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Biomedical subjects

A N Johnson

Publications and source records attributed to A N Johnson.

At least 19 recordsLinked to original sources

Embryonic enhancers in the dpp disk region regulate a second round of Dpp signaling from the dorsal ectoderm to the mesoderm that represses Zfh-1 expression in a subset of pericardial cells.

During germ band elongation, widespread decapentaplegic (dpp) expression in the dorsal ectoderm patterns the underlying mesoderm. These Dpp signals specify cardial and pericardial cell fates in the developing heart. At maximum germ band extension, dpp dorsal ectoderm expression becomes restricted to the dorsal-most or leading edge cells (LE). A second round of Dpp signaling then specifies cell shape changes in ectodermal cells leading to dorsal closure. Here we show that a third round of dpp dorsal ectoderm expression initiates during germ band retraction. This round of dpp expression is also restricted to LE cells but Dpp signaling specifies the repression of the transcription factor Zfh-1 in a subset of pericardial cells in the underlying mesoderm. Surprisingly, we found that cis-regulatory sequences that activate the third round of dpp dorsal ectoderm expression are found in the dpp disk region. We also show that the activation of this round of dpp expression is dependent upon prior Dpp signals, the signal transducer Medea, and possibly release from dTCF-mediated repression. Our results demonstrate that a second round of Dpp signaling from the dorsal ectoderm to the mesoderm is required to pattern the developing heart and that this round of dpp expression may be activated by combinatorial interactions between Dpp and Wingless.

Animals↗

Combinatorial signaling by an unconventional Wg pathway and the Dpp pathway requires Nejire (CBP/p300) to regulate dpp expression in posterior tracheal branches.

The decapentaplegic (dpp) gene influences many developmental events in Drosophila melanogaster. We have been analyzing dpp expression in two groups of dorsal ectoderm cells at the posterior end of the embryo, in abdominal segment 8 and the telson. These dpp-expressing cells become tracheal cells in the posterior-most branches of the tracheal system (Dorsal Branch10, Spiracular Branch10, and the Posterior Spiracle). These branches are not identified by reagents typically used in analyses of tracheal development, suggesting that dpp expression confers a distinct identity upon posterior tracheal cells. We have determined that dpp posterior ectoderm expression begins during germ band extension and continues throughout development. We have isolated the sequences responsible for these aspects of dpp expression in a reporter gene. We have determined that an unconventional form of Wingless (Wg) signaling, Dpp signaling, and the transcriptional coactivator Nejire (CBP/p300) are required for the initiation and maintenance of dpp expression in the posterior-most branches of the tracheal system. Our data suggest a model for the integration of Wg and Dpp signals that may be applicable to branching morphogenesis in other developmental systems.

Animals↗

Serological and molecular evidence of rhesus papillomavirus type 1 infections in tissues from geographically distinct institutions.

We have previously demonstrated the presence of rhesus monkey papillomavirus type 1 (RhPV-1), from molecular and pathological evidence, in a mating group within a single institution. We have now also obtained a number of fresh or archival tissues of rhesus monkeys from other geographically distinct institutions. Using PCR amplification, we observed two animals from one of these institutions and five animals from another which demonstrated RhPV-1 DNA sequences. In addition we molecularly cloned the E7, E2, E4, L2 and L1 genes of RhPV-1 into bacterial expression vectors. The fusion gene products were used to test for serological response to RhPV-1 antigens by Western blot analysis. Responses were observed in up to 52% of the animals tested. While some serologically positive animals were also RhPV-1 DNA-positive, most were not.

Animals↗

Comparative aspects of contraceptive steroids--effects observed in beagle dogs.

The effects of oral contraceptives have been studied in the beagle bitch for periods up to 7 yr. High doses of these potent estrogen: progestogen (E:P) combinations have been shown to promote tumors in the mammary glands, smooth muscle of the tubular genitalia, and occasionally in the transitional epithelium of the neck/trigone area of the urinary bladder. The contraceptive formulations used in humans are balanced with an E:P ratio of about 1:5 to 1:80 to produce a desired decidual response in the uterus. The corresponding ratio for producing the decidual reaction in the dog is 1:1,000 to 1:3,000 with the result that the dog is grossly overdosed with estrogens when given the human formulation at the usual multiples of up to 25 times the human dose. Smooth muscle tumors of the tubular reproductive tract are common sequelae to estrogen overstimulation in the dog and are known to occur in other species, including the humans. The dog also has major differences in hormonal control and sensitivity when compared to humans. Progestogens stimulate synthesis and release of growth hormone (GH) in dogs which in turn is the major stimulant (with progestogens) of mammary growth and tumors. Evidence is accumulating which indicates that most if not all progestogens can produce mammary tumors in the dog if given by the correct route and at high enough dosage. In contrast, GH in humans is not increased nor does it have any significant mammotrophic role. Mammary tumors in dogs related to oral contraceptives are now widely considered to be irrelevant as a model or predictor for human tumors. Transitional cell tumors in the urinary bladder seem to be a species specific phenomenon seen on occasion in the dog, but not in the rat, monkey, or human. The usual location in the neck/trigone area may be related to the embryologic origin of this portion of the bladder, which derives from tissues more closely related to the genital organs than does the rest of the bladder.

Animals↗

Differences in inpatient resource use by type of health plan.

Approximately 50% of the annual increase in hospital costs comes from increased resource use per hospital admission. Health maintenance organizations (HMOs), given their fixed financial resources for patient care, have an incentive to constrain their enrollees' use of hospital resources. Our analysis investigates differences in length of stay, total charges, and the ancillary to total charge ratio for hospitalized patients in network HMOs, independent practice associations (IPAs), and fee-for-service (FFS) health plans in the Twin Cities from 1982 to 1984. Network HMO patients in several diagnostic categories are found to use significantly fewer resources, once hospitalized, than patients in either IPA or FFS plans. This difference may give network HMOs a competitive advantage in the market for health plans.

Group Practice↗

Inpatient length of stay in Twin Cities health plans.

In this paper we examine the relationship between inpatient length of stay and the patient's type of health insurance. The data consist of discharges in seven diagnosis-related groups (DRGs) from community hospitals in Minneapolis and St. Paul during 1982. After controlling for the effects of the patient's age, sex, medical condition, and severity of illness, as well as the hospital's size, teaching and ownership status, and average annual occupancy rate, we must reject the null hypothesis that the patient's type of health plan is unrelated to inpatient length of stay in Twin Cities community hospitals. We find that, in most cases, patients in prepaid group practices and independent practice associations exhibit significantly shorter lengths of stay than similar patients in Blue Cross and commercial health insurance plans, while Medicare and Medicaid patients exhibit significantly longer lengths of stay than those of similar commercially insured patients.

Blue Cross Blue Shield Insurance Plans↗

The impact of health maintenance organizations and competition on hospitals in Minneapolis/St. Paul.

The Healthcare Educational and Research Foundation (HERF) in Minneapolis undertook a two-year research project to study the effects of health maintenance organizations (HMOs) and competition on the hospital industry in Minneapolis/St. Paul. This article summarizes HERF's major findings surrounding three key questions: (1) do the HMOs in Minneapolis/St. Paul use fewer hospital resources relative to conventional payers?; (2) do recent overall community trends in inpatient use suggest evidence of hospital utilization-reducing effects attributable to HMOs?; and (3) given the highly visible competitive process among Minneapolis/St. Paul providers, do hospital cost and revenue data suggest any evidence of cost-containment? The findings (based on data through 1982) indicate that for comparable patients, Twin Cities HMOs appear to use fewer medical care resources per hospitalized patient. There was, however, no clear evidence of community-wide, utilization-reducing effects directly attributable to the "competitive effect" of HMO introduction and development in the market. In addition, there was no empirical evidence that HMOs (which had enrolled 25 percent of the consumer market by 1982), or other large buyers of inpatient services, have selected hospitals on the basis of price as hypothesized by competition advocates.

Cost Control↗

Cost-shifting: the discount dilemma.

Cost-shifting, the practice by hospitals of raising their prices to make up for reimbursement shortfalls from payers that do not pay full charges, is an important and controversial issue. Concerns about cost-shifting, particularly its effects on payment equity and cost escalation, have led many insurers, business groups, and legislators to advocate rate-setting regulation for hospitals. This article seeks to clarify the definition of cost-shifting, and quantifies its magnitude in Minneapolis/St. Paul. We believe that cost-shifting is the consequential result of the failure of both public and private payers to structure payment policies that reward cost-effective hospitals, and we outline a market-oriented alternative to rate-setting to address the discount dilemma caused by cost-shifting.

Charities↗

DRGs and hospital case records: implications for Medicare case mix accuracy.

As Medicare moves to DRG-based prospective payment, it is not clear whether the federal government has adequate data upon which to formulate DRG prices and assess hospital case mix. This study compares the Medicare case mix of Minneapolis-St. Paul hospitals based on the historical information submitted for billing purposes on the Medicare claim with the actual case mix of hospitals as described in the medical record chart. It was found that for the same patients, the DRG based on the claim matched the DRG on the medical record approximately half of the time. These "mismatches" resulted in a statistically significant understatement of hospitals' case mix, and have obvious implications for the setting of DRG prices and equitable hospital reimbursement.

Centers for Medicare and Medicaid Services, U.S.↗