastic↗

MR findings in spinal hemangioblastoma: correlation with symptoms and with angiographic and surgical findings.

BACKGROUND AND PURPOSE: To our knowledge, a detailed analysis of MR findings in spinal hemangioblastoma has not been conducted to date. Our purpose was to elucidate the MR features of this disease with special attention to tumor size, correlation with MR findings and clinical symptoms, and any differences between patients with and without von Hippel-Lindau disease (VHLD). METHODS: MR images in five patients with VHLD and seven patients without VHLD were reviewed retrospectively for spinal hemangioblastoma by two neuroradiologists. The MR findings were correlated with clinical symptoms and with angiographic and surgical findings. RESULTS: The MR features depended on the size of the spinal hemangioblastoma. Small (10 mm or less) hemangioblastomas were mostly isointense on T1-weighted images, hyperintense on T2-weighted images, and showed homogeneous enhancement. Larger hemangioblastomas tended to be hypointense or mixed hypo- and isointense on T1-weighted images, heterogeneous on T2-weighted images, and tended to show heterogeneous enhancement. Small hemangioblastomas were located at the surface of the spinal cord, most frequently along its posterior aspect. These were subpial in location at surgery and showed well-demarcated, intense enhancement. Symptomatic small hemangioblastomas had relatively large associated syringes, whereas asymptomatic ones did not. A hemangioblastoma larger than 24 mm was invariably accompanied by vascular flow voids. There was no difference in the MR findings between the two patient groups except for the multiplicity and higher percentage of small tumors in patients with VHLD. CONCLUSION: Knowledge of these MR features helps to differentiate spinal hemangioblastoma from other diseases that show enhancing nodules.

Adolescent↗

Retrospective self-reports of therapist flexibility in a manual-based treatment for youths with anxiety disorders.

Evaluated retrospective therapist ratings of the flexibility used when applying the procedures and strategies prescribed in the treatment manual. Flexibility ratings were collected from 18 therapists who had treated 148 children with anxiety disorders (ages 9 through 13). Analyses revealed strong reliabilities for a flexibility questionnaire and that flexibility was used by therapists; however, significant relations between therapist-rated flexibility and treatment outcome were not found. Discussion focuses on the role of flexibility in manual-based psychological treatments and future directions for study.

Adolescent↗

MRI of the brain in the Kearns-Sayre syndrome: report of four cases and a review.

We report brain MRI findings in four patients with typical Kearns-Sayre syndrome (KSS) and correlate them with clinical manifestations. MRI was interpreted as normal in two patients; cerebral and cerebellar atrophy was seen in the other two. On T2-weighted spin-echo images, two patients had high-signal lesions bilaterally in subcortical white matter, thalamus and brain stem. In one patient, the white matter lesion extended into the deep cerebral white matter and the cerebellum was also affected. The other also had bilateral high-signal lesions in the globus pallidus. There was little correlation between neurological deficits and MRI findings. A review of the literature revealed that 10 of the 13 patients with typical KSS previously studied had bilateral subcortical white-matter lesions on T2-weighted images; at least 7 also had high-signal lesions in the brain stem, globus pallidus, thalamus or cerebellum. Although MRI may be normal or show atrophy, the characteristic finding in KSS is a combination of the high-signal foci in subcortical cerebral white matter and in the brain stem, globus pallidus or thalamus.

Adolescent↗

Peptide-formation on cysteine-containing peptide scaffolds.

Monomeric cysteine residues attached to cysteine-containing peptides by disulfide bonds can be activated by carbonyldiimidazole. If two monomeric cysteine residues, attached to a 'scaffold' peptide Gly-Cys-Glyn-Cys-Glu10, (n = 0, 1, 2, 3) are activated, they react to form the dipeptide Cys-Cys. in 25-65% yield. Similarly, the activation of a cysteine residue attached to the 'scaffold' peptide Gly-Cys-Gly-Glu10 in the presence of Arg5 leads to the formation of Cys-Arg5 in 50% yield. The significance of these results for prebiotic chemistry is discussed.

Amino Acid Sequence↗

[The clinical application of diffusion weighted magnetic resonance imaging to acute cerebrovascular disorders].

Diffusion is a measure of motion freedom and is a sensitive parameter to characterize the tissue at the microscopic level. The methods of measuring in vivo diffusion by magnetic resonance imaging (MRI) have been based mainly on the addition of two motion-probing gradients (MPG) to the spin echo sequence to produce signal attenuation for the spins moving at random. The resultant MR images reflect the intravoxel incoherent motions (IVIM), which contain both water molecule diffusion and perfusion in the capillary network, and can be quantified by an apparent diffusion coefficient (ADC). Diffusion weighted MRI, acquired from IVIM MR imaging by the addition of the very strong MPG predicate water diffusion and anisotropy. High signal or reduced ADC can be observed in case of the slower diffusion. The anisotropy depends upon the orientation of the subjects and the gradients. Greater signal attenuation (faster diffusion) can be observed when the relative orientation of white matter tracts to the MPG is parallel as compared to that obtained with a perpendicular alignment. This anisotropy may preclude the detection or delineation of an ischemic lesion. Diffusion tensor trace has been designated to eliminate this anisotropy effect. In ischemic animal models, low signal (fast diffusion) and high signal (slow diffusion) have been noted in the vasogenic edema and cytotoxic edema, respectively. High signal appears only in case of cerebral blood flow below 15-20 ml/100 g per minute, a value identical to the threshold of tissue at high energetic metabolism and ion homeostasis. ADC value decreases following the cerebral vessel occlusion, or remains unchanged when collateral circulation develops. It has been speculated that reduction in ADC reflects the water shift from extracellular space to intracellular space due to the membrane permeability and/or intracellular osmolality increase. These results suggest that diffusion weighted MRI correlates well with the cell metabolism, and cytotoxic edema plays an important role in the acute cerebral stroke. In clinical setting of acute cerebral ischemia, diffusion weighted MRI may detect superacute infarction by showing high signal (slower ADC) over the 6 hours following the insult, whereas conventional MRI generally fails to do so. In chronic liquefied cerebral infarction, increased ADC, or attenuated signal are the most frequent findings, suggestive of an elevated diffusion. Therefore, diffusion weighted MRI improves early diagnosis of stroke and help differentiate acute from chronic stroke. One disadvantage of diffusion weighted MRI is motion artifact, which may be reduced by the introduction of a navigator echo to correct for the phase shift caused by the first imaging echo, or by the utility of ultrafast imaging technique, such as echo planar. Another shortcomings is the susceptibility artifact incorporating the diffusion weighted MRI. The eddy current may also result from the strong gradients, producing shiftlike artifact. Such artifacts can be compensated for by appropriate shaping of the current pulses sent into the gradient coils, or by use of shielded gradients. As with rapid progresses in perfusion imaging of ischemia penumbra, misery perfusion and luxury perfusion, new insight into the diffusion weighted MRI will be significant.

Acute Disease↗

Demonstration of the distal end of the oesophagus by transabdominal ultrasound.

This study aimed to demonstrate the distal end of the oesophagus using a transabdominal ultrasound technique (TUS) and to measure the normal oesophageal wall thickness in adults. 65 patients without oesophageal disease and 38 normal volunteers were examined by TUS. A left subcostal approach was used to demonstrate the oesophagus. The wall thickness and length were measured in both the supine and 45 degrees right side up oblique (RUO) positions. The abdominal oesophagus was visualized in 80% of patients in the supine position and 92% in the RUO position. Satisfactory demonstration was obtained in 67% of patients in the supine and 85% in the RUO position. The oesophageal wall thickness averaged 2.8 mm (range 2.0-4.0 mm, SD 0.7 mm). The visualized length in these subjects averaged 2.3 cm in the supine position and 3.0 cm in the RUO position, which included approximately 1.5 cm of the lowest portion of the thoracic oesophagus in addition to the abdominal oesophagus. TUS can demonstrate the abdominal oesophagus in the majority of patients and has the potential to provide information on disorders of structure and motility.

Abdomen↗

Crosslinking transcription factors to their recognition sequences with PtII complexes.

We have prepared phosphorothioate-containing cyclic oligodeoxynucleotides that fold into 'dumbbells' containing CRE and TRE sequences, the binding sequences for the CREB and JUN proteins, respectively. Six phosphorothioate residues were introduced into each of the recognition sequences. K2PtCl4 crosslinks CRE to CREB and TRE to JUN. The extent of crosslinking is about eight times greater than that observed with standard oligodeoxynucleotides and amounts to 30-50% of the efficiency of non-covalent association as estimated by gel-shift assays. Crosslinking is reversed by incubation with NaCN. The crosslinking reaction is specific--a dumbbell oligonucleotide with six phosphorothioate groups introduced into the Sp1 recognition sequence could not be crosslinked efficiently to CREB or JUN proteins with K2PtCl4. The binding of TRE to CREB is not strong enough for effective detection by gel-shift assays, but the TRE-CREB complex is crosslinked efficiently by K2PtCl4 and can then readily be detected.

Base Sequence↗

Optimization of the efficiency of cross-linking PtII oligonucleotide phosphorothioate complexes to complementary oligonucleotides.

We have investigated the efficiency with which PtII complexes cross-link phosphorothioates of oligonucleotides to complementary DNA targets. The A and G residues 2-5 bases downstream from the 5'-phosphorothioate group are preferred sites for cross-linking. Replacement of residues in this part of the target by T residues results in greatly decreased cross-linking when cis platinum diammine dichloride (cisPtII) or potassium platinous chloride (K2PtCl4) are used. Trans platinum diammine dichloride (transPtII) forms cross-links with T residues if A and G residues are absent from the susceptible region of the target. Oligomers containing an internal phosphorothioate group can also be linked to their templates with transPtII, but not with cisPtII or K2PtCl4. Cross-linking via an internal phosphorothioate group tends to be less efficient than cross-linking via a 5'-terminal phosphorothioate. The Sp isomers of internal phosphorothioates are cross-linked more efficiently than the Rp isomers. Preliminary experiments suggest that the efficiency of cross-linking to RNA targets will prove similar to that found for DNA targets.

Base Sequence↗

Inhibition of DNA synthesis by cross-linking the template to platinum-thiol derivatives of complementary oligodeoxynucleotides.

Unsubstituted oligodeoxynucleotides, or oligodeoxynucleotides linked to poly-(L)-lysine, when hybridized to a 322 base long template, did not inhibit the production of full length DNA copies by the Klenow fragment of E. coli DNA polymerase I. However, synthesis was inhibited if the cysteamine derivative of the same oligomer was cross-linked to the template via PtII. Truncated products were formed by termination of DNA synthesis a small number of bases upstream from the 5'-end of the cross-linked oligomer. AMV reverse transcriptase behaved similarly but was also slightly inhibited by the hybridized oligomer or its poly-lysine derivative.

Base Composition↗

The lack of effect of pentoxifylline on random skin flap survival.

The effects of pentoxifylline on skin flap survival were studied in rabbits. A total of 40 rabbits had caudally based single-pedicle flaps measuring 4 x 14 cm raised on the mid dorsum of each animal. Twenty of these rabbits were given intraperitoneal injections of pentoxifylline in doses of 24 mg/kg per day beginning 48 hours prior to flap construction and continued daily for 7 days postoperatively. The remaining 20 control rabbits received intraperitoneal injections of saline in equal volumes as the experimental groups. At the end of 7 days, viable flap length was visually inspected and measured in all 40 rabbits. There was no significant difference in skin flap viability in rabbits treated with pentoxifylline compared to the control group.

Animals↗

Ligation of oligonucleotides to nucleic acids or proteins via disulfide bonds.

We have developed general methods for joining together, via cleavable disulfide bonds, either two unprotected polynucleotides or a polynucleotide and a peptide or protein. To join two oligonucleotides, each is first converted to an adduct in which cystamine is joined to the 5'-terminal phosphate of the oligonucleotide by a phosphoramidate bond. The adducts are mixed and reduced with dithiothreitol. The dithiothreitol is then removed by dialysis. Oxidation by atmospheric oxygen occurs to yield the required dimer. To join an oligonucleotide to a cysteine-containing peptide or protein, the 5'-cystamine oligomer is first converted to a 2'-pyridyldisulfide adduct and then reacted with an excess of the peptide or protein. If the peptide does not contain a free cysteine residue, it is first treated with iminothiolane to introduce one or more sulfhydryl groups. We have used these procedures to join a 16 mer deoxynucleotide probe and MDV-1 RNA, a substrate of Q beta RNA polymerase. This adduct hybridizes with a complementary target DNA. We have also joined a 16mer probe to peroxidase and MDV-1 RNA to human IgG. The probe-peroxidase adduct maintains enzymatic activity and the MDV-1 RNA-IgG adduct binds to a complementary anti-IgG.

Chemical Phenomena↗