Biomedical subjects

M Sole

Publications and source records attributed to M Sole.

At least 19 recordsLinked to original sources

PubMed2005

Diagnostic value of C4d in renal allograft biopsies in different clinical settings: absence of C4d in grafts from non-heart-beating donors.

UNLABELLED: Humoral mechanisms of rejection after kidney transplantation (TX) can be identified through the detection of diffuse complement C4d deposits in peritubular capillaries (PTC) in graft biopsies or donor-specific antibodies (DSA) in serum samples. It has been hypothesized that ischemic injury in the graft may facilitate humoral responses. Kidney grafts from non-heart-beating donors (NHBD) present more often severe ischemia lesions than grafts from heart-beating or living donors. METHODS: We reviewed kidney TX biopsies performed from May 2002 to November 2004 with special interest paid to recipients from NHBD. We checked corresponding frozen tissue for the detection of C4d in PTC using immunofluorescence with a monoclonal antibody against C4d. We also collected post-TX contemporaneous DSA data, either flow crossmatches or cytotoxic PRA. RESULTS: During this period, we performed 22 kidney TXs from NHBD of a total of 326 kidney TX (either single or combined with other grafts). Nine patients of this group underwent 12 biopsies for delayed graft function over 15 days or deteriorating scans. All biopsies showed acute tubular necrosis, but one also presented IA Banff acute rejection and another one had neutrophils in PTC. Frozen tissue from these 12 biopsies did not have diffuse C4d deposits in PTC. Serum samples of seven of nine patients were available: four had negative DSA flow crossmatches and three had 0% PRA within the same period. We diagnosed acute humoral rejection (AHR) in 13 patients-with acute renal dysfunction, C4d in biopsies and DSA after kidney TX-of 38 with high clinical suspicion for AHR. We detected C4d in seven biopsies of 30 patients performed more than 6 months after TX. CONCLUSIONS: Severe ischemic injury does not necessarily determine the activation of humoral mechanisms of rejection mediated through DSA. Therefore, C4d is extremely interesting for the identification of humoral rejection in any clinical setting after kidney TX.

Antibody Formation↗

PubMed2003

Diagnosis and treatment of acute humoral rejection after kidney transplantation: preliminary experience.

BACKGROUND: Acute humoral rejection, or rejection associated with de novo production of anti-HLA donor-specific antibodies (DSA) after kidney transplantation (KTx), is a clinicopathologic entity that is not completely understood. Recent studies have proposed criteria for its diagnosis, including: (1) steroid-resistant acute dysfunction; (2) positive post-Tx donor-specific crossmatch (XM); and (3) widespread C4d deposits in peritubular capillaries (PTC) upon renal biopsy. METHODS: During 2002, prospective screening for AHR was established at our unit, seeking DSA post-KTx in selected cases of steroid-resistant acute rejection or acute dysfunction in high-risk sensitized or re-Tx patients. Frozen donor lymphocytes were used for post-Tx flow cytometry (FC) XM and high-definition flow PRA for patients with no frozen donor cells. We treated patients diagnosed with DSA using plasma exchange and polyclonal immunoglobulin. RESULTS: Post-Tx DSA studies were performed in 9 of 94 patients transplanted during 2002. We detected DSA post-Tx in 3 of 9 recipients: 2 by FCXM and 1 using high-definition flow PRA. Two were highly sensitized pre-Tx, but the third patient was a 70-year-old woman receiving a first Tx (PRA=0%). All 3 recipients presented with severe steroid-resistant acute renal dysfunction during the first 2 weeks post-Tx. Biopsies showed some features of AHR (neutrophils in PTC); 1 case showed no signs of concomitant cellular rejection. All rejection episodes were treated successfully (XM became negative and renal function recovered) by combining plasma exchange and polyclonal immunoglobulin. CONCLUSIONS: The use of specific tools, like the crossmatch, in cases of acute, steroid-resistant renal graft dysfunction is important to identify and treat otherwise undetected humoral mechanisms of rejection.

Acute Disease↗

PubMed2001

[A familial case of chronic progressive external ophthalmoplegia associated with mitochondrial disease].

Mitochondrial myopathies are rare hereditary diseases that affect the energy functions of the mitochondria. Clinical manifestations are variable and sometimes multisystemic. Progressive external ophthalmoplegia constitutes the most frequent clinical form. Unfortunately, the diagnosis and the treatment of these mitochondrial abnormalities stay, today, even difficult. We report ophthalmic findings and the course of the disease in members of a family with chronic progressive external ophthalmoplegia presenting with severe acquired blepharoptosis. From study at the family background, the inheritance seemed autosomal dominant. In one case, a comprehensive workup, including muscular biopsy and molecular genetics disclosed a mitochondrial myopathy. During the 30-year follow-up, the patients were operated on for their ptosis several times, because of recurrences and uneven results.

Adult↗

PubMed1998

Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy.

BACKGROUND: Mutations in the gene for cardiac myosin-binding protein C account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy. The spectrum of disease-causing mutations and the associated clinical features of these gene defects are unknown. METHODS: DNA sequences encoding cardiac myosin-binding protein C were determined in unrelated patients with familial hypertrophic cardiomyopathy. Mutations were found in 16 probands, who had 574 family members at risk of inheriting these defects. The genotypes of these family members were determined, and the clinical status of 212 family members with mutations in the gene for cardiac myosin-binding protein C was assessed. RESULTS: Twelve novel mutations were identified in probands from 16 families. Four were missense mutations; eight defects (insertions, deletions, and splice mutations) were predicted to truncate cardiac myosin-binding protein C. The clinical expression of either missense or truncation mutations was similar to that observed for other genetic causes of hypertrophic cardiomyopathy, but the age at onset of the disease differed markedly. Only 58 percent of adults under the age of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68 of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete through the age of 60 years. Survival was generally better than that observed among patients with hypertrophic cardiomyopathy caused by other mutations in the genes for sarcomere proteins. Most deaths due to cardiac causes in these families occurred suddenly. CONCLUSIONS: The clinical expression of mutations in the gene for cardiac myosin-binding protein C is often delayed until middle age or old age. Delayed expression of cardiac hypertrophy and a favorable clinical course may hinder recognition of the heritable nature of mutations in the cardiac myosin-binding protein C gene. Clinical screening in adult life may be warranted for members of families characterized by hypertrophic cardiomyopathy.

Adolescent↗

PubMed1997

Secondary amyloidosis in ankylosing spondylitis. A systematic survey of 137 patients using abdominal fat aspiration.

OBJECTIVE: To assess the frequency and clinical significance of amyloid deposits in abdominal fat in patients with ankylosing spondylitis (AS). METHODS: Abdominal subcutaneous fat aspiration (ASFA) by fine needle was performed in 137 unselected patients with AS of more than 5 years of disease evolution. A followup study was done of patients with amyloidosis in the abdominal fat (ASFA positive test) to evaluate the development of clinical amyloidosis. RESULTS: In 10 (9M/1F) patients with AS, the ASFA revealed amyloid deposits (prevalence of 7%). Patients with AS and an ASFA+ test were older and had more active and severe disease than those without AS. Only 2 ASFA positive test patients had clinical amyloidosis at the time of the test. After a followup period of 2-10 yrs (mean 5.4 +/- 3.2 yrs), 3 more patients developed symptomatology due to amyloidosis. All 5 patients with clinical amyloidosis showed nephropathy, and proteinuria was found in each. The remaining patients did not develop clinical amyloidosis during followup. CONCLUSION: Amyloid deposits in abdominal fat are not a rare finding in AS. A significant proportion of these patients do not develop clinical amyloidosis after a followup of several years. Thus, an ASFA + test in patients with AS is not always associated with a poor prognosis at least in the short term, although longer followup is required.

Adipose Tissue↗

PubMed1997

Role of candidate modifier genes on the phenotypic expression of hypertrophy in patients with hypertrophic cardiomyopathy.

BACKGROUND: The phenotypic expression of left ventricular hypertrophy (LVH) in patients with hypertrophic cardiomyopathy (HCM) is variable. This phenotypic variability is not completely explained by the responsible mutations or other known factors. Recent data denote a role for the modifier genes and environmental factors. We studied the role of 3 potential modifier genes, i.e., angiotensinogen (AGT), angiotensin II receptor 1a (AT1a), and endothelin-1 (END1) on the phenotypic expression of LVH in patients with hypertrophic cardiomyopathy (HCM). METHODS: The study population was comprised of 108 genetically independent patients with HCM. Left ventricular mass index (LVMI) and LVH score were determined per published protocols. The genotypes of AGT (M235T, T174M, and G-6A), AT1a, and END1 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or mutation-specific PCR (MS-PCR). RESULTS: Male patients had higher mean LVMI and LVH score than female patients (146.0 +/- 33.5 vs 129.4 +/- 33.6, p = 0.01 and 6.0 vs 5.0, p = 0.010, respectively). Gender accounted for 4.8% and 5.4% of the variability of LVMI and LVH score, respectively. The END1 genotypes also had a significant influence on LVH scores accounting for 2.9% of their variability (p = 0.042). The median LVH score was greater in patients with the AA and AG genotypes, as compared to patients with the GG genotype (7.0 vs 5.0, p = 0.034). Neither the AGT nor the AT1 genotypes had a significant influence on the expression of LVH. In multivariate regression analysis, END1 and gender accounted for 7.3% of the variability of the LVH score (p = 0.007). CONCLUSIONS: Our results show that gender and the END1 gene modify the phenotypic expression of hypertrophy in patients with HCM.

Adult↗

PubMed1995

Angiotensin-I converting enzyme genotypes and left ventricular hypertrophy in patients with hypertrophic cardiomyopathy.

BACKGROUND: The variability of the phenotypic expression of left ventricular hypertrophy (LVH) in patients with hypertrophic cardiomyopathy (HCM) indicates a potential role for additional modifying genes. Variants of angiotensin-I converting enzyme (ACE) gene have been implicated in cardiac hypertrophy. To assess whether ACE genotypes influence the phenotypic expression of hypertrophy, we determined the left ventricular mass index (LVMI) and extent of hypertrophy in 183 patients with HCM. METHODS AND RESULTS: LVMI was derived by the area-length method using two-dimensional echocardiograms. Extent of LVH was determined by a point score method (1 to 10 points). DNA was extracted from blood, and ACE genotyping was performed by polymerase chain reaction (PCR) with an established protocol. Amplification of DNA in the region of polymorphism by PCR of alleles I and D showed 490- and 190-bp products, respectively. ACE genotypes DD, ID, and II were present in 60, 90, and 33 patients with HCM, respectively. In genetically independent patients (n = 108), the mean LVMI (g/m2) was 148 +/- 35.3 in those with DD (n = 35) and 134.2 +/- 33.3 in those with ID and II (n = 73) genotypes (P = .046). LVH score was 6.69 +/- 1.71 in patients with DD and 5.55 +/- 2.19 in those with ID and II genotypes (P = .004). Regression analysis showed that ACE genotypes accounted for 3.7% and 6.5% of the variability of LVMI and LVH score (P = .046 and P = .008, respectively). In 26 patients from a single family, LVMI and LVH score were also greater in patients with DD than in those with ID and II genotypes. ACE genotypes accounted for 14.7% and 10.4% of the variability of the LVMI and extent of hypertrophy, respectively. CONCLUSIONS: ACE genotypes influence the phenotypic expression of hypertrophy in HCM.

Adult↗

PubMed1995

The role of transgenic knockout models in defining the pathogenesis of viral heart disease.

The pathogenesis of viral myocarditis involves contributions from the virus, the immune system and myocytes. In defining the molecular contributions in the disease process, modulations of the components of the immune system through transgenic knockout models provide useful insights. Advantages of the transgenic knockout models are that they allow biological evaluation of the importance of a particular molecule in the physiological context of an intact organism. Furthermore, the techniques of transgenic knockout models are now standardized, even though they are still technically challenging and time consuming. An example in myocarditis is the IRF-1 knockout mouse, where there is a complete absence of the inducible form of nitric oxide synthetase in the tissues. These animals are exquisitely sensitive to coxsackieviral infection, with extremely high mortality. On the other hand, CD4 knockouts appear to still have myocarditis in an autoimmune myocarditis model, while p56lck knockouts (the T-cell tyrosine kinase signalling molecule) appears to be free of viral myocarditis. These elegant systems of molecular manipu-lation should allow us unique insights into the pathogenesis of myocarditis.

Animals↗

PubMed1994

nm23-H1 expression and disease recurrence after surgical resection of small hepatocellular carcinoma.

BACKGROUND/AIMS: The nm23-H1 gene is thought to act as a metastasis-suppressor gene. This study investigates the relationship between nm23-H1 messenger RNA (mRNA) expression and intrahepatic tumor recurrence after surgical resection of small hepatocellular carcinoma. METHODS: Seventeen cirrhotic patients with solitary hepatocellular carcinoma < 5 cm underwent surgical resection. In 7 patients, the neoplasm recurred after a 12-month median follow-up, whereas the other 10 patients were free of disease after a 30-month median follow-up. Both groups were similar according to age, sex, etiology, status of the underlying liver, tumor size, and other pathological characteristics of the neoplasm. nm23-H1 mRNA levels were assessed in matched tumor and surrounding cirrhotic liver samples by Northern blot hybridization using a 900-base pair probe, which is a BamHI fragment of pnm23-H1 recombinant complementary DNA clone encoding the nm23-H1 human gene. RESULTS: Eight of the 10 patients without disease recurrence during follow-up showed nm23-H1 overexpression with an increase ranging between three- and 45-fold when compared with the nontumoral surrounding liver. Only 1 of the 7 patients with tumor recurrence showed higher nm23-H1 mRNA levels in the tumor than in the nonneoplastic sample (P = 0.013). CONCLUSIONS: nm23 mRNA overexpression in small solitary hepatocellular carcinoma is associated with a lower recurrence rate after surgical resection, suggesting that this gene may participate in the metastatic dissemination of this neoplasm.

Aged↗

PubMed1993

Spirosymplokos deltaeiberi nov. gen., nov. sp.: variable-diameter composite spirochete from microbial mats.

Large (up to 100 micrometers long), loosely coiled, free-living spirochetes with variable diameters (from 0.4 to 3 micrometers in the same cell) were seen at least 40 times between August 1990 and January 1993. These spirochetes were observed in mud water and enrichment media from highly specific habitats in intertidal evaporite flats at three disjunct localities, one in Spain and two in Mexico. All three are sites of commercial saltworks. Associated with Microcoleus chthonoplastes the large spirochetes from Spain display phototaxis and a composite organization. Shorter and smaller-diameter spirochetes are seen inside both healthy and spent periplasm of larger ones. Small spirochetes attached to large ones have been observed live. From two to twelve spirochete protoplasmic cylinders were seen inside a single common outer membrane. A distinctive granulated cytoplasm in which the granules are of similar diameter (20-32 nanometers) to that of the flagella (26 nanometers) was present. Granule diameters were measured in thin section and in negatively-stained whole-mount preparations. Based on their ultrastructure, large size, variable diameter, number of flagella (3 to 6), and phototactic behavior these unique spirochetes are formally named Spirosymplokos deltaeiberi. Under anoxic (or low oxygen) conditions they formed blooms in mixed culture in media selective for spirochetes. Cellobiose was the major carbon source in 80% seawater, the antibiotic rifampicin was added, mat from the original field site was present and tubes were incubated in the light at from 18-31 degrees C. Within 1-2 weeks populations of the large spirochete developed at 25 degrees C but they could not be transferred to fresh medium.

Environmental Microbiology↗

PubMed1993

Blood and graft eosinophilia as a rejection index in kidney transplant.

The relevance of eosinophilia in the physiopathology of transplant rejection has yet to be established. The appearance of eosinophilia has been occasionally associated with an adverse prognosis on graft rejection episodes. The aim of the present study was to evaluate the role and prognostic implications of blood and graft eosinophilia in kidney transplant rejection. We have examined the intrarenal infiltrate in 173 fine-needle aspiration biopsies from 36 consecutively transplant patients, and blood samples obtained simultaneously with fine-needle aspirations. Two different immunosuppressive regimens were administered: triple therapy (azathioprine + prednisone + antilymphocytic globulin) in patients with posttransplant acute tubular necrosis and cyclosporine A monotherapy in the rest of the patients. Comparing the two immunosuppressive groups, more elevated eosinophil values were observed in the monotherapy group during stable graft and also at the rejection episode. In the monotherapy group, a significant increase in the eosinophil values, in peripheral blood samples and in the intragraft infiltrates were noted at the rejection episode with respect to the stable situation. Following pulsed-steroid treatment an immediate disappearance of the eosinophils was evident. In contrast, no differences could be demonstrated between these two clinical situations in the TT group. Higher rates of eosinophils in the intrarenal infiltrate with respect to peripheral blood samples were observed during rejection episodes, suggesting some role of the eosinophils in the physiopathology of graft rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Fine-needle aspiration biopsy of portal vein thrombus: value in detecting malignant thrombosis.

OBJECTIVE: The purpose of this study was to assess the usefulness of fine-needle aspiration biopsy of portal vein thrombus to identify or exclude tumor. SUBJECTS AND METHODS: A series of 18 consecutive patients with portal vein thrombosis underwent fine-needle aspiration biopsy of the thrombus. Sixteen had underlying cirrhosis. Fifteen had clinical, biochemical, and imaging evidence of neoplastic invasion of the vein. Two patients had metastatic involvement of the left lobe of the liver, and the others had multinodular (eight cases) or diffuse (five cases) hepatocellular carcinoma. In four cases, the tumor was not clearly identified at sonography. RESULTS: Aspiration biopsy was positive for malignant tumor in 14 cases and negative for malignancy in one. In the three patients with benign portal vein thrombosis, fine-needle aspiration biopsy yielded only hepatocytes, fibrin, and blood cells. No results were false-positive. No complications were detected. CONCLUSION: Fine-needle aspiration biopsy is safe and sensitive for establishing the benign or malignant nature of portal vein thrombosis. This technique may be useful in selecting patients for liver transplantation.

Biopsy, Needle↗

PubMed1992

Characterization of a strong positive cis-acting element of the human beta-myosin heavy chain gene in fetal rat heart cells.

A strong positive element within the proximal promoter region of the human beta-myosin heavy chain (beta-MHC) gene that is required for high level expression in primary cultures of fetal rat heart cells was localized by transient assays and DNase I footprinting to positions- 277/-298. Using gel shift studies, this sequence was found to bind specifically at high affinity (Kd approximately 4 x 10(-9) M) to a transcriptional factor (beta F1) found in nuclear extracts from rabbit heart. Dimethyl sulfate interference studies suggested that beta F1 may bind as a dimer to two hexameric imperfect direct repeats containing the consensus sequence 5'-(C/G)-T-G-(T/A)-G-G-3'. Gel shift analyses suggested that beta F1 is related to the M-CAT factor, which is known to control muscle-specific expression of the cardiac troponin T gene. A clustered mutation of the region between the putative binding half-sites and within the "M-CAT"-like domain abolished beta-MHC promoter activity. The sequence of the positive element also contains binding motifs for several transcriptional factors that regulate viral and cellular genes, including AP4, AP5, TEF-1, and MyoD-like proteins. When multiple copies of the beta-MHC element were inserted downstream from the transcriptional initiation site of the thymidine kinase gene, it did not act as a classical enhancer, showing some dependence upon orientation.

Animals↗

PubMed1992

Bladder wash cytology and flow cytometry for the diagnosis of transitional cell carcinoma of the urinary bladder.

The role of bladder wash (BW) cytology and flow cytometry in the diagnosis of low-grade transitional cell carcinoma (TCC) of the bladder is yet to be demonstrated. We have studied a series of BW specimens by both conventional cytology and flow cytometry: there were 16 BW from patients with histologically proven TCC and 14 BW from patients with clinical suspicion of tumor or under follow-up for previous TCC in which no evidence of tumor was found by cystoscopy and multiple biopsies. As control group, 21 BW were studied from patients undergoing cystoscopy for causes other than TCC. In conclusion, the conventional cytologic study of BW specimens was highly sensitive for grade II-III TCC, but missed most grade I TCC; flow cytometric analysis did not improve significantly the detection rate in low-grade TCC.

Carcinoma, Transitional Cell↗

PubMed1992