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Biomedical subjects

M E Smith

Publications and source records attributed to M E Smith.

At least 19 recordsLinked to original sources
PubMed2005

Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment.

AIMS/HYPOTHESIS: Glucose toxicity and glucosamine-induced insulin resistance have been attributed to products of glucosamine metabolism. In addition, endothelial cell nitric oxide synthase is inhibited by glucosamine. Since insulin has endothelial nitric-oxide-dependent vasodilatory effects in muscle, we hypothesise that glucosamine-induced insulin resistance in muscle in vivo is associated with impaired vascular responses including capillary recruitment. MATERIALS AND METHODS: Glucosamine (6.48 mg kg(-1) min(-1) for 3 h) was infused with or without insulin (10 mU kg(-1) min(-1)) into anaesthetised rats under euglycaemic conditions. RESULTS: Glucosamine infusion alone increased blood glucosamine (1.9+/-0.1 mmol/l) and glucose (5.4+/-0.2 to 7.7+/-0.3 mmol/l) (p<0.05) but not insulin. Glucosamine induced both hepatic and muscle insulin resistance as evident from measures of glucose appearance and disposal as well as hind-leg glucose uptake, which was inhibited by approx. 50% (p<0.05). Insulin-mediated increases in femoral arterial blood flow and capillary recruitment were completely blocked by glucosamine. CONCLUSION/INTERPRETATION: Glucosamine mediates a major impairment of insulin action in muscle vasculature associated with the insulin resistance of muscle. Further studies will be required to assess whether the impaired capillary recruitment contributes to insulin resistance.

Algorithms↗
PubMed2005

A multinuclear solid state NMR study of the sol-gel formation of amorphous Nb2O5-SiO2 materials.

Multinuclear 1H, 13C, 17O, 29Si MAS and 93Nb static NMR is reported from a series of sol-gel prepared (Nb2O5)x(SiO2)(1-x) materials with x=0.03, 0.075 or 0.30. 13C NMR shows that by 500 degrees C the organic precursor fragments have been removed although some residual carbon remains as a separate phase. The 29Si NMR typically shows three Q-species (Q2,3,4) in the initial gels, and that with increasing heat treatment the average n of the Qn-species increases as the organic fragments and hydroxyl groups are removed. 17O shows unequivocally that the x=0.03 and 0.075 samples are not phase separated, while at the much higher niobia-content of x=0.30 Nb-O-Nb signals are readily detected, a definite indication of the atomic scale phase separation of Nb2O5. The x=0.03 and 0.075 samples heated to 750 degrees C are thus representative of amorphous niobium silicates. Comparison is made to other sol-gel prepared metal silicates especially with another Group Va metal tantalum. The effects of tantalum and niobium on the silica network are very different and it is suggested here that most of the niobium is present as NbO4, forming part of the silicate network.

Journal Article↗
PubMed2005

Solid-state NMR characterisation of the thermal transformation of a Hungarian white illite.

(1)H, (27)Al, (29)Si and (39)K solid-state NMR are reported from a Hungarian illite 2:1 clay for samples heated up 1600 degrees C. This single-phase sample has a small amount of aluminium substitution in the silica layer and very low iron-content ( approximately 0.4wt%). Thermal analysis shows several events that can be related to features in the NMR spectra, and hence changes in the atomic scale structure. As dehydroxylation occurs there is increasing AlO(4) and AlO(5)-contents. The silica and gibbsite layers become increasingly separated as the dehydroxylation progresses. Between 900 and 1000 degrees C the silica layer forms a potassium aluminosilicate glass. The gibbsite-layer forms spinel/gamma-Al(2)O(3) and some aluminium-rich mullite. Then on heating to 1600 degrees C changes in the (29)Si and (27)Al MAS NMR spectra are consistent with the aluminosilicate glass increasing its aluminium-content, the amount of mullite increasing probably with its silicon-content also increasing, and some alpha-Al(2)O(3) forming.

Journal Article↗
PubMed2003

Guinea-pig heart acetylcholinesterase after continuous physostigmine administration.

G1 and G4 acetylcholinesterase (AChE) molecular forms were separated in different regions of guinea-pig heart. The activities of both were highest in the left side of the left ventricle (LV(L)). The reversible anticholinesterase physostigmine, or saline, was administered continuously for six days. In saline-treated animals the activity of both molecular forms was markedly increased in both atria, G1 activity was increased on the left side of the right ventricle (LV(R)), and G4 activity was increased on both sides of the right ventricle compared to untreated animals. However, G1 activity was significantly decreased on the left side of the left ventricle. Physostigmine administration caused a significant reduction in G4 activity in the left atrium (LA), the left side of the right ventricle, and the left side of the left ventricle, and a significant increase in G1 activity on the right side of the right ventricle compared to saline-treated animals. The distribution of AChE indicates a role for parasympathetic nerves in the control of both ventricles and atria. The changes in AChE in saline-treated animals could have been due to the anaesthesia or stress of the surgical procedures. Physostigmine caused delayed changes in the enzyme in some regions, consistent with an effect on its expression.

Acetylcholinesterase↗
PubMed2002

Nonnutritive flow impairs uptake of fatty acid by white muscles of the perfused rat hindlimb.

Triglyceride hydrolysis by the perfused rat hindlimb is enhanced with serotonin-induced nonnutritive flow (NNF) and may be due to the presence of nonnutritive route-associated connective tissue fat cells. Here, we assess whether NNF influences muscle uptake of 0.55 mM palmitate in the perfused hindlimb. Comparisons were made with insulin-mediated glucose uptake. NNF induced during 60 nM insulin infusion inhibited hindlimb oxygen uptake from 22.0 +/- 0.5 to 9.7 +/- 0.8 micromol x g(-1) x h(-1) (P < 0.001), 1-methylxanthine metabolism (indicator of nutritive flow) from 5.8 +/- 0.4 to 3.8 +/- 0.4 nmol x min(-1) x g(-1) (P = 0.004), glucose uptake from 29.2 +/- 1.7 to 23.1 +/- 1.8 micromol x g(-1) x h(-1) (P = 0.005) and muscle 2-deoxyglucose uptake from 82.1 +/- 4.6 to 41.6 +/- 6.7 micromol x g(-1) x h(-1) (P < 0.001). Palmitate uptake, unaffected by insulin alone, was inhibited by NNF in extensor digitorum longus, white gastrocnemius, and tibialis anterior muscles; average inhibition was from 13.9 +/- 1.2 to 6.9 +/- 1.4 micromol x g(-1) x h(-1) (P = 0.02). Thus NNF impairs both fatty acid and glucose uptake by muscle by restricting flow to myocytes but, as shown previously, favors triglyceride hydrolysis and uptake into nearby connective tissue fat cells. The findings have implications for lipid partitioning in limb muscles between myocytes and attendant adipocytes.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Long-term treatment with recombinant nerve growth factor for HIV-associated sensory neuropathy.

HIV-associated distal sensory polyneuropathy (DSP) is a common complication of AIDS. No effective treatment is available. The authors investigated the long-term effect (48 weeks) of the neurotrophin nerve growth factor (NGF) in an open-label study of 200 subjects with HIV-associated DSP. Similar to their previously reported double-blind study, the authors showed that NGF was safe and well tolerated and significantly improved pain symptoms. However, there was no improvement of neuropathy severity as assessed by neurologic examination, quantitative sensory testing, and epidermal nerve fiber density.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Phagocytic properties of microglia in vitro: implications for a role in multiple sclerosis and EAE.

The microglial cell, after many years of neglect, has become recognized as the sole representative cell of the immune system that resides in the normal central nervous system. While normally dormant, microglia can be activated by secretory substances or signals associated with disease or injury, and becomes a phagocytic cell, which also produces its own injurious molecules. In the activating process, its morphology is changed from a resting process-bearing cell, into a rounded amoebic form, and displays new or increased amounts of functional markers, such as receptors and Class I and Class II MHC molecules. Microglia prepared from newborn mice or rats for tissue culture are already activated, and can be used for studies of their phagocytic properties. Although they can phagocytize foreign substances, their uptake and metabolism of myelin are emphasized here, in keeping with their role in demyelinating diseases. A number of receptors have been implicated and appear to be important in the attachment to, and ingestion of, myelin particles in vitro, including the Fc, complement, macrophage scavenger, and the Galectin-3/MAC-2 receptors, although the alpha2-macroglobulin/low-density lipoprotein receptor and mannose receptors have also been suggested as participants in myelin phagocytosis. Certain cytokines and adhesion molecules also regulate the phagocytic activity of microglia. Comparative in vitro studies of phagocytosis by peritoneal macrophages and microglia have shown that the two kinds of cells respond differently to regulatory molecules, and it is concluded that they have different innate properties. The role of microglia in the demyelinative diseases experimental autoimmune encephalomyelitis and multiple sclerosis is emphasized here, and the possible means of intervention in the process leading to myelin destruction is discussed. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed2001

Novel heteroaryl replacements of aromatic 3-tetrafluoroethoxy substituents in trifluoro-3-(tertiaryamino)-2-propanols as potent inhibitors of cholesteryl ester transfer protein.

A series of novel N,N-disubstituted trifluoro-3-amino-2-propanols has been prepared as potent inhibitors of cholesteryl ester transfer protein (CETP). Modifying the aromatic 3-tetrafluoroethoxy group in the lead molecule 1a with various heteroaryl moieties produced new 2-furyl analogues 2a,b with submicromolar potency in vitro.

Carrier Proteins↗
PubMed2001

Clicking in the throat: cinematic fiction or surgical fact?

The complaint of a clicking in the throat when swallowing is uncommon but very discomforting and painful for those who experience it. It is such an unusual complaint that symptoms may be dismissed as psychogenic because a cause for the problem may not be readily apparent. We present a series of 11 cases in which all patients had an audible clicking or popping noise in the throat associated with neck and throat pain when swallowing or turning the neck. The most helpful diagnostic procedure was careful examination and palpation of the neck while the patient swallowed to localize the side and source of the clicking. Laryngeal computed tomographic (CT) scans helped in some cases to demonstrate thyroid-cartilage and/or vertebral body asymmetry. Each case was treated with surgery of the neck and larynx to trim the portion of the thyroid cartilage causing the clicking. In most cases the superior cornu of the thyroid cartilage projected posteriorly and medially. Surgery was successful in all cases to eliminate the symptoms. Though an uncommon complaint, our experience suggests that the clicking throat is a surgically treatable problem.

Adolescent↗
PubMed2001

The effect of continuous pyridostigmine administration on functional (A12) acetylcholinesterase activity in guinea-pig muscles.

Pyridostigmine which causes a reversible inhibition of acetylcholinesterase (AChE), was administered continuously for 6 days to guinea-pigs, via a subcutaneously implanted osmotic pump. This produced 40-50% inhibition of red cell acetylcholinesterase (AChE). Controls were animals treated with saline via pumps, and untreated animals. The activities of the functional A12 molecular form of AChE were compared in diaphragm, extensor digitorum longus (EDL) and soleus muscles in the three animal groups at 6 days. The pumps were removed at 6 days and the A12 AChE activities were determined at various times thereafter As the enzyme separation procedure was lengthy, drug-induced inhibition was no longer present when the enzyme activity was measured. At 6 days, the activity was significantly higher in EDL (over 50% higher) and soleus (over two-fold higher) in pyridostigmine-treated animals than saline-treated animals. In the diaphragm, the activities in pyridostigmine and saline-treated animals were similar but both were significantly (over two-fold) higher than in untreated animals. At 1 day after pump removal (day 7) the activity had declined in all three muscles of the pyridostigmine-treated animals and in the diaphragm of saline-treated animals. Thereafter, in the diaphragm (but not the EDL or soleus) in pyridostigmine-treated animals, there were marked variations in the enzyme activity up to day 20. In saline-treated animals there was a marked transient increase in activity at day 13 in all muscles. The results indicate that the homeostatic control offunctional AChE had been affected in both the pyridostigmine and saline treatment groups.

Acetylcholinesterase↗
PubMed2001

Neurophysiological signals of working memory in normal aging.

To examine how neurophysiological signals of working memory (WM) change with normal aging, we recorded EEGs from healthy groups (n=10 each) of young (mean age=21 years), middle-aged (mean=47 years), and older (mean=69 years) adults. EEGs were recorded while subjects performed easy and difficult versions of a spatial WM task. Groups were matched for IQ (mean=123; WAIS-R) and practiced in task performance. Responses slowed with age, particularly in the more difficult task. Advanced age was associated with decreased amplitude and increased latency of the parietal P300 component of the event-related potential and an increase in the amplitude of a frontal P200 component. Spectral features of the EEG also differed between groups. Younger subjects displayed an increase in the frontal midline &theta; rhythm with increased task difficulty, a result not observed in older subjects. Age-related changes were also observed in the task-related alpha signal, the amplitude of which decreases as more neurons become involved in task-related processing. Young adults showed a decrease in alpha power with increased task difficulty over parietal regions but not over frontal regions. Middle-aged and older adults showed decreased alpha power with increased task difficulty over both frontal and parietal regions. This suggests that normal aging may be associated with changes in the fronto-parietal networks involved with spatial WM processes. Younger subjects appear to use a strategy that relies on parietal areas involved with spatial processing, whereas older subjects appear to use a strategy that relies more on frontal areas.

Adult↗
PubMed2001

The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking.

Phosphoinositides play key regulatory roles in vesicular transport pathways in eukaryotic cells. Clathrin-mediated membrane trafficking has been shown to require phosphoinositides, but little is known about the enzyme(s) responsible for their formation. Here we report that clathrin functions as an adaptor for the class II PI 3-kinase C2alpha (PI3K-C2alpha), binding to its N-terminal region and stimulating its catalytic activity, especially toward phosphorylated inositide substrates. Further, we show that endogenous PI3K-C2alpha is localized in coated pits and that exogenous expression affects clathrin-mediated endocytosis and sorting in the trans-Golgi network. These findings provide a mechanistic basis for localized inositide generation at sites of clathrin-coated bud formation, which, with recruitment of inositide binding proteins and subsequent synaptojanin-mediated phosphoinositide hydrolysis, may regulate coated vesicle formation and uncoating.

Amino Acid Sequence↗
PubMed2001

Control of vocal loudness in young and old adults.

This study examined the effect of aging on respiratory and laryngeal mechanisms involved in vocal loudness control. Simultaneous measures of subglottal pressure and electromyographic (EMG) activity from the thyroarytenoid (TA), lateral cricoarytenoid (LCA), and cricothyroid (CT) muscles were investigated in young and old individuals while they attempted to phonate at three loudness levels, "soft," "comfortable," and "loud." Voice sound pressure level (SPL) and fundamental frequency (F ) measures were also obtained. Across loudness conditions, subglottal pressure levels were similar for both age groups. Laryngeal EMG measures tended to be lower and more variable for old compared with young individuals. These differences were most apparent for the TA muscle. Finally, across the three loudness conditions, the old individuals generated SPLs that were lower overall than those produced by the young individuals but modulated loudness levels in a manner similar to that of the young subjects. These findings suggest that the laryngeal mechanism may be more affected than the respiratory system in these old individuals and that these changes may affect vocal loudness levels.

Adult↗
PubMed2001

Intravascular lymphomatosis presenting within angiolipomas.

This report presents a case of intravascular lymphomatosis identified within an angiolipoma. The patient was a 73-year-old woman with a history of lobular carcinoma of the breast who presented with a chest wall nodule near the site of prior mastectomy. Microscopically, the nodule was composed of encapsulated adipose tissue with an associated vascular proliferation. Many of the vascular lumina were expanded by collections of large pleomorphic cells with vesicular nuclei and prominent nucleoli. These atypical cells displayed immunoreactivity for CD45RB (leukocyte common antigen) and the pan-B cell marker CD20 (L26). The patient subsequently developed multiple lesions of the extremities and died soon after developing symptoms referable to the central nervous system. Intravascular lymphomatosis most commonly presents with central nervous system and dermatologic involvement although any organ system may be affected. Intravascular lymphomatosis is an aggressive neoplasm that is generally diagnosed at postmortem examination. This case shows the protean manifestations of intravascular lymphomatosis and highlights the necessity of considering this malignancy in the differential diagnosis when entertaining the diagnosis of vascular invasion by carcinoma. Ann Diagn pathol 5:103-106, 2001. This is a US government work. There are no restrictions on its use.

Aged↗
PubMed2001

Delta opioid receptors mediate glucose uptake in skeletal muscles of lean and obese-diabetic (ob/ob) mice.

Specific binding sites for [125I]beta-endorphin and the delta1-opioid [3H][D-pen(2), D-pen(5)]enkephalin (DPDPE) were quantified using autoradiography in soleus and extensor digitorum longus (EDL) muscles of lean and obese-diabetic (ob/ob) mice. The density of binding was significantly higher in obese-diabetic than lean mice. The uptake of 2-deoxy-D-[1-3H]deoxyglucose, a nonmetabolized glucose analogue, into isolated soleus and EDL muscles was stimulated by beta-endorphin, beta-endorphin 1-27, and DPDPE, but not by the delta2-opioid deltorphin II. Both beta-endorphin and DPDPE stimulated deoxyglucose uptake in obese-diabetic mice. Thus, glucose transport in skeletal muscle may be partly mediated via delta1-opioid receptors. The increased receptor density in obese-diabetic mice may be an adaptive response.

Animals↗
PubMed2001

The journey of recovery after a rape experience.

In this existential-phenomenological investigation seven women were interviewed about their experiences of recovering from rape trauma. The purpose of the study was to discover the meaning of recovery from the perception of the victim, how recovery is experienced, and what contributed to the growth and recovery of the woman who has been raped. Transcribed interviews were analyzed using a hermeneutic process. The thematic structure of a woman's recovery from rape comprises three main themes: reaching out, reframing the rape, and redefining the self. These findings are important to professionals working with women who have been raped because it is the raped woman, rather than the clinician, who is able to define what constitutes recovery.

Adaptation, Psychological↗