Results from the Survey of Antibiotic Resistance (SOAR) 2016-18 in Vietnam, Cambodia, Singapore and the Philippines: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates collected from community-acquired respiratory tract infections (CA-RTIs) in 2016-18 in four Asian countries. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: In total, 260 S. pneumoniae and 258 H. influenzae isolates were tested. Pneumococci from Vietnam (n = 161) were the least susceptible, with rates of susceptibility >90% for fluoroquinolones by CLSI breakpoints, ∼60% for amoxicillin, amoxicillin/clavulanic acid and ceftriaxone but <14% for most other agents. Pneumococcal isolates from Cambodia (n = 48) and Singapore (n = 34) showed susceptibilities ranging from ∼30% for trimethoprim/sulfamethoxazole and oral penicillin to 100% for fluoroquinolones. Among isolates of H. influenzae from Cambodia (n = 30), the Philippines (n = 59) and Singapore (n = 80), rates of susceptibility using CLSI breakpoints were >90% for amoxicillin/clavulanic acid, cephalosporins [except cefaclor in Singapore (77.5%)], macrolides and fluoroquinolones; for isolates from Vietnam (n = 89) the rates of susceptibility were >85% only for amoxicillin/clavulanic acid (95.5%), ceftriaxone (100%) and macrolides (87.6%-89.9%). Susceptibility to other antibiotics ranged from 7.9% (trimethoprim/sulfamethoxazole) to 57.3%-59.6% (fluoroquinolones) and 70.8% (cefixime). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. A limitation of the study was the small sample sizes and only one or two sites participating per country; however, since susceptibility data are scarce in some of the participating countries any information concerning antibiotic susceptibility is of value. CONCLUSIONS: Antibiotic susceptibility varied across countries and species, with isolates from Vietnam demonstrating the lowest susceptibility. Knowledge of resistance patterns can be helpful for clinicians when choosing empirical therapy options for CA-RTIs.

Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma.

Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored. Patients and methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes. Results: Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells. Conclusion: Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.

Phylogenetic group distributions, virulence factors and antimicrobial resistance properties of uropathogenic Escherichia coli strains isolated from patients with urinary tract infections in South Korea.

UNLABELLED: Urinary tract infections (UTIs) are one of the most common diseases by which humans seek medical help and are caused mainly by uropathogenic Escherichia coli (UPEC). Studying the virulence and antibiotic resistance of UPEC with respect to various phylogenetic groups is of utmost importance in developing new therapeutic agents. Thus, in this study, we analysed the virulence factors, antibiotic resistance and phylogenetic groups among various UPEC isolates from children with UTIs. The phylogenetic analysis revealed that majority of the strains responsible for UTIs belonged to the phylogenetic groups B2 and D. Of the 58 E. coli isolates, 79·31% belonged to group B2, 15·51% to group D, 3·44% to group A and 1·72% to B1. Simultaneously, the number of virulence factors and antibiotic resistance exhibited were also significantly high in groups B2 and D compared to other groups. Among the isolates, 44·8% were multidrug resistant and of that 73% belonged to the phylogenetic group B2, indicating the compatibility of antibiotic resistance and certain strains carrying virulence factor genes. The antibiotic resistance profiling of UPEC strains elucidates that the antimicrobial agents such as chloramphenicol, cefoxitin, cefepime, ceftazidime might still be used in the therapy for treating UTIs. SIGNIFICANCE AND IMPACT OF THE STUDY: As the antibiotic resistance pattern of uropathogenic Escherichia coli varies depending on different geographical regions, the antibiotic resistance pattern from this study will help the physicians to effectively administer antibiotic therapy for urinary tract infections. In addition, the frequency of virulence factors and antibiotic resistance genes among various phylogenic groups could be effectively used to draw new targets for uropathogenic Escherichia coli antibiotic-independent therapies. The study emphasizes need of public awareness on multidrug resistance and for more prudent use of antimicrobials.

Fibroblast growth factor 21 analogue LY2405319 lowers blood glucose in streptozotocin-induced insulin-deficient diabetic mice by restoring brown adipose tissue function.

AIM: To investigate the effects of LY2405319, an analogue of fibroblast growth factor 21 (FGF21), on glucose homeostasis in streptozotocin (STZ)-induced insulin-deficient mice (STZ mice). METHODS: Nine-week-old male C57BL/6J mice were administered a single intraperitoneal injection of STZ (150 mg/kg). One week later, after confirmation of hyperglycaemia, saline or LY2405319 (5 mg/kg) was injected subcutaneously daily for 4 weeks. Changes in glucose homeostasis, energy metabolism and brown adipose tissue (BAT) function were assessed. RESULTS: The STZ mice had elevated blood glucose and reduced plasma FGF21 levels, impaired glucose uptake in the BAT, and BAT mitochondria with absent or swollen cristae and fewer lipid vacuoles. LY2405319 significantly reduced blood glucose levels and this was associated with increased BAT glucose uptake and changes in gene expression and morphology, indicating improved mitochondrial lipid metabolism in the BAT. Importantly, the ability of LY2405319 to lower blood glucose in STZ mice was compromised after removing interscapular BAT. CONCLUSIONS: Our results show that LY2405319 reduces blood glucose levels in insulin-deficient diabetes by improving BAT metabolism. Additional studies investigating the therapeutic potential of FGF21 for the treatment of type 1 diabetes are warranted.

Pharmacogenomic diversity in Singaporean populations and Europeans.

Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ∼ 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes.

Genomic imbalances in key ion channel genes and telomere shortening in sudden cardiac death victims.

Sudden cardiac death (SCD) can be caused by a number of reasons. Previous works have identified the genetic causes, such as alterations in the DNA sequence, for many of these diseases. We hypothesize that some patients may show genomic imbalances and changes in the gene copy number leading to genetic instability. To clarify this, we analysed DNA samples from SCD victims using comparative genomic hybridization (CGH), a molecular cytogenetic technique that permits the genome-wide screening of chromosomal imbalances, and telomere length measurement. DNA derived from peripheral blood and heart tissue of 14 SCD cases and six apparently healthy control individuals were subjected to CGH analysis. Telomere length measurements were done by the Southern blotting method. Eight out of 14 SCD cases exhibited changes in DNA/gene copy number. CGH analysis showed variation in the gene copy number of some of the genes associated with potassium (KCNAB1, KCNH2, and KCNA4) and calcium (RyR2, ATP2A2) ions which are involved in maintaining the ionic balance of the heart. Alterations in TERC and TERT genes were also detected in SCD victims. In nine SCD victims shorter telomeres were detected. This might have resulted from excessive cellular proliferation and/or oxidative stress in these individuals. Copy number changes observed and telomere shortening detected in SCD cases would possibly explain at least some of the causes of SCD at early ages in humans. Identification of biomarkers of SCD is of great importance and thus the present study will facilitate the identification of some of the biomarkers.

Distribution of the FcgammaRIIIa 176 F/V polymorphism amongst healthy Chinese, Malays and Asian Indians in Singapore.

AIMS: To determine and compare the distribution of the FcgammaRIIIa 176 F/V polymorphism across three ethnically distinct populations (Chinese, Asian Indians and Malays) in Singapore. METHODS: The FcgammaRIIIa 176 F/V polymorphism was genotyped by direct sequencing from genomic DNA samples obtained from normal healthy Chinese, Asian Indians and Malays (n = 192 from each population). RESULTS: The allelic frequencies of the high binding affinity FcgammaRIIIa 176 V allele for Chinese, Asian Indians and Malays were 35%, 33% and 46%, respectively (F allele frequencies were 65%, 67% and 54%, respectively). Genotype distributions were found to conform to the Hardy-Weinberg law (P > 0.05) in each group. chi(2) comparisons revealed significant differences in the genotype distributions of the FcgammaRIIIa 176 V/F polymorphism of Malays from the other two populations (Chinese and Asian Indians). However, no significant difference in the genotype distributions of the FcgammaRIIIa 176 V/F polymorphism was observed between Chinese and Asian Indian populations. CONCLUSIONS: The genotype distributions of the FcgammaRIIIa 176 V/F polymorphism in healthy Malays are significantly different from both Chinese and Indians. These observations provide the fundamentals on which future disease associations may be built and also present important implications for the design of therapeutic regimens amongst various ethnic groups.

Genetic alterations in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

In the following study, we used comparative genomic hybridization (CGH) to screen and compare for genetic alterations of hepatocellular carcinoma (HCC) and intrahepatic choalgiocarcinoma (ICC). The studies showed distinctive features of genetic alterations between the two tumors. Characteristic abnormal changes for HCC were 1q gain and loss of 4q, 10q and 13q regions. In contrast, gains of 5p, 7p, 13q and 20q were more predominant in ICC. Losses of 16q, 17p, and 18q, and gain of 8q region showed a similar high frequency of incidence in both tumors. The most striking and different findings were 1q amplification in HCC and 20q gain in ICC. Our data indicate that ICC shows the pattern of genetic alterations similar to pancreatic and colorectal cancers. This suggests that the genetic alterations in tumorigenesis show a similar pattern depending on the origin of cells, not the organ.

The transforming growth factor-beta 3 knock-out mouse: an animal model for cleft palate.

The recent report of a transforming growth factor-beta 3 (TGF-beta 3) knock-out mouse in which 100 percent of the homozygous pups have cleft palate raised the question as to the potential usefulness of these animals as a model for cleft palate research. The specific aim in this study was to carefully document the anatomy of the cleft palate in the TGF-beta 3 knock-out mice as compared with wild type controls. Special attention was paid to the levator veli palatini muscle, the tensor veli palatini muscle, and their respective innervation. Because the TGF-beta 3 knock-out is lethal in the early perinatal period and because the heterozygotes are phenotypically normal, polymerase chain reaction was required to genotype the animals before mating. Time-mated pregnancies between proven heterozygotes were then delivered by cesarean section at gestational day 18.5 to prevent maternal cannibalism of homozygote pups. All delivered pups were killed and their tails processed by polymerase chain reaction to verify genotype. The heads were then fixed and sectioned in axial, coronal, or sagittal planes. Sections were stained with hematoxylin and eosin or processed for immunohistochemistry with nerve specific protein gene product 9.5 and calcitonin gene-related peptide antibodies. Sections were analyzed in a serial fashion. Nine wild type control animals were analyzed along with nine TGF-beta 3 knock-out homozygotes. Time matings between proven heterozygotes yielded wild type pups, heterozygote pups, and homozygote knock-out pups in the expected mendelian ratios (28 percent to 46 percent to 26 percent; n = 43). The results demonstrated 100 percent clefting in the homozygous TGF-beta 3 knock-out pups. Complete clefting of the secondary palate was seen in four of nine and incomplete clefting was seen in five of nine. The levator veli palatini and tensor veli palatini muscles were demonstrated coursing parallel to the cleft margin in all cleft mice. The orientation of these muscles differs from the normal transverse sling of the levator veli palatini muscle and the normal palatine aponeurosis of the tensor veli palatini muscle at the soft palate in control animals. Innervation of the levator veli palatini muscle by cranial nerve IX and the tensor veli palatini muscle by cranial nerve V were demonstrated in both cleft and control animals by use of immunohistochemistry with nerve-specific antibodies. Demonstration of a teratogen-free, reproducible animal model of clefting of the palate with a known, single-gene etiology is an important step in the systematic understanding of a congenital defect whose multifactorial etiology has hampered previous research efforts. This study presents a detailed anatomic description of such a model, including a description of the muscular anatomy and the innervation of the muscles of the palate. Because of early perinatal mortality, this model has limited applications for postnatal studies.

Laser blepharoplasty for making double eyelids in Asians.

The double-eyelid operation is a cosmetic procedure performed primarily on Asians who have no supratarsal folds. The goal in Oriental blepharoplasty is to ensure a stable double-eyelid fold with predictable and long-lasting results. Candidates for this procedure desire attractive eyelids with a natural-looking fold. Today, the CO2 laser is used as a surgical tool by plastic surgeons, and its use in cosmetic surgery has recently been expanded to blepharoplasties. We used the high-power CO2 laser (UltraPulse; Coherent, Santa Clara, Calif.) in the double-eyelid operation. Between September of 1995 and September of 1999, a total of 241 patients underwent laser double-eyelid operations at Korea University Medical Center and Dr. Choi's Aesthetic Clinic, with an average follow-up of 18 months. By using the CO2 laser, we could create a stable double-eyelid fold with long-lasting results. The rate of fold release was 2 percent, which was less than the rate using the conventional scalpel incision method. The CO2 laser contributed to a reduction in pain or discomfort after the operation; therefore, patient comfort and early recovery could be enhanced after double-eyelid surgery. In the healing of the incision line, it showed mild redness for 3 weeks, but long-term follow-up showed the scar produced by the laser appeared to be equal in quality compared with the conventional method. Laser blepharoplasty is a useful and effective method to create a stable and attractive double eyelid for Asian patients.

Glucose regulation of the acetyl-CoA carboxylase promoter PI in rat hepatocytes.

The rat acetyl-CoA carboxylase (ACC) alpha gene is transcribed from two promoters, denoted PI and PII, that direct regulated expression in a tissue-specific manner. Induction of ACC, the rate-controlling enzyme of fatty acid biosynthesis, occurs in the liver in response to feeding of a high carbohydrate, low fat diet, conditions that favor enhanced lipogenesis. This induction is mainly due to increases in PI promoter activity. We have used primary cultured hepatocytes from the rat to investigate glucose regulation of ACC expression. Glucose and insulin synergistically activated expression of ACC mRNAs transcribed from the PI promoter with little or no effect on PII mRNAs. Glucose treatment stimulated PI promoter activity in transfection assays and a glucose-regulated element was identified (-126/-102), homologous to those previously described in other responsive genes, including l-type pyruvate kinase, S(14) and fatty acid synthase. Mutation of this element eliminated the response to glucose. This region of the ACC PI promoter was able to bind a liver nuclear factor designated ChoRF that interacts with other conserved glucose-regulated elements. This ACC PI element is also capable of conferring a strong response to glucose when linked to a heterologous promoter. We conclude that induction of ACC gene expression under lipogenic conditions in hepatocytes is mediated in part by the activation of a glucose-regulated transcription factor, ChoRF, which stimulates transcription from the PI promoter. Similar mechanisms operate on related genes permitting the coordinate induction of the lipogenic pathway.

Laser punch-out for acne scars.

Patients with acne scars want smooth facial skin. However, achieving this is difficult with dermabrasion or chemical peeling. Nor can acne scars be covered with cosmetics, due to their ice-picked or cobblestone appearance. Laser resurfacing is more effective and safer than other conventional methods due to its precision with depth control and variable methods of surface cutting. Even depth resurfacing with a laser shows unsatisfactory results, therefore, for the deep-sited acne scar the cutting methods have to be changed according to the depth and pattern of the scar. For 2 years, starting in January 1996, we treated 71 patients with a high-powered CO2 laser (Ultrapulse). Different resurfacing methods were applied according to the depth and pattern of the scars. For mild depressed scars, even depth resurfacing was done. For moderate-depth acne scars, the shoulder technique was also used. For the deepest and ice-picked scars, the laser punch-out was combined. Laser resurfacing was carried out at 300-500 mJ, with two to five passes. Laser punch-out was done at 500 mJ, with three to seven continuous passes on the ice-picked scar. From the pathologic findings of acne scars showing that there was thick intradermal scar, we knew that laser punch-out was necessary for improvement of acne scars. Depth-wide, the ice-picked scars improved by over 80% and the sharp demarcated margin of the acne scar faded out. Most of the patients with acne scars were satisfied with laser resurfacing. Only six patients had a second laser treatment, with an interval of 12 months. There were no hypertrophic scars after laser resurfacing, but erythema lasted for 3-12 months. Patients taking oral retinoic acid were not contraindicated for laser resurfacing but required special caution because they had atrophic skin and delayed wound healing. Laser resurfacing is the most versatile method for acne scars, with a high-powered CO2 laser. The laser punch-out method is better than even depth resurfacing for improving deep acne scars and can be combined with the shoulder technique or even depth resurfacing according to the type of acne scar.

Involvement of a unique carbohydrate-responsive factor in the glucose regulation of rat liver fatty-acid synthase gene transcription.

Refeeding carbohydrate to fasted rats induces the transcription of genes encoding enzymes of fatty acid biosynthesis, e.g. fatty-acid synthase (FAS). Part of this transcriptional induction is mediated by insulin. An insulin response element has been described for the fatty-acid synthase gene region of -600 to +65, but the 2-3-fold increase in fatty-acid synthase promoter activity attributable to this region is small compared with the 20-30-fold induction in fatty-acid synthase gene transcription observed in fasted rats refed carbohydrate. We have previously reported that the fatty-acid synthase gene region between -7382 and -6970 was essential for achieving high in vivo rates of gene transcription. The studies of the current report demonstrate that the region of -7382 to -6970 of the fatty-acid synthase gene contains a carbohydrate response element (CHO-RE(FAS)) with a palindrome sequence (CATGTGn(5)GGCGTG) that is nearly identical to the CHO-RE of the l-type pyruvate kinase and S(14) genes. The glucose responsiveness imparted by CHO-RE(FAS) was independent of insulin. Moreover, CHO-RE(FAS) conferred glucose responsiveness to a heterologous promoter (i.e. l-type pyruvate kinase). Electrophoretic mobility shift assays demonstrated that CHO-RE(FAS) readily bound a unique hepatic ChoRF and that CHO-RE(FAS) competed with the CHO-RE of the l-type pyruvate kinase and S(14) genes for ChoRF binding. In vivo footprinting revealed that fasting reduced and refeeding increased ChoRF binding to CHO-RE(FAS). Thus, carbohydrate responsiveness of rat liver fatty-acid synthase appears to require both insulin and glucose signaling pathways. More importantly, a unique hepatic ChoRF has now been shown to recognize glucose responsive sequences that are common to three different genes: fatty-acid synthase, l-type pyruvate kinase, and S(14).

Combined laser therapy for difficult dermal pigmentation: resurfacing and selective photothermolysis.

Treating pigmented lesions of the skin, especially deep dermal pigmentations, are difficult to achieve satisfactory results without complications. To treat dermal pigmentations, such as nevus of Ota and congenital nevus, the combined therapy of a resurfacing laser (CO2) and a selective photothermolytic laser (the Q-Switched Ruby Laser [QSRL]) was tried, and the results were compared with those treated with the QSRL alone. Combined laser therapy has been performed in 47 patients with nevus of Ota since 1995. The mean treatment period was 6 months and the mean number of treatment was five. Of 47 patients, 46 (98%) showed excellent results. To treat congenital nevus, combined laser therapy was used in 15 patients, and 12 (80%) showed good to excellent results. By combining resurfacing and selective lasers, the treatment period has been reduced by 2 to 3 months, and the number of treatments has been reduced two- to threefold. Furthermore, treatment of congenital nevus has become possible, which was not the case with the QSRL alone. The Er:YAG laser can be used for resurfacing instead of the CO2 laser because it causes less thermal damage and faster wound healing.

Genetic Alterations in Gastric Carcinomas and Adjacent Mucosa Detected by Comparative Genomic Hybridization (CGH).

PURPOSE: Comparative genomic hybridization (CGH) was used to detect any amplified or deleted chromosomal regions in tumors by mapping their locations on normal metaphase chromosomes. METERIALS AND METHODS: Twenty-six gastric carcinomas and their adjacent mucosa were screened for chromosomal aberrations using CGH. RESULTS: All carcinomas had chromosomal aberrations, and chromosomal material was more likely to be gained than lost. Ten out of 26 adjacent mucosa had chromosomal aberrations, and a gain was less frequently observed than a tumor (1.6/2.6). The most common gains were detected on 13q (58.3%), 8q (30.8%), 6q (27.0%), and 20p (19.2%), while the most frequent losses were detected on 17p (38.5%) and 16q (7.2%). The most commonchromosomal aberrations in the adjacent mucosa were a gain of 13q (11.5%) and a loss of 17q (11.5%). The tumors had more chromosomal gains of 2q, 3q, and 13q and more losses of 17p and 16q than the adjacent mucosa. CONCLUSION: S: The most common gain in the tumors was detected on 13q, 8q, 6q, and 20p, and the most frequent loss was on 17p and 16q. While CGH may be useful in predicting the prognosis or therapeutic decision of gastric carcinomas, further study of several candidate genes, such as DP1, FLT1, c-myb, AIB1, BTAK, is needed to clarify gastric carcinogenesis and its progression.

Glucose and insulin function through two distinct transcription factors to stimulate expression of lipogenic enzyme genes in liver.

Transcription of a number of genes involved in lipogenesis is stimulated by dietary carbohydrate in the mammalian liver. Both insulin and increased glucose metabolism have been proposed to be initiating signals for this process, but the pathways by which these effectors act to alter transcription have not been resolved. We have previously defined by electrophoretic mobility shift assay a factor in nuclear extracts from rat liver, designated the carbohydrate-responsive factor (Cho- RF), that binds to liver-type pyruvate kinase and S(14) promoters at sites critical for regulation by carbohydrate. The sterol regulatory element binding protein-1c (SREBP-1c) has also emerged as a major transcription factor involved in this nutritional response. In this study, we examined the relationship between SREBP-1c and ChoRF in lipogenic gene induction. The two factors were found to possess distinct DNA binding specificities both in vitro and in hepatocytes. Reporter constructs containing binding sites for ChoRF were responsive to glucose but not directly to insulin. On the other hand, reporter constructs with an SREBP-1c site responded directly to insulin. The S(14) gene possesses binding sites for both ChoRF and SREBP, and both sites were found to be functionally important for the response of this promoter to glucose and insulin in hepatocytes. Consequently, we propose that SREBP-1c and ChoRF are independent transcription factors that mediate signals generated by insulin and glucose, respectively. For many lipogenic enzyme genes, these two factors may provide an integrated signaling system to support the overall nutritional response to dietary carbohydrate.

Characterization of chromosomal breakpoints in an ALL patient using cross-species color banding.

Cross-species color-banded karyotype (Rx-FISH) results were compared with those of conventional G-banded metaphases from the same sample. Breakpoints and karyotype were confirmed as 46,XX,t(8;22)(q24;q11), der(9)t(1;9)(q21;p13) through the novel technology of cross-species color banding in an acute leukemic patient (ALL, L3); the karyotype was 46,XX,t(8;22)(q24;q11),der(9)t(1;9)(q25;p24) by conventional G-banding.

A new classification of male pattern baldness and a clinical study of the anterior hairline.

Male pattern baldness is the most common type of baldness occurring after the age of puberty. Various surgical techniques for hair reconstruction have been introduced. Since the Norwood classification method is too detailed and complicated to be used for various surgical operations, there is a strong need for a simpler classification. Selection of the shape and height of the frontal and temporal hairlines is important in hair restoration surgery. But due to lack of standard measures, there have been difficulties in performing surgical operations for male pattern baldness. We therefore studied the prevalence of male pattern baldness in 1731 Korean men according to age and types, based on the new classification method, between September 1995 and February 1996. At the same time, we also measured the average heights of the frontal and temporal hairlines and identified the morphology and the incidence of various types of anterior hairlines in 108 normal male adults. There are six types of male pattern baldness according to the new classification method. One peculiar type could not be classified by the Norwood classification method. The six types are designated types M, C, O, U, MO, and CO. In the morphological classification of the anterior hairline, the linear type was most common (70.37%). The heights of the frontal and temporal hairlines were 6.53 cm for the median line, 5.9 cm (left side) and 5.95 cm (right side) for the paramedian line, 8.49 cm (left and right side) for the temporal recession line, and 6.61 cm (left side) and 6.62 cm (right side) for the temporal hairline. The authors present the research outcomes as baselines that can be used for hair restoration surgery and further study of male pattern baldness.

Genetic alterations of gastric cancer: comparative genomic hybridization and fluorescence In situ hybridization studies.

Genetic changes leading to the development of gastric cancers are still in dispute. In the following study, we used comparative genomic hybridization (CGH) to screen for DNA copy number changes along all chromosomes in 37 gastric carcinomas, and fluorescence in situ hybridization (FISH) with the C-MYC and TP53 probes in 14 cases for comparison. The aim of this study was to identify those chromosome regions that contain genes important for the development of gastric carcinomas and to identify genetic markers associated with tumor progression. The most often involved gains were 2q, 7pq, 8pq, 13q, 17q, 18q, and 20pq. The most commonly deleted regions were 17p. The pattern of genetic changes was different depending on the existence of nodal metastasis and histologic types. Gains in 8q and losses in 17p were the most common features of the CGH changes. However, only 3 among the available 10 cases (30%) showed an amplification of the C-MYC gene by FISH. Allelic loss of TP53 was found in 2 of 4 cases (50%). This difference might be due to another rearrangement of these 2 genes which cannot be detected by FISH, or other possible genes in that area may be involved in the tumorigenesis and nodal metastasis of gastric carcinomas.