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Biomedical subjects

E K Mitchell

Publications and source records attributed to E K Mitchell.

13 recordsLinked to original sources
PubMed1996

MHC class I molecules form ternary complexes with calnexin and TAP and undergo peptide-regulated interaction with TAP via their extracellular domains.

Newly assembled heavy chain-beta 2m heterodimers of class I histocompatibility molecules associate with the endoplasmic reticulum (ER) peptide transporter, TAP, and subsequently dissociate from TAP in parallel with their transport from the ER to the Golgi apparatus. It appears that TAP-associated class I molecules are waiting to bind appropriate peptides before they dissociate from TAP and leave the ER since binding of high affinity peptides to class I molecules in vitro leads to dissociation of TAP-class I complexes. In further support of this notion, we report that limiting peptide supply through inhibition of proteasome activities prolongs the association of mouse class I molecules with TAP and concomitantly slows their transport to the Golgi apparatus. By using a series of deletion mutants and hybrid class I molecules we demonstrate that the extracellular domains of class I molecules are sufficient for their peptide-regulated interaction with TAP. Furthermore, based on the inability of an alpha 3 domain-specific mAb to recognize TAP-class I complexes and the fact that a point mutant of the Dd molecule at residue 222 is unable to bind to TAP, it is likely that a major site of interaction with TAP resides in the membrane-proximal region of the heavy chain alpha 3 domain. Finally, we examined the relationship between the interaction of mouse heavy chain-beta 2m heterodimers with TAP and with the resident ER chaperone, calnexin. Most heterodimers that bound to TAP were found to associate simultaneously with calnexin. Upon delivery of peptide to class I molecules in permeabilized cells, dissociation from TAP was observed but the interaction with calnexin was largely maintained. Therefore, both TAP and calnexin may participate in the ER retention of peptide-deficient class I molecules. However, since release from calnexin occurs after dissociation from TAP, it appears that calnexin ultimately determines if a class I molecule is to be exported from the ER.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Where have all the autopsies gone? A proposal for a centralized autopsy service.

A litany of reasons have been advanced to account for the decrease in hospital autopsy rates. Increased attention has recently been centered on the difficulty hospital and medical examiner morgues are encountering in controlling infectious disease and attempting to comply with federal and state environmental regulatory agencies. The problem has been highlighted by autopsy examinations upon increased numbers of immuno-compromised patients harboring both the HIV and secondary drug resistant tuberculosis organisms. These developments occur at a time when there are budgetary restraints on hospitals and medical examiners' offices facing large expenditures involving morgue reconstruction to comply with ventilatory and infection control procedures mandated by state and federal agencies. Challenging, also, are the liability aspects, as patients and staff are potentially exposed to a variety of infectious agents. A possible solution is presented involving central off-hospital site facilities to which hospital autopsies can be funneled. A community morgue meeting the strict standards of infection control would allow economy of scale from daily use with a full time support staff trained in the protocol of infectious disease control.

Autopsy↗
PubMed1993

Asphyxial deaths due to physical restraint. A case series.

OBJECTIVE: To assess the common factors and the pattern of deaths related to the use of physical restraints. DESIGN: Case series. PARTICIPANTS: The chief death investigators of 37 large jurisdictions were sent questionnaires for all cases of restraint-related deaths. Sixty-three questionnaires from 23 jurisdictions were returned. MEASURES: The questionnaires allowed us to determine the restraint type used, the age and sex of the deceased, the furniture type with which restraints were used, the type of facility where the deceased was restrained, and whether the application of restraints was incorrect. RESULTS: We report 63 cases of asphyxial deaths from the use of physical restraints. Ages of decedents ranged from 26 weeks to 98 years. The greatest number of deaths occurred in the 80- to 89-year-old patients. There is a higher frequency for females of all ages, but the distribution for males and females is roughly the same for all age groups. Deaths occurred while the patient was restrained in a chair (wheelchair or geriatric recliner) or a bed. Most chair-related deaths (six of 19) and bed-related deaths (16 of 42) involved the use of vest restraints. Thirteen of the 42 bed-related deaths involved bedrails. The majority of deaths (61%) occurred in nursing homes and 57 of these 63 cases occurred while restraints were properly applied. CONCLUSIONS: Our report of 63 cases is an underrepresentation of the true number of restraint deaths. Our finding that the vast majority of restraint deaths occurred while restraints were correctly applied implies an inherent danger in the use of physical restraints. The safety of restraining patients and the efficacy of physical restraint needs to be examined and alternate means of assuring the safety of patients need to be developed.

Adolescent↗
PubMed1989

Wischnewski revisited. The diagnostic value of gastric mucosal ulcers in hypothermic deaths.

Hypothermia is defined as a subnormal body temperature. In this article, hypothermia refers to the loss of core temperature from exposure. When death results from hypothermia, a series of gastric mucosal erosions known as "Wischnewski ulcers" (1) frequently occur. In examining case material of the Onondaga County Medical Examiner's Office, a characteristic pattern of these ulcerations was seen that was indicative of severe physiologic stress and/or hypothermia. While not pathognomonic of hypothermia, the incidence of the erosions in a specific pattern has been closely associated with deaths in which hypothermia played a significant role. In hypothermia, the erosions, usually shallow and approximately 0.1-0.5 cm in diameter, are set in lines with roughly equidistant spacing, thereby forming a pattern of rectangles with the corners marked by the ulcerations.

Autopsy↗
PubMed1984

Spontaneous births into toilets.

Since inception of the Dade County Medical Examiner Department in 1956 and the end of 1982 a total of 18 spontaneous births into toilets were investigated. A retrospective review of these cases revealed a high degree of maternal denial of pregnancy and refusal of responsibility for the fetus by primiparous mothers of term births, the instances of most questionable manner of death. A consideration in the examination of these natal deaths should be investigation of maternal postnatal behavior along with the circumstances of birth and autopsy findings.

Adult↗
PubMed1984

Electrocution by street lighting.

Four lethal and one nonlethal electrocutions from street lighting equipment are described. These cases have in common old installations, metal light poles, wet environment, 480-V power sources, and intact fuses. Identification of causative factors may permit future accommodation in design to reduce risk.

Adolescent↗
PubMed1983

Bacterial interference with urine osmolality measurements.

We report bacterial interference with urine osmolality measurements using an instrument based on the principle of freezing point depression. Although the exact nature of the interfering activity has not been defined, the phenomenon is associated with a bacterium, identified as Pseudomonas putida, and is removed from the specimens by filtration at 0.45 micron. The bacteria led to osmometer dysfunction presumably by acting as a nidus for crystallization and preventing proper supercooling of specimens.

Freezing↗