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Biomedical subjects

A Nanda

Publications and source records attributed to A Nanda.

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

Activation of multiple pH-regulatory pathways in granulocytes by a phosphotyrosine phosphatase antagonist.

Activated phagocytes undergo a massive burst of metabolic acid generation, yet must be able to maintain their cytosolic pH (pHi) within physiological limits. Peroxides of vanadate (V(4+)-OOH), potent inhibitors of phosphotyrosine phosphatases, have recently been shown to produce activation of the respiratory burst in HL60 granulocytes. We therefore investigated the effects of V(4+)-OOH on pHi homoeostasis in HL60 granulocytes, using a pH-sensitive fluorescent dye. V(4+)-OOH stimulation induced a biphasic pH change: a transient cytosolic acidification followed by a significant alkalinization. The initial acidification was prevented by inhibition of the NADPH oxidase and was absent in undifferentiated cells lacking oxidase activity. Analysis of the alkalinization phase demonstrated the involvement of the Na+/H+ antiporter, and also provided evidence for activation of two alternative H(+)-extrusion pathways: a bafilomycin-sensitive component, likely reflecting vacuolar-type H(+)-ATPase activity, and a Zn(2+)-sensitive H(+)-conductive pathway. Our results indicate that V(4+)-OOH stimulation not only activated the NADPH oxidase but concomitantly stimulated H(+)-extrusion pathways, enabling the cells to compensate for the massive production of intracellular H+ associated with the respiratory burst.

Culture Media↗
PubMed1994

Spinal epidural compression in head and neck cancer. Report of five cases.

Patients with newly diagnosed head and neck cancer (HNC) during a 13-year period were retrospectively studied for the development of spinal epidural compression (SEC). Of the 759 patients studied, 5 developed epidural compression (1%), 4 of whom were relatively young. SEC occurred simultaneously with HNC in 2 patients and long after the diagnosis of HNC in 3 individuals. There was no observed tendency to involve a particular segment of the spine. Local control of HNC following definitive treatment along with regained ability to walk after palliative radiotherapy in a patient was associated with long-term survival. Recommendations are made for aggressive treatment of SEC to achieve a satisfactory outcome.

Adult↗
PubMed1994

A survey of childhood psoriasis in Kuwait.

One hundred ninety cases of childhood (age birth-12 yrs) psoriasis constituted 0.3% of the total of new dermatologic outpatients. Girls outnumbered boys by a ratio of 1.5:1. Plaque psoriasis was the commonest clinical variant (84%), followed by guttate psoriasis. The scalp was the most common site of onset (22%). Sites predominantly affected later were the extensor surfaces of the legs and the scalp (63% and 53%, respectively). A majority of the children had a milder form of disease. Nail involvement was seen in 36%, with pitting the most common feature (87%). Seven percent had mucosal involvement. A positive family history of psoriasis was obtained in 28%. Topical therapy (coal tar, anthralin, steroids) was the main treatment in the majority of patients (92%). Sixteen patients (8%) required more aggressive intervention (ultraviolet B, psoralin-UVA, retinoids). This is the first study of this kind from the Middle East, the findings are compared with those reported from other parts of the world.

Age Distribution↗
PubMed1994

Use of dihydroergotamine in patients with postconcussion syndrome.

The experience with 34 patients who came to the Shreveport Headache Clinic for treatment of postconcussion headache is reviewed. All had been suffering from postconcussion (posttraumatic) syndrome for periods ranging from one day to more than three years, and all displayed, in addition to headache, at least three other symptoms characteristic of the syndrome, eg, memory problems, impaired concentration, sleep problems, dizziness, and anxiety. After initial evaluation at the clinic, the patients were admitted to Willis Knighton Medical Center and treated with repetitive administration of intravenous dihydroergotamine (DHE) and metoclopramide. A good to excellent overall response to DHE therapy was achieved by 88% (29) of the patients. The percentages and numbers of patients obtaining good to excellent relief of selected key symptoms were: 85% (28) - headache, 91% (30) - memory problems, 94% (31) - sleep problems, and 88% (29) - dizziness. DHE was well-tolerated, and no serious or unexpected adverse reactions were reported. The most frequently reported adverse reactions were mild nausea and brief worsening of headache.

Adult↗
PubMed1994

Development of a H(+)-selective conductance during granulocytic differentiation of HL-60 cells.

The NADPH oxidase is one of the main microbicidal systems of granulocytes. Stimulation of the oxidase during infection leads to a burst of metabolic acid generation. Potentially deleterious cytosolic acidification is prevented by the simultaneous activation of homeostatic H+ extrusion mechanisms, including a recently described H+ conductance. Studies in granulocytes from chronic granulomatous disease patients have suggested a relationship between the oxidase and the H+ conductive pathway. In this report we compared the expression of the H+ conductance and the NADPH oxidase during granulocytic differentiation of dimethyl sulfoxide-induced HL-60 cells. Patch-clamp determinations demonstrated that the H(+)-selective current detectable in differentiated HL-60 cells is virtually absent in uninduced cells. The H+ conductance was also estimated fluorimetrically, measuring changes in the cytosolic pH of suspended cells. Imposition of an inward protonmotive force failed to induce significant cytosolic acidification. In contrast, a sizable conductive H+ extrusion was detected in acid-loaded differentiated cells, consistent with the rectifying properties of the current measured electrophysiologically. By the spectroscopic method, the H+ conductance was not detectable in uninduced cells, developing gradually during granulocytic differentiation. Development of the conductive pathway was found to parallel the biochemical and functional appearance of the NADPH oxidase. These findings suggest that the H+ extrusion mechanisms required for the maintenance of the intracellular pH during granulocyte activation develop pari passu with the acid generating systems and suggest a functional and possibly structural association between the H+ conductance and the NADPH oxidase.

Amino Acid Sequence↗
PubMed1994

Activation of H+ conductance in neutrophils requires assembly of components of the respiratory burst oxidase but not its redox function.

In phagocytes, superoxide generation by the NADPH oxidase is accompanied by metabolic acid production. Cytoplasmic acidification during this metabolic burst is prevented by a combination of H+ extrusion mechanisms, including a unique H+ conductance. NADPH oxidase is deficient in chronic granulomatous disease (CGD) patients. The burst of acid production is absent in CGD patients lacking the 47-kD (p47-phox) or the 91-kD (gp91-phox) subunits of the oxidase. Activation of the H+ conductance is also defective in these patients suggesting that (a) the oxidase itself undertakes H+ translocation or (b) oxidase assembly is required to stimulate a separate H+ conducting entity. To discern between these possibilities, three rare forms of CGD were studied. In neutrophils expressing nonfunctional cytochrome b, the conductance was activated to near-normal levels, implying that functional oxidase is not required to activate H+ extrusion. CGD cells expressing diminished amounts of cytochrome displayed H+ conductance approaching normal levels, suggesting that the oxidase itself does not translocate H+. Finally, the conductance was only partially inhibited in patients lacking the 67-kD subunit, indicating that this component is not essential for stimulation of H+ transport. We propose that normal assembly of the oxidase subunits is required for optimal activation of a closely associated but distinct H+ conducting entity.

Female↗
PubMed1993

Abnormal activation of H+ conductance in NADPH oxidase-defective neutrophils.

To combat bacterial infection, phagocytes generate superoxide (O2-) and other microbicidal oxygen radicals. NADPH oxidase, the enzyme responsible for O2- synthesis, is deficient in chronic granulomatous disease (CGD) patients. Although O2- generation is accompanied by a large burst of metabolic acid production, intracellular pH (pHi) remains near neutrality due to the concomitant stimulation of H+ extrusion. Three major pathways contribute to pHi regulation in activated phagocytes: Na+/H+ exchange, vacuolar-type H+ pumps, and a H+ conductance. The present study analyzed the relationship between activation of the NADPH oxidase and stimulation of the H+ extrusion mechanisms in human blood neutrophils. Phorbol ester-induced activation of Na+/H+ exchange and H+ pumping occurred normally in cells from CGD patients. Unlike normal individuals, however, CGD patients were unable to activate the H+ conductive pathway. Thus, activation of the H+ conductance appears to be contingent on the assembly of a functional NADPH oxidase. These findings imply a dual role of the NADPH oxidase in O2- synthesis and in the regulation of pHi. The oxidase (or some components thereof) may itself undertake H+ translocation or, alternatively, may signal the activation of a separate H+ conducting entity.

Biological Transport, Active↗
PubMed1993

Dermatophytosis of children in Kuwait: a prospective survey.

BACKGROUND: Tinea capitis in children is widely reported, whereas there have been only isolated reports on involvement of sites other than the scalp. The purpose of this study was to examine the epidemiological features and treatment responses of dermatophytosis of children in Kuwait. METHODS: Epidemiological features and the treatment responses of 202 consecutive children with dermatophytosis were studied. RESULTS: The 202 children constituted 44% of the total dermatophytic infections seen during a period of 1 year. Tinea capitis was the most commonly encountered infection (78%), followed by tinea corporis, tinea faciei, tinea cruris and manus, respectively. Microsporum canis was the most prevalent species (96%) in this region. A history of pets at home could be elicited in 52% of the cases. A familial occurrence of similar infections was seen in 56% of the patients. In patients with tinea capitis, addition of topical clotrimazole or ketoconazole to oral griseofulvin produced better therapeutic results compared to griseofulvin alone or in combination with selenium sulfide shampoo. CONCLUSIONS: Tinea capitis is the most common dermatophytic infection in children. Thirty percent of the children may have dermatophytosis at sites other than the scalp. A combination of topical clotrimazole or ketoconazole with oral griseofulvin is superior to griseofulvin alone or in combination with selenium sulfide shampoo in the treatment of tinea capitis.

Animals↗
PubMed1993

Proton conductance of the plasma membrane: properties, regulation, and functional role.

H+ conductive pathways have been detected in the plasma membranes of a variety of cell types. The large exquisitely H(+)-selective permeability of the conductive pathway can support sizable net H+ fluxes. Although subtle differences exist among tissues and species, certain common features suggest that related transport systems are involved in all cases. The H+ conductance is gated by depolarizing voltages and is promoted by intracellular acidification. Conversely, extracellular acidification inhibits the conductance. These features facilitate net H+ efflux, while precluding potentially deleterious H+ uptake. In some cell types, activation of the conductance is additionally controlled by physiological ligands and by second messengers. The conductance most likely functions in the regulation of intracellular pH, contributing to the extrusion of H+ during repetitive depolarization of the plasma membrane, as occurs in neurons and muscle cells. This pathway may be particularly relevant in the case of phagocytes. When stimulated, these cells undergo a sustained depolarization, while generating large amounts of metabolic acid. In addition, conductive H+ fluxes may also provide counterions to neutralize the activity of electrogenic enzymes, as suggested for the phagocyte NADPH oxidase.

Animals↗
PubMed1993

Health in the central and eastern countries of the WHO European Region: an overview.

The enormous social, political and economic changes that began in the CCEE/NIS in the late 1980s included the revelation and public discussion of a widening health gap between these countries and the other Member States of the European Region. The continuing economic problems and their effects on health increase the urgency of the need for assistance from the international community. Diverging trends in life expectancy became evident in the mid-1970s, and the gap continued to widen in the 1980s for all major causes of death, particularly cardiovascular diseases. The situation is worse in the NIS than in the CCEE, and worst in the central Asian countries. In 1990, the worst infant mortality rate in these countries was eight times the best rate elsewhere in the Region. Non-mortality data, while patchy, confirm the indications given by mortality data. There is no single reason for the health gap, but contributory factors include the increasing prevalence of major risk factors in lifestyles and the environment, and the low efficiency and effectiveness of health care systems. The current situation and short-term prospects are mixed, but the negative trends in mortality and morbidity patterns are likely to continue for some time. While the worst health problems of the transition period in the CCEE/NIS could largely have been avoided, there is no doubt that economizing on health today will exact large costs tomorrow.

Europe↗
PubMed1992

Activation of vacuolar-type proton pumps by protein kinase C. Role in neutrophil pH regulation.

Activated neutrophils undergo a large burst of metabolic acid generation, yet maintain their cytosolic pH (pHi) within physiological limits. To analyze the underlying regulatory mechanisms, pHi was measured fluorimetrically in suspensions of human neutrophils. In acid loaded but otherwise unstimulated cells, pHi recovered rapidly via Na+/H+ exchange. Upon Na+ removal, recovery from an imposed acid load was negligible. Phorbol ester activation of acidified cells induced a rapid recovery of pHi partly due to a Zn(2+)-sensitive H(+)-conductive pathway. A third component of the regulatory response was apparent in Na(+)-free media containing Zn2+. Acid extrusion through this alternate pathway was voltage sensitive and capable of translocating H+ equivalents against their electrochemical gradient. This active H+ transport was inhibited by N-ethylmaleimide, by N,N'-dicyclohexylcarbodiimide and by nanomolar doses of bafilomycins A1 or B1, suggesting the involvement of vacuolar (V)-type H+ pumps. Cytosolic alkalinization was accompanied by extracellular acidification, indicative of translocation of H+ equivalents across the surface membrane and consistent with the sensitivity of the alkalinization to changes in plasma membrane potential. The activity of the V-type H+ pumps was virtually undetectable in resting cells, becoming apparent only after treatment with phorbol esters or other, chemically unrelated agonists of protein kinase C. These H+ pumps are likely to play a role in pHi homeostasis during the metabolic burst that accompanies neutrophil activation during infection and inflammation.

Adult↗
PubMed1992

Dermatophytosis of children in Kuwait.

Five hundred fifty-six children constituted 39.5% of total smear- and culture-positive cases of dermatophytosis and 0.6% of the total new dermatology outpatients seen over a period of five years. Males outnumbered females. The youngest child was a 20-day-old neonate (age range 20 days-12 yrs) with a peak of fungal infections seen in patients between 4 and 6 years of age. Microsporum canis was the most prevalent (70.5%) species, followed by Trichophyton violaceum, Microsporum audouinii, Trichophyton rubrum, and Epidermophyton floccosum. Rarely, other species were also isolated. Tinea capitis was the most common (73.7%) clinical type, followed by tinea corporis (19.1%), tinea faciei (3.4%), tinea cruris (3.4%), tinea pedis (0.9%), tinea unguium (0.9%), and tinea manus (0.2%). No racial variations were observed; however, the predominant species differed with the clinical types.

Age Factors↗
PubMed1992

V-ATPases in phagocytic cells.

V-ATPases in phagocytic cells are known to mediate the acidification of most intracellular organelles. Proton-pump-mediated acidification of these organellar compartments is vital to numerous cell processes, including receptor recycling, protein processing and sorting and microbial degradation. Recent studies have suggested a role for V-ATPases in cytoplasmic pH homeostasis. The present discussion will review the current knowledge regarding the presence of V-ATPases in both the plasmalemmal and organellar membranes of phagocytic cells, the regulation of proton pump activity in these locations and the functional significance of pump-mediated proton translocation.

Adenosine Triphosphatases↗
PubMed1992

The extended frontal approach to tumors of the anterior, middle, and posterior skull base.

The extended frontal approach is a modification of the transbasal approach of Derome. The addition of a bilateral orbitofrontal or orbitofrontoethmoidal osteotomy improves the exposure of midline lesions of the anterior, middle, and posterior skull base, while minimizing the need for frontal lobe retraction. The authors present a 5-year experience with 49 patients operated on via the extended frontal approach. In seven patients, the extended frontal approach was used alone; in the remaining 42, it was combined with other skull base approaches. Highly malignant tumors were removed en bloc, whereas benign tumors and low-grade malignancies were removed either en bloc or piecemeal. Reconstruction was usually performed using fascia lata, a pericranial flap, and/or autologous fat. A temporalis muscle flap or a distant microvascular free flap was required for some patients. One patient died 1 month postoperatively due to superior mesenteric artery thrombosis. Three patients had postoperative infections, two had cerebrospinal fluid leaks requiring reoperation, and four had brain contusions or hematomas. All but two patients recovered to their preoperative functional level. After an average follow-up period of 26 months (range 6 to 56 months), 64% of patients with benign lesions, 64% of patients with low-grade malignancies, and 44% of patients with high-grade lesions were alive with no evidence of disease.

Adolescent↗
PubMed1991

Protein kinase C activates an H+ (equivalent) conductance in the plasma membrane of human neutrophils.

The rate of metabolic acid generation by neutrophils increases greatly when they are activated. Intracellular acidification is prevented in part by Na+/H+ exchange, but a sizable component of H+ extrusion persists in the nominal absence of Na+ and HCO3-. In this report we determined the contribution to H+ extrusion of a putative H+ conductive pathway and its mode of activation. In unstimulated cells, H+ conductance was found to be low and unaffected by depolarization. An experimental system was designed to minimize the metabolic acid generation and membrane potential changes associated with neutrophil activation. By using this system, beta-phorbol esters were shown to increase the H+ (equivalent) permeability of the plasma membrane. The direction of the phorbol ester-induced fluxes was dictated by the electrochemical H+ gradient. Moreover, the parallel migration of a counterion through a rheogenic pathway was necessary for the displacement of measurable amounts of H+ equivalents across the membrane. These findings suggest that the H+ flux is conductive. The effect of beta-phorbol esters was mimicked by diacylglycerol and mezerein and was blocked by staurosporine, whereas alpha-phorbol esters were ineffective. Together, these findings indicate that stimulation of protein kinase C induces the activation of an H+ conductance in the plasma membrane of human neutrophils. Preliminary evidence for activation of a separate, bafilomycin A1-sensitive H+ extrusion mechanism, likely a vacuolar type H(+)-ATPase, is also presented.

Alkaloids↗