Comparison of bacterial strains and antibiotic susceptibilities in urinary isolates of spinal cord injury patients from the community and hospital.

STUDY DESIGN: A one-year epidemiological survey. OBJECTIVE: To compare bacterial strains and antimicrobial susceptibilities of urinary isolates from hospital and community spinal cord injury (SCI) patients. SETTING: A specialized SCI unit in a freestanding rehabilitation hospital. METHODS: From June 2012 through May 2013, urine cultures were obtained from all of the newly admitted patients. Bacterial strains and antimicrobial susceptibilities were compared between patients from community and hospital settings. RESULTS: The proportion of Enterobacteriaceae in the total urinary isolates from hospital-dwelling patients was smaller than that from community-dwelling patients (66.0 vs. 85.5%, P<0.001), while the proportions of Pseudomonas, Acinetobacter and Enterococcus species were relatively larger (8.7%, 6.0% and 12.0% vs. 2.8%, 0.7% and 2.8%, respectively, P<0.05). The isolates from hospital-dwelling patients showed lower susceptibility to ampicillin, amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole and all generations of cephalosporin (P<0.05), and a higher prevalence of extended-spectrum beta-lactamase (ESBL)-producers (41.7 vs. 5.4%, P<0.001), compared with those from community-dwelling patients. The susceptibility rates to levofloxacin were lower than 50% in both community and hospital-dwelling patients. CONCLUSION: Broader-spectrum antibiotics should be considered in treating nosocomial urinary tract infection (UTI) of SCI patients because of the relatively wide variety of organisms and higher frequency of antibiotic-resistant strains, including ESBL-producing Enterobacteriaceae in hospital-derived specimens. Furthermore, in areas with high prevalence of fluoroquinolone resistance, fluoroquinolones should be used with caution during empirical treatment for UTI in SCI patients.

Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues.

Successful treatment of multiple cancer types requires early detection and identification of reliable biomarkers present in specific cancer tissues. To test the feasibility of identifying proteins from archival cancer tissues, we have developed a methodology, termed direct tissue proteomics (DTP), which can be used to identify proteins directly from formalin-fixed paraffin-embedded prostate cancer tissue samples. Using minute prostate biopsy sections, we demonstrate the identification of 428 prostate-expressed proteins using the shotgun method. Because the DTP method is not quantitative, we employed the absolute quantification method and demonstrate picogram level quantification of prostate-specific antigen. In depth bioinformatics analysis of these expressed proteins affords the categorization of metabolic pathways that may be important for distinct stages of prostate carcinogenesis. Furthermore, we validate Wnt-3 as an upregulated protein in cancerous prostate cells by immunohistochemistry. We propose that this general strategy provides a roadmap for successful identification of critical molecular targets of multiple cancer types.

Incidence of c-Ki-ras activation in N-methyl-N-nitrosourea-induced mammary carcinomas in pituitary-isografted mice.

We found previously that mouse mammary epithelial cells cultured in the presence of the mammogenic hormones progesterone and prolactin and treated with the carcinogen N-methyl-N-nitrosourea produced a high frequency of hyperplastic alveolar nodules and carcinomas with squamous metaplasia upon transplantation to syngeneic mice. The majority of these mammary transformants had an activated c-Ki-ras proto-oncogene with a specific point mutation in codon 12 (G35 to A35). To determine whether these in vitro findings parallel mammary carcinogenesis in vivo, virgin female mice were pituitary isografted to increase their circulating levels of progesterone and prolactin. The pituitary isograft results in an increase in proliferation, leading to lobulo-alveolar development and differentiation of the mammary epithelial cells. Five weeks after pituitary isografting, the mice were treated with a single injection of N-methyl-N-nitrosourea (50 micrograms/g body weight). Greater than 90% of the N-methyl-N-nitrosourea-treated mice developed mammary carcinomas between 3 and 7 months after treatment. The majority (75%) of the carcinomas had histopathology identical to that of tumors induced in vitro in the presence of progesterone and prolactin. A number of the mammary cancers (17%) induced in pituitary-isografted mice also had the identical point mutation in the c-Ki-ras proto-oncogene found in the in vitro studies. These results suggest that the hormonal milieu around the time of carcinogen exposure affects not only the incidence and phenotype of the mammary transformants but also the molecular events associated with mammary carcinogenesis.

Hormone dependent and independent mammary tumor development form N-methyl-N-nitrosourea-treated rat mammary epithelial cell xenografts in the nude mouse: multiple pathways and H-ras activation.

A nude mouse mammary fat pad xenograft system was developed to examine hormone dependent and independent mammary tumorigenesis and progression from N-methyl-N-nitrosourea (MNU)-induced hyperplastic lesions. Ninety-one percent of transplanted mammary tumors grew, with an orthotopic preference, and maintained their hormone dependence, histopathology, and H-ras mutation frequency. Grafted mammary epithelial cells, from MNU-treated rats, developed normal; and hyperplastic outgrowths, representative of those found in the rat mammary gland after MNU-treatment. Hyperplasias developed into neoplasias that were both hormone dependent and independent. We demonstrate that hormone independent tumors can develop directly either from lobuloalveolar or ductal hyperplasias or from hormone dependent tumors. H-ras mutation was detected in mammary preneoplasias (4 lines) before they developed into tumors and was associated with an elevated tumorigenic potential. Our observations suggest that there are multiple histopathogenic pathways in the development and progression to hormone independent rat mammary tumors.

Expression of MAT1/PEA-15 mRNA isoforms during physiological and neoplastic changes in the mouse mammary gland.

MAT1 is a novel transforming gene which was cloned from a mouse mammary tumor induced by N-methyl-N-nitrosourea in vitro in the presence of lithium as a mitogen. Later, it was found to be identical to the 3' untranslated region (UTR) of the 2.5 kb isoform of PEA-15 (phosphoprotein enriched in astrocytes-15 kDa). We re-cloned MAT1/PEA-15 cDNAs and showed 2.5, 2.0 and 1.8 kb isoforms and confirmed MAT1 localization as reported. The 2.0 and 1.8 kb isoforms were produced by alternative splicing and alternative polyadenylation at the 3' UTR, respectively. To analyze the role of MAT1/PEA-15, we examined the expression of MAT1/PEA-15 mRNA in normal mammary tissues and in mammary tumors. The mammary gland during pregnancy, lactation and weaning showed weak but stable expression. Compared with normal mammary gland, mammary tumors showed stronger expression. Aberrant expression of MAT1/PEA-15 isoforms was found in mouse mammary epithelial cell lines, FSK7 and TM6, which lost the 2.5/2.0 and 2.5 kb isoforms, respectively. In contrast to other oncogenes like c-myc, MAT1/PEA-15 mRNA was extremely stable after actinomycin D and cycloheximide treatments suggesting that other protein expression is prerequisite for degradation of MAT1/PEA-15 mRNA. It evoked the possibility of the 3' UTR of MAT1/PEA-15 (designated as MAT1-T) as a riboregulator in mammary tumorigenesis and necessity for further analysis of human breast cancers as well as mouse mammary tumors.

Comparative analysis of MR imaging, positron emission tomography, and ictal single-photon emission CT in patients with neocortical epilepsy.

BACKGROUND AND PURPOSE: MR imaging, positron emission tomography (PET), and single-photon emission CT (SPECT) play important roles in presurgical localization of epileptic foci. However, comparative study of these imaging methods for cases of neocortical epilepsy has been limited. The purpose of this study was to compare the sensitivities of these three imaging methods for presurgical localization of neocortical epileptogenic foci. METHODS: We studied 117 consecutive patients who underwent surgery for intractable neocortical epilepsy. The pathologic substrates were neuronal migration disorder (n = 77), tumor (n = 15), and others (n = 25). MR imaging was compared retrospectively with (18)F-fluorodeoxyglucose PET and ictal technetium-99m hexamethylpropyleneamine oxime SPECT regarding their capability to correctly localize the epileptogenic foci. The pathologic findings were used as the standard of reference. RESULTS: Overall, MR imaging, PET, and ictal SPECT correctly localized the lesions for 59.8%, 77.7%, and 70.3% of the patients, respectively, with a 38% concordance rate among the three methods. PET was most sensitive (71-100%) in detecting all substrates. MR imaging was as sensitive (100%) as PET in detecting tumor but was least sensitive (48.1%) in detecting neuronal migration disorder. Ictal SPECT was more sensitive (75.8%) than MR imaging in detecting neuronal migration disorder. Patients with imaging abnormalities achieved good outcomes in 81.4% of the cases, in contrast to 59.5% for those without imaging abnormalities (P <.05). CONCLUSION: PET and ictal SPECT were overall more sensitive than was MR imaging, despite the low concordance rate and variable sensitivity depending on substrates. The detection of abnormalities by MR imaging was associated with good outcome. PET or ictal SPECT can be well used as complementary tools, particularly in cases of negative MR imaging findings.

Effectiveness of MR urography in the evaluation of kidney which failed to opacify during excretory urography: comparison with ultrasonography.

OBJECTIVE: The purpose of this study was to compare the effectiveness of MR urography (MRU) with that of ultrasonography (US) in the evaluation of urinary tract when this failed to opacify during excretory urography (EXU). MATERIALS AND METHODS: Twelve urinary tracts in 11 patients were studied. In each case, during EXU, the urinary system failed to opacify within one hour of the injection of contrast media, and US revealed dilatation of the pelvocalyceal system. Patients underwent MRU, using a HASTE sequence with the breath-hold technique; multi-slice acquisition was then performed, and the images were reconstructed using maximal intensity projection. Each set of images was evaluated by three radiologists to determine the presence, level, and cause of urinary tract obstruction. RESULTS: Obstruction was present in all twelve cases, and in all of these, MRU accurately demonstrated its level. In this respect, however, US was successful in only ten. The cause of obstruction was determined by MRU in eight cases, but by US in only six. In all of these six, MRU also successfully demonstrated the cause. CONCLUSION: MRU is an effective modality for evaluation of the urinary tract when this fails to opacify during EXU, and appears to be superior to US in demonstrating the level and cause of obstruction.

[Dr. Yoo Suk-Chang as a physician].

Dr. Yoo Suk - Chang (1900 - 1972) has been praised for his contribution to the development of the Korean society as an educator and an agricultural reformer as well as a physician. This paper describes his medical career, mainly his contribution to establish and administrate the Min - Jung Hospital (The People's Hospital) and publish a medical paper entitled Bokun Sibo (The Doctors' News) in the Colonial Period. I appreciate such his effort as the embodiment of his idea, "medical care for his people" and the medical reform in that period. I think his services as a physician correspond well with the activities against Japanese imperialism in his early age and the contribution to the education and agricultural reform in his late age. I stress that his medical achievement should not be supposed to be only his own, because it is not possible without the help of all his supporter - colleagues and the people.

[Reform of the medical education in the early 20th century America and the Flexner Report of 1910].

Reform of the medical education in the early 20th century America caused many consequences in the various aspects of the medical fields as well as the improvement of the medical education itself such as the reinforcement of the laboratory training in the basic science courses and hospital instruction in the clinical courses. The reform brought about the direct or indirect elimination of the irregular sectarian practitioners and the minority groups such as black and women from the medical market place, established the concrete position of the regular physicians in the American society, reinforced the biomedical aspects which would become the general tendency in the 20th century Western medicine. And the author stressed that the reform was neither initiated nor invoked but just accelerated by the so-called Flexner Report of 1910, rather it had been performed through the processes of the interaction and struggle between the various contradictory trends, tendencies, and forces such as american Medical Association (AMA), some leading medical educators and scientists, medical colleges, and philanthropic foundations in the socio-cultural millieu gradually moving to favor the "science".

[Vitalism and mechanism: their meanings in the milieu of the 17th and 18th centuries].

The views on the life in the early modern period (the 17th and 18th centuries) with their socio-cultural backgrounds and their meanings at that time were discussed in this paper. Those views discussed here were the dualistic, mechanistic one of Rene Descartes (1596-1650), the animistic, vitalistic one of Georg Ernst Stahl (1660-1734), and the monistic, mechanistic one of Julien Offray de la Mettrie (1709-1751). Author stressed that the processes of their view formation were influenced by the wide range of the various political and religious factors as well as the scientific, medical facts and opinions at that time, and that not only the contents of the views but also their historical contexts should be pursued in the study on the medical thoughts.

[Introduction of the modern western medicine in late Choson period (I)].

Generally it has been thought that the modern western medicine was introduced into Korea by Japanese physicians and Western missionaries. But some recent studies have revealed that in the late Choson period, Koreans and Korean government played the essential roles in the introduction of it. This paper summarized and discussed the self-reliant activities of Koreans at the time, mainly in introducing the smallpox vaccination method and establishing Jejoong-Won Hospital, the first modern hospital in Korea.

[Analysis of services of medical missionaries during the late Yi-Dynasty and the era of the Japanese occupation of Korea].

Authors investigated the services of medical missionaries during the late Yi-Dynasty and the era of the Japanese Occupation in Korea. The information and materials were got from the following primary sources: The Searching Report on the European and American Residents in Korea (1907-1942); The Korean Mission Field, Vol 1 (1905.11)-Vol 37 (1941.11); Christian Newspapers, No 1 (1915.2)-No 1128 (1937.7). Through this study we found that 280 medical missionaries came to Korea to do the medical services during the period from 1884 to 1941. Among them were 133 medical doctors, 5 dentists, 6 pharmacists and 136 nurses. And it was found that 71 medical missionaries (25%) belonged to US Northern Presbyterian Church, 50 (18%) to US Northern Methodist Church, 38 (14%) to US Southern Presbyterian Church, each 32 (11%) to US Southern Methodist Church and Society for the Proppagation of the Gospel (Anglican Church), 20 (7%) to Canadian Presbyterian Church, each 12 (4%) to Australian Presbyterian Church and Catholic Church, 9 (3%) to Seventh Day Adventist Church, and 31 Western medical personnels without connection to any missionary society. ...

[A historical study on the introduction and development of anatomy in Japan].

Japan received the Western medicine through Portuguese, Spanish and Netherlanders. Especially Netherlanders established House of Trade in Nagasaki, where doctors from their homeland stayed for several years for the health care of their tradesmen, and taught Japanese Western medicine (mainly surgery). By them Anatomy books written in western languages were introduced into Japan and some Japanese had the eager to identify the real structures of human body. At last Yamawaki Toyo became the first dissector of human body in Japan (1754) and he made his own dissection records. In 1774 Sukita Kenpaku translated the Anatomy book of Kulmus into the classic Chinese. From that time on Japanese translated a lot of Anatomy books in western languages and they themselves wrote Anatomy books of their own.

[On the education of the history of medicine in the Korean medical schools].

Authors got the following information on the present state of the education on the history of medicine in the Korean medical schools through analyzing the responses of the medical schools to the questionnaires that we sent and the related parts of The Present State of Medical Education in Medical Schools, 1994 (published by the Committee of Deans of Korean Medical Schools). In 1994, 27 of 32 medical schools (except Kon-kuk, Pusan, Yonsei, Inje and Chungnam Medical Schools) offered 41 lectures of the related subjects, of which 'History of Medicine' and 'Introduction to Medicine' were offered mainly to the premedical students, and 'Medical Ethics' largely to junior or senior students. And we found that the lectures varied widely in lecture-hours, credits, the specialties of instructors (most of the lectures were not conducted by medical historians), and so on. In the latter part of this paper (based on the discussions at the 1st Workshop for the Improvement of the Education on the History of Medicine held on the 9th of February 1995) which was focused on the goals and objectives of the lectures, credits and lecture-hours of the course, ideal style and method of the course operation, contents of the lecture, authors stressed the topic-oriented lecture and the voluntary participation of the students in the courses.

[Division and specialization of the Western European physiology].

The 19th century has been thought to be the turning point that the experimental method began to take strong root as the core to solve many physiological subjects, and the discipline of physiology got firmly fixed as the specialized one in the western Europe. Authors found the following characteristics in the process of the division and specialization of the 19th century western physiology. 1) It was the process of its separation from the discipline of anatomy that was necessary in the development of physiology as the independent, specialized division. Newly grown ideas, that there were working functions specialized study, were the important background and basis of the development of physiology as the specialized discipline. 2) It was not until the force and influence of the metaphysical concept on the living things (vitalism) grew weak that physiology could become the specialized discipline. The new materialistic concept about living things made it possible for the researchers of that time to apply the physico-chemical method in the study of physiological problems. 3) Institutionalization of the physiological research and education accelerated its development and specialization. The followings appeared in the mid-19th century: specialized professorship, division as the separated subject in the undergraduated medical school curriculum, laboratory settings for the purpose of physiological study, establishment of independent academic societies and publication of their own journals. Two main factors, namely, both the settlement of the new physiological thought and method of the very scientific nature and the institutionalization within the academic and medical societies, exerted influences on each other in the ground of the 19th century western Europe. Through that process, the discipline of physiology took root deep as the independent specialized division in the societies of science and medicine.

[History of the Korean medical journals (1945-1995) - principally on the basic science journals].

The development of Korean medical journals is summarized as the following: 1) Until the early 1960s there were not basic medical journals except Journal of the Korean Society for Microbiology (first issued in the year of 1958), so researchers of basic medical science had difficulty in publishing their articles. 2) Many of the basic medical journals made their first appearance around the mid-1960s, but the progress was not striking until the mid-1980s. 3) From the mid-1980s most of the journals rapidly developed in the aspect of quality as well as quantity. The increase in the number of issues per year and articles per an issue, and the increment of the articles written in English are remarkably found. The increase in the number of researchers, appropriate education and training, improvement of the research facilities, the growth of research fund, and increment of the international academic exchange are thought to be the main factors of such development. Besides those factors, the devotion of the editors of the journals played the important role.

[People's way to fight the epidemic diseases in the early Choson period].

Epidemic diseases in the early Choson period were big problems to the people and society. However, the weapons to the epidemic diseases were very limited at that time. There were few drugs and well-trained practitioners for people. Most people could only depend on religious means and simple folklore medicine including inhalation of specific flavor. People tried to overcome or prevent the epidemics by praying, sorcery, ornaments, runaway and isolation. In most cases, the epidemic diseases came with or broke out from the famine, severe labour (especially in civil engineering) imposed by the ruling class. The epidemics of that time are thought to be typhoid fever, epidemic typhus, or similar febrile diseases.

[Study on the transition of intestinal parasites in Korea from 1913 to 1989].

This study was performed to review the transition of infection rate and major factor in decreasing pattern of intestinal parasites infection in Korea. The results of this review study are as follows: 1) The first study on the intestinal parasites of Korean was performed by Muta (1913): he reported egg positive rate of A.lumbricoides 80%; that of T.trichiura 93%; that of Hook worm 65%. 2) After then the egg positive rates of A.lumbricoides among Korean people has been higher than 80% until and after Korean war. Owing to the biannual mass chemotherapy for 20 years by K.A.P.E. (Korea Association for Parasite Eradication), a decreasing pattern was recognized after 1960's. 3) The nationwide egg positive rate A.lumbricoides was estimated by M.H.S.A. (Ministry of Health and Social Affairs) and K.A.P.E. (1971, 1976, 1981, 1986) to be 54.89%, 41.0%, 13.0%, 2.1%. 4) The causal ageants in decreasing pattern of intestinal parasites in Korea are multifactorial such as mass chemotherapy, environmental sanitation, public education, improvement in socio-economic status, development in antihelminths, increase in use of chemical fertilizer, acceleration in national industrialization and so forth. 5) The infection rate of Korea is still higher than that of Japan and Taiwan but lower than any other countries in Southeast Asia. Nevertheless it is apparent that the present situation is not satisfactory and in this sense more effective and efficient control program is desirable.

[On the traditional surgery of Choson period (II)].

In this paper, authors discussed the classification of swelling (Chong), swelling-treatment methods (Chi-Chong) in Choson period, traditional notions about the natural history, treatment principles, popular healing methods of swelling, and depicted specially designed acupuncture instruments applied to it. Among the six professional guide books at that time, A Secret Recipe of Swelling Treatment (16th century) introduced the invasive surgical method into the narrow disease category i.e. carbuncle and furuncle, cellulitis, erysipelae, and gravitation abscess. The writer named these diseases as 'fire, stone, water, hemp, silk carbuncle', following each specific characteristics. Another surgical book, Orientation to Swelling Treatment (16th century) extended the surgical method to 'non-external' but 'looks-like swelling' diseases, such as pleurisy, tympanitis, testicular swelling, sequestrum of osteomyelitis. It is natural that some researchers doubted whether the book was used in real practice. However, the content of the book is too detailed to be regarded as an imaginary product. From these books and other materials, we found that the traditional notion of swelling was closely related with the notions of 'knotted' or 'pent in'. So 'pent-up rancor' or grudge was thought to aggravate any kind of swelling, and was tabooed or contraindicated in swelling treatment. 'Knotting in mind' was regarded as one of the principal etiologies of 'swelling and abscess formation in the body'. 'Fire in mind' was also regarded as one of the causes of phlegm aggregation resulting in swelling.

MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition.

Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this process by repressing E-cadherin and enhancing vimentin and N-cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic ductal adenocarcinomas (PDA). In this study, we show that over expression of MUC1 in pancreatic cancer cells triggers the molecular process of EMT, which translates to increased invasiveness and metastasis. EMT was significantly reduced when MUC1 was genetically deleted in a mouse model of PDA or when all seven tyrosines in the cytoplasmic tail of MUC1 were mutated to phenylalanine (mutated MUC1 CT). Using proteomics, RT-PCR and western blotting, we revealed a significant increase in vimentin, Slug and Snail expression with repression of E-Cadherin in MUC1-expressing cells compared with cells expressing the mutated MUC1 CT. In the cells that carried the mutated MUC1 CT, MUC1 failed to co-immunoprecipitate with ß-catenin and translocate to the nucleus, thereby blocking transcription of the genes associated with EMT and metastasis. Thus, functional tyrosines are critical in stimulating the interactions between MUC1 and ß-catenin and their nuclear translocation to initiate the process of EMT. This study signifies the oncogenic role of MUC1 CT and is the first to identify a direct role of the MUC1 in initiating EMT during pancreatic cancer. The data may have implications in future design of MUC1-targeted therapies for pancreatic cancer.