SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
We have direct evidence of neurogenic stimulation of human exocrine sweating by muscular exercise. Sweating was markedly increased when warmed venous blood was prevented fromn reaching the heat-loss center in the hypothalamus.
Screening of sweat chloride in newborn infants with the Orion Skin Chloride Measuring System and incorporating some procedural innovations is described. The results indicate that while diagnostic screening for cystic fibrosis can be readily undertaken, the test with the chloride ion-selective electrode is best left at least to the second day of life or later because of insufficient sweating in very young babies. Measurements on 2 babies with cystic fibrosis are also discussed.
The cystic fibrosis (CF) clinical spectrum has greatly expanded in the past few years, including atypical forms with low sweat chloride concentrations. Two cases are presented which suggest that children detected by neonatal CF screening whose trypsinogen concentrations are still raised by the second month of age could, despite a negative sweat test, be affected by an atypical CF with fully expressed pulmonary involvement.
The difficulty in taking sweat during heavy physical exercise has drawn the authors into testing a technique of sampling generally used in paediatrics. The fact that the results, which have been dealt with statistically, should coincide with the physiological facts already published allows us to consider a use of the technique in order to investigate the physiological mechanisms in action during sweating under different metabolic conditions.
The changes in peripheral (hand) blood flow that occurred when deep body temperature was raised were measured in 13 patients with anorexia nervosa and 13 control subjects. The relation between blood flow and core temperature was shifted to the left in the patients with anorexia, with the onset of vasodilatation occurring at lower core and mean skin temperatures: no significant differences in the slopes of the responses were evident. The onset of thermal sweating occurred at lower core and mean skin temperatures in the patients with anorexia than in the controls. After ingestion of a high-energy liquid meal core temperature increased in the patients, and this was accompanied by a significant rise in peripheral blood flow in most cases. A similar meal in the normal subjects was followed by either no change in core temperature or a slight fall, and no consistent change in peripheral blood flow. These findings suggest that the lowering of thresholds for thermoregulatory sweating and vasodilatation may be a contributory factor to the abnormally low core temperature of patients with anorexia and may also explain some of their common complaints relating to feelings of warmth in the hands and feet after meals.
The influence of profuse sweating on systolic time intervals was investigated. Systolic time intervals were recorded in 21 healthy men before and after sauna bathing. After sauna bathing the ejection time was significantly shortened and the pre-ejection time and ratio of pre-ejection time to ejection time (PEP:ET) were significantly increased. The upper limit of the PEP:ET ratio is generally believed to be 0.42 and this ratio increases when left ventricular performance is impaired. Before sauna bathing the PEP:ET ratio was less than 0.42 in all 21 men, but after sauna bathing it was greater than 0.43 in six (28.5%) of them. Systolic time intervals measured after profuse sweating can give a false impression of cardiac function.
Small cell sweat gland carcinoma appears to represent a very unusual histological type of sweat gland anlage tumour presenting in children. The differential diagnosis from other small blue cell tumours involving the skin is often difficult. The present report confirms the original observation describing two patients of 2 and 5 years of age harbouring cutaneous tumours. The histology of these lesions showed a monomorphic proliferation of small cells with a high mitotic rate and areas of necrosis. Immunohistochemically, the cells were negative for desmin, cytokeratin 7, cytokeratin 20, Cam 5.2, CD99, chromogranin, CD56, synaptophysin, and S-100, and focally positive for the pancytokeratin marker AE1/AE3, carcinoembryonic antigen (one case), and neurone specific enolase (one case). The prognosis of this type of tumour seems to be good. As more cases are added, the clinical pathological spectrum of the lesion will become better defined.
Neonates positive for immunoreactive trypsinogen assay (IRT) and negative for sweat test have formerly been found to carry the major cystic fibrosis (CF) mutation, delta F508, much more frequently than the general population. Among the 716 IRT positive newborns detected by a three tier (IRT, mutation analysis plus meconium lactase assay, sweat test) CF screening programme in north eastern Italy during the period January 1993 to March 1996, we found 45 carriers, a number significantly higher than the expected 17 (p < 0.001). We speculated that some of these heterozygotes could actually be affected by a very mild form of CF, and carry on the other chromosome an undetected CFTR mutation or a DNA variant, such as the 5-thymidine allele in intron 8 of the CFTR gene (IVS8-5T). This hypothesis was tested in four samples; group A (the 45 carriers mentioned above), group B (51 non-carrier, IRT positive neonates), group C (50 IRT negative neonates), and group D (90 CF adult female carriers). Chromosomes with IVS8-5T were seven (7.78%) in group A, seven (6.86%) in group B, five (5%) in group C, and four in group D (2.22%). The 5T prevalence in group A was significantly higher (p < 0.05) compared to group D; similarly, a higher (p < 0.05) 5T frequency in group A compared to group C was detected by considering the chromosomes free from CFTR mutations. This study is consistent with previous papers in finding among neonates with high trypsin levels a CF carrier frequency significantly higher than that expected. It is also suggested that in at least some babies raised trypsin levels at birth could be a phenotypic expression of compound heterozygosity for a major CF mutation plus IVS8-5T.
Excessive sweating of the face and, to a lesser degree, of the thorax and limbs, occurred after basilar artery occlusion in a 15 year old Saudi boy. Magnetic resonance imaging (MRI) showed a limited bilateral paramedian infarction of the rostral ventral pons. Basilar artery occlusion in children and adolescents is a rarity. Excessive sweating following such a stroke is rare in any age group. Clinico-anatomical correlations are discussed.
The dye-coupling status of secretory and reabsorptive cells in micro-dissected lengths of human eccrine sweat gland was investigated by means of intracellular microiontophoresis of the fluorescent naphthalimide dye Lucifer yellow CH (Mr 457), which passes through gap junctions. Cells of the reabsorptive duct exhibited complete dye coupling between the apical and basal layers of the epithelium. Conversely, cells of the secretory tubule exhibited selective dye coupling. Of the three cell types present, clear, dark, and myoepithelial, the dark cells were impaled and labeled almost exclusively in the present study. These cells were observed either as single cells or as dye-coupled groups of neighboring dark cells. In no instance were dark cells observed to be dye coupled to clear cells or to myoepithelial cells. Because myoepithelial cells are known to be dye coupled exclusively to neighboring myoepithelial cells, the remaining clear cells must either be uncoupled or show selective dye coupling to neighboring clear cells. The significance of these findings is considered with respect to the regulation and function of the different cell types present in the human eccrine sweat gland.
This study characterized the various adenosine 3',5'-cyclic monophosphate (cAMP)-binding proteins in epithelial cells cultured from human sweat glands to identify potential pathways of cAMP action in this tissue. The cAMP-binding proteins were identified by specific labeling with the photoprobe 8-azido-[32P]-cAMP and visualized by autoradiography after electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate. Three cAMP-binding proteins, with molecular masses of 48, 52, and 54 kDa, were identified in subcellular fractions of the cultured sweat glands. On the basis of their relative electrophoretic mobilities and reactivity with specific antisera, the 48-kDa protein was identified as the regulatory subunit of the type 1 cAMP-dependent protein isozyme, and the 54-kDa protein was identified as the regulatory subunit of the type 2 cAMP-dependent protein kinase isozyme. The 52-kDa cAMP-binding protein appeared to be a distinct isoform of the regulatory subunit, possibly related to the subclass associated with neural tissue. As determined from the relative distributions of the photolabel, the 48-, 52-, and 54-kDa binding proteins were present in the cell cytosol at a ratio of 1:2:1. The 48- and 52-kDa proteins bound the photoprobe with apparent dissociation constants (Kd) of 20-40 nM, whereas the 54-kDa protein bound the photoprobe with much lower affinity (Kd 230 nM). Only the 48- and 52-kDa proteins were associated with cell membranes. They were present in the membrane fractions in approximately equal amounts and bound the photoprobe with apparent Kd values of greater than 100 nM.(ABSTRACT TRUNCATED AT 250 WORDS)
The human sweat gland secretory coil consists of three histologically distinct cell types: myoepithelial (ME), light (or clear), and dark cells. The electrophysiological properties of all these cells are poorly defined. Employing electrophysiological techniques, we report distinct pharmacological responses of three different cell types from freshly isolated human sweat gland secretory coil. The superficial ME cells are characterized by 1) spontaneous depolarizing spikes (2 to 50 mV), 2) high cell membrane potentials [Vm = -68.6 +/- 3.9 (SE) mV; n = 21], 3) a K(+)-selective cell membrane (slope response = 54.2 +/- 6.7 mV per decade K+ concentration; n = 4), 4) depolarizing responses to cholinergic agonist mecholyl (delta Vm = 29.1 +/- 3.1 mV, n = 21), and 5) insensitivity to beta-adrenergic stimulation (n = 12). Two other types of cells, presumably secretory, were also observed. We arbitrarily labeled these cells as beta-adrenergic sensitive (beta-S) and beta-adrenergic insensitive (beta-I) cells based on their respective sensitivity to isoproterenol (IPR), a beta-adrenomimetic. Properties of the beta-S cells include 1) relatively higher basolateral membrane potentials (Vm = -57.3 +/- 3.1 mV; n = 13), 2) depolarizing responses to IPR (delta Vm = 16.8 +/- 2.6 mV; n = 9) inhibitable by the beta-adrenergic antagonist propranolol, and 3) hyperpolarizing responses to mecholyl (delta Vm = -21.8 +/- 2.0 mV; n = 13). The beta-I cells are characterized by 1) low basolateral membrane potentials (Vm = -23.6 +/- 2.1 mV; n = 16), 2) insensitivity to beta-adrenergic stimulation, and 3) hyperpolarizating responses to mecholyl (delta Vm = -16.1 +/- 2.1 mV; n = 16).
The sweat gland has three distinct cell types: a myoepithelial (ME) cell, a beta-adrenergic-insensitive (beta-I) cell, and a beta-adrenergic-sensitive (beta-S) cell. Using intracellular microelectrodes, we sought to functionally identify the specific cell type(s) affected in cystic fibrosis (CF). We found that in CF secretory coils 1) the ME calls are unaffected, as indicated by normal cell membrane potentials and spontaneous and cholinergically induced depolarizing potentials, 2) the beta-I cells showed normal physiological properties, including a relatively smaller cell membrane potential (approx -25 mV) and a Ba(2+)-inhibitable cholinergic response, and, in contrast, 3) the beta-S cell is abnormal, as shown by the lack of a beta-adrenergically activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- conductance (GCl). Lack of CFTR GCl in this cell type does not affect either the magnitude of cell membrane potential (approx -56 mV) or the relative cell membrane GCl or the cholinergic response, as compared with that of normal beta-S cells. We conclude that, of the three cell types in secretory coil, only the beta-S cell is specifically affected in the CF secretory tissue of the human sweat gland.
Bumetanide is well known for its ability to inhibit the nonconductive Na+-K+-2Cl- cotransporter. We were surprised in preliminary studies to find that bumetanide in the contraluminal bath also inhibited NaCl absorption in the human sweat duct, which is apparently poor in cotransporter activity. Inhibition was accompanied by a marked decrease in the transepithelial electrical conductance. Because the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is richly expressed in the sweat duct, we asked whether bumetanide acts by blocking this anion channel. We found that bumetanide 1) significantly increased whole cell input impedance, 2) hyperpolarized transepithelial and basolateral membrane potentials, 3) depolarized apical membrane potential, 4) increased the ratio of apical-to-basolateral membrane resistance, and 5) decreased transepithelial Cl- conductance (GCl). These results indicate that bumetanide inhibits CFTR GCl in both cell membranes of this epithelium. We excluded bumetanide interference with the protein kinase A phosphorylation activation process by "irreversibly" phosphorylating CFTR [by using adenosine 5'-O-(3-thiotriphosphate) in the presence of a phosphatase inhibition cocktail] before bumetanide application. We then activated CFTR GCl by adding 5 mM ATP. Bumetanide in the cytoplasmic bath (10(-3) M) inhibited approximately 71% of this ATP-activated CFTR GCl, indicating possible direct inhibition of CFTR GCl. We conclude that bumetanide inhibits CFTR GCl in apical and basolateral membranes independent of phosphorylation. The results also suggest that >10(-5) M bumetanide cannot be used to specifically block the Na+-K+-2Cl- cotransporter.
It is generally believed that cAMP-dependent phosphorylation is the principle mechanism for activating cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. However, we showed that activating G proteins in the sweat duct stimulated CFTR Cl(-) conductance (G(Cl)) in the presence of ATP alone without cAMP. The objective of this study was to test whether the G protein stimulation of CFTR G(Cl) is independent of protein kinase A. We activated G proteins and monitored CFTR G(Cl) in basolaterally permeabilized sweat duct. Activating G proteins with guanosine 5'-O-(3-thiotriphosphate) (10-100 microM) stimulated CFTR G(Cl) in the presence of 5 mM ATP alone without cAMP. G protein activation of CFTR G(Cl) required Mg(2+) and ATP hydrolysis (5'-adenylylimidodiphosphate could not substitute for ATP). G protein activation of CFTR G(Cl) was 1) sensitive to inhibition by the kinase inhibitor staurosporine (1 microM), indicating that the activation process requires phosphorylation; 2) insensitive to the adenylate cyclase (AC) inhibitors 2',5'-dideoxyadenosine (1 mM) and SQ-22536 (100 microM); and 3) independent of Ca(2+), suggesting that Ca(2+)-dependent protein kinase C and Ca(2+)/calmodulin-dependent kinase(s) are not involved in the activation process. Activating AC with 10(-6) M forskolin plus 10(-6) M IBMX (in the presence of 5 mM ATP) did not activate CFTR, indicating that cAMP cannot accumulate sufficiently to activate CFTR in permeabilized cells. We concluded that heterotrimeric G proteins activate CFTR G(Cl) endogenously via a cAMP-independent pathway in this native absorptive epithelium.
To gain better insight into the interaction between thermoregulation and osmoregulation, we examined the thermal sweating response to drinking in cell-dehydrated humans. Cell dehydration (CDH) was induced by infusion of a 3% NaCl solution, at 1.2 ml/kg, for 2 h; infusion of a 0.9% NaCl solution in a separate experiment served as a control (euhydrated condition, EH). After infusion, subjects were heated by immersion of the lower legs in 42 degrees C water at an ambient temperature of 28 degrees C for 90 min. Subjects drank 4.3 ml/kg of H2O (approximately 38 degrees C) at 60 min of heating. The 3% NaCl infusion increased plasma osmolality by 13.6 +/- 0.8 mosmol/kgH2O and plasma arginine vasopressin concentration ([AVP]) by 3.3 +/- 0.7 pg/ml. Neither variable was altered with 0.9% NaCl infusion. Before drinking, esophageal temperature (Tes) had increased by 0.91 +/- 0.08 degrees C in CDH and by 0.40 +/- 0.11 degrees C in EH. Local chest sweating rate (SRch) had increased by 0.67 +/- 0.08 and 0.63 +/- 0.07 mg.min-1.cm-2 in CDH and EH, respectively. Thus the change in SRch per unit rise in Tes was much lower in CDH than in EH. Drinking immediately increased SRch and reduced Tes in CDH, with a reduction in plasma [AVP] and thirst rating. Drinking did not change thermoregulatory and osmoregulatory responses in EH. These results suggest that the act of drinking itself eliminates, at least partially, an osmotic inhibitory input to the thermoregulatory center, as well as osmotic AVP secretion and thirst.
Six subjects exercised on a bicycle ergometer at 60-70% of maximal aerobic power in a 25 degrees C ambient. Experiments on each subject were conducted at night (4:00-5:30 A.M.) and in daytime (noon-4:30 P.M.). Chest sweating rate (msw) was measured with resistance hygrometry. Forearm blood flow (BF), with an arm skin temperature of 35.5 +/- 1.2 degrees C (SD), was measured with electrocapacitance plethysmography. Esophageal temperature (Tes) was measured with a thermocouple at the level of the left atrium, and mean skin temperature (Tsk) was calculated from a weighted average of temperatures at three sites. Tes was corrected to a skin temperature of 33 degrees C as follows: T'es = Tes + (Tsk - 33 degrees C)/8. This correction reflects the relative contributions of Tes and Tsk to control of msw:T'es and BF:T'es relations were not consistently changed. In any given subject, thresholds for sweating and vasodilation were shifted about equally. These shifts averaged 0.57 degrees C (range: 0.23-0.93 degrees C)for msw and 0.63 degrees C (range: 0.17-0.98 degrees C) for BF.
To find whether exercise or upright posture affected the internal temperature threshold for cutaneous vasodilation or the relationship between skin blood flow (SkBF) and sweat rate (SR), the relationship of esophageal temperature (Tes) to forearm SkBF and SR was measured in four settings: supine rest, upright rest, supine exercise, and upright exercise. All studies were performed at an elevated skin temperature (38-38.5 degrees C). Compared with values from supine rest, upright exercise was associated with an increase in the internal temperature threshold for vasodilation of 0.39 +/- 0.07 degrees C (P less than 0.01), whereas there was no significant alteration in the threshold for the onset of sweating. Neither the ultimate slope of the SkBF-Tes relationship nor that of the SR-Tes relationship was altered by upright exercise. The upright posture and exercise each contributed to the elevation in the threshold for cutaneous vasodilation, with the average shifts being 0.11 +/- 0.05 degrees C (P less than 0.05) and 0.28 +/- 0.08 degrees C (P less than 0.01), respectively. The net effect of this shift in threshold was to reduce the level of SkBF at any level of Tes during exercise and to increase the difference in threshold between vasomotor and sudomotor responses.