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Biomedical subjects

A Ayala

Publications and source records attributed to A Ayala.

At least 235 records · Page 13Linked to original sources
PubMed1990

Immunoprotective effect of a calcium channel blocker on macrophage antigen presentation function, major histocompatability class II antigen expression, and interleukin-1 synthesis after hemorrhage.

Hemorrhage induces a severe suppression of the immune system resulting in increased susceptibility to sepsis. Although studies indicate beneficial effects of calcium channel blockers on cell and organ functions after low-flow conditions, it remains unknown whether such agents have any effects on different immune responses after hemorrhage. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg and were maintained for 60 minutes, followed by resuscitation with their own shed blood and adequate fluid. The mice received either the water-soluble calcium channel blocker diltiazem (400 or 2400 micrograms/kg body weight) or saline solution (vehicle). Peritoneal macrophages were obtained by lavage 24 hours later. Antigen presentation was measured by coculturing peritoneal macrophages with the D10.G4.1 helper T-lymphocyte clone. Immune associated antigen (Ia) expression was determined by direct immunofluorescence. Interleukin (IL)-1, 6, and tumor necrosis factor-alpha (TNF) levels in peritoneal macrophage supernatants were measured by use of cytokine-specific cellular assays. Hemorrhage caused a significant decrease in peritoneal macrophage antigen presentation function, Ia expression, and IL-1 and IL-6 synthesis in the vehicle-treated group, whereas TNF levels were increased. However, both doses of diltiazem significantly improved peritoneal macrophage antigen presentation, Ia expression, and IL-1 synthesis. IL-6 synthesis was only increased with high doses of diltiazem, whereas both diltiazem doses decreased TNF production. These results indicate that the calcium channel blocker diltiazem can markedly improve macrophage functions after hemorrhage. The use of diltiazem might offer a new therapeutic modality in the treatment of immunosuppression and in decreasing the susceptibility to sepsis after hemorrhagic shock.

Animals↗
PubMed1989

Implication of lysine residues in the loss of enzymatic activity in rat liver 6-phosphogluconate dehydrogenase found in aging.

During aging, there is a decrease in the activity of the 6-phosphogluconate dehydrogenase enzyme in rat liver. The "old" 6-phosphogluconate dehydrogenase enzyme is about 26% less active than the "young" enzyme. In this paper, some biochemical and chemical properties of this enzyme are studied. 2,4,6-Trinitro-benzenesulfonic acid measurements indicate that the old enzyme has 11 lysine residues less than the young enzyme. The proteolysis with trypsin produces more peptides in the young enzyme than in the old one. However, similar numbers of peptides were produced when endoproteinase Arg-C was used on both enzymes. Moreover, the treatment of the young enzyme with ascorbate for 15 min produces the loss of 8 lysine residues. These results suggest that during aging there is a modification of the lysine residue, and this could be involved in the loss of its enzymatic activity.

Aging↗
PubMed1989

cDNA-derived amino acid sequence of the 86-kDa subunit of the Ku antigen.

The Ku antigen is a DNA-associated nuclear protein recognized by sera from patients with autoimmune diseases. It consists of two polypeptides of 86 and 70 kDa. cDNA clones encoding the 86-kDa subunit of the Ku antigen were isolated by probing lambda gt11 recombinant cDNA expression libraries with a monoclonal antibody specific for this protein. The amino acid sequence deduced from the cDNA comprises 732 amino acids and corresponds to a protein with molecular weight of 81.914. Nineteen residues at the NH2 terminus determined by protein sequencing corresponded to the sequence deduced from the cDNA. The predicted amino acid sequence contains a region with repeating leucine residues similar to the "leucine zipper" structure observed in the c-myc, v-myc, and c-fos oncogene products. The largest cDNA hybridized to 2.7- and 3.4-kilobase poly(A)+ mRNAs from HeLa cells. The cDNA clones expressed fusion proteins immunoreactive with the monoclonal antibody and sera from patients with autoimmune diseases.

Amino Acid Sequence↗
PubMed1989

Effect of cumulative courses of intraarterial cis-diamminedichloroplatin-II on the primary tumor in osteosarcoma.

Preoperative chemotherapy with intraarterial cis-diamminedichloroplatin-II (CDP) and mannitol diuresis was administered to the primary tumor in 42 patients with osteosarcoma. The dose was 150 mg/m2 and more than 90% of the infusions were administered during a 2-week period. On occasion this period was extended to 3 weeks because of temporary renal insufficiency or logistical circumstances. Definitive surgical specimens were prepared by means of an arteriogram-directed plane of dissection with mapping and random sections. Histologically, tumor destruction was evaluated in terms of necrosis, inflammatory response, and fibrovascular regeneration. Quantification of the percent of tumor necrosis was as follows: less than 40% (consistent with spontaneous necrosis and/or no chemotherapy effect); 40% to 60% (possible chemotherapy effect); 60% to 90% (chemotherapy effect--partial response); and 90% to 100% (complete response). Therapeutic efficacy also was correlated with the number of CDP courses (one to three, four to five, and six to seven) and tumor subtype. Significant therapeutic effect (greater than 60% destruction) was observed with four or more CDP courses (one of nine tumors [one to three courses] versus 26 of 33 tumors [four to seven courses] [P = 0.01]). More than 60% of the tumor destruction was observed in the following subtypes: osteoblastic (22 of 28), fibroblastic (three of six), and telangiectatic (two of five). These data demonstrate that four or more courses of intraarterial CDP are required to achieve optimum effects and that osteoblastic osteosarcoma is highly responsive.

Cisplatin↗
PubMed1989

Inflammatory metachronous hyperostosis of the clavicle and femur in children. Report of two cases, one with long-term follow-up.

Two preteenage girls developed painful swelling of the left clavicle. This was followed by painful swelling of the femur, 7 months later in one girl and 8 years later in the other. Radiographic studies showed a predominantly sclerotic process in one patient and destruction associated with cortical thickening in the other. The patients received analgesic medications only, followed by gradual healing with cortical and medullary sclerosis. Long-term follow-up suggests that the condition is self-limited and that, with or without treatment, the bones eventually return to normal. Although the etiology of the lesions remains unknown, the radiographic features suggest an inflammatory reaction.

Biopsy↗
PubMed1989

Mechanism of immunosuppression following hemorrhage: defective antigen presentation by macrophages.

The mechanism by which simple hemorrhage profoundly impairs the proliferative response of T lymphocytes to mitogen and alloantigen, produces a defect in interleukin-2 generation, and increases the susceptibility to sepsis remains unknown. Since antigen presentation (AP) by the macrophage (M phi) plays a critical role in the antigen-specific activation of T-helper cells and lymphokine production, we investigated whether the function of the M phi as an AP cell is altered following hemorrhage. C3H/HEJ mice were bled to a mean BP of 35 mm Hg, maintained at that level for 1 hr, and then resuscitated. There was no mortality with this model. Control mice were not bled but otherwise treated identically. Immediately after resuscitation the mice were sacrificed and peritoneal M phi (PM phi) as well as splenic adherent cells (SAC) were harvested. AP function was tested by coculturing different numbers of PM phi and SAC with D10.G4.1 cells (2 x 10(4) cells/well) in the presence of conalbumin (300 micrograms/ml). This T-helper cell clone proliferates upon recognition of conalbumin in the context of Iak (a M phi surface membrane glycoprotein), thus directly reflecting M phi AP capability. After 72 hr of incubation, the cultures were pulsed with [3H]thymidine and harvested. D10.G4.1 proliferations induced via AP by PM phi and SAC from hemorrhaged-resuscitated mice were 29 and 24% of control, respectively (P less than 0.05). Thus, we conclude that AP by M phi following hemorrhage is defective despite adequate resuscitation, a mechanism which could explain the state of immunosuppression and enhanced susceptibility to sepsis.

Animals↗
PubMed1989

[Pseudocyesis: clinical and hormonal evaluation].

Hormonal and clinical evaluation was performed in eleven females with diagnosis of pseudocyesis. Plasma levels of pituitary gonadotropins (FSH-LH), progesterone, estradiol and thyroid hormones (T3, T4, TSH) under basal conditions were measured through radioimmunoassay. Diagnosis of pseudocyesis was made according to the following criteria: a) secondary amenorrhea (greater than 12 weeks); b) two or more symptoms of gestation; c) conviction of being pregnant; d) negative HCG or pelvic ultrasound study. The circulation levels of gonadotropins were within normal limits. Progesterone exhibited a ovulatory pattern and thyroid hormones were normal for every instance. Once case had slight hyperprolactinemia (26.0 ng/ml) with impaired gonadotropin production and ovulatory progesterone. All patients had galactorrhea. The psychological study disclosed a tendency toward depression. Our findings partially confirmed previous observations, differing basically on that we observed normal hormonal trend.

Diagnosis, Differential↗
PubMed1989

[Efficacy of propafenone in supraventricular arrhythmias].

We evaluated the results of intravenous administration of propafenone in 44 patients with rapid symptomatic supraventricular arrhythmia of less than 1 month duration. Mean age was 54 years and 22 were females. Propafenone, 2 mg/kg was given over 15 min and blood pressure and heart rate were monitored in the following hour. Sixteen out of 19 (84%) episodes of paroxysmal supraventricular tachycardia in 15 patients reverted to sinus rhythm at a mean interval of 11 min. None of 14 patients with atrial flutter reverted to sinus rhythm, but the ventricular rate decreased from 143 +/- 38 to 110 +/- 41 (p less than 0.02). The mechanism involved was slowing of the atrial cycle with associated increase A-V block in 7 patients. One patient experienced 1:1 conduction at a rate of 214 per min. Twenty seven % of 15 patients with atrial fibrillation reverted to sinus rhythm; ventricular rate decreased from 134 +/- 40 to 98 +/- 22 (p less than 0.05) in the remaining cases. There were no significant side effects of the drug and systolic blood pressure decreased from 109 +/- 27 to 99 +/- 30 beats per min (p less than 0.05) with no change in diastolic pressure.

Adult↗
PubMed1989

[Molar pregnancy (primary or recurrent?)].

A peculiar case of gestational trophoblastic disease is described. A 24 year old female with former history of three molar pregnancies, spontaneous abortion and anembryoic pregnancy was admitted because of a newly diagnosed hydatiform mole (ex novo). After uterine curettage followed by a low oral dose of methotrexate (0.5 mg/kg/day) for five days. The HCG levels determined in plasma by beta-HCG- radioinmmunoassay, became negative until four months of follow3 up. An intrauterine device was installed. She resumed HCG positivity a year later and a histerectomy was performed. A post-surgical diagnosis of invasive mole was made. Since the possibility of intercurrent pregnancy was lowered by the presence of a intrauterine device, we assumed that trophoblastic transformation into an invasive mole adopted a sort of dormant period before its resurge (resurrection) independently either from curettage of chemotherapy.

Adult↗
PubMed1988

Possible involvement of histidine residues in the loss of enzymatic activity of rat liver malic enzyme during aging.

During aging there is a decrease in activity of the malic enzyme in rat liver. The "old" malic enzyme is about 36% less active than the "young" enzyme. Some properties and modifications of amino acid residues are studied here (--SH, arginine, methionine, histidine, lysine) to try and check on the existence of any relationship between them and the loss of enzymatic activity during aging. Diethyl pyrocarbonate measurements indicate that the old enzyme has 1 histidine residue less than the young enzyme. Moreover, the treatment of the young enzyme with ascorbate for 15 min produces the loss of 36% of the enzymatic activity and the loss of 1.2 histidine residues. These results suggest that during aging the modification of the histidine residue could be involved in the loss of its enzymatic activity.

Aging↗
PubMed1988

Adjuvant chemotherapy of bladder cancer: a preliminary report.

Adjuvant combination chemotherapy with cyclophosphamide, doxorubicin and cisplatin was administered to 36 patients after cystectomy for bladder cancer. Therapy was tolerated well except for 1 patient who suffered a fatal chemotherapy complication. Indications for adjuvant chemotherapy included vascular invasion of the primary tumor, perivesicular tumor involvement, invasion of adjacent pelvic viscera (vagina and prostate) and nodal metastases. There were 53 concurrently treated patients who did not receive adjuvant chemotherapy despite similar unfavorable pathological indications (high risk control group). Survival rates (61 and 73 per cent, respectively) were not significantly different for those patients treated with adjuvant chemotherapy and an additional group of 158 patients who underwent cystectomy during the study period but who had no adverse pathological findings (low risk control group). Survival rates differed significantly between the low risk (73 per cent) and high risk (38 per cent) control groups (p less than 0.001). Patients with unfavorable histological findings who received adjuvant chemotherapy had a significant survival advantage over the high risk control groups (61 versus 38 per cent, p equals 0.03). These data confirm the predictive value of post-cystectomy pathological findings and suggest that adjuvant chemotherapy with cyclophosphamide, doxorubicin and cisplatin not only prolongs the survival free of disease for patients at high risk for recurrence but it also may ultimately increase the cure fraction of such patients.

Adult↗
PubMed1988

Effects of alpha- and beta-adrenergic agonists on Trypanosoma cruzi interaction with host cells.

We studied the effects of adrenergic agonists on the capacity of blood trypomastigote forms of Trypanosoma cruzi to associate with (i.e., bind and/or penetrate) host cells in vitro. The extent of T. cruzi association with mouse macrophages in the presence of the beta-adrenergic agonist L-isoproterenol was significantly decreased with respect to mock-treated controls. Similar results were obtained when the parasite was pretreated with L-isoproterenol and was then allowed to interact with untreated macrophages. In contrast, pretreatment of trypomastigotes with either L-phenylephrine or methoxamine-alpha-adrenergic agonists--enhanced their reactivity with macrophages. Interaction with a nonphagocytic host cell was also decreased and increased by parasite pretreatment with beta- and alpha-adrenergic agonists, respectively. The L-isoproterenol and L-phenylephrine effects were no longer detectable 2 and 3 hr after their removal, respectively, and were therefore reversible. Atenolol, a specific beta 1 adrenoreceptor blocker inhibited the L-isoproterenol effect, whereas butoxamine, a specific beta 2 blocker, did not. Thus, beta 1-like but not beta 2-like binding sites appeared to be expressed on T. cruzi. Both prazosin and yohimbine, preferential alpha 1- and alpha 2-receptor blockers, respectively, abolished the L-phenylephrine effect. The opposite effects of alpha- and beta-adrenergic agonists suggested that the infectivity of T. cruzi may be regulated by activation of surface components comparable to the adreno-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1987

Pathologic fracture in osteosarcoma. Impact of chemotherapy on primary tumor and survival.

Twenty patients with osteosarcoma and pathologic fractures were treated with a chemotherapeutic regimen consisting of cis-diamminedichloroplatinum-II (CDP), Adriamycin (ADR) (doxorubicin) and high-dose methotrexate with citrovorum factor "rescue" (MTX-CF). Before the introduction of the regimen, the primary tumor in two patients was treated by immediate amputation and in 13 with preoperative intra-arterial CDP. Among these 13 patients, responses (healing) were observed in 11 (one required the addition of radiation therapy). In three patients, the responses were so dramatic that, at their request, surgery was deferred and treatment exclusively with chemotherapy was instituted. Based on this experience, treatment exclusively with chemotherapy was also administered to an additional five patients who were admitted without pathologic fractures. In the course of such treatment, pathologic fractures also developed; notwithstanding, chemotherapy was maintained and healing also occurred. One of the 20 patients had pulmonary metastases at diagnosis; these were resected after treatment and pathologic examination revealed no evidence of viable tumor. The remaining 19 patients were free of pulmonary metastases but these later developed in seven patients. These data were compared to a historical control series in which 16 of 21 patients with pathologic fractures developed pulmonary metastases. Three of the chemotherapy treated patients died of nonosteosarcoma related causes (leukemia, generalized varicella, and a metabolic complication). Overall, survival was improved in the chemotherapy treated patients as compared to the historical control series: 10 of 20 versus 6 of 21, respectively. Pathologic fractures in osteosarcoma may heal under treatment with chemotherapy, which also has a favorable impact on the eradication of pulmonary metastases and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

The effects of p-chloromercuriphenylsulfonic acid on Trypanosoma cruzi infection of mammalian host cells in vitro.

Treatment of Trypanosoma cruzi blood trypomastigotes with p-chloromercuriphenylsulfonic acid (PCMS) increased the association of the parasite with either mouse resident peritoneal macrophages or rat heart myoblasts in vitro. The effect was evidenced by elevation of both the percentage of host cells with parasites and the number of flagellates per 100 cells. The effect of PCMS appeared to be largely on the process of parasite penetration rather than surface binding as it was seen at 37 degrees C but not at 4 degrees C. A short pretreatment time, 5 min, was sufficient to elicit the enhancement, suggesting that the primary effect of PCMS might be at the parasite's cell surface. The PCMS effect was reversible as the parasite returned to normal levels of association with the host cells in less than 4 h after removal of excess PCMS. That sulfhydryl groups were involved in the PCMS effect was indicated by the abilities of excess cysteine and glutathione to block it. These results suggest a role for free sulfhydryl groups on the parasite surface in the process of host cell invasion.

4-Chloromercuribenzenesulfonate↗
PubMed1987

Measurement ex-vivo of the inhibition of fatty acid biosynthesis by bezafibrate administration in different rat tissues.

The action of bezafibrate on fatty acid biosynthesis pathways has been examined in rat tissues. The drug abolished the induction of fatty acid synthesis that occurs on refeeding the animals with a high carbohydrate diet and by insulin administration in liver and adipose tissue. The rates of fatty acid biosynthesis in these tissues were estimated from the incorporation of 3H into lipids from 3H2O.

Adipose Tissue↗