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Biomedical subjects

M L Wright

Publications and source records attributed to M L Wright.

35 records · Page 2Linked to original sources

Metamorphic rate in Rana pipiens larvae treated with thyroxine or prolactin at different times in the light/dark cycle.

Premetamorphic Rana pipiens tadpoles at Stages V to VIII on a 12L/12D cycle with photoperiod from 0800 to 2000 hr were treated with 30 micrograms/liter thyroxine (T4) by immersion for various daily 8-hr spans, or by daily intraperitoneal injection at different times with 0.1 to 10 micrograms T4 or 10 micrograms prolactin (PRL), in order to see if the rate of metamorphosis varied with the time of hormone treatment. T4 was most effective in promoting tail resorption and hindlimb growth and development if tadpoles were immersed at least partly in the light or if the hormone was injected late in the dark or in the early or mid light phase. T4 was least effective in accelerating metamorphosis when immersion was totally in the dark or injection early in the dark. PRL antagonized metamorphosis just as well at any time of the day except that tail fin growth was faster when PRL was administered early in the dark. The findings show circadian variations in target tissue responsiveness to exogenous T4 that depend on the occurrence of light during T4 immersion or following T4 injection. The data suggest rhythmicity in the secretion of endogenous T4 in the tadpole and a diurnal effect on T4 utilization by target cells.

Animals↗

Non-circadian periodicity in the duration of the cell cycle and the G1 phase in the hindlimb epidermis of the anuran tadpole, Rana pipiens.

Using the percentage labeled mitoses method, seven cell cycle determinations were initiated at 6-hr intervals over a 36-hr span in order to see if the cell cycle in the tadpole hindlimb epidermis varied with time or showed rhythmicity. There was a pattern of two long cell cycles followed by a shorter one. Total cell cycle length (Tc) and the length of the G1 phase plus one-half of the mitotic time (TG1 + 1/2M) fluctuated the most, although only TG1 + 1/2M varied significantly with the Chi-square test. The proportion of TC spent in each phase was also calculated. Only TG1 + 1/2M/TC had statistically significant fluctuations with time. Rhythmicity was analyzed by a computer program using the method of least squares for cosine curve fitting. Statistically significant ultradian rhythms of 18.4 hr in TC, 18.5 hr in TG1 + 1/2M and 18.6 hr in TG1 + 1/2M/TC and the length of the DNA synthetic phase/total cell cycle length (TS/TC) were found. Circadian rhythmicity was not observed. The acrophases of the ultradian rhythms of TC and TG1 + 1/2M coincided, suggesting that the rhythm of TC was due mainly to variation in TG1 + 1/2M. In the absence of significant variation in TS, the longest phase of the cell cycle, whenever G1 + 1/2M was short, TS/TC increased, so that the 18.6 hr rhythm in TS/TC was also a result of the periodicity in TG1 + 1/2M.

Animals↗

Rhythms of cell proliferation in the hindlimb epidermis of control and thyroxine-treated Rana pipiens tadpoles.

Labeling and mitotic index rhythms were studied in premetamorphic tadpoles under an LD 12:12 with the light phase beginning at 0800 hr. In a 72-hr experiment, control labeling and mitotic index curves showed a peak in the light and a peak in the dark with labeling index rhythms of 12.4, 17.7, and 23.6 hr and a 21.4-hr mitotic index rhythm. Thyroxine (T4) treatment resulted in a marked elevation of labeling index by 24 hr and of mitotic index by 48 hr, obscured the control bimodal pattern of peaks, and altered the rhythms. During the first 3 days of T4 treatment, a labeling index rhythm of 22 hr and a mitotic index rhythm of 37.5 hr occurred. However, additional work demonstrated that the dominant control rhythms of labeling and mitotic indices returned in the T4-treated during Days 4 and 5. The same pattern of change in labeling index occurred during Day 3 of T4 treatment when hormone administration began at different times in the diurnal phase of the light-dark cycle. The findings suggest that cell proliferation rhythms can be temporarily disturbed by an exogenous T4 stimulus without apparent reference to the phase of the circadian rhythm.

Animals↗

Pulmonary vascular changes in young and aging rats exposed to 5,486 m altitude.

Young (YNG) and middle-aged (MA) male rats were exposed to 5,486 m for durations ranging from 1 to 42 days to determine the effect of age on the progression of polycythemia, right ventricular hypertrophy (RVH), lung vascular muscularization, and pulmonary vascular responsiveness. Other rats were exposed for 42 days at 5,486 m and were then allowed to recover at 1,520 m for periods up to 42 days. The progression and subsequent regression of polycythemia and RVH with altitude exposure were similar for YNG and MA rats. However, YNG rats exhibited vascular muscularization during the altitude exposure, characterized by hypertrophy of smooth muscle cells, whereas MA rats exhibited little or no change in vascular morphology. Lungs from both altitude-exposed YNG and MA rats exhibited blunting of acute hypoxic pulmonary vasoconstriction upon exposure to 5,486 m, with more severe blunting apparent in MA rats. Pressor responses to angiotensin II (AII) were potentiated in lungs from high altitude rats, particularly in the YNG rats, and this increased responsiveness persisted during the recovery period. A positive correlation was found in YNG rats between the degree of vascular muscularization and the pressor response to AII, suggesting that increased muscle mass was partially responsible for the potentiated AII responses. However, MA rats did not exhibit the same correlation for AII, and neither YNG nor MA rats exhibited increased responsiveness to 5-hydroxytryptamine. The results indicate that age influences the morphologic responses to altitude exposure and vascular responsiveness to AII, but does not affect the polycythemic response or the degree of RVH.

Aging↗

Altered vascular responsiveness in isolated perfused lungs from aging rats.

Systemic vascular hyporesponsiveness has been well documented in aged rats, but a similar decreased vasoreactivity of the pulmonary vasculature has not been reported. Isolated lungs from young (3-5 months) and middle-aged (12-14 months) rats were perfused with whole blood and challenged alternately with alveolar hypoxia, angiotensin II, and 5-hydroxytryptamine. Hypoxic pulmonary vasoconstriction was less in the aging rats during both 5-min and 10-min hypoxic exposures. Likewise, log-dose response curves for angiotensin II and 5-hydroxytryptamine were right-shifted in the aging rats, indicating decreased responsiveness to the vasoactive agents. Since the vascular responses to all three vasoconstrictors were lower in the older animals, a generalized pulmonary vascular hyporeactivity with advancing age is suggested.

5-Hydroxytryptophan↗

Application of benefit-to-cost analysis to an X-linked recessive cardiac and humeroperoneal neuromuscular disease.

Benefit-to-cost analysis (using standard economic methods) and the predictive tools of genetics are important in the assessment of genetic services for high burden, single gene disorders. We have studied 6 generations of a 167-member, stable, North Georgia kindred at risk for X-linked recessive humeroperoneal neuromuscular disease with cardiac conduction defects. This disorder began in affected males in the teen years, with total disability expected by the 3rd decade and death by age 50. Using known fecundity rates and Mendelian probabilities, 26.6 heterozygous females and 9.4 hemizygous affected males were expected in the currently developing generation. We compared the compensatory costs for families with affected males against costs of genetic intervention for this disorder. All costs and benefits were discounted to present values at 6% and 10% and a benefit-to-cost ratio was derived. At a 6% discount rate the benefit-to-cost ratio was 21 to 1 while at a 10% discount rate the benefit-to-cost ratio was 14 to 1. We conclude that although this is an unusual X-linked muscular dystrophy, it constitutes a prototypic public and private expense which is largely preventable. The method of cost accounting within pedigrees has wide applicability. The results reemphasize the economic benefit of comprehensive public health programs in genetics, particularly in areas with stable, high risk-populations.

Cost-Benefit Analysis↗

A bitter struggle for integration survival.

The state of California created the El Camino Hospital District in 1961, one of 77 such districts created as a way to fund rural hospitals. During the 1990s, hospital administrators began to look for ways to streamline operations and cut costs to remain competitive. In 1992, the hospital District Board voted to turn over El Camino's management to a nonprofit company, believing the hospital could form business partnerships with doctors. The District created a private, nonprofit corporation, approved the appointment of volunteers and physicians to the board, and instructed the board to develop on alliance with other physicians. It became evident that several philosophies were at work regarding the healthcare system. In 1995, the District attempted to void the 1992 agreements and take back the hospital. Legal investigations were initiated. Meanwhile, reimbursement rates were decreasing and the hospital's 600 doctors were dissatisfied. Legal struggles continue, public controversy and physician anger are ongoing, and the Santa Clara County District Attorney's office has begun an audit of records. Camino Healthcare, despite all the ongoing difficulties, continues to provide excellent care to patients and the community.

Attitude of Health Personnel↗