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Biomedical subjects

M McCaffery

Publications and source records attributed to M McCaffery.

At least 91 records · Page 5Linked to original sources
PubMed1994

A Rab1 mutant affecting guanine nucleotide exchange promotes disassembly of the Golgi apparatus.

The Golgi apparatus is a dynamic organelle whose structure is sensitive to vesicular traffic and to cell cycle control. We have examined the potential role for rab1a, a GTPase previously associated with ER to Golgi and intra-Golgi transport, in the formation and maintenance of Golgi structure. Bacterially expressed, recombinant rab1a protein was microinjected into rat embryonic fibroblasts, followed by analysis of Golgi morphology by fluorescence and electron microscopy. Three recombinant proteins were tested: wild-type rab, mutant rab1a(S25N), a constitutively GDP-bound form (Nuoffer, C., H. W. Davidson, J. Matteson, J. Meinkoth, and W. E. Balch, 1994. J. Cell Biol. 125: 225-237), and mutant rab1a(N124I) defective in guanine nucleotide binding. Microinjection of wild-type rab1a protein or a variety of negative controls (injection buffer alone or activated ras protein) did not affect the appearance of the Golgi, as visualized by immunofluorescence of alpha-mannosidase II (Man II), used as a Golgi marker. In contrast, microinjection of the mutant forms promoted the disassembly of the Golgi stacks into dispersed vesicular structures visualized by immunofluorescence. When S25N-injected cells were analyzed by EM after immunoperoxidase labeling, Man II was found in isolated ministacks and large vesicular elements that were often surrounded by numerous smaller unlabeled vesicles resembling carrier vesicles. Golgi disassembly caused by rab1a mutants differs from BFA-induced disruption, since beta-COP remains membrane associated, and Man II does not redistribute to the ER. BFA can still cause these residual Golgi elements to fuse and disperse, albeit at a slower rate. Moreover, BFA recovery is incomplete in the presence of rab1 mutants or GTP gamma S. We conclude that GTP exchange and hydrolysis by GTPases, specifically rab1a, are required to form and maintain normal Golgi stacks. The similarity of Golgi disassembly seen with rab1a mutants to that occurring during mitosis, may point to a molecular basis involving rab1a for fragmentation of the Golgi apparatus during cell division.

Animals↗
PubMed1994

Nurses' assessment of pain intensity and choice of analgesic dose.

Under-treatment of all types of pain has been identified in many countries throughout the world. For example, the World Health Organization states that unrelieved cancer pain is an international problem. Lack of education of health care professionals, including nurses, is frequently cited as a major reason for under-treatment of pain. This survey of 517 Australian nurses suggests that they have some of the same educational needs as nurses in North America, such as how to assess pain intensity and how to select a dose of an opioid analgesic that is appropriate for the individual patient.

Education, Nursing, Continuing↗
PubMed1993

Giardia lamblia: absence of cyst antigens and reduced secretory vesicle formation and bile salt uptake in an encystation-deficient subline.

Encystation of Giardia lamblia entails the appearance of a number of new antigens, as well as formation of a novel class of large encystation-specific secretory vesicles (ESV) that transport stage-specific proteins to the nascent cyst wall. The monoclonal antibody GCSA-1, which was raised against purified cyst walls, recognizes protein species of approximately 26-46 kDa that are regulated by exposure to bile (plus lactic acid) and alkaline pH, the factors that induce encystation. The GCSA-1 epitope is maximally expressed after approximately 14 hr of encystation and localizes to the interior, but not the membrane of the ESV as shown by frozen section immunoelectron microscopy. To further understand the process of encystation, we compared two sublines of strain WB that differ in their ability to encyst in vitro. Water-resistant cysts were not detected in subline A6 under conditions in which subline C6 formed approximately 2 x 10(5) cysts/ml. Moreover, subline A6 did not form ESV efficiently or detectably express antigens recognized by mAb GCSA-1 or by polyclonal anti-cyst sera. Finally, uptake of the bile salt taurocholate by A6 was reduced 4- to 20-fold, compared with that of C6, although transport by both strains was sodium-dependent and regulated by bile salt starvation. The decrease in bile salt uptake by A6 may be related to its defect in encystation.

Animals↗
PubMed1993

Disruption of endoplasmic reticulum to Golgi transport leads to the accumulation of large aggregates containing beta-COP in pancreatic acinar cells.

When transport between the rough endoplasmic reticulum (ER) and Golgi complex is blocked by Brefeldin A (BFA) treatment or ATP depletion, the Golgi apparatus and associated transport vesicles undergo a dramatic reorganization. Because recent studies suggest that coat proteins such as beta-COP play an important role in the maintenance of the Golgi complex, we have used immunocytochemistry to determine the distribution of beta-COP in pancreatic acinar cells (PAC) in which ER to Golgi transport was blocked by BFA treatment or ATP depletion. In controls, beta-COP was associated with Golgi cisternae and transport vesicles as expected. Upon BFA treatment, PAC Golgi cisternae are dismantled and replaced by clusters of remnant vesicles surrounded by typical ER transitional elements that are generally assumed to represent the exit site of vesicular carriers for ER to Golgi transport. In BFA-treated PAC, beta-COP was concentrated in large (0.5-1.0 micron) aggregates closely associated with remnant Golgi membranes. In addition to typical ER transitional elements, we detected a new type of transitional element that consists of specialized regions of rough ER (RER) with ribosome-free ends that touched or extended into the beta-COP containing aggregates. In ATP-depleted PAC, beta-COP was not detected on Golgi membranes but was concentrated in similar large aggregates found on the cis side of the Golgi stacks. The data indicate that upon arrest of ER to Golgi transport by either BFA treatment or energy depletion, beta-COP dissociates from PAC Golgi membranes and accumulates as large aggregates closely associated with specialized ER elements. The latter may correspond to either the site of entry or exit for vesicles recycling between the Golgi and the RER.

Adenosine Triphosphate↗
PubMed1992

Pain control. Barriers to the use of available information. World Health Organization Expert Committee on Cancer Pain Relief and Active Supportive Care.

One of the World Health Organization's (WHO) top priorities is cancer pain relief. Simple guidelines for assessing and relieving pain have been developed, published, and field tested. WHO has concluded that there is enough knowledge currently to permit an approach to cancer pain relief that can be implemented on a worldwide basis. This information, when used correctly, allows pain control in 75% or more of patients with cancer pain. However, numerous barriers prevent the application of this knowledge and the achievement of cancer pain relief. Assessing the patient's cancer pain and effective use of analgesic drugs, especially opioid agents, are hampered by a lack of education of health-care professionals and the fact that the pain sensation is entirely subjective. Unfortunately, these factors often result in pain management being determined on the basis of personal opinion rather than scientific knowledge. This leads to inconsistent and often inadequate care of patients with cancer pain. The extent of the cancer pain problem and the WHO analgesic-ladder approach to cancer pain relief are reviewed along with recommendations from the American Pain Society. Lack of education of health-care professionals is discussed, focusing on pain assessment, underuse of oral and rectal routes of administration, fears of addiction, and titration of doses of opioid drugs. Simple strategies for beginning to correct these problems are presented.

Humans↗
PubMed1992

Pain and addiction: an urgent need for change in nursing education.

Lack of education of health care professionals, including nurses, is frequently cited as a major reason for undertreatment of patients with pain. A reason for undertreatment of pain with opioid analgesics is the irrational fear of creating opioid addiction. To characterize the information nurses receive in their basic education that could contribute to misinformation about this issue, the authors reviewed 14 nursing textbooks, published since 1985, including 8 pharmacology texts and 6 medical surgical texts. An analysis of content revealed that only one textbook correctly stated the definition of opioid addiction and its likelihood following use of opioid analgesics for pain control. Almost all of the texts used confusing terminology, and some erroneously promoted the fear of addiction when opioids are used for pain relief. A simple solution to this problem is to encourage nursing educators to use the American Pain Society publication "Guidelines for Analgesic Use" until textbooks have the opportunity to incorporate correct information.

Attitude of Health Personnel↗
PubMed1992

Pain relief using cutaneous modalities, positioning, and movement.

Positioning, movement, and certain cutaneous modalities may be easily used by all caregivers, including the family, to bring comfort and pain relief to terminally ill patients with pain. For such patients, these techniques are most appropriately used in addition to pharmacologic control of pain. Patients themselves may use some of the cutaneous modalities with minimal assistance from others, thereby promoting a sense of independence. Other techniques may be performed by family and friends, providing them with the assurance that they are assisting a loved one. The techniques presented here can be readily used in the home or hospital setting and are relatively low risk, simple, and inexpensive. This paper presents specific guidelines for patients and caregivers in relation to the use of superficial massage, superficial heat and cold, menthol application to skin, transcutaneous electrical nerve stimulation (TENS), positioning, and movement. Because of their simplicity and ease of use, these techniques tend to be overlooked. However, taking the time to introduce these techniques to patients and families often results in a significant contribution to the comfort of the dying patient.

Cryotherapy↗