Biomedical subjects

C Simpkins

Publications and source records attributed to C Simpkins.

14 recordsLinked to original sources

PubMed1998

Metallothionein-induced increase in mitochondrial inner membrane permeability.

OBJECTIVE: To elucidate the effect of metallothionein on the permeability of the mitochondrial inner membrane. BACKGROUND: Metallothionein (MT) is a 6-7-kDa protein which is rapidly produced by stressed cells. MT is induced by cytokines and other factors thought to mediate the stress response. The organelle with the highest concentration of MT is the mitochondrion. Therefore we studied the effect of MT on mitochondrial function. We chose to study the effect of MT on mitochondrial inner membrane permeability because of the role of this function in numerous cellular processes. METHODS: Mitochondria were isolated from livers of Sprague-Dawley rats by differential centrifugation and suspended in sucrose-containing buffer. Changes in mitochondrial inner membrane permeability were monitored by following the change in absorbance at 540 nm. All experiments were of a paired design. RESULTS: We found that an increase in inner membrane permeability was induced by physiological metallothionein 1 (MT1) concentrations between 6 and 50 microM. There was no increase in the effect beyond 50 microM. The metals of MT1, zinc, and cadmium alone had no effect at physiological concentrations. The action of MT1 was inhibited by the aliphatic polyamine, spermine, as well as magnesium both at physiological concentrations. Spermine was effective whether added before or after MT1. Metallothionein 2 of different Zn2+ and Cd2+ compositions induced different kinetics of pore opening. CONCLUSIONS: These experiments reveal the possibility that the permeability of the mitochondrial inner membrane is regulated by relative concentrations of MT, spermine, and magnesium. The metal composition of MT could also play a role in this regulation.

Animals↗

PubMed1998

Mitochondrial oxygen consumption is synergistically inhibited by metallothionein and calcium.

OBJECTIVE: To determine the combined effect of metallothionein and calcium on the oxygen consumption of mitochondria. BACKGROUND: We previously showed that mitochondrial oxygen consumption was inhibited by the intracellular acute-phase reactant, metallothionein, which is rapidly induced by nearly all stressed cells. Other investigators have demonstrated that calcium also inhibited oxygen consumption. However, the calcium concentrations used in their experiments were supraphysiologic. Our hypothesis was that metallothionein would enhance the effect of calcium. METHODS: We conducted these experiments, of a paired design, on the effects of combinations of metallothionein and calcium using mitochondria isolated from rat liver. An oxygen electrode implanted into a 600-microliter chamber with a stir bar was used to measure oxygen consumption. Various concentrations of calcium, metallothionein, and other reagents were added while oxygen consumption was being continuously recorded. Metals were removed from metallothionein by gel filtration to produce apometallothionein. RESULTS: Physiological levels of metallothionein synergistically enhanced the inhibitory effect of calcium so that its action occurred at physiological concentrations. Metallothionein devoid of its metals, zinc and cadmium, had no effect on oxygen consumption. CONCLUSION: In isolated mitochondria metallothionein inhibits ADP-initiated oxygen consumption. This effect is synergistic with the inhibitory action of calcium. These observations suggest a possible enhancement by metallothionein of the effect of fluxes in intracellular calcium in stressed cells.

Adenosine Diphosphate↗

PubMed1994

Evidence that carbon monoxide is a mediator of critical illness.

We have measured arterial carboxyhemoglobin levels as an indicator of endogenous carbon monoxide production in 32 consecutive admissions to our Surgical Intensive Care Unit. A severity of illness score (APACHE II) was determined for each patient at the same time that blood was drawn. An increase in the APACHE II score indicates a worsening of the patient's condition. There was a positive correlation between arterial carboxyhemoglobin levels and the APACHE II score (p < 0.005). An increase in the white blood cell count indicates an increase in the severity of illness. Carboxyhemoglobin levels correlated with an increase in the white blood cell count to greater than the normal maximum count of 10.5 x 10(3) cells/mm3 within a 24 hour period (p < 0.05). These findings support our hypothesis that endogenously produced carbon monoxide may play a role in the pathogenesis of critical illness.

Carbon Monoxide↗

PubMed1993

Metallothionein I reduction of cytochrome c.

Using absorption spectroscopy we have found that metallothionein I at concentrations as low as 1 microM reduces ferricytochrome c. This reduction is more potent than that of another abundant intracellular thiol, glutathione. Also, oxidation of ferricytochrome c which had been reduced by metallothionein I occurs more slowly than when the reductant was glutathione. Over a pH range of 6 through 9 there is no variation in the initial rate of metallothionein I reduction of ferricytochrome c. These data demonstrate a potent interaction between metallothionein I and ferricytochrome c.

Animals↗

PubMed1992

Changes in diagnostic case mix in psychiatric care in general hospitals, 1980-85.

The Hospital Discharge Survey of 1980 and 1985 was used to assess changes in diagnostic case mix of psychiatric inpatient care in short-term, nonfederal general hospitals. Information regarding presence of psychiatric and chemical dependency units was added to both surveys, and information regarding exemption from Medicare's PPS system was noted for 1985. The largest increase was in ICD-9 code 296 (affective disorder), which more than doubled in frequency, along with a similar decrease in Diagnosis-Related Group 426, depressive neurosis. One explanation for this sizable shift was "gaming the system." One cannot conclusively, however, distinguish between gaming the system and the effects of changing professional views of depression during this time period. Other variables potentially contributing to the effect are described as well.

Affective Disorders, Psychotic↗

PubMed1992

Recurrent intentional injury.

Recurrent intentional injury (RII) is a phenomenon that is often noted by those who treat the injured. The authors have observed two groups of assault-related injured patients at the District of Columbia General Hospital Level I urban trauma center to determine the magnitude of this phenomenon in the patient population, to examine the characteristics of such a group of patients, and to identify the risk factors that predispose to repeated assault-related injuries. In a retrospective group of 232 patients admitted over a 4-year period who had sustained penetrating abdominal trauma there were 76 (33%) patients who had been previously treated at our center for assault-related injury. A prospective study of 78 consecutive assault-related injured patients admitted during a 4-month period revealed that 35 patients (45%) had a history of previous hospitalization for injuries as a result of assault. Within the male group (72 patients) 49% exhibited RII. When comparing this group of patients with those patients who had no previous injuries secondary to assault, there was a significantly higher rate of unemployment for the RII group and no difference in educational level. Also, the RII group incurred significantly higher hospital charges when compared to the group of patients who had their first of such injuries ($9673 versus $6973). Efforts to reduce unemployment should be included in preventive strategies if the high incidence of assault-related injury is to be decreased.

Abdominal Injuries↗

PubMed1991

Interaction between cytochrome C and di- and tripeptides.

By observing changes in the absorbance spectrum between 340 and 650 nm, we found that tyrosyltyrosylphenylalanine (TTP) interacts with cytochrome C (CC). TTP caused the characteristic changes of CC reduction, namely, an increased optical density at 524 and 550 nm and a hyperchromic shift at 416 nm. The apparent dissociation constant (Kd) was 2.9 x 10(-3) M. Most of the reducible CC at 20 uM concentration was reduced by 10 mM TTP. TTP was more potent than all other peptides tested, including the previously reported tyrosylphenylalanine. That the carboxyl terminal phenyl group was essential for reduction was shown by comparing variously substituted di- and tripeptides. Reduction by TTP increased with increasing pH and buffer concentration at constant pH. A combination of superoxide dismutase and catalase failed to inhibit the reduction. We found no effect of TTP on O2 consumption of isolated intact mitochondria. Our data demonstrate that small peptides can serve as probes of the topography and electron density of CC and that the TTP-CC interaction may provide insight as an analog of in-vivo processes.

Amino Acid Sequence↗

PubMed1991

The de facto national system of psychiatric inpatient care. Piecing together the national puzzle.

National data regarding psychiatric inpatient episodes can be viewed in 2 ways. The normative method surveys the "specialty mental health sector." A more inclusive method includes smaller sites (e.g., the military), all of general hospital treatment (rather than only the psychiatric unit), residential treatment centers, and other residential care. The difference between the 2 methods represents approximately 725,000 episodes, at a direct cost of more than $6 billion. The more inclusive analysis of the years 1980 and 1985 reveals a strong shift to the private sector and an increase in inpatient care of children and youth that might be obscured by limiting national treatment statistics to the specialty mental health sector.

Cost Control↗

PubMed1991

The emergence of psychiatric departments as quasi-units in general hospitals.

The organization of inpatient psychiatric treatment in general hospitals was investigated using data from the Hospital Discharge Surveys for 1980 and 1985 and definitions of psychiatric services used by the American Hospital Association and the National Institute of Mental Health. The definitions differ in that psychiatric services meeting the AHA definition are formally organized and physically separate units, while those meeting the NIMH definition may have a less formal structure. The number of psychiatric inpatient episodes in psychiatric departments as defined by NIMH increased sixfold between 1980 and 1985, while those in formal psychiatric units as defined by AHA decreased by 16 percent. The increase was completely accounted for by episodes of mental disorders; episodes of alcohol and drug disorders decreased in both settings. The implications of the psychiatric department as an entrepreneurial newcomer in the competitive general hospital market are discussed.

Alcoholism↗

PubMed1991

Changes in psychiatric inpatient treatment of children and youth in general hospitals: 1980-1985.

Changes in the prevalence of inpatient psychiatric treatment of children and youth in short-term general hospitals between 1980 and 1985 were investigated. During that period, the locus of treatment of mental illness among children and youth shifted dramatically away from specialized facilities to general hospitals without psychiatric units. Among general hospitals without psychiatric units, the number of inpatient psychiatric episodes treated increased dramatically, patients' average length of stay almost doubled, and the total days of care provided more than tripled. The increased care was paid for primarily by Medicaid and commercial insurance. Total days of care for drug and alcohol problems among children and youth in general hospitals decreased substantially. The results suggest that general hospitals may be relying on psychiatric treatment to supplement revenues that were limited by Medicare's prospective payment system, which became effective during the period under study.

Adolescent↗

PubMed1990

Predicting length of hospital stay for psychiatric inpatients.

Medicare's use of diagnosis-related groups and the frequent acceptance of length of stay as an indicator of resource utilization has caused a surge of interest in the predictability of length of hospital stay for psychiatric inpatients. By constructing a weighted least squares regression model using data from the 1980 Hospital Discharge Survey, the authors were able to account for an increased amount of variance in length of stay for the major diagnostic categories of mental disorder and substance abuse for Medicare and Blue Cross/Blue Shield patients. The enhanced ability to predict length of stay is attributed to a carefully constructed data base and an increased number of predictor variables, particularly comorbidity. Knowledge of the presence or absence of a chemical dependency unit in the hospitals from which patients were discharged substantially increased the proportion of variance accounted for in the analysis.

Blue Cross Blue Shield Insurance Plans↗

PubMed1990

A new cytochrome C reducing dipeptide.

Using absorption spectroscopy, it has been found that tyrosylphenylalanine specifically reduces cytochrome C. This effect is pH and concentration dependent with the EC +/- SE = 4.42 x 10(-3) M. At 10(-2) 2 M, tyrosylphenylalanine caused reduction which was 50% complete. The same amino acids linked together in reverse order as phenylalanyltyrosine produced only a minimal effect. Tyrosine and phenylalanine alone, serylphenylalanine, formylphenylalanine, tyrosyllysine, and tyrosylarginine did not reduce cytochrome C. Comparison of tyrosylphenylalanine to tyrosylalanine and tyrosyltyrosine showed that the phenyl group is essential to reduction. This approach may illuminate some of the unanswered questions of the chemiosmotic theory of mitochondrial energy production.

Cytochrome c Group↗

PubMed1989

The psychiatric inpatient treatment of children and youth in general hospitals.

National attention has recently focused on the mental health needs and services of children and youth. The lack of outpatient services and their coordination has been noted, as well as the consequent press towards inpatient care. We describe the inpatient treatment of children and adolescents (ages 0-18) in short-term, non-Federal general hospitals in 1980. Nationally, 128,300 children were treated for mental disorders in general hospitals at an estimated cost of over $1.5 billion. Compared to adults, children were more likely to be treated in scatter beds (vs. specialty units); have a diagnosis of mental disorder (vs. alcohol/drug disorder); stay much longer; and pay with commercial insurance. Previous work focusing on psychiatric units of general hospitals identified less than 40% of the total episodes, a figure very similar to that for adults. The majority of psychiatric inpatient episodes for children and youth in the United States takes place in short-term general hospitals. Community psychologists need to be aware of national trends in inpatient care and be involved in the development and promulgation of alternative models of care.

Adolescent↗

PubMed1983

Thyroid hormone in biological rhythms.

An essential role for thyroid hormone in the production of biological rhythms is proposed. In order for a system to oscillate it must have two stable states. It is possible that thyroid hormone alters the concentration of substrate and product in such a way that the system moves cyclically between these two states. Experimental evidence and clinical facts are invoked to complement the theoretical considerations.

Adrenal Cortex Hormones↗