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Biomedical subjects

J K Lim

Publications and source records attributed to J K Lim.

At least 37 records · Page 2Linked to original sources
PubMed1998

Synthesis and evaluation of a monocationic copper(II) radiopharmaceutical derived from N-(2-pyridylmethyl)-N'-(salicylaldimino)-1,3-propanediamine.

The monocationic 67Cu complex of N-(2-pyridylmethyl)-N'-(salicylaldimino)-1,3-propanediamine was obtained in high radiochemical purity by reaction of 67Cu2+ with the ligand in ethanol solution. Although this compound exhibited low heart uptake, the desired myocardial retention was observed over the 30 min time period studied in a rat model. Since the octanol/water partition coefficient of [67Cu]Cu(II)-N-(2-pyridylmethyl)-N'-(salicylaldiminato)-1,3- propanediamine] is lower than a value believed to be the optimal myocardial uptake, it is likely that derivatives of this compound with a higher lipophilicity merit further investigation for use in myocardial imaging with copper radioisotopes.

Animals↗
PubMed1998

In vivo phase variation of Escherichia coli type 1 fimbrial genes in women with urinary tract infection.

Type 1 fimbriae, expressed by most Escherichia coli strains, are thought to attach to human uroepithelium as an initial step in the pathogenesis of urinary tract infections (UTI). Numerous reports using both in vitro and murine models support this role for type 1 fimbriae in colonization. Unfortunately, only a limited number of studies have directly examined the expression of fimbriae in vivo. To determine whether type 1 fimbrial genes are transcribed during an acute UTI, we employed a modification of an established method. The orientation (ON or OFF) of the invertible promoter element, which drives transcription of type 1 fimbrial genes, was determined by PCR amplification using primers that flank the invertible element, followed by SnaBI digestion. The orientation of the type 1 fimbrial switch was determined under three experimental conditions. First, E. coli strains from different clinical sources (acute pyelonephritis patients, cystitis patients, and fecal controls) were tested under different in vitro culture conditions (agar versus broth; aerated versus static). The genes in the more-virulent strains (those causing acute pyelonephritis) demonstrated a resistance, in aerated broth, to switching from OFF to ON, while those in fecal strains readily switched from OFF to ON. Second, bladder and kidney tissue from CBA mice transurethrally inoculated with E. coli CFT073 (an established murine model of ascending UTI) was assayed. The switches directly amplified from infected bladder and kidney tissues were estimated to be 33 and 39% ON, respectively, by using a standard curve. Finally, bacteria present in urine samples collected from women with cystitis were tested for type 1 fimbria switch orientation. For all 11 cases, an average of only 4% of the switches in the bacteria in the urine were ON. In 7 of the 11 cases, we found that all of the visible type 1 fimbrial switches were in the OFF position (upper limit of detection of assay, 98% OFF). Strains recovered from these urine samples, however, were shown after culture in vitro to be capable of switching the fimbrial gene to the ON position and expressing mannose-sensitive hemagglutinin. The results from experimental infections and cases of cystitis in women suggest that type 1 fimbrial genes are transcribed both in the bladder and in the kidney. However, those bacteria found in the urine and not attached to the uroepithelium are not transcriptionally active for type 1 fimbrial genes.

Adolescent↗
PubMed1997

Mixed bis(thiosemicarbazone) ligands for the preparation of copper radiopharmaceuticals: synthesis and evaluation of tetradentate ligands containing two dissimilar thiosemicarbazone functions.

A series of four "mixed" bis(thiosemicarbazone) keto aldehyde derivatives containing dissimilar thiosemicarbazone functions were synthesized and evaluated as ligands for preparation of radiocopper-labeled radiopharmaceuticals. The pyruvaldehyde-based mixed bis(thiosemicarbazone) ligands CH3C[=NNHC(S)NH2]CH[=NNHC(S)NHMe] (4a), CH3C[=NNHC(S)NHMe]-CH[=NNHC(S)NH2] (4b), CH3C[=NNHC(S)NH2]CH[=NNHC(S)NMe2] (4c), and CH3C[=NNHC-(S)NHMe]CH[=NNHC(S)NMe2] (4d) were obtained by reaction of thiosemicarbazide, N4-methylthiosemicarbazide, or N4,N4-dimethylthiosemicarbazide with pyruvaldehyde 2-thiosemicarbazones that had been generated by oxidative cleavage of the appropriate pyruvic aldehyde dimethyl acetal 2-thiosemicarbazone. The 67Cu-labeled complexes of ligands 4a-d were prepared and screened in a rat model to assess the potential of each chelate as a 62Cu radiopharmaceutical for imaging with positron emission tomography. In the rat model the 67Cu complexes of ligands 4a-d exhibit significant uptake into the brain and heart after intravenous injection, following trends similar to those previously reported for the related bis(thiosemicarbazone) complexes, Cu-PTS, Cu-PTSM, and Cu-PTSM2 (derived from pyruvaldehyde bis(thiosemicarbazone), pyruvaldehyde bis(N4-methylthiosemicarbazone), and pyruvaldehyde bis(N4,N4-dimethylthiosemicarbazone), respectively). Ultrafiltration studies using solutions of dog and human serum albumin reveal that the 67Cu complexes of ligands 4a-d, like the Cu(II) complex of pyruvaldehyde bis(N4-methylthiosemicarbazone), interact more strongly with human albumin than dog albumin.

Animals↗
PubMed1996

Variable bile retention on cholescintigraphy after morphine administration.

Intravenous morphine sulfate has been used in conjunction with cholescintigraphy. We studied the variations in the degree and duration of the effects of 2 mg morphine on biliary kinetics in patients with gallbladder nonvisualization and undertook a comparison with biliary kinetics in patients not given morphine. Of 24 morphine-augmented cholescintigrams that were obtained without additional injection of technetium-99m diisopropyl-iminodiacetic acid (DISIDA), 19 showed continued gallbladder nonvisualization. Time-activity curves (TACs) of the liver parenchyma and common bile/hepatic duct (CD) of the entire study (before and after morphine) were obtained. In two patients, the CD was not sufficiently visualized to define a region of interest. In 17 patients, the peak CD activity was observed between 14 and 47 min after injection of 99mTc-DISIDA. In these 17, the TAC of the CD was declining essentially in parallel with the TAC of the liver parenchyma at the end of the first hour before morphine. After morphine injection, CD activity slowly increased for a variable duration in nine patients, while it continued to decrease in eight. CD activity between 1 h and 2 h showed a continuously decreasing pattern in another group of 20 patients who did not receive morphine despite gallbladder nonvisualization at 1 h. In summary, no significant effect of 2 mg of intravenous morphine on biliary kinetics was detected scintigraphically in a considerable proportion of patients. Also, there was considerable variation in the duration of the effect of morphine, when such an effect was present. This observation may have significant clinical implications for morphine-augmented cholescintigraphy.

Bile↗
PubMed1996

Molecular characterization of hobo-mediated inversions in Drosophila melanogaster.

The structure of chromosomal inversions mediated by hobo transposable elements in the Uc-1 X chromosome was investigated using cytogenetic and molecular methods. Uc-1 contains a phenotypically silent hobo element inserted in an intron of the Notch locus. Cytological screening identified six independent Notch mutations resulting from chromosomal inversions with one breakpoint at cytological position 3C7, the location of Notch. In situ hybridization to salivary gland polytene chromosomes determined that both ends of each inversion contained hobo and Notch sequences. Southern blot analyses showed that both breakpoints in each inversion had hobo-Notch junction fragments indistinguishable in structure from those present in the Uc-1 X chromosome prior to the rearrangements. Polymerase chain reaction amplification of the 12 hobo-Notch junction fragments in the six inversions, followed by DNA sequence analysis, determined that each was identical to one of the two hobo-Notch junctions present in Uc-1. These results are consistent with a model in which hobo-mediated inversions result from homologous pairing and recombination between a pair of hobo elements in reverse orientation.

Animals↗
PubMed1996

Re-operation for failed anti-reflux surgery.

BACKGROUND: Between 1993 and 1995, 315 anti-reflux procedures were undertaken on our service. A previous antireflux procedure had been performed in 31 patients referred (10%). Previous surgery was, in the main (80%), a Nissen fundoplication. METHODS: Pre-operative investigations in all patients were manometry, 24h pH monitoring, oesophagoscopy and barium radiology. On this basis the causes of failure of the previous surgery were established as hiatal failure in 20 (65%), unrecognized oesophageal dysmotility in three (10%) and fundoplication failure (slipped and disrupted) in eight (25%). Contrary to standard recommendations for re-operation most re-operative surgery was performed transabdominally (94%). Complications occurred in 16%. RESULTS: Review was undertaken at a mean of 21 months following surgery, and 91% of patients reported a good to excellent symptomatic outcome. CONCLUSIONS: Transabdominal re-operative anti-reflux surgery has an acceptable complication rate and a surprisingly good symptomatic outcome in the medium term.

Adult↗
PubMed1996

Laparoscopic exploration of the common bile duct-report on two cases and literature review.

The optimal management of the common bile duct stone in the era of laparoscopic surgery is not certain. The common policy is selective preoperative endoscopic retrograde cholangio-pancreatography (ERCP) followed by laparoscopic cholecystectomy. When ERCP fails, the common bile duct is explored via open surgery. New techniques of laparoscopic trancystic exploration of the common bile duct and laparoscopic choledochotomy exploration of the common bile duct are now being tried. The results of two case reports are discussed.

Adult↗
PubMed1994

Intrinsic ligand binding properties of the human and bovine alpha-interferon receptors.

The Type I interferon receptor (IFN-alpha R) interacts with all IFN-alpha s, IFN-beta and IFN-omega, and seems to be a multisubunit receptor. To investigate the role of a cloned receptor subunit (IFN-alpha R1), we have examined the intrinsic ligand binding properties of the bovine and human IFN-alpha R1 polypeptides expressed in Xenopus laevis oocytes. Albeit with different efficiencies, Xenopus oocytes expressing either the human or bovine IFN-alpha R1 polypeptide exhibit significant binding and formation of crosslinked complexes with human IFN-alpha A and IFN-alpha B. Thus, the IFN-alpha R1 polypeptide most likely plays a direct role in ligand binding.

Animals↗
PubMed1994

Expression of a functional human type I interferon receptor in hamster cells: application of functional yeast artificial chromosome (YAC) screening.

The previously cloned human interferon alpha/beta (Hu-IFN-alpha/beta; Type I interferon) receptor cDNA appears to be only one component of a receptor complex since expression of the cDNA in mouse cells confers sensitivity only to Hu-IFN-alpha B2, but a monoclonal antibody against this cloned receptor subunit inhibits biological activities of Hu-IFN-alpha A, Hu-IFN-alpha B2, Hu-IFN-omega, and Hu-IFN-beta. Here we report that a yeast artificial chromosome (YAC) containing a segment of human chromosome 21 introduced into Chinese hamster ovary (CHO) cells confers upon these cells a greatly enhanced response to Hu-IFN-alpha A and Hu-IFN-alpha B2 as well as an increased response to Hu-IFN-omega, Hu-IFN-alpha A/D(Bgl), andd Hu-IFN-beta. These responses were measured by induction of class I MHC antigens and by protection against encephalomyocarditis virus and vesicular stomatitis virus. Furthermore, these cells exhibit specific high affinity binding of Hu-IFN-alpha A and Hu-IFN-alpha B2, Hu-IFN-beta, and Hu-IFN-omega. The results indicate that all the genes necessary to reconstitute a biologically active Type I human IFN receptor complex are located within the human DNA insert of this YAC clone.

Animals↗
PubMed1994

Gross chromosome rearrangements mediated by transposable elements in Drosophila melanogaster.

A combination of cytogenetic and molecular analyses has shown that several different transposable elements are involved in the restructuring of Drosophila chromosomes. Two kinds of elements, P and hobo, are especially prone to induce chromosome rearrangements. The mechanistic details of this process are unclear, but, at least some of the time, it seems to involve ectopic recombination between elements inserted at different chromosomal sites; the available data suggest that these ectopic recombination events are much more likely to occur between elements in the same chromosome than between elements in different chromosomes. Other Drosophila transposons also appear to mediate chromosome restructuring by ectopic recombination; these include the retrotransposons BEL, roo, Doc and I and the foldback element FB. In addition, two retrotransposons, HeT-A and TART, have been found to be associated specifically with the ends of Drosophila chromosomes. Very limited data indicate that transposon-mediated chromosome restructuring is occurring in natural populations of Drosophila. This suggests that transposable elements may help to shape the structure of the Drosophila genome and implies that they may have a similar role in other organisms.

Animals↗
PubMed1993

Cloning and characterization of a bovine alpha interferon receptor.

A bovine interferon alpha receptor (BoIFN-alpha R1) cDNA, homologous to the human cDNA, was isolated. Transfection of the BoIFN-alpha R1 cDNA into monkey COS cells results in a large increase in high-affinity binding sites for human IFN-alpha A and IFN-alpha B. Covalent crosslinking of radiolabeled HuIFN-alpha A and -alpha B demonstrates that the complex of [32P]HuIFN with the BoIFN-alpha R1 protein (predicted mass, 61,375) expressed in COS cells migrates as a 140-150 kDa band.

Amino Acid Sequence↗
PubMed1993

Generation and characterization of anti-idiotypic antibodies recognizing the interferon-alpha receptor: implications for ligand-receptor interactions.

Monoclonal antibodies LI-1 and LI-8 against interferon-alpha A (IFN-alpha A) block IFN-alpha A activity and binding to its receptor, but they recognize distinct epitopes. Surprisingly, anti-idiotypic antibodies to both LI-1 and LI-8 have properties consistent with recognition of the receptor: anti-LI-1 and anti-LI-8 antibodies inhibit the binding of IFN-alpha A to its receptor. However, anti-LI-1 is an antagonist of IFN-alpha A, while anti-LI-8 is an agonist. Thus, at least some part of the epitopes on IFN-alpha A recognized by LI-1 and LI-8 are directly involved in receptor binding. Because these epitopes are spatially distinct, the implication is that the receptor binding site on IFN-alpha A must be extensive, or there are minimally two regions of IFN-alpha A involved in receptor interactions.

Antibodies, Anti-Idiotypic↗
PubMed1993

Genetic instability in Drosophila melanogaster mediated by hobo transposable elements.

Eight independent recessive lethal mutations that occurred on derivatives of an unstable X chromosome (Uc) in Drosophila melanogaster were analyzed by a combination of genetic and molecular techniques. Seven of the mutations were localized to complementation groups in polytene chromosome bands 6E; 7A. In situ hybridization and genomic Southern analysis established that hobo transposable elements were associated with all seven of the mutations. Six mutations involved deletions of DNA, some of which were large enough to be seen cytologically, and in each case, a hobo element was inserted at the junction of the deletion's breakpoints. A seventh mutation was associated with a small inversion between 6F and 7A-B and a hobo element was inserted at one of its breakpoints. One of the mutant chromosomes had an active hobo-mediated instability, manifested by the recurrent production of mutations of the carmine (cm) locus in bands 6E5-6. This instability persisted for many generations in several sublines of an inbred stock. Two levels of instability, high and basal, were distinguished. Sublines with high instability had two hobo elements in the 6E-F region and produced cm mutations by deleting the segment between the two hobos; a single hobo element remained at the junction of the deletion breakpoints. Sublines with low instability had only one hobo element in the 6E-F region, but they also produced deletion mutations of cm. Both types of sublines also acquired hobo-mediated inversions on the X chromosome. Collectively, these results suggest that interactions between hobo elements are responsible for the instability of Uc. It is proposed that interactions between widely separated elements produce gross rearrangements that restructure the chromosome and that interactions between nearby elements cause regional instabilities manifested by the recurrence of specific mutations. These regional instabilities may arise when a copy of hobo transposes a short distance, creating a pair of hobos that can interact to produce small rearrangements.

Animals↗
PubMed1993

Interacting hobo transposons in an inbred strain and interaction regulation in hybrids of Drosophila melanogaster.

A transposable hobo element in the Notch locus of the Uc-1 X chromosome, which does not interfere with the normal expression of the locus, interacts with other hobo elements in the same X chromosome to produce Notch mutations. Almost all of these mutations are associated with deficiencies, inversions or other rearrangements, and hobo elements are present at each of the breakpoints. The Uc-1 X chromosome produces the Notch mutations at a rate of 4-8% in both sexes of flies in a strain that has been inbred for 96 generations. At least two-thirds of the mutations are produced in clusters suggesting that they have originated in mitotic (premeiotic) germ cells of the Uc-1 inbred strain. The interaction of hobo elements in the Uc-1 X chromosome can be repressed by at least two different mechanisms. One found in three inbred strains not related to the Uc-1 strain involves a maternal effect that is not attributable to the actions or products of hobo elements. Repression by this mechanism is manifested by a clear reciprocal cross effect so that the production of Notch mutations is repressed in the daughters of Uc-1 males, but not in the daughters of Uc-1 females. The other mechanism apparently requires genetic factors and/or hobo elements in a particular strain of Oregon-R; complete repression is present in both types of hybrids between Uc-1 and this strain.

Animals↗
PubMed1993

Botulinum a toxin treatment of hemifacial spasm and blepharospasm.

We studied the effects of botulinum A toxin in 101 patients with hemifacial spasm and 11 patients with blepharospasm in an open trial and double blind manner. All patients in the open trial and 6 patients in the double blind trial improved after the first injection of botulinum toxin. There was no improvement with placebo. The peak effect ranged from one to 6 days after injection and mean peak effect was 3.6 days in blepharospasm, and 4 days in hemifacial spasm. Of 144 treatments, 98.6% had excellent results, (below grade I). The duration of beneficial effect ranged 11 to 40 weeks (mean 16.5 weeks) in hemifacial spasm and 9 to 30 weeks (mean 14.2 weeks) in blepharospasm. Complications were encountered in 63.4% in hemifacial spasm and 72.7% in blepharospasm. The common side effects were dry eyes, mouth droop, ptosis and lid edema in order of frequency. These side effects were mild and resolved spontaneously in 1 to 3 weeks. Botulinum A toxin therapy is effective and convenient, and the treatment of choice for patients with hemifacial spasm and blepharospasm.

Adult↗
PubMed1993

Ligand binding characteristics of [3H] dihydroalprenolol in cerebral cortical membranes of young and old senescence-accelerated mouse.

1. The values of both Kd and Bmax of [3H] dihydroalprenolol binding in the cerebral cortical membranes of old-aged (12 month old) SAM-P/1 were not significantly different compared with those of young (2 month old) SAM-P/1. 2. The values of Ki of metoprolol in the young and old aged SAM were 119 +/- 39.5 nM and 157 +/- 55 nM, respectively. 3. The values of beta 1/beta 2 ratio of the young and old aged SAM were 1.67 +/- 0.15 and 1.64 +/- 0.13, respectively. 4. These results suggest that there were no significant changes of binding characteristics of beta 1 and beta 2 adrenoceptors during aging in the cerebral cortex of SAM.

Aging↗
PubMed1992

Microscopically controlled excision of skin cancer.

OBJECTIVE: To describe the technique of microscopically controlled excision of skin cancer (Moh's surgery) and to review the early experience of the use of this technique at Royal Prince Alfred Hospital. DESIGN: A review of 170 clinical records of patients with 198 skin malignancies treated by microscopically controlled excision from 1981 to 1983. PATIENTS: Long term follow-up of 148 patients with 170 lesions was possible. An analysis of these patients' sex and age, and the site, size and histopathological diagnosis of their lesions was carried out. INTERVENTIONS: All patients underwent microscopically controlled excision of their skin cancer. Analysis of the operative procedure revealed an average of 2.1 excision stages and 14.8 blocks examined by frozen section for each tumour. RESULTS: The overall cure rate was 97.1% for this group of patients. This rate is comparable with that of other centres performing this procedure. CONCLUSIONS: Microscopically controlled excision offers an excellent cure rate for skin cancers, especially recurrent, difficult basal cell carcinomas in areas known to be at high risk for recurrence, for example, central areas on the face. The application of this technique to selected patients and tumours offers a higher cure rate than conventional treatment methods.

Bowen's Disease↗