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Biomedical subjects

M Chin

Publications and source records attributed to M Chin.

At least 19 recordsLinked to original sources

Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19.

Hypercalcemia is relatively rare but clinically important complication in childhood leukemic patients. To clarify the clinical characteristics, mechanisms of hypercalcemia, response to management for hypercalcemia, incidence of t(17;19) and final outcome of childhood acute lymphoblastic leukemia (ALL) accompanied by hypercalcemia, clinical data of 22 cases of childhood ALL accompanied by hypercalcemia (>12 mg/dl) reported in Japan from 1990 to 2005 were retrospectively analyzed. Eleven patients were 10 years and older. Twenty patients had low white blood cell count (<20 x 10(9)/l), 15 showed hemoglobin> or =8 g/dl and 14 showed platelet count > or =100 x 10(9)/l. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcemia was confirmed in 11 of the 16 patients in whom elevated-serum level or positive immunohistochemistry of PTHrP was observed. Hypercalcemia and accompanying renal insufficiency resolved quickly, particularly in patients treated with bisphosphonate. t(17;19) or add(19)(p13) was detected in five patients among 17 patients in whom karyotypic data were available, and the presence of E2A-HLF was confirmed in these five patients. All five patients with t(17;19)-ALL relapsed very early. Excluding the t(17;19)-ALL patients, the final outcome of ALL accompanied by hypercalcemia was similar to that of all childhood ALL patients, indicating that the development of hypercalcemia itself is not a poor prognostic factor.

Adolescent↗

Laparoscopic resection of colorectal cancer.

Laparoscopic surgery has revolutionised procedures such as cholecystectomy since its inception in the 1980s. After initial enthusiasm with laparoscopic colorectal resections in the early 1990s, resection of colorectal malignancy was largely abandoned outside clinical trials because of reports of inferior oncological outcomes including local and port-site recurrence. More recently, however, an increasing number of reports have demonstrated that laparoscopic surgery for colorectal cancer though technically demanding is feasible, and the results of large multi-centred randomised trials showing oncological equivalence are becoming available. Technological advances in laparoscopic equipment along with the increasing skills and experience of laparoscopic surgeons have extended the indications and reduced the contraindications for laparoscopic colectomy. This, along with the use of fast- track protocols is changing the way we manage patients. The future of laparoscopic colorectal surgery is assured, driven not only by the physical benefits to the patient in the short and medium term, the reduced financial burden on in-patient stay, and post-operative return to work, but also increasing patient demand. This in turn requires that surgeons should ensure high quality training and operative competence to maintain the high standards achieved by the pioneers in this field.

Colorectal Neoplasms↗

The effect of haematopoietic stem cell transplant on papules with 'pebbly' appearance in Hunter's syndrome.

BACKGROUND: Hunter's syndrome is associated with several cutaneous findings. For instance, papules with 'pebbly' appearance are a specific marker for the disease. However, it remains uncertain whether they disappear after haematopoietic stem cell transplant (HSCT). OBJECTIVES: To investigate the papules with 'pebbly' appearance before and after HSCT in infants with Hunter's syndrome, and to clarify the effect of HSCT on papules. PATIENTS: We observed five Japanese boys with Hunter's syndrome who had received HSCT at 4-11 years of age. RESULTS: The post-HSCT physical examinations revealed that papules disappeared completely within 35 days after the transplant with progressive reduction of cutaneous tightness in all the patients. Histochemical findings showed that papules contained a large amount of hyaluronic acid in the extracellular materials of the dermis and sulphated acid mucopolysaccharides in dermal fibroblasts before HSCT. CONCLUSIONS: These results suggest that papules with a 'pebbly' appearance fade away through the digestion of a large amount of hyaluronic acid in cutaneous tissues by normal tissue histiocytes or enzymes of donor origin at an early stage after HSCT.

Child↗

Significance of extensive Mongolian spots in Hunter's syndrome.

BACKGROUND: The importance of early diagnosis in infants with a mild form of Hunter's syndrome should be emphasized. If applied sufficiently early, haematopoietic stem cell transplantation (HSCT) or recombinant enzyme therapy may improve the prognosis. At present, however, diagnosis of the mild form of Hunter's syndrome tends to be delayed, especially in infants with relatively normal intelligence. OBJECTIVES: To investigate the occurrence of Mongolian spots in infants with Hunter's syndrome, and to clarify the relationship between the Mongolian spots and Hunter's syndrome clinically and histopathologically. METHODS: Seven Japanese boys with Hunter's syndrome who had received HSCT at ages 4-11 years were observed. The cutaneous manifestations of Mongolian spots before HSCT were evaluated, and compared with those after HSCT. In two patients, the hyperpigmentation from the Mongolian spots was examined by light and electron microscopy. RESULTS: Pre-HSCT observation revealed that all the patients had an extensive Mongolian spot. These were present at birth and have shown no signs of resolution during the post-HSCT period. Electron microscopic findings showed that pigment-bearing dermal melanocytes contained many free melanosomes in stage IV. These were surrounded by extracellular sheaths and encircled by elastic fibres. CONCLUSIONS: Our results indicate a strong clinical correlation between the extensive Mongolian spots and Hunter's syndrome. Ultrastructural findings also clearly suggest that the hyperpigmentation is a long-lasting symptom. The recognition of the extensive Mongolian spots is essential as it may lead to early diagnosis in patients with a mild form of Hunter's syndrome.

Child↗

Cell death by apoptosis is a feature of the rheumatoid nodule.

OBJECTIVE: To examine the site and extent of apoptosis in the rheumatoid nodule and to determine whether this process make a significant contribution to the control of inflammation in the rheumatoid nodule as in other granulomas. METHODS: Nine nodules and seven synovial membranes were examined by terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) in situ and a subset was further examined by DNA electrophoresis. The phenotype of apoptotic cells was identified using monoclonal antibodies and immunohistology. RESULTS: Apoptosis occurred in all zones of the nodule and, except in one case, was not focused adjacent to the necrotic centre. Apoptosis occurred in 3.5 (4.5)% (mean (SD)) of cells in the nodule and 3.6 (3.1)% of cells in synovial membranes. Apoptosis was more common in nodule T cells (4.1 (2.9)%) than fibroblasts (1.0 (1.4)%), p = 0.01. Among macrophages 3.2 (4.7)% were apoptotic. Banding of DNA consistent with apoptosis was seen in two of three nodules examined. CONCLUSION: Apoptosis occurs at a low level in the nodule, similar to the synovial membrane. The results suggest that two modes of cell death occur in the nodule: apoptosis, which occurs throughout the nodule; and necrosis, which is concentrated near the necrotic centre. Apoptosis was more common in infiltrating inflammatory cells than in resident fibroblasts. These results are consistent with the proposal that apoptosis of infiltrating inflammatory cells is important in controlling accumulation of cells in the rheumatoid nodule as has been established in experimental granulomas.

Adult↗

Long-term outcome after allogeneic bone marrow transplantation for hematological malignancies with non-remission status. Results of a single-center study of 24 patients.

To investigate the problem of allogeneic bone marrow transplantation (allo-BMT) for advanced stage patients, we retrospectively analyzed 24 consecutive patients who underwent allo-BMT in the non-remission stage. Twenty-four patients (19 males and 5 females) with acute leukemia, chronic myelogenous leukemia, and malignant lymphoma underwent allo-BMT. The patients had a median age of 30 years. There were eight cases of acute myelogenous leukemia (AML), six cases acute lymphocytic leukemia (ALL), nine cases of chronic myelogenous leukemia (CML), and one case of Burkitt's lymphoma. The 3-year overall survival rate was 22.5%, with a median survival time of 206 days in AML, 345 days in ALL, and 363 days in CML. Overall survival was associated with a recovery of platelets of less than 30 days and an acute graft-versus-host disease (acute GVHD) presence of less than grade II ( p=0.042). Fourteen patients died of transplantation-related diseases. Our important problem is to decrease transplantation-related deaths in allo-BMT during the non-remission stage, and longer survival can be expected with better pretreatment and prophylaxis for GVHD. In addition, the selection of the source of hematopoietic stem cell transplantation at an optimal time is considered to be another problem to be approached.

Adolescent↗

t(10;11)-acute leukemias with MLL-AF10 and MLL-ABI1 chimeric transcripts: specific expression patterns of ABI1 gene in leukemia and solid tumor cell lines.

The recurrent translocation t(10;11) is associated with acute myeloid leukemia (AML). The AF10 gene on chromosome 10 at band p12 and MLL at 11q23 fuse in the t(10;11)(p12;q23). Recently, we have identified ABI1 as a new partner gene for MLL in an AML patient with a t(10;11)(p11.2;q23). The ABI1 is a human homologue of the mouse Abl-interactor 1 (Abi1), encoding an Abl-binding protein. The ABI1 protein exhibits sequence similarity to homeotic genes, and contains several polyproline stretches and a src homology 3 (SH3) domain. To clarify the clinical features of t(10;11)-leukemias, we investigated 6 samples from acute leukemia patients with t(10;11) and MLL rearrangement and detected MLL-AF10 chimeric transcripts in 5 samples and MLL-ABI1 in one. The patient with MLL-ABI1 chimeric transcript is the second case described, thus confirming that the fusion of the MLL and ABI1 genes is a recurring abnormality. Both of the patients with MLL-ABI1 chimeric transcript are surviving, suggesting that these patients have a better prognosis than the patients with MLL-AF10. To investigate the roles of AF10 and ABI1 further, we examined the expression of these genes in various cell lines and fresh tumor samples using the reverse transcriptase-polymerase chain reaction method. Although AF10 was expressed in almost all cell lines similarly, the expression patterns of ABI1 were different between leukemia and solid tumor cell lines, suggesting the distinctive role of each isoform of ABI1 in these cell lines. We also determined the complete mouse Abi1 sequence and found that the sequence matched with human ABI1 better than the originally reported Abi1 sequence. Further functional analysis of the MLL-AF10 and MLL-ABI1 fusion proteins will provide new insights into the leukemogenesis of t(10;11)-AML.

Acute Disease↗

[Magnetic resonance imaging findings of postresuscitation encephalopathy: sequential change and correlation with clinical outcome].

OBJECTIVE: The purpose of this study was to describe the findings of sequential magnetic resonance imaging (MRI) in postresuscitation encephalopathy. Although its outcome is known to be overwhelming, but its acute findings by variable imaging methods are subtle and show only limited values. The correlation of the findings of MRI with clinical outcome were also analyzed. METHODS: Twelve patients with global cerebral anoxia who underwent MRI with conventional and diffusion-weighted imaging were enrolled in this study. Compared with normal MRI images, abnormal signal regions were checked and described in cortex, basal ganglia and white matter. Also medical records were carefully reviewed to study the cause, the time necessary for resuscitation and long term clinical outcome. RESULTS: The earliest finding was obtained by diffusion-weighted image less than 24 hours (acute period) in bilateral cerebral cortex as bright high signal intensity regions. Similar abnormality of bright high signal area in FLAIR and T 2 was followed according to the time elapsed in early subacute period (1-13 days). Succeedingly, white matter was involved and laminar necrosis in cortical area was observed in late subacute period (14-20 days). Finally, diffuse brain atrophy and obtundation of gray-white matter junction were seen in chronic stage (after 21 days). These MR findings were coincided well with histopathological findings reported in literatures. The poor outcome was closely and significantly correlated with abnormality in MR images. CONCLUSION: MRI was a useful diagnostic modality to diagnose the whole brain ischemic encephalopathy and to predict the prognosis.

Adult↗

Heterogeneous sympathetic innervation influences local myocardial repolarization in normally perfused rabbit hearts.

BACKGROUND: Heterogeneity of sympathetic innervation is thought to contribute to the potential for fatal arrhythmia. However, little is known about the effects of heterogeneous innervation on repolarization. METHODS AND RESULTS: To assess this relationship, we measured activation recovery intervals (ARIs) from 64 epicardial sites in 11 rabbits studied 2 weeks after regional denervation produced by phenol and 4 sham-operated rabbits. ARI results were compared with the distribution of sympathetic innervation measured from 3D reconstructions of serial autoradiographs of [(125)I]metaiodobenzylguanidine and (99m)Tc-sestamibi. ARIs were recorded during baseline sinus rhythm, norepinephrine (NE) infusion (0.1 microg. kg(-1). min(-1)), and left stellate ganglion stimulation (SS). NE shortened ARI in 98% of electrodes in the denervated region. The degree of ARI shortening and dispersion increased (P<0.001 and P<0.01, respectively) as denervation became more severe. SS shortened ARI in 30% of electrodes in the denervated area, with increased shortening and dispersion related to increased severity of denervation (P<0.01). SS prolonged ARI in 70% of electrodes in the denervated area, with no correlation with severity of denervation. CONCLUSIONS: The magnitude and dispersion of local repolarization responses are related to the severity of denervation, as well as the type of stimulation: neural (SS) versus humoral (NE). The differences may relate to the concentration of NE released.

3-Iodobenzylguanidine↗

The high level of hCDC10 gene expression in neuroblastoma may be associated with favorable characteristics of the tumor.

BACKGROUND: The biological behavior of neuroblastomas detected through mass screening (MS, </=1 year of age) and that of mass screening-negative later-presenting (MSN, >1 year of age) neuroblastomas have been reported to differ in many studies. To investigate the biological differences between these two groups, we analyzed the differences in mRNA profiles. MATERIALS AND METHODS: We analyzed the mRNA profiles of MS and MSN neuroblastomas using differential display, and cloned and sequenced the bands differentially expressed between these two groups. Using the RNA analysis by polymerase chain reaction (RNA-PCR) method, the relative amount of mRNA in tumor tissue in each sample was measured. Associations between relative amount of mRNA and clinical and genetic variables related to patient prognosis and the effect of the level of mRNA expression on survival probability were investigated using statistical methods. RESULTS: Using differential display and RNA-PCR, we found that the mRNA for the human homologue of the yeast cdc10 gene (hCDC10) identified in Saccharomyces cerevisiae was expressed at a higher level in the MS group of patients than in the MSN group of patients (0.554 +/- 0.197 for MS neuroblastoma, n = 24 and 0.244 +/- 0.179 for MSN neuroblastoma, n = 10, P < 0.01), and this difference was suggested to be independent of the histologic subtype of tumor. A high level of hCDC10 mRNA expression in neuroblastomas (relative amount of hCDC10 mRNA > 0.35) was also suggested to be associated with younger age at diagnosis (</=1 year of age, P < 0.01), favorable clinical stage (I, II, and IVs, P < 0. 01), and favorable histology in the Shimada classification (P < 0. 01), whereas a low level of hCDC10 mRNA expression (relative amount of hCDC10 mRNA </=0.35) was suggested to be associated with the progression of clinical stage (P < 0.01) and N-myc gene amplification (>1 copy, P < 0.05). Patients with neuroblastomas with a high level of hCDC10 mRNA expression were suggested to have a better prognosis than those with a low level of hCDC10 mRNA expression (P < 0.01). CONCLUSIONS: A high level of hCDC10 mRNA expression in neuroblastomas may be associated with favorable clinical and biological characteristics, and the expression of hCDC10 mRNA in neuroblastomas may affect the clinical and biological characteristics of this type of tumor.

Cell Cycle Proteins↗

Effects of metal phytoextraction practices on the indigenous community of arbuscular mycorrhizal fungi at a metal-contaminated landfill.

Phytoextraction involves use of plants to remove toxic metals from soil. We examined the effects of phytoextraction practices with three plant species (Silene vulgaris, Thlaspi caerulescens, and Zea mays) and a factorial variation of soil amendments (either an ammonium or nitrate source of nitrogen and the presence or absence of an elemental sulfur supplement) on arbuscular mycorrhizal (AM) fungi (Glomales, Zygomycetes) at a moderately metal-contaminated landfill located in St. Paul, Minn. Specifically, we tested whether the applied treatments affected the density of glomalean spores and AM root colonization in maize. Glomalean fungi from the landfill were grouped into two morphotypes characterized by either light-colored spores (LCS) or dark-colored spores (DCS). Dominant species of the LCS morphotype were Glomus mosseae and an unidentified Glomus sp., whereas the DCS morphotype was dominated by Glomus constrictum. The density of spores of the LCS morphotype from the phytoremediated area was lower than the density of these spores in the untreated landfill soil. Within the experimental area, spore density of the LCS morphotype in the rhizosphere of mycorrhizal maize was significantly higher than in rhizospheres of nonmycorrhizal S. vulgaris or T. caerulescens. Sulfur supplement increased vesicular root colonization in maize and exerted a negative effect on spore density in maize rhizosphere. We conclude that phytoextraction practices, e.g., the choice of plant species and soil amendments, may have a great impact on the quantity and species composition of glomalean propagules as well as on mycorrhiza functioning during long-term metal-remediation treatments.

Biodegradation, Environmental↗

Knowledge, attitudes and practices of anabolic steroid usage among gym users in Trinidad.

Self-administered questionnaires were completed by 1062 gym-users in 14 gyms in Trinidad from February 1997 to July 1997 to determine the knowledge, attitudes and practices regarding anabolic steroids (AS). Five hundred and sixty (52.7%) females and 502 (48.3%) males completed the questionnaire. Half of the total sample were individuals in the 20 to 29 year age group. From the 17 questions that tested knowledge about AS, the median number of correct responses was 7 with a mode of 8. Increased muscle mass was correctly identified as one of the effects of AS by 841 respondents (79.2%), while 249 (23.6%) of the total sample thought asthma was treated with AS. Most (872 or 82.1%) felt that their knowledge about AS was inadequate and 700 (66.0%) were of the opinion that AS should be banned from use in competitive sports. Similarly, 733 (70.0%) of the gym-users thought AS should only be available by prescription. Thirty respondents reported having used AS (2.9%, 95% CI 2.0-4.1). The prevalence of AS use was higher among males than females (p < 0.001). Improvement of physical appearance and not competitive advantage in sport was the main reason cited for AS use. Anabolic steroid users knew more about the adverse effects of AS than non-AS users but the therapeutic uses of AS were comparatively less well known. This study demonstrated a general lack of knowledge concerning AS use and that a small but significant proportion of persons using gyms admitted to abusing AS.

Adult↗

Karyotypic analyses of hepatoblastoma. Report of two cases and review of the literature suggesting chromosomal loci responsible for the pathogenesis of this disease.

Two cases of fetal hepatoblastoma with unique karyotypic changes are described. One was a 17-month-old boy with multiple unbalanced chromosomal translocations, resulting in four types of derivative chromosomes involving chromosomal loci at 1q21, 1q32, 2q23, 6q27, 7p22, and 21p12, partial tetrasomy of 1q, partial trisomy of 2q, and partial monosomy of 21p. The clonal karyotype of this tumor was 46,XY,der(2)t(1;2)(q32;q37), der(6)t(1;6)(q12;q27), der(7)t(2;7)(q23;p22), der(21)t(2;21) (q23;p12). In the other case, a 4-year-old girl, karyotypic analyses revealed trisomy 2 and 8, and the clonal karyotype of this case was 48,XX,+2,+8. Review of these cases together with previous reports suggested the significance of chromosomal changes including numerical abnormalities of 1q, 2(or 2q), 20, and 8 (or 8q), and breakage of 1q and 2q in the development of hepatoblastoma. The results presented herein underscore the significance of numerical abnormalities of chromosomal regions 1q and 2q and of chromosome 8 in the development of hepatoblastoma, in addition to abnormalities of 6q27, 7p22, and 21p12-13 as other chromosomal loci that may be responsible for the pathogenesis of this embryonal type of tumor.

Child, Preschool↗

Effects of long-term cryopreservation on hematopoietic progenitor cells in umbilical cord blood.

There is considerable interest in developing banks of frozen umbilical cord blood cells for transplants but it is uncertain how long frozen cells survive. Our objective was to determine the recovery of frozen umbilical cord blood cells. We quantitated recovery of hematopoietic progenitor cells (CFU-GM, BFU-E, and CFU-GEMM) from frozen umbilical cord blood cells stored for up to 12 years. Decay rates of CFU-GM, BFU-E and CFU-GEMM (d, expressed as percent of viable cells recovered (95% confidence interval) were 0.9930 (0.9889-0.9970), 0.9840 (0.9769-0.9911) and 0.9817 (0.9707-0.9927). Time-dependent recoveries, calculated by the formula d(k), (k = frozen storage interval in years) were >90% at 10 years. We conclude that frozen cord blood cells can be stored safely for prolonged intervals without substantial loss in hematopoietic progenitor cells.

Cryopreservation↗

Advancement of the midface using distraction techniques.

Fourteen patients underwent Le Fort III midface advancement using distraction techniques. Six have cephalometric documentation extending beyond 1 year postoperatively, and the positions of cephalometric points A and orbitale over time are reported here. Excellent stability of advancement at the occlusal level and some relapse at the level of orbitale are documented. Elimination or diminution of obstructive sleep apnea occurred in all patients so affected, and one of two patients with tracheostomy has been decannulated. Speech effects have been mild or transient. No untoward effects on extraocular muscle function have occurred.

Cephalometry↗

Digital Imaging as a Detection Method for a Fluorescent Protease Assay in 96-Well and Miniaturized Assay Plate Formats.

The demand to increase throughput in HTS programs, without a concomitant addition to costs, has grown significantly during the past few years. One approach to handle this demand is assay miniaturization, which can provide greater throughput, as well as significant cost savings through reduced reagent costs. Currently, one of the major challenges facing assay miniaturization is the ability to detect the assay signal accurately and rapidly in miniaturized formats. Digital imaging is a detection method that can measure fluorescent or luminescent signals in these miniaturized formats. In this study, an imaging system capable of detecting the signal from a fluorescent protease assay in multiple plate formats was used to evaluate this detection method in an HTS environment. A direct comparison was made between the results obtained from the imaging system and a fluorescent plate reader by screening 8,800 compounds in a 96-well plate format. The imaging system generated similar changes in relative signal for each well in the screen, identified the same active compounds, and yielded similar IC(50) values as compared to the plate reader. When a standard protease inhibitor was evaluated in 96-, 384-, 864-, and 1536-well plates using imaging detection, similar IC(50) values were obtained. Furthermore, similar dose-response curves were generated for the compound in 96- and 384-well assay plates read in a plate reader. These results provide support for digital imaging as an accurate and rapid detection method for high-density microtiter plates.

Journal Article↗