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Biomedical subjects

D K Miller

Publications and source records attributed to D K Miller.

At least 19 recordsLinked to original sources
PubMed1995

The interleukin-1 beta-converting enzyme (ICE) is localized on the external cell surface membranes and in the cytoplasmic ground substance of human monocytes by immuno-electron microscopy.

Interleukin-1 beta (IL-1 beta)-converting enzyme (ICE) is a novel cysteine protease that cleaves the 31-kD inactive cytoplasmic IL-1 beta precursor into active extracellular 17-kD IL-1 beta. The ICE gene product is a 45-kD proenzyme that requires proteolytic processing to activate ICE. Active ICE is a heterodimer consisting of equal amounts of p20 and p10 subunits. Generation of active ICE is affected by the removal of an 11-kD NH2-terminal precursor domain (p11) and an internal 19-amino acid sequence that separates the 20- and 10-kD subunits. Immuno-electron microscopy was performed on human monocytes with immunoglobulins recognizing the active (p20) or precursor (p11) domains of ICE. Elutriated monocytes were stimulated with 50 pM lipopolysaccharide followed by heat-killed Staphylococcus aureus under conditions that induce maximal rates of IL-1 beta secretion. Ultrathin cryosections were cut from fixed frozen pellets of these monocytes and were immunogold labeled with either antibody. Active and precursor domain ICE epitopes were localized in the cytoplasmic ground substance, but they were not detected within the endoplasmic reticulum, the Golgi apparatus, and secretory granules of activated or inactive monocytes. Importantly, numerous ICE p20 epitopes were also observed on the extracellular surfaces of the cell membrane, and were concentrated on the microvilli. Very similar patterns of ICE localization were obtained with unstimulated blood monocytes. In contrast, ICE p11 epitopes were not detected on the surfaces of these monocytes. Likewise, labeling of fixed ultrathin cryosections of monocytes with a biotinylated irreversible ICE inhibitor [Ac-Tyr-Val-Lys(biotin)-Asp-(acyloxy)-methyl-ketone] showed that the compound localized on the outer cell surface as well, and to a lesser extent, within the cytoplasmic ground substance. Furthermore, antipeptide antibodies specific for either the mature or precursor domains of IL-1 beta were both localized upon the cell membrane after stimulation of IL-1 beta secretion. Lipopolysaccaride-primed monocytes that synthesized, but did not secrete IL-1 beta, exhibited only cytoplasmic staining. The data suggests that mature IL-1 beta is generated via cleavage of the 31-kD inactive cytoplasmic IL-1 beta precursor by ICE after association with the plasma membrane during secretion.

Amino Acid Sequence↗
PubMed1995

Molecular cloning and pro-apoptotic activity of ICErelII and ICErelIII, members of the ICE/CED-3 family of cysteine proteases.

Cysteine proteases related to mammalian interleukin-1 beta-converting enzyme (ICE) and the nematode cell death abnormal ced-3 gene product have been implicated in the effector mechanism of apoptotic cell death. Two novel members of this new family of ICE/CED-3-related proteases, designated ICErel-II and ICErel-III, were cloned from human monocytic cells. Both were highly homologous to human ICE (52% identical) and CED-3 (25% identical) and both contained the absolutely conserved pentapeptide sequence Gln-Ala-Cys-Arg-Asp containing the catalytic cysteine residue. Other structural motifs that were comparable with ICE suggest that ICErel-II and ICErel-III are also synthesized as larger proenzymes which are proteolytically processed to form heterodimeric active enzymes. Pro-interleukin-1 beta processing activity could not be detected in cells transfected with ICErel-II or ICErel-III, but pro-domain-less truncated forms of ICErel-II and ICErel-III were capable of effectively inducing fibroblast apoptosis. ICErel-II and ICErel-III may, therefore, participate in proteolytic events culminating in the apoptotic death of human cells.

Amino Acid Sequence↗
PubMed1995

Unrecognized delirium in ED geriatric patients.

To determine the sensitivity of an emergency physician's conventional evaluation compared with the validated Confusion Assessment Method (CAM) regarding the recognition of acute confusional states (delirium) in elderly Emergency Department (ED) patients, a cohort of 385 patients presenting to an urban teaching hospital ED was systematically assembled. Patients had to be conscious, able to speak and older than 64 years of age. After the ED physician had examined the patient and test results had been obtained, a series of geriatric assessment results, including one for the likely presence of delirium, was made available to the ED physician; however, no result was specifically highlighted. All patients were assessed by an attending ED physician in the customary fashion. In addition, a study nurse interviewed patients using the CAM and followed patient outcomes for three months. The ED record for all patients with delirium or "probable" delirium, as determined by the CAM, were reviewed for physician diagnosis and disposition to determine how often delirium had been recognized by the emergency physician. Thirty-eight of the 385 patients screened (10%) met criteria for delirium or "probable" delirium; ED charts were complete for 35 of these, which constituted the study sample. The ED diagnosis included delirium or an acceptable synonym in 6 (17%) of these patients. In the 21 patients (62%) admitted to the hospital, the most common ED diagnosis was infection "rule out sepsis" (n = 7). Six of 13 patients discharged (46%) were diagnosed as "status post fall" without evidence of significant injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death.

The U1 small nuclear ribonucleoprotein particle is essential for splicing of precursor mRNA, an activity that depends upon both the RNA and protein components of the U1 particle. One of the U1-specific proteins that is functionally important in this splicing reaction is the 70-kDa protein (U1-70kDa). We report here that U1-70kDa is specifically cleaved in apoptotic cells, resulting in the generation of a 40-kDa fragment. The kinetics of this cleavage coincided with the appearance of cells with apoptotic morphology in the population, and the proportion of 40-kDa fragment observed was markedly increased in apoptotic cells that had become detached from the substratum. Although the inhibitor characteristics of the activity cleaving U1-70kDa suggest that interleukin 1 beta-converting enzyme (ICE) might be responsible, the specific ICE inhibitor N-(N-acetyl-tyrosinyl-valinyl-alaninyl)-3-amino-4-oxob utanoic acid (YVAD-CHO) did not prevent cleavage, and U1-70kDa was not cleaved by purified ICE in vitro. Further study of this novel cleavage and the enzyme responsible will yield information about proteolytic events that might be central in the mechanism and control of apoptosis.

Apoptosis↗
PubMed1992

A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes.

Interleukin-1 beta (IL-1 beta)-converting enzyme cleaves the IL-1 beta precursor to mature IL-1 beta, an important mediator of inflammation. The identification of the enzyme as a unique cysteine protease and the design of potent peptide aldehyde inhibitors are described. Purification and cloning of the complementary DNA indicates that IL-1 beta-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Selective inhibition of the enzyme in human blood monocytes blocks production of mature IL-1 beta, indicating that it is a potential therapeutic target.

Amino Acid Sequence↗
PubMed1992

Impact on caregivers of supporting urinary function in noninstitutionalized, chronically ill seniors.

In a multivariate study of 148 caregivers of chronically ill older persons, 22% of those caring for a continent senior reported that maintaining continence was a burden, and 75% of caregivers of incontinent seniors reported it as burdensome. The burden of maintaining urinary function was associated with lack of social support, time spent providing care, and care receiver's immobility. Caregivers' depressive symptoms were associated with perceived burden from providing care for urinary function, a confused care receiver, and post-stroke support.

Activities of Daily Living↗
PubMed1992

Effects of low levels of lice and internal nematodes on weight gain and blood parameters in calves in central Texas.

The effects of low levels of both biting and sucking lice, a mixed population of nematodes, and a combination of all these parasites were evaluated in calves held in a barn with no environmental controls in central Texas. Observations at 122 sites on each animal for 16 wk consecutively in 1987 revealed that the largest numbers of all louse species [Haematopinus eurysternus (Nitzsch). Linognathus vituli (L.), and Bovicola bovis (L.)] occurred 3-7 wk after infestation. In 1988 L. vituli populations decreased rapidly after the 3rd wk and B. bovis remained fairly constant for 20 wk consecutively. Average nematode egg counts increased to approximately 300 eggs per gram of feces in 1987 and approximately 600 eggs per gram of feces in 1988. The nematodes Ostertagia ostertagia, Haemonchus placei, Oesophagostomum radiatum, Cooperia spp., and Trichostrongylus spp. were present at the end of the study in both years as determined by necropsy. No significant differences in erythrocyte count, mean cell volume, hematocrit, hemoglobin concentration, leukocyte counts, or serum albumin concentration were detected. However, significant increases in total serum protein concentration and serum globulin levels in calves harboring both groups of parasites were observed. Mean weight gain in calves infested with lice and nematodes was 11.4 and 10 kg less than that of uninfested controls during 16 wk in 1987 and 20 wk in 1988, respectively.

Animals↗
PubMed1992

Osteomyelitis caused by Mycobacterium haemophilum: successful therapy in two patients with AIDS.

OBJECTIVE: Difficulties involved in diagnosis and response to antimicrobial therapy are described in detail for two cases of biopsy-proven osteomyelitis caused by Mycobacterium haemophilum in AIDS patients. SETTING: Two large, private teaching hospitals in New York City, New York, USA. PATIENTS, PARTICIPANTS: A 31-year-old woman with previous diagnoses of candida esophagitis and peripheral neuropathy (patient 1), and a 37-year-old man with Kaposi's sarcoma (patient 2). INTERVENTIONS: One patient was treated with a combination of rifampin, ethambutol, clofazimine, and ciprofloxacin, while the other received rifampin, ciprofloxacin and doxycycline. Both patients also received a short course of intravenous amikacin. MAIN OUTCOME MEASURES: Disease activity was monitored clinically by observing resolution of skin ulcers, lymphadenopathy, and pain and swelling in areas affected by osteomyelitis. RESULTS: Both patients experienced complete resolution of signs and symptoms of M. haemophilum infection. Patient 1 was treated for 17 months and remains well after 10 months without therapy. Patient 2 shows no evidence of infection after 14 months of therapy. CONCLUSIONS: M. haemophilum infection must be considered in the differential diagnosis of osteomyelitis in AIDS patients, although specialized culture techniques are required to isolate and identify this pathogen. Excellent clinical response can be achieved with oral antimicrobial therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Efficacy of two formulations of albendazole against liver flukes in cattle.

Albendazole (10 mg/kg of body weight) was administered as a drench suspension or as a feed additive to 24 cattle with naturally acquired infections of Fasciola hepatica and Fascioloides magna. Cattle were euthanatized 16 to 30 days after treatment, and the number of viable flukes was counted. Viable F hepatica and F magna were decreased by 91.4% and 70.6% for drench administration and by 82.9% and 71.9% for the feed additive treatment, respectively. There was no significant difference between the efficacy of the 2 formulations in decreasing viable fluke numbers, compared with untreated controls.

Administration, Oral↗
PubMed1991

Opinions about management of geriatric syndromes given by internal medicine residents in two programs.

Internal medicine residents in two programs providing different amounts of training in geriatrics were surveyed in 1988 regarding their opinions about the management of four geriatric problems and two traditional internal medicine problems. The residents generally agreed that geriatric problems were legitimate concerns in a general internal medicine practice but demonstrated less confidence in the management of geriatric problems than in the management of traditional problems. Residents from the program that provided more extensive training in geriatrics evidenced greater support for nondiscriminatory care of elderly diabetics; otherwise there was no convincing evidence of differences between the two programs. The authors conclude that educational efforts in geriatrics need to target trainees' confidence in the management of geriatric problems.

California↗
PubMed1991

Abnormal eating attitudes and body image in older undernourished individuals.

An anorexia nervosa-like syndrome has been reported in older persons. To gain additional insight into this condition, a questionnaire designed to assess the severity of eating disorders (the EAT-26) was administered to 183 male outpatients. Thirty-four subjects were found to be undernourished by midarm circumference measurement and 21 by weight adjusted for age-sex-height. Approximately 60% of malnourished subjects acknowledged inappropriate self-control around food, up to 26% described other unsuitable eating attitudes, and 3% to 52% evidenced various forms of distorted body image. They scored high on EAT-26 Oral Control subscale but low to normal on Dieting and Bulimia and Food Preoccupation subscales. These results indicate that abnormal eating attitudes and body image occur in an important minority of undernourished elderly males, but the pattern of abnormalities differs from that seen in classical anorexia nervosa. This association deserves additional investigation, with special attention to the psychopathology producing high Oral Control responses and to females as well as males. In the meantime, clinicians need to consider anorexia-like attitudes when caring for malnourished seniors.

Aged↗
PubMed1991

Acute upper gastrointestinal bleeding in elderly persons.

We have seen that UGI bleeding is a serious and apparently growing problem for seniors. Of special concern in the older patient are the frequency with which serious peptic disease presents silently, the limitation frequently imposed on adequate pain relief from NSAIDs, and the higher complication rates from most of the causes of UGI bleeding. Care of the elderly would be enhanced by research focused on defining those older patients most at risk of experiencing NSAID-induced peptic complications, improved methods for preventing or treating NSAID-induced ulceration that are well tolerated and cost-effective, and better regimens for preventing the recurrence of ulcers and UGI bleeding in these patients. In regard to the last, future investigation of the role of H. pylori, methods for successfully eliminating the organism, and the effect of eradication on patients' subsequent course may be particularly helpful.

Age Factors↗