Prdm1 overexpression causes a photoreceptor fate-shift in nascent, but not mature, bipolar cells.

The transcription factors Prdm1 (Blimp1) and Vsx2 (Chx10) work downstream of Otx2 to regulate photoreceptor and bipolar cell fates in the developing retina. Mice that lack Vsx2 fail to form bipolar cells while Prdm1 mutants form excess bipolars at the direct expense of photoreceptors. Excess bipolars in Prdm1 mutants appear to derive from rods, suggesting that photoreceptor fate remains mutable for some time after cells become specified. Here we tested whether bipolar cell fate is also plastic during development. To do this, we created a system to conditionally misexpress Prdm1 at different stages of bipolar cell development. We found that Prdm1 blocks bipolar cell formation if expressed before the fate choice decision occurred. When we misexpressed Prdm1 just after the decision to become a bipolar cell was made, some cells were reprogrammed into photoreceptors. In contrast, Prdm1 misexpression in mature bipolar cells did not affect cell fate. We also provide evidence that sustained misexpression of Prdm1 was selectively toxic to photoreceptors. Our data show that bipolar fate is malleable, but only for a short temporal window following fate specification. Prdm1 and Vsx2 act by stabilizing photoreceptor and bipolar fates in developing OTX2+ cells of the retina.

Simultaneous deletion of Prdm1 and Vsx2 enhancers in the retina alters photoreceptor and bipolar cell fate specification, yet differs from deleting both genes.

The transcription factor OTX2 is required for photoreceptor and bipolar cell formation in the retina. It directly activates the transcription factors Prdm1 and Vsx2 through cell type-specific enhancers. PRDM1 and VSX2 work in opposition, such that PRDM1 promotes photoreceptor fate and VSX2 bipolar cell fate. To determine how OTX2+ cell fates are regulated in mice, we deleted Prdm1 and Vsx2 or their cell type-specific enhancers simultaneously using a CRISPR/Cas9 in vivo retina electroporation strategy. Double gene or enhancer targeting effectively removed PRDM1 and VSX2 protein expression. However, double enhancer targeting favored bipolar fate outcomes, whereas double gene targeting favored photoreceptor fate. Both conditions generated excess amacrine cells. Combined, these fate changes suggest that photoreceptors are a default fate outcome in OTX2+ cells and that VSX2 must be present in a narrow temporal window to drive bipolar cell formation. Prdm1 and Vsx2 also appear to redundantly restrict the competence of OTX2+ cells, preventing amacrine cell formation. By taking a combinatorial deletion approach of both coding sequences and enhancers, our work provides new insights into the complex regulatory mechanisms that control cell fate choice.

Aptamers-in-liposomes for selective and multiplexed capture of small organic compounds.

Small, organic, toxic compounds are not well eliminated by water-treatment systems and eventually become concentrated in the human body. In this study, liposomes are employed to house aptamers with their own binding buffer. When small, organic, toxic compounds in water pass through a liposome barrier, only the target molecules are captured by the DNA aptamers inside the liposomes. The capture efficiency is not high when DNA aptamers are used in tap water. When DNA aptamers in liposomes are used, the capture efficiency increases more than 80%. The simultaneous and selective elimination of target toxicants is successfully performed for tap-water samples containing toxicant mixtures.

1991 cancer incidence in Seoul, Korea: results of the Implementation Study of the Seoul Cancer Registry.

This article presents the results of the Implementation Study of the Seoul Cancer Registry, which started in July, 1991 as a population based cancer registry in Seoul, Korea. The completeness and validity of the registered data were evaluated using Mortality/Incidence ratio (M/I ratio), Histologically Verified Cases (HV%), Primary Site Uncertain (PSU%), and Age Unknown (Age UNK%). Owing to the additional active surveillance, the completeness of the data turned out to be fairly acceptable, except for the aged over 75(Mortality/Incidence ratio was over 100%). Eventhough the Seoul cancer registry(SCR) has further way to go in the completeness especially among elderly persons, the validity of SCR data was also acceptable in terms of HV%, PSU%, and Age UNK%. However, PSU% and Age UNK% might need to be further reduced to be comparable with other well established cancer registries. The age standardized incidence rates(ASR) of all cancers between July 1, 1991 and June 30, 1992 were 232.4/100,000 in males and 147.9/100,000 in females. The top five major sites of cancers in Seoul were the stomach, liver, lung, colo-rectum, and bladder in order in males, and the uterine cervix, stomach, breast, colo-rectum, and liver in females. Those 5 cancer sites comprised 68.9% and 64.7% of the total cancer incidence in males and females, respectively.

Glutathione S-transferase in intestine, liver and hepatic lesions of mummichog (Fundulus heteroclitus) from a creosote-contaminated environment.

Cytosolic glutathione S-transferase (GSH transferase) activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was elevated approximately three to four-fold in intestine and liver of mummichog (Fundulus heteroclitus) collected from a creosote-contaminated site in the Elizabeth River, Virginia. Intestinal GSH transferase activity at the most heavily contaminated site, at a moderately contaminated site and at a relatively clean site averaged 3.64, 2.83 and 1.11µmoles/min/mg respectively, while values for liver at these sites averaged 2.84, 1.75 and 0.93µmoles/min/mg. In addition, densitometric tracings of sodium dodecylsulfate-polyacrylamide gels of intestine and liver cytosol revealed a similar trend in the staining intensity of a 25.8 kD protein band, which lies within the molecular weight range of GSH transferase subunits. Activity in putative preneoplastic and neoplastic hepatic lesions of fish collected from the creosote-contaminated site was not significantly different from that of adjacent normal tissue. In the laboratory, dietary betanaphthoflavone (ßNF) treatment resulted in a three-fold increase in intestinal GSH transferase. Hepatic GSH transferase activity in the same fish was not affected by dietary ßNF although hepatic monooxygenase activity, measured as ethoxyresorufin O-deethylase (EROD), was. The results of this study indicate a response of the intestinal detoxification system to environmental contaminants and supports previous studies on the importance of intestinal metabolism of foreign compounds. Further, our results indicate the trend towards elevated GSH transferase in liver of feral fish could not be attributed to a cancerous disease state in these fish but indicates chemical induction in this organ as well.

Vasectomy and non-fatal acute myocardial infarction: a hospital-based case-control study in Seoul, Korea.

One hundred and sixty-three Korean men aged 35-64 who were admitted to a university-affiliated hospital diagnosed for the first time with acute myocardial infarction (AMI) were compared with 326 matched non-AMI patients hospitalized with a diagnosis considered unrelated to vasectomy. When other potentially confounding variables were controlled for, vasectomized men were found to be 2.6 times (adjusted odds ratio) more likely to have had an AMI as compared to the non-vasectomized men (95% CL: 1.1, 6.1). The adjusted odds ratio of AMI for subjects having had a vasectomy less than or equal to 9 years ago was the same as those who had a vasectomy greater than or equal to 15 years (OR = 2.5), although those who had had a vasectomy 10-14 years ago were associated with a higher odds ratio of 4.2. Among those subjects with vasectomies who were also cigarette-smokers and/or hypertensive, the risk of development of AMI increased multiplicatively compared with those with none of these conditions. We suspect that our finding of this positive association may be spurious due to possible bias introduced during selection of controls and during the process of data collection. Cancer patients may have been less likely to undergo an elective surgical procedure such as vasectomy prior to the admission. When multivariate analysis included only controls who were non-cancer patients (N = 241 controls), the adjusted odds ratio between vasectomy and hospitalization for AMI was reduced to 2.1, (95% CL: 0.8, 5.7), which is no longer statistically significant. When the analysis was further limited to only those control subjects admitted with a diagnosis of digestive system problems, the adjusted odds ratio was reduced to close to unity (1.1). Recognizing the importance of the study topic and the fact that all previous epidemiological studies showed no association between vasectomy and cardiovascular diseases, we urge further studies. A historical cohort study in the Korean setting is considered feasible and is recommended.

[Changes in life expectancy of Koreans due to reduction in leading causes of death in 1985].

"This study examines potential gains in life expectancy of Korean males and females in 1985 when the three leading causes of death are totally eliminated. The greatest increase in life expectancy of Korean males would result from the elimination of malignant neoplasms (2.2 years at birth), whereas the life expectancy of Korean females would be lengthened the most (2.4 years) by elimination of cerebrovascular diseases. The implications of the results can provide useful information for the evaluation of the public health programs and health planning policy for [the Republic of Korea] in the future." (SUMMARY IN ENG)

Some problems in the analysis of hospital in-patients morbidity statistics--on the usefulness of rank distribution of morbidity.

Though the application of the hospital morbidity is very limited due mainly to the biasing aspect of the data, some important uses can be made by formulating a norm of hospital disease pattern in investigating the deviation of a hospital's patients morbidity or in time-series analysis of such morbidity. A most feasible way of establishing a representative norm of inpatients morbidity from the hospital statistics is to use the modal rank distribution of disease categories according to the magnitude of its relative proportion. The level of classification recommendable for this purpose is the three-digits code disease categories listed in International Classification of Disease (the latest edition), World Health Organization. The distribution of disease in the ordered ranks demonstrated a high degree of consistency in both intra and inter hospital comparison with rank correlation reaching the level of as high as 0.99.

Persistence of herpes simplex virus type-2 genome in a human leukemic cell line.

To study the nature of virus-cell interaction in persistently infected cells we have examined production of infectious virus, synthesis of viral DNA and DNA polymerase in a human leukemic cell line K562. It was found that only one of three K562 cell lines was permissive for limited growth of HSV-2 and infectious virus was released in a cyclical fashion. Intranuclear inclusions with electron-dense fibrils and particles resembling viral structures were observed in the virus-infected but not control K562 cells. Viral DNA synthesis could not be detected by centrifugation in CsCl density gradients; but was readily identified by Southern blot hydridization of virus-infected intracellular DNA with purified viral DNA. Viral DNa polymerase was synthesized by infected cells during active infectious virus production. In one of the two K562 cell lines that did not produce infectious virus, a few DNA fragments from infected cells were found to hybridize with purified viral DNA. These results suggest that variable lengths of HSV-2 genome can be harbored and propagated by different human leukemic K562 cells.