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Biomedical subjects

C K Tan

Publications and source records attributed to C K Tan.

At least 73 records · Page 4Linked to original sources

Blood aflatoxin levels in patients with hepatocellular carcinoma in Singapore.

Aflatoxin (AF), a highly potent hepatocarcinogen, is strongly implicated in the pathogenesis of human hepatocellular carcinoma (HCC). In this study, our aim was to determine if this carcinogen is associated with cases of HCC in Singapore. Blood levels of the naturally-occurring AFs--B1, B2, G1 and G2--were assayed in 56 cases of HCC. AF was detected in only 2/56 (3.6%) cases of HCC, one each of AF-B1 and AF-G1. In contrast, in a similar survey done in Singapore on normal subjects, AF was positive in 64/423 (15.1%) cases. The low frequency of AF detection in our patients suggests that HCC in Singapore is not associated with significant chronic exposure to AF.

Adult↗

Efferent connections from the external cuneate nucleus to the medulla oblongata in the gerbil.

The present study revealed the efferent projections from the external cuneate nucleus (ECN) to various medullary nuclei in the gerbil as demonstrated in fresh living brainstem slices by using in vitro anterogradely tracing with the dextran-tetramethyl-rhodamine-biotin. The tracer-labelled ECN axon terminals were observed (1) in most of the vital autonomic-related nuclei: the nucleus solitary tractus, nucleus ambiguus, rostroventrolateral reticular nucleus and C2 adrenergic area, (2) in the reticular formation: the medullary, parvocellular, intermediate, gigantocellular, dorsal paragigantocellular and lateral paragigantocellular reticular nuclei and medullary linear nucleus, and (3) in sensory nuclei: the cuneate nucleus, spinal trigeminal nuclei caudalis and interpolaris, paratrigeminal nucleus, medial and spinal vestibular nuclei, inferior olive and prepositus hypoglossal nucleus. These new findings are discussed in relation to possible roles of the ECN in cardiovascular, respiratory and sensorimotor controls.

Animals↗

Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors.

A variety of analogues of 1-[4-methoxy-3,5-dimethylbenzyl]-4-[3-(ethylamino)-2-pyridyl]piperazine hydrochloride (U-80493E) were synthesized and evaluated for their inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Replacement of the substituted aryl moiety with various substituted indoles provided bis(heteroaryl)piperazines (BHAPs) that were 10-100-fold more potent than U-80493E. The pyridyl portion of the lead molecule was found to be very sensitive to modifications. Extensive preclinical evaluations of several of these compounds led to the selection of 1-[(5-methoxyindol-2-yl)carbonyl]-4-[3-(ethylamino)-2- pyridyl]piperazine methanesulfonate (U-87201E, atevirdine mesylate) for clinical evaluation.

Aminopyridines↗

Catalytically distinct conformations of the ribonuclease H of HIV-1 reverse transcriptase by substrate cleavage patterns and inhibition by azidothymidylate and N-ethylmaleimide.

The RNase H activity of recombinant HIV-1 reverse transcriptase (RT) has been characterized with respect to inhibition by azidothymidylate (AZTMP) and N-ethylmaleimide (NEM) and to cleavage patterns using either poly(rA)/poly(dT) or poly(rG)/poly(dC) as model substrate and either Mg2+ or Mn2+ as divalent cation activator. The inhibitory potency of AZTMP and other nucleotide analogues was found to be dependent on both the composition of the substrate and the divalent cation. The enzyme was significantly more sensitive to AZTMP inhibition with poly(rG)/poly(dC) than with poly(rA)/poly(dT) as substrate and in Mn2+ than in Mg2+ with either substrate. Kinetic studies indicated that AZTMP is a competitive inhibitor with respect to the substrate in Mn2+ whereas it behaves as an uncompetitive inhibitor in Mg2+. These results suggest that the enzyme may exist in two distinct forms depending on whether Mg2+ or Mn2+ is the divalent cation activator. Consistent with this suggestion is the alteration in the mode of cleavage of the substrate upon substitution of Mg2+ with Mn2+. In Mg2+, hydrolysis of poly(rA)/poly(dT) appears to be solely endonucleolytic, whereas in Mn2+, hydrolysis is both endonucleolytic and exonucleolytic. With poly(rG)/poly(dC) as substrate, hydrolysis is both endonucleolytic and exonucleolytic in either Mg2+ or Mn2+. There is a positive correlation between sensitivity to AZTMP and production of mononucleotides, suggesting that the exonuclease activity of RNase H is preferentially inhibited by AZTMP. The sensitivity of RNase H to inhibition by N-ethylmaleimide was also found to be markedly influenced by the substrate composition and the divalent cation activator, being most sensitive under conditions in which endonucleolytic activity predominates.(ABSTRACT TRUNCATED AT 250 WORDS)

Catalysis↗

Localisation of substance P-like immunoreactivity in the ciliary ganglia of monkey (Macaca fascicularis) and cat: a light- and electron-microscopic study.

The present study describes substance P-like immunoreactivity in the ciliary ganglia of monkey (Macaca fascicularis) and cat. About 60% of neurons in the monkey ciliary ganglion and 40% in the cat ciliary ganglion were substance P-like immunoreactive, ranging from faint to moderate staining. Substance P-like immunoreactivity was located in cell bodies, dendritic profiles and axons. In the monkey, substance P-like immunoreactive pericellular arborisations were associated with about 0.5%-3% of the ganglion cells, which were either negatively, faintly or moderately stained. An electron-microscopic study demonstrated the presence of either substance P-like immunoreactive positive or negative axon terminals synapsing or closely associated with positive dendritic profiles in both the monkey and cat ciliary ganglia. The results suggest that substance P plays an important role in the ciliary ganglion, perhaps as a modulator or transmitter.

Animals↗

Orthotopic liver transplantation for preoperative early-stage hepatocellular carcinoma.

OBJECTIVE: To report our experience with orthotopic liver transplantation (OLT) for highly selected patients with early-stage hepatocellular carcinoma (HCC). DESIGN: We retrospectively analyzed the demographic, clinical, pathologic, and survival data on 21 patients with HCC who underwent OLT at the Mayo Clinic between 1985 and 1993. MATERIAL AND METHODS: The 21 patients were categorized into three groups: (1) those with incidental HCC (no evidence of HCC preoperatively), (2) those with a unicentric hepatic lesion without vascular invasion, and (3) those with an increased serum alpha-fetoprotein (AFP) concentration but no detectable mass lesion in the liver. RESULTS: For the seven patients with incidental HCC, the 2-year disease-free survival was 68.5%. For the eight patients with a mass lesion, the 2-year disease-free survival was only 50%. Operative staging revealed more advanced stage disease than had been found on preoperative assessment in five of these eight patients. For the six patients with an increased serum AFP value but no mass lesion, the 2-year disease-free survival was 80%. Tumor recurrence was the major cause of all deaths in this series. CONCLUSION: Disease-free survival for patients with radiographic early-stage HCC was suboptimal because of understaging of the disease preoperatively. In contrast, our initial experience with OLT for patients with an increased serum AFP value in the absence of a mass lesion in the liver was favorable.

Adult↗

Mucopolysaccharide histochemistry of the oviduct of the toad, Bufo melanostictus, before and during ovulation.

In both non-ovulating and ovulating toads of the species, Bufo melanostictus, the fimbrium stained only weakly for mucopolysaccharides (MPs) whereas the infundibulum stained strongly for neutral MPs and also for glycogen. In the non-ovulating toad, only neutral and sulphated MPs were detected in the goblet cells of the upper magnum, whereas sulphated, neutral and sialomucins were detected in the glands. In the middle magnum, sulphated and sialic acid-containing carboxylated MPs were detected in both the goblet cells and glands. In the lower magnum, neutral, sulphated, and sialic acid-containing MPs were detected in the goblet cells and only sulphated and sialic acid-containing MPs were detected in the glands. In the isthmus and ovisac, only sulphated MPs were present in the goblet cells. During ovulation, there was no change in the distribution of sulphated MPs throughout the oviduct. Sialic acid-containing MPs could not be detected in many of the goblet cells of the upper and lower magnum nor in most of the glands of the lower magnum.

Animals↗

An ultrastructural study of the ciliary ganglia of cat and monkey (Macaca fascicularis) following section of the short ciliary nerves.

The ultrastructural changes in the ciliary ganglion of the cat and monkey after postganglionic (short ciliary) nerve section are described. They were similar in both cat and monkey. The nucleus became irregular with prominent indentations on the 3rd day after operation and was peripherally located in the neuron from the 5th postoperative day; by 1 month postoperatively, however it had reverted to its former round or oval shape and became centrally located. In the cytoplasm, glycogen-like granules were increased. At 5 d after operation, profiles of dilated endoplasmic reticulum (ER) and vacuoles were observed at the periphery of some neurons. At 7 d after operation, there was an increase in the number of dense bodies in the cytoplasm of the neurons. By 1-3 months after operation, most of the neurons appeared normal, but there was an increase of profiles of the Golgi apparatus in the perinuclear region. In the cat, there was an increase in profiles of glycogen-like granules associated with ER stacks. In the monkey, the glycogen-like granules were randomly distributed in the cytoplasm. Dendritic profiles with large numbers of mitochondria and glycogen-like granules were observed as early as the 1st postoperative day and were increased on the 3rd postoperative day. Some of the profiles were contacted synaptically by axon terminals. Such profiles measured between 0.8 to 4.5 microns in the cat and 1.1-7.0 microns in the monkey. The number of mitochondria per dendritic profile in cross section varied from 8 to 155 in the cat and 28 to 230 in the monkey. Dilated and almost empty mitochondria and dense bodies were encountered in such profiles. Dendritic profiles packed with mitochondria were still present 1-3 months after operation, but were reduced in number and dense bodies were only occasionally observed. Some of the myelinated and unmyelinated axons underwent degeneration, but no ultrastructural change was observed in the axon terminals. In some axonal profiles, vesiculotubular structures were also present. At 7-14 d after operation, some of the satellite cells became less electron dense. At this stage, some of the cells contained phagocytosed electron-dense profiles resembling degenerating myelinated axons and cellular debris. Macrophages were encountered frequently 3-7 d after operation; some of these were believed to be derived from circulating monocytes since they were occasionally observed to penetrate the vascular wall. Most of the engulfed material in the cytoplasm of the macrophages were myelin-like figures and vesiculated profiles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

An unusual course and relations of the human axillary artery.

The axillary artery was studied by dissection of 50 human cadavers over a two-year period. Except in one instance, the course and relations of the axillary artery of all the other cadavers conformed to the normal description found in standard textbooks of Anatomy. In the exceptional cadaver, the axillary artery of the right side showed two unique features: (1) it pursued a tortuous course and made two sharp bends, and (2) it was situated superficial, rather than deep to, the pectoralis minor muscle. Its branches and relationship to the brachial plexus were also altered. On the left side, the artery was not tortuous but was also situated in front of the pectoralis minor. The present observation has several implications: (1) such a configuration of the artery would render it more prone to kinking and hence compression; (2) surgically, it might make axillary block of the brachial plexus and block dissection of the axillary lymph nodes during radical mastectomy more difficult; (3) it is at risk during infraclavicular percutaneous cannulation of the subclavian vein for a central line insertion or for insertion of a subclavian cannula for haemodialysis.

Axillary Artery↗

The ciliary ganglion of the monkey: a light and electron microscope study.

The results of light and electron microscope studies of the ciliary ganglion of 5 monkeys (Macaca fascicularis) are described. The ganglion, measuring about 2 mm in length, was consistently observed to be attached to the nerve supplying the inferior oblique muscle at its origin from the oculomotor nerve. A very fine branch was found to connect the nasociliary nerve to the ganglion. The number of neurons varied from 2824 to 3545 after applying Abercrombie's (1946) correction. The mean of the maximum diameter was 43.1 microns (S.D. = 8.0), that of the minimum diameter was 30.5 microns (S.D. = 5.4); the mean of the average diameters was 36.8 microns (S.D. = 5.5) and that of the soma ratios of the maximum to minimum diameters was 1.4 (S.D. = 0.3). The frequency distributions of the maximum diameter, the minimum diameter, the average diameter and the soma ratio were all unimodal. On light microscopy, the Nissl granules in the neurons were prominent and randomly distributed in the cytoplasm. Under the electron microscope, the rough endoplasmic reticulum was distributed either peripherally, perinuclearly or randomly in the cytoplasm of the neuron. Most of the dendrites were short protrusions from the cell body; occasionally such dendritic protrusions were electron dense. Most of the synapses encountered were axodendritic; a few were axosomatic. Synaptic complexes were frequently observed. The axon terminals usually contained a mixture of both round, measuring 30-50 nm in diameter, and flattened vesicles. Tilt analyses showed that the flattened vesicles which measured 20 nm by 50 nm were either discoid or cylindrical in shape. Large dense-cored vesicles measuring 80-100 nm, with core diameters of between 40 and 60 nm, were frequently present.

Animals↗

Interaction of DNA polymerase delta, proliferating cell nuclear antigen, and synthetic oligonucleotide template-primers. Analysis by polyacrylamide gel electrophoresis-band mobility shift assay.

A polyacrylamide gel electrophoresis band-mobility shift assay was developed to study the binding of synthetic oligonucleotides by DNA polymerase delta (pol delta) and proliferating cell nuclear antigen (PCNA). As measured by this assay, neither calf thymus pol delta core enzyme nor PCNA alone bind DNA stably. However, mammalian PCNA but not Drosophila PCNA promotes the formation of a distinct pol delta.PCNA.template-primer complex. Appearance of this complex is primer-dependent but does not require Mg2+. Complex stability is also influenced by the presence or absence of individual dNTPs. A model for the ordered sequential interaction of pol delta, PCNA, and DNA template-primers is proposed.

Animals↗

The ciliary ganglion of the cat: a light and electron microscopic study.

The ciliary ganglia of eight healthy adult cats were studied by light and electron microscopy. The ganglion, measuring about 2 mm in length, was consistently found to be attached to the branch from the oculomotor nerve supplying the inferior oblique muscle. The number of neurons varied from 2773 to 3794 after applying Abercrombie's correction. The mean of average somal diameter of the neurons was 36.5 microns (SD = 5.0 microns) and the mean of somal cross-sectional area was 904.2 microns 2 (SD = 262.8 microns 2). The mean of average nuclear diameter was 13.9 microns (SD = 1.8 microns) and the mean of nuclear cross-sectional area was 142.2 microns 2 (SD = 37.1 microns 2). The mean of the aspect ratios of the soma and nucleus were 1.2 (SD = 0.1) and 1.1 (SD = 0.1) respectively. The frequency distributions of these parameters were all unimodal. Under the light microscope, the Nissl granules in the neurons were prominent and were distributed peripherally, perinuclearly or randomly in the cytoplasm. Under the electron microscope, the rough endoplasmic reticulum showed a similar pattern of distribution in the cytoplasm. In some neurons, glycogen-like granules were present; these were either distributed randomly throughout the cell, or aligned in single rows in relation to subsurface cisterns and between the cisterns of smooth and rough endoplasmic reticulum. Most of the dendrites were short protrusions from the cell body; some contained glycogen-like granules. Occasionally, the dendritic protrusions were electron-dense. All the synapses encountered were axodendritic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute intestinal pseudo-obstruction due to malignant thymoma.

Acute intestinal pseudo-obstruction has been associated with various diverse aetiologies, including several types of malignancies. Malignant thymoma has never been reported before as a cause of acute intestinal pseudo-obstruction. We report here a case of malignant thymoma presenting as acute intestinal pseudo-obstruction. Existing literature on malignant causes of intestinal pseudo-obstruction is also reviewed and discussed.

Adult↗

A scanning electron microscopic study of the oviduct of the toad, before and during ovulation.

The surface features of the oviduct of the toad, Bufo melanostictus, was studied under the scanning electron microscope. The epithelial folds show regional variations, being longitudinally disposed in the upper part of the oviduct, spirally arranged in the middle and convoluted in the lower part. There is an abundance of cilia through the oviduct except in the ovisac. Goblet cells are interspersed among the epithelial cells. In between the epithelial folds are openings of tubular secretory glands. During ovulation, there is patchy loss of cilia throughout the oviduct. Most of the goblet cells are empty. On the surface, the cilia are matted together by secretory material which are laid down in layers.

Animals↗

Purification and characterization of delta helicase from fetal calf thymus.

A DNA helicase (delta helicase) which partially copurifies with DNA polymerase delta has been highly purified from fetal calf thymus. delta helicase differs in physical and enzymatic properties from other eukaryotic DNA helicases described thus far. The enzyme has an apparent mass of 57 kDa by gel filtration and is associated with polypeptides of 56 and 52 kDa by SDS-polyacrylamide gel electrophoresis. Photo-cross-linking of the purified enzyme with [alpha-32P]ATP resulted in labeling of a polypeptide of approximately 58 kDa, suggesting that the active site is present on the larger polypeptide. Unwinding of a partial duplex requires a nucleoside triphosphate which can be either ATP or dATP but not a nonhydrolyzable analogue of ATP. Other ribo- and deoxyribonucleoside triphosphates have little or no activity as cofactors. delta helicase also has DNA-dependent ATPase activity which has a relatively low Km for ATP (40 microM). delta helicase binds to single-stranded DNA but has little or no affinity for double-stranded DNA or single-stranded RNA. Similar to replicative DNA helicases from prokaryotes and the herpes simplex virus type 1 helicase-primase, delta helicase translocates in the 5'-3' direction along the strand to which it is bound and preferentially unwinds DNA substrates with a forklike structure.

Adenosine Triphosphatases↗

Central projection of the sensory fibres of the recurrent laryngeal nerve of the cat.

There have been few studies of the central projection of the sensory fibres of the recurrent laryngeal nerve into the medulla oblongata. In the present study terminal degeneration was observed in both the nucleus of the tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve after transection of the nerve and after injection of a lectin, Ricinus communis agglutinin (RCA). Degeneration was observed to be more extensive after RCA injection than after nerve transection. In both instances, however, degeneration was observed bilaterally.

Animals↗

Mycoplasma infection in children.

One hundred and eleven children with Mycoplasma pneumonia infection were studied. Their mean age was 6.2 +/- 3.1 years. The two commonest symptoms were cough (98%) and fever (95%). Only 23% of children had cough of greater than one week's duration. Ninety one per cent had positive chest signs. Radiological abnormalities were seen in 95% of chest x-ray. Complications included dermatological (10%), pleural effusion (5%), neurological disorder (3%), septicaemia (1%), bronchiectasis (1%). Two children with Down's Syndrome died. A rare case of Mycoplasma bronchitis with Reye's Syndrome was observed.

Anti-Bacterial Agents↗

Complications of severe lower respiratory tract infections in Singapore children.

Over one year period, 240 children with severe lower respiratory infection was admitted to a general paediatric department. The mortality was 1.6%. Apart from pleural effusions and skin exanthems, several major complications were noted. These were septicaemia (1), apnoea (2), encephalopathy (3), meningitis (1), Stevens Johnson Syndrome (1), bronchiectasis (1) and lung abscess (1).

Child↗