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Biomedical subjects

P Camacho

Publications and source records attributed to P Camacho.

29 records · Page 2Linked to original sources
PubMed1995

Calreticulin inhibits repetitive intracellular Ca2+ waves.

Inositol 1,4,5-trisphosphate (IP3)-mediated calcium (Ca2+) signaling is subject to cytosolic and luminal regulatory mechanisms. In Xenopus oocytes, Ca(2+)-sensitive gating of the IP3 receptor (IP3R) produces repetitive waves of Ca2+ release. We examined the role of the luminal Ca(2+)-binding protein calreticulin (CRT) in IP3-mediated Ca2+ signaling by using Ca2+ wave activity as a sensitive Ca2+ release assay. Overexpression of CRT inhibited repetitive IP3-induced Ca2+ waves. Deletion mutagenesis demonstrated that CRT inhibition was mediated by the high affinity-low capacity Ca(2+)-binding domain, which contributes little to Ca2+ storage. This novel function of CRT in intracellular Ca2+ signaling may be regulated by Ca2+ occupancy of the high affinity binding site.

Animals↗
PubMed1995

Spiral calcium waves: implications for signalling.

Spiral patterns of intracellular Ca2+ release demonstrate a direct relationship between increasing wavefront curvature and increasing propagation velocity. An equally important phenomenon is the annihilation of colliding Ca2+ waves, which reveals an underlying refractory period during which further Ca2+ release is temporarily inhibited. Treatment of intracellular Ca2+ release as an excitable medium accounts for both observations. This theoretical framework is analogous to the more familiar concept of electrical excitability in neuronal membranes. In this analogy, the inositol 1,4,5-trisphosphate receptor ion channel plays a role analogous to that of Na+ channels while Ca(2+)-induced Ca2+ release provides the mechanism for excitation. Furthermore, Ca(2+)-ATPases play a role similar to that of the K+ channels in neuronal excitation, that is, they return the system to rest. We demonstrated that overexpression of a sarco/endoplasmic reticulum Ca(2+)-ATPase increases the frequency of Ca2+ wave activity. More recent experiments reveal a strong dependence of the propagation velocity on wavelength as predicted by the dispersion relation of excitability. This important result accounts for an observed correlation between wave frequency and spatial dominance of Ca2+ foci and suggests a new mechanism for the encoding of signal information.

Animals↗
PubMed1994

Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.

The antihypertensive effect and safety of fosinopril and hydrochlorothiazide combined were compared with each drug singly and placebo in a controlled manner. After a 4- to 5-week placebo lead-in period, 67 mild to moderate essential hypertensive patients (seated diastolic blood pressure > or = 95 and < or = 110 mm Hg) were randomized in a double-blind fashion into four parallel treatment groups: 20 mg fosinopril plus 12.5 mg hydrochlorothiazide, 20 mg fosinopril, 12.5 mg hydrochlorothiazide, and placebo during 8 weeks. Patients were seen biweekly. Sitting diastolic blood pressure was the outcome variable defining therapeutic response. The efficacy of fosinopril plus hydrochlorothiazide as a combined therapy was superior to any single drug (P < .05) and placebo (P < .01) in the treatment of mild to moderate essential hypertension. Mean adjusted systolic/diastolic blood pressure decrements at week 8 were -18.8/-13.7, -12.9/-11.8, -8.5/-9.3, and -2.7/-6.9 mm Hg for the fosinopril plus hydrochlorothiazide, fosinopril, hydrochlorothiazide, and placebo groups, respectively. Clinical adverse events and laboratory changes documented throughout the study were similar to placebo and were mild in severity in all groups.

Adult↗
PubMed1993

Increased frequency of calcium waves in Xenopus laevis oocytes that express a calcium-ATPase.

When inositol 1,4,5-triphosphate (IP3) receptors are activated, calcium is released from intracellular stores in excitatory propagating waves that annihilate each other upon collision. The annihilation phenomenon suggests the presence of an underlying refractory period that controls excitability. Enhanced calcium-adenosine triphosphatase (ATPase) activity might alter the refractory period of calcium release. Expression of messenger RNA encoding the avian calcium-ATPase (SERCA1) in Xenopus laevis oocytes increased the frequency of IP3-induced calcium waves and narrowed the width of individual calcium waves. The effect of SERCA1 expression on calcium wave frequency was dependent on the concentration of IP3 and was larger at higher (1 microM) than at lower (0.1 microM) concentrations of IP3. The results demonstrate that calcium pump activity can control IP3-mediated calcium signaling.

Animals↗
PubMed1993

The epsilon subunit confers fast channel gating on multiple classes of acetylcholine receptors.

During vertebrate skeletal muscle development, multiple forms of long-open-time (slow-type) ACh receptor channels are replaced by at least two different types of short-open-time (fast-type) ACh receptors. Expression of ACh receptors in Xenopus oocytes indicates that the substitution of an epsilon subunit for a gamma subunit may account for both types of fast-gated channel types in adult muscle. Unlike the various forms of the embryonic receptor, in which functional diversity is achieved through alterations in subunit composition, the two major fast-gated forms expressed in oocytes have identical subunit composition. These findings provide a structural basis for both types of short-open-time ACh receptor types found in adult muscle.

Animals↗
PubMed1991

Identification of two amino acid residues in the epsilon subunit that promote mammalian muscle acetylcholine receptor assembly in COS cells.

We have used a species difference in epsilon subunits of the acetylcholine receptor (AChR) to investigate regions of the subunit protein that are important in receptor assembly. Upon transient transfection of COS cells, mouse epsilon subunit cDNA is approximately 10 times more effective than that of the rat in supporting expression of surface AChRs when the other subunits are from either mouse or rat. In cells transfected with only alpha and epsilon subunit cDNAs, the formation of an alpha epsilon heterodimer, a presumed assembly intermediate, is also less efficient with rat than with mouse epsilon subunit. By site-directed mutagenesis, we have found that these differences can be accounted for by 2 amino acid differences in the N-terminal domain at positions 106 and 115 of the rat and mouse epsilon subunits, suggesting that the region near these 2 amino acid residues is important for AChR assembly.

Amino Acid Sequence↗
PubMed1990

Multiple conductance classes of mouse nicotinic acetylcholine receptors expressed in Xenopus oocytes.

Acetylcholine receptor (AcChoR) subunit mRNAs transcribed from mouse BC3H-1 cDNAs were injected into Xenopus oocytes and the expressed AcChoR channels were examined by single channel recording. Injection of alpha-, beta-, gamma-, and delta-subunit mRNAs produced two predominant channel classes with conductances of approximately 50 and approximately 12 pS, while infrequent openings of approximately 25-pS channels were also observed. Injection of alpha-, beta-, and gamma-subunit mRNAs produced a single class of approximately 12-pS AcChoR channels, which resembled the smallest conductance channels present in alpha beta gamma omega-injected oocytes. Assembly of delta-less channels may thus explain the lowest conductance AcChoR channels in alpha beta gamma delta-injected oocytes and might also account for similar channels that have been observed in vertebrate skeletal muscle.

Amino Acid Sequence↗
PubMedDate not supplied

Thyrotropin-secreting pituitary adenoma responsive to bromocriptine therapy.

OBJECTIVE: To describe a case of a thyrotropin-secreting pituitary adenoma that responded to bromocriptine therapy by suppression of thyrotropin and tumor shrinkage. METHODS: We present the clinical course, laboratory data, and radiographic findings in a 32-year-old woman with a thyrotropin-secreting pituitary adenoma before and after treatment with bromocriptine. RESULTS: The patient's pituitary tumor was detected after she had been treated with radioactive iodine for thyrotoxicosis presumed to be due to Graves' disease. After thyroid ablation, the thyrotropin levels could not be brought into the normal range, even while the patient was receiving supraphysiologic doses of orally administered levothyroxine. Magnetic resonance imaging of the pituitary, along with hormonal workup, confirmed the diagnosis of a thyrotropin-secreting pituitary adenoma. Because the tumor was not threatening vital structures and was considered incurable by operation, medical therapy was elected. A trial of bromocriptine was initiated at 15 mg/day and increased to 30 mg/day in three divided doses. Follow-up hormonal studies showed that thyrotropin levels declined into the suppressed range, and repeated magnetic resonance imaging scans showed substantial shrinkage of the pituitary lesion. CONCLUSION: Thyrotropin-secreting tumors may respond hormonally and structurally to bromocriptine therapy. In patients with such tumors, a trial of dopamine agonists at high dose may be considered before initiation of more invasive medical treatment.

Journal Article↗
PubMedDate not supplied

[Structural and functional changes in the heart of the hypertensive patient. An echocardiographic study].

We studied 15 patients with essential hypertension (EH) in whom the diagnosis was corroborated with ambulatory blood pressure monitoring (ABPM). The blood pressure levels (BP) were compared with values obtained from healthy people (HP). We studied 31 HP with 2-D echocardiogram and the parameters of ventricular performance were compared with the values obtained from EH people. ABPM shown that the EH people has higher BP values than HP around 24 hs (EH loss the circadian rhythm of BP). On the other hand the EH had left ventricular hypertrophy (LVH) with normal systolic ventricular function (VF). The systolic wall stress was low because the LVH was inappropriate. The LVH as adaptative mechanism maintains normal the VF in spite of pressure overload without increasing MVO2. When the pressure overload is not eradicated in a variable amount of time the adaptative mechanisms slowly change to a pathologic process caused by collagen deposition in the interstitium of the heart. In advanced stages the remodeling process causes diastolic disfunction, myocardial ischemia, arrhythmias and death by heart failure or suddenly. This last stage is the real hypertensive heart disease.

Adaptation, Physiological↗
PubMedDate not supplied

[The correlation of atrial natriuretic peptide values with those of renin, angiotensin and aldosterone in hypertension patients below and above 50].

A comparison of ANP and RAA. In 6 healthy subjects < 50 y, 5 healthy subjects > 50 y, 44 patients with essential hypertension < 50 y, and 41 patients with essential hypertension > 50 y, was performed. ANP values in healthy subjects < 50 y, were means = 44 +/- 7 PG/ml, and means = 87.33 +/- 14 PG/ml in those > 50 y. (P < 0.01). 80% of hypertensives < 50 y, had normal values of ANP (means = 63.8 +/- 10 PG/ml) and 20% high values (means = 131 +/- 6 PG/ml) (P < 0.001). 70% of hypertensives > 50 y, had high ANP values (means = 260 +/- 114 PG/ml) and 30% normal values (means = 75 +/- 5 PG/ml) (P < 0.001). Values for RAA were low or normal in 96% of cases with high ANP values (P < 0.001), and 100% of the cases with high RAA values, had low or normal ANP values. (P < 0.0001). This correlation had an statistically significant value for groups over 50 years (high ANP values, low RAA values) (P < 0.001) and high RAA values with low or normal ANP values in groups below 50 y (P < 0.001). We observed no significant correlation between ANP values and LVH. According to our results, essential hypertensives < 50 y, have low or normal ANP values in the majority of cases (P < 0.001). Essential hypertensives over 50 y. Have high ANP values also in the majority of cases (P < 0.001). As previously reported, an inversely proportional ratio between RAA and ANP was found in our study. The significance of ANP in regulating blood pressure in the elderly is considered.

Adult↗