Biomedical subjects

F Vargas

Publications and source records attributed to F Vargas.

At least 109 records · Page 6Linked to original sources

PubMed1996

Importance of nitric oxide and prostaglandins in the control of rat renal papillary blood flow.

The role of nitric oxide and prostaglandins in the control of rat renal papillary blood flow has been studied in anesthetized Munich-Wistar rats by use of laser Doppler flowmeter. Acute administration of N omega-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg IV (n=8) increased mean arterial pressure by 27.8 +/- 3.6%, decreased papillary blood flow by 39.4 +/- 3.8%, and decreased renal blood flow by 47.4 +/- 1.9%. The subsequent administration of indomethacin (7.5 mg/kg IV) further decreased papillary blood flow (35.2 +/- 2.5%) without significant changes in mean arterial pressure or renal blood flow. In a second group (n = 6), administration of indomethacin before L-NAME decreased papillary blood flow by 39.6 +/- 2.1% without significantly altering mean arterial ressure or renal blood flow. The subsequent injection of L-NAME further decreased papillary blood flow (32.9 +/- 1.8%) and renal blood flow (49.8 +/- 6.6%) while increasing mean arterial pressure to a level not significantly different from that found in the first group. Autoregulation studies showed that L-NAME but not indomethacin reduced the renal perfusion pressure-renal blood flow relationship without altering autoregulation. However, both nitric oxide and prostaglandins importantly affected the renal perfusion pressure-papillary blood flow relationship because L-NAME and indomethacin significantly decreased this relationship in an additive fashion. Although both drugs reduced the sensitivity of the pressure-papillary flow relationship, only L-NAME affected autoregulation so that papillary blood flow was autoregulated at higher renal perfusion pressures. Thus, the present results indicate that both nitric oxide and prostaglandins control a similar percentage of rat renal papillary blood flow, but nitric oxide seems to be more important than prostaglandins as a mediator of the pressure-blood flow relationship. In contrast, only nitric oxide modifies the renal blood flow level, although it does not disturb whole-kidney blood flow autoregulation.

Animals↗

PubMed1996

Effects of methimazole in the early and established phases of NG-nitro-L-arginine methyl ester hypertension.

In the present study we evaluated the effects of methimazole, an antithyroid drug, on blood pressure and other variables in the early and established phases of hypertension induced by the inhibition of nitric oxide synthesis with the oral administration of NG-nitro-L-arginine methyl ester (L-NAME), 75 mg/100 ml in the drinking water. Moreover, we also evaluated the acute pressor effect of L-NAME on systemic blood pressure in control and rats treated chronically with methimazole, administered via drinking water (30 mg/100 ml). Oral administration of methimazole maintained the blood pressure of L-NAME-treated rats at normal levels 25 days after induction of hypertension. However, after 25 days of methimazole treatment in rats made hypertensive with L-NAME (for 25 days), high blood pressure was similar in methimazole-treated and non-treated L-NAME rats, despite the fact that a hypothyroid state had been achieved in the methimazole-treated rats. Acute intravenous injection of L-NAME caused a similar increase in mean arterial pressure in control and methimazole-treated rats at the lowest dose; however, smaller pressor responses were observed with increasing doses in hypothyroid rats. These results clearly demonstrate that hypothyroidism induced by methimazole prevents, but does not reverse, L-NAME hypertension and reduces the acute pressor responsiveness to L-NAME administration.

Administration, Oral↗

PubMed1996

Expression of transporter associated with antigen processing-1 in the endocrine cells of human pancreatic islets: effect of cytokines and evidence of hyperexpression in IDDM.

A possible role of transporter associated with antigen processing (TAP)-1 in the pathogenesis of IDDM has been investigated by examining the level of TAP-1 expression in the islets of IDDM pancreas and by studying in vitro the effect of interferon (IFN)-gamma, IFN-alpha, and tumor necrosis factor-alpha in TAP-1 expression by cultured islet cells. A remarkable hyperexpression of TAP-1 has been found in the endocrine cells (beta and non-beta) of IDDM islets, which constitutes first evidence of hyperexpression of this molecule in the target organ of an autoimmune disease. TAP-1 hyperexpression correlated clearly with HLA class I hyperexpression but only very partially with HLA class II ectopic expression. IFN-gamma and IFN-alpha, both cytokines putatively implicated in IDDM pathogenesis, were capable of inducing TAP-1 protein (as assessed by immunofluorescence flow cytometry) and message (by Northern blot analysis and reverse transcription polymerase chain reaction). These findings suggest that under the influence of cytokines (most probably IFN-alpha) beta-cells may express in their surface a high density of HLA class I-peptide complexes that may facilitate their recognition and lysis by low-affinity CD8+ T-cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

The tumor association of a trisaccharide epitope: specificity of antiserum developed to galactose beta1->3 N-acetyl glucosamine beta1-->3 galactose.

A pentasaccharide carbohydrate epitope described by Nozawa et at (1) is expressed by 35% of the neoplastic tissue samples from patients with endometrial cancer but not by normal endometrium. This epitope was detected using a human monoclonal antibody (HMST-1) produced by fusion of lymphocytes from an endometrial cancer patient. We chemically linked a synthetically produced nonreducing terminal trisaccharide portion of this pentasaccharide to bovine serum albumin to create an effective immunogen, Galbeta1->3GlcNAcbeta1->3Gal-BSA. A rabbit polyclonal antibody was produced and tested against panels of tumor and normal tissues. In contrast to the results obtained with HMST-1, 100% of the endometrial adenocarcinomas we studied stained with this polyclonal antiserum while normal endometrium was non-reactive. The reactivity with other tyes of adenocarcinomas was approximately 80%, whereas most normal tissues were not reactive with the antiserum. Immunological specificity analysis was performed with structurally related carbohydrates and this shows the fine specificity reaction of the antiserum. This antigen may be clinically useful for immunolocalization and for immunotargeting.

Animals↗

PubMed1996

Photodegradation of bezafibrate in aqueous media. Studies of its in vitro phototoxicity.

Aqueous solutions of the antihyperlipoproteinemic drug bezafibrate (CAS 41859-67-0) are photolabile towards UV-B light under aerobic conditions. Two compounds were isolated and identified spectroscopically as well as by alternative synthesis as the only photoproducts formed. Their formation involves primary cleavage of the aryloxy-carbon bond and decarboxylation followed by hydrogen abstraction or dimerization. Bezafibrate is phototoxic in vitro as indicated by the photohemolysis test. Furthermore bezafibrate photo-sensitizes peroxidation of linoleic acid as monitored by the UV detection of dienic hydroperoxides. Partial inhibition of these processes on addition of butylated hydroxyanisole (BHA), reduced glutathione (GSH), sodium azide (NaN3) or 1,4-diazabicyclo [2.2.2] octane (DABCO) suggests the involvement of type I as well as type II mechanisms.

Aerobiosis↗

PubMed1996

[Mechanism of phototoxicity induced by drugs].

First of all some general concepts are given on phototoxic activity of pharmaceutical products which full fill the structural characteristics required to decompose by light and to cause biological damage, either themselves, their photoproducts or the products of their metabolism. These considerations are important due to the fact that this field of research is fairly new. Next, a review is given on recent research carried out in this laboratory on the photochemistry and phototoxicity of fibric acid and their derivatives and finally a review is made as well on the photochemistry and phototoxicity of antibacterial quinolones. Mechanisms are postulated for the photochemical decomposition of the substances investigated and possible mechanism for the in vitro activity at cellular level are also presented.

4-Quinolones↗

PubMed1995

Hyperinducibility of HLA class II expression of thyroid follicular cells from Graves' disease. A primary defect?

Thyroid follicular cells (thyrocytes) from Graves' disease (GD) patients' thyroid glands express HLA class II molecules "ectopically." This phenomenon has been attributed to induction by locally produced cytokines and may be relevant to disease pathogenesis. We have compared IFN-gamma-mediated induction of HLA class II in thyrocytes from glands affected with GD and a nonautoimmune disease (MNG), to investigate a possible differential regulation of HLA expression between these two pathologies. HLA induction has been measured in primary thyrocyte cultures and control autologous macrophages stimulated or not stimulated with IFN-gamma. Comparison of flow cytometric data using an improved algorithm demonstrated that expression of HLA class II molecules is more readily induced in thyrocytes from GD than from MNG thyroid glands. This higher inducibility was parallel to a faster and stronger induction of HLA class II message in GD thyrocytes but did not correlate with the levels of HLA class II or class I originally expressed by thyrocytes in the tissue or with the degree of lymphocytic infiltration of the gland. There was no association with a particular HLA class II allele or with the presence of IFN-gamma and IL-2 in the tissue, as assessed by reverse transcription-PCR. No differences in the induction of class II were found in macrophages from each group of patients. These results suggest that an intrinsic feature of thyrocytes from GD patients is an up-regulation of HLA class II expression and that this is a characteristic that may facilitate the triggering of autoimmunity to "hyperinducible" thyroid glands.

Adolescent↗

PubMed1995

rHuGM-CSF after high-dose chemotherapy in post-remission acute leukemia.

Post-remission high-dose chemotherapy has been an important advance in the treatment of adult acute leukemia (AAL). Without the use of colony-stimulating factors (CSFs) in this program, the mortality rate varies from 5 to 17%, and infectious complications arise in more than 50%. These findings limit the widespread use of such forms of therapy. The use of high-dose ara-C (HIDAC) alone or in combination with other drugs is the most common regimen studied, however neither other drug combinations nor the addition of supporting CSFs have been extensively explored. For this reason we studied the effect of high-dose cyclosphosphamide-etoposide (CECY) plus recombinant human granulocyte-macrophage (rHuGM)-CSF with the intention of decreasing morbimortality and prolonging disease-free survival (DFS). Since 1992 we have included 51 complete remission patients with AAL in the CECY plus rHuGM-CSF protocol. The maximal myelosuppression occurred in a mean of 6.4 days, and the mean days required for absolute neutrophil count recovery was 13 days and for platelets 21 days (p < 0.0001). No toxic deaths occurred and only two serious infectious complications were seen. After two years of follow-up, 50% of de novo acute myelogenous leukemia patients had relapsed at 13 months, and 50% of de novo adult acute lymphocytic leukemia patients had relapsed at 15 months. In a recent update, we have not seen a significant difference when compared to historic groups. The CECY protocol does not appear to be superior in prolonging DFS compared to HIDAC as a post-remission strategy for newly diagnosed AAL. The main difference was the absence of toxic deaths and minimal serious infectious complications in the CECY protocol. Therefore, we suggest that the use of rHuGM-CSF in post-remission programs should be included in future studies.

Acute Disease↗

PubMed1995

Characterization of a serine peptidase responsible for the inactivation of endogenous cholecystokinin in human brain.

Depolarization of slices of human cerebral cortex releases cholecystokinin-8 immunoreactivity, only a fraction of which is recovered in intact immunoreactive form in the medium. This suggests that extensive hydrolysis takes place during short incubations. In the presence of diisopropylfluorophosphate, a serine reagent, the recovery is nearly doubled, however, consistent with the involvement of a serine peptidase activity. The latter was characterized by assessing the protective effects of a series of serine protease inhibitors belonging to the families of peptide chloromethylketones or boronic acids. The relative potency of these inhibitors was similar to corresponding values previously found with rat brain slices indicating that a similar serine peptidase activity is responsible for endogenous cholecystokinin inactivation in the two species.

Amino Acid Sequence↗

PubMed1995

Sylvatic triatomines (Hemiptera: Reduviidae) in Bolivia: trends toward domesticity and possible infection with Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae).

The risk of domestic transmission of Trypanosoma cruzi (Chagas) by sylvatic triatomines was assessed in an isolated area of the subandean region of Bolivia. None of the 390 residents examined had serological evidence of infection. Two sylvatic triatomine species, Eratyrus mucronatus (Stål) and Triatoma sordida (Stål), were found in houses and in peridomestic structures. The collection of nymphal instars of both species from some houses indicated possible domesticity. Microscopic examination of feces from 92 insects showed no parasites, and cultures from the guts of 30 insects were negative. Nevertheless, a polymerase chain reaction (PCR) test performed on the same fecal samples showed the presence of T. cruzi DNA in 19.1 and 12.5% of E. mucronatus and T. sordida, respectively. These 16 PCR-positive samples were hybridized with 2 T. cruzi-specific probes known from the domestic cycle in Bolivia (clones 20 and 39). At least 1 of these clones was identified in 7 bugs (5 E. mucronatus and 2 T. sordida). Moreover, no hybridization was observed with these probes in S E. mucronatus and 1 T. sordida samples that showed an amplified band by PCR. These data indicated that T. cruzi clones, genetically unrelated to clones 20 and 39, also were circulating in this area. Based on these results, the 2 sylvatic triatomine species encountered in Apolo should not be overlooked as possible local vectors of T. cruzi.

Animals↗

PubMed1995

Involvement of renin-angiotensin system in the reduced pressure natriuresis response of hyperthyroid rats.

Previous studies have indicated that the pressure diuresis and natriuresis (PDN) response is greatly impaired in thyroxine-treated hypertensive rats. In the present study, we have examined the role of the renin angiotensin system (RAS) as a mediator of these alterations by characterizing the relationships between renal perfusion pressure and urine flow and sodium excretion in hyperthyroid rats acutely treated with a converting-enzyme inhibitor (captopril, 2 mg/kg) or an AT1 angiotensin II receptor blocker (losartan, 10 mg/kg). In the control animals, captopril did not change mean arterial pressure (MAP) or renal blood flow (RBF) but significantly decreased MAP and increased RBF and glomerular filtration rate in the hyperthyroid rats. Captopril did not change the PDN response of the control animals but improved significantly that of the hyperthyroid rats, although it was not completely normalized. Losartan also significantly improved renal hemodynamics and excretion in hyperthyroid rats. These results indicate that an increased intrarenal activity of the RAS is partly responsible for the blunted renal PDN mechanism of the hyperthyroid rats.

Animals↗

PubMed1995

Endothelium-dependent and endothelium-independent vasodilation in hyperthyroid and hypothyroid rats.

The effects of hyper- and hypothyroidism on the vasorelaxing responses to acetylcholine (ACh), sodium nitroprusside (NP), and CaCl2 were investigated in aortic strips and isolated perfused kidneys. The renal vascular reactivity to ACh and NP was increased in hyperthyroid rats, whereas the concentration-response curve to ACh in hypothyroid rats was flattened. In the renal vasculature from hypothyroid rats, NP produced a dual response: vasoconstriction at low doses and vasodilation at medium to high doses. Aortic strips from hyperthyroid rats showed an increased response to ACh without significant differences between hypothyroid and control groups. Aortic strips from all three experimental groups showed a similar relaxing response to CaCl2. These results indicate that: (1) the raised arterial pressure of hyperthyroid rats is not associated with a reduced endothelium-dependent and calcium-induced vasodilation, and (2) the changes in responsiveness to vasodilators in resistance vessels from hyper- and hypothyroid rats may play a role in the increased and decreased peripheral vascular resistances, respectively, previously reported in such animals.

Animals↗

PubMed1995

Comparison of the end-tidal arterial PCO2 gradient during exercise in normal subjects and in patients with severe COPD.

We undertook the present study with the following objectives: (1) to compare the difference between the end-tidal and the arterial carbondioxide concentration (P[ETa] CO2) gradients at rest and during exercise in normal subjects and patients with COPD; and (2) to analyze the factors contributing to this gradient. We studied seven normal subjects and seven patients with COPD using a symptom-limited exercise test on a cycle ergometer. Our results show that the P(ET-a)CO2 increased progressively as the individuals went from rest to higher workloads in both the normal group and in the COPD group. The P(ET-a)CO2 in patients with COPD both at rest (-3.24 +/- 2.78 mm Hg) and during exercise (1.03 +/- 2.23 mm Hg) is significantly lower than that in normal individuals at rest (1.84 +/- 3.68 mm Hg) and during exercise (10.3 +/- 6.5 mm Hg) (p < 0.01). However, the slope for the relationship between the P(ET-a)CO2 and the workload is actually significantly steeper in the patients with COPD. Although the P(ET-a)CO2 correlated significantly with the workload in both normal subjects (r = 0.63, p < 0.001) and patients (r = 0.55, p < 0.005), the P(ET-a)CO2 was much more closely correlated with the ratio of dead space to tidal volume (VD/VT) (r values of -0.86 and -0.77, respectively). Moreover, when multiple regression analysis was performed, addition of any other physiologic measure (eg, oxygen consumption [VO2], carbon dioxide production [VCO2], minute ventilation [VE], or workload) as a second independent variable after the VD/VT did not improve the correlation. This indicates that the correlation between the P(ET-a)CO2 and the workload is probably related to the dependence of the VD/VT on the workload. The PaCO2 in normal subjects and in the COPD group correlated significantly with the partial pressure of end-tidal carbon dioxide (PETCO2). Using multiple regression analysis, with the PaCO2 as the dependent variable and the PETCO2 (along with other physiologic measures) as the independent variables, we found that the standard error of the estimate was still above 2.1 mm Hg in normal subjects and in patients with COPD. We conclude that (1) during exercise, the P(ET-a)CO2 in normal subjects and in patients with COPD increases significantly, (2) the P(ET-a)CO2 gradient is more closely correlated with the VD/VT than any other physiologic variable, and (3) changes in the PETCO2 during exercise are not correlated closely with changes in the PaCO2.

Adult↗

PubMed1995

Field application of polymerase chain reaction diagnosis and strain typing of Trypanosoma cruzi in Bolivian triatomines.

A new approach for direct identification and characterization of Trypanosoma cruzi stocks in biological samples was tested for field applicability on an extensive sample of feces collected from triatomine vectors from four different species found in Bolivia. The first step of the technique is polymerase chain reaction (PCR) amplification of the hypervariable region of kinetoplast DNA minicircles of T. cruzi parasites. In this report, 345 fecal samples were analyzed and the PCR results were compared with microscopic examination. For Triatoma infestans, the principal Bolivian vector, both techniques were in concordance 85.3% of the time. For the three other species, Rhodnius pictipes, Eratyrus mucronatus, and Triatoma sordida, the fecal samples were all negative by microscopic examination whereas PCR results showed several T. cruzi-infected insects in each species. The second step of the procedure is the characterization of the T. cruzi clones by means of hybridization of the PCR products with clone-specific probes generated by the PCR. We used two probes corresponding to major clones circulating in high frequency in Bolivia (as shown by previous population genetic studies using isoenzyme characterization). We obtained four primary results: 1) we confirm the importance of two major clones in Bolivia in two distinct regions; 2) we report high rates of mixed infections (multiple clones in a single vector) in Triatoma infestans, up to 22% and 35% in Cochabamba and La Paz departments, respectively; 3) the results favor the absence of interaction between different clones; and 4) we find, for the first time, evidence of the major clones circulating in three species of triatomines that are known as mainly sylvatic species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effects of chronic increased salt intake on nitric oxide synthesis inhibition-induced hypertension.

OBJECTIVE AND METHOD: Experimental evidence suggests that endogenous nitric oxide plays an important role in the homeostatic response to an increase in sodium intake. In the present study we evaluated the influence of a high sodium intake (1% NaCl as drinking water) on arterial hypertension induced by long-term (6-7 weeks) inhibition of nitric oxide synthesis [NG-nitro-L-arginine methyl ester (L-NAME), 75 mg/100 ml in the drinking fluid] in rats. RESULTS: Treatment with L-NAME induced progressive elevations in tail-cuff systolic blood pressure, but there were no differences between rats drinking tap water and rats drinking 1% NaCl. Direct measurement of blood pressure at the end of the treatment confirmed the hypertension and the lack of differences between the two groups treated with L-NAME. Metabolic studies performed at the end of L-NAME treatment showed a reduced glomerular filtration rate and elevated urinary excretion of immunoreactive endothelin in the two hypertensive groups treated with L-NAME. Drinking intake, diuresis and natriuresis were significantly higher only in the L-NAME group drinking 1% NaCl. Both groups treated with L-NAME showed an accelerated and increased diuretic and natriuretic response to an isotonic 0.9% NaCl load (2.5 ml/100 g body weight, intraperitoneally). At the end of the study ventricular hypertrophy was observed in both L-NAME groups. CONCLUSION: The present results indicate that the time-dependent elevation in blood pressure produced by long-term inhibition of nitric oxide production is not affected by an increased sodium intake. However, salt supplementation induced the development of a polyuria and polydipsia syndrome in rats treated with L-NAME. The elevated excretion of endothelin in both groups treated with L-NAME suggests the possible participation of endothelin in the development of L-NAME hypertension.

Animals↗

PubMed1995

Photodegradation and in vitro phototoxicity of the antidiabetic drug chlorpropamide.

Methanolic solutions of the phototoxic antidiabetic drug chlorpropamide (CAS 94-20-2, 1) are photolabile towards UVB light under aerobic conditions. Irradiation of 1 produces the formation of the stable compounds p-chlorobenzenesulfonamide (2), N-(p-chlorophenylsulfonyl)formamide (3) and the dimer 4. A radical intermediate was evidenced by thiobarbituric acid that was used as a radical sonde, as well as by the dimerization of cysteine. The compound 1 showed moderate lytic activity upon the photohemolysis in vitro test on human erythrocytes which was increased with the addition of traces of its aggregate excipient. Inhibition of this process on addition of reduced glutathione (GSH), superoxide dismutase (SOD) or ascorbic acid suggests the involvement of radicals and superoxide ion in the photohemolysis process. The absence of inhibition with 1,4-diazabicyclo[2.2.2]octane (DABCO) and sodium azide (NaN3), and the lack of formation of singlet oxygen during the photolysis (confirmed with 2,5-dimethylfuran) rule out the possibility of participation of 1O2 in this process. Glutathione depletion was also observed. No photohemolysis was detected in the presence of the isolated photoproduct.

Antioxidants↗

PubMed1995

Infective endocarditis in children: clinical analyses and evaluation of two diagnostic criteria.

A new diagnostic schema for infective endocarditis (IE), the Duke criteria, has been compared with the previously published criteria of von Reyn in adult patients. This study was designed to analyze the clinical characteristics of a group of pediatric patients with IE and to compare the diagnostic efficiency of both sets of criteria. We reviewed retrospectively the clinical records of 38 patients, 22 with predisposing heart disease (Subgroup A) and 16 with no known cardiologic abnormality (Subgroup B). Ventricular septal defect was the most frequent preexisting heart disease (31.8%) and central venous catheters were the most frequent predisposing factor (68.7%). Comparison of the clinical features between subgroups (A vs. B) showed differences only for the presence of a new regurgitant murmur (9% vs. 44%, P < 0.05) and a hemoglobin value < or = 10 g/dl (50% vs. 94%, P < 0.05). The most frequent microorganisms isolated were viridans streptococci (36%) in Subgroup A and Staphylococcus aureus (50%) in Subgroup B. Of the 6 pathologically confirmed cases all would have been classified as clinically definite by the Duke criteria, as compared with 2 of 6 being defined as probable and one being rejected by von Reyn criteria. Of the 32 cases clinically defined 19 (59%) were classified as definite by the Duke criteria, and 11 (34%) were probable by the von Reyn criteria (difference 25%, P < 0.01). Although no case of IE was rejected by Duke criteria, 8 (25%) were rejected by von Reyn criteria (difference 25%, P < 0.01), with all 8 classified as possible by Duke criteria. We conclude that the Duke criteria were superior to the von Reyn criteria for the diagnosis of pediatric IE, including more cases as definite and significantly fewer cases as rejected.

Adolescent↗

PubMed1994

Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor V beta usage, and cytokine profile.

Insulin-dependent diabetes mellitus (IDDM), in which only the pancreatic beta cells are destroyed by the autoimmune response, is the paradigm of organ-specific autoimmunity. As a result of a combination of factors, the number of immunohistologic/cellular/molecular studies of pancreas in IDDM is very limited. We report here studies conducted in the pancreata of two IDDM patients: one newly diagnosed (case 1) and one long standing (case 2). In case 1, we demonstrated the presence of morphologically normal viable beta cells without evidence of viral infection. In both cases the expression of the autoantigens defined by islet cell Abs and by glutamic acid decarboxylase was markedly reduced in the islet cells whereas expression of hsp60, another putative autoantigen, was normal. Over-expression of HLA class I was detected in 58% of the islets in pancreatic sections and in cultured beta cells in case 1 and also in 30% of islets in case 2 but it was not restricted to any insular cell type. In case 1, there was "inappropriate" HLA class II expression in islets cells but it was a rare finding and not beta cell specific. The analysis of the correlation between class I overexpression, residual insulin, and insulitis suggests that the first event is the increase of HLA class I expression. Of adhesion molecules, ICAM-1, VLA, VCAM, and LFA-3 were normal and only ICAM-1 was moderately overexpressed in and around the islets of case 1 insulitis, as was detected by immunofluorescence which showed that 18% of the islets of case 1 had CD8+ lymphocytes as the predominant population. Reverse transcription-PCR demonstrated moderate V beta skewing and the profile of cytokines expected in CTLs: IL-2, IL-4, IL-10, and IFN-gamma negative, perforin positive. In addition, IFN-alpha, IFN-beta, and IL-6 transcripts were detected in the case 1 pancreas, consistent with the existence of a silent viral infection. Overall, the results indicated that, differently from spontaneous animal models of diabetes, in the pancreas of IDDM patients there are no elements of the inductive phase of the autoimmune response.

Acute Disease↗