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Biomedical subjects

J M Rodriguez

Publications and source records attributed to J M Rodriguez.

At least 73 records · Page 4Linked to original sources

Localization of metallothionein in breast carcinomas. An immunohistochemical study.

Metallothionein (MT) is a cysteine-rich, low molecular weight protein that binds zinc, copper, and cadmium. It is present in a number of normal cells including hepatocytes particularly during fetal and early postnatal life. It has been suggested that developmental profile of MT is similar to other oncofetal gene products and hence, it could be used as a marker for aggressive tumour behaviour. In order to test that hypothesis, we used a monoclonal antibody to MT and immunohistochemically evaluated formalin-fixed, paraffin-embedded tissues from 79 breast carcinomas. In non-neoplastic breast tissue, a strong nuclear and cytoplasmic staining was observed in myoepithelial cells. Positive staining for MT was present in 35 (44%) of breast carcinomas. In most positive cases, nuclear, or both nuclear and cytoplasmic staining was seen. All positive tumours were invasive ductal carcinomas, including a medullary and a metaplastic carcinoma. None of the mucinous, lobular, or intraductal papillary carcinomas reacted for MT. A statistically significant association was found between MT immunostaining and histological grade (P < 0.01) as well as with nuclear grade (P < 0.01). We also observed an inverse relationship between MT staining and oestrogen receptor content of tumours (P < 0.01). Similarly, a statistically significant association was found between moderate and strong MT immunostaining and decreased overall survival and shorter disease-free survival (P < 0.01). MT immunostaining was also predictive of a worse prognosis in the subgroup of lymph node negative (P < 0.001) and oestrogen receptor negative patients (P < 0.01). No statistically significant association was found between MT staining and size of tumour or the presence of lymph node metastasis. We conclude that MT staining may be a useful marker of less differentiated and more aggressive carcinomas of the breast.

Breast Neoplasms↗

Rearrangement of the N-myc oncogene in acute leukemias: a case report.

Rearrangements of the N-myc oncogene have not been described in the literature. The authors present a case of ANLL with the N-myc gene rearranged out of 16 ANLLs and 11 ALLs. While the proportion of the blast cells in the case reported was 85%, the rearranged gene gave a hybridization band which was less intense than that of the germline band, making it probable that this gene rearrangement is present in a leukemia subclone. The c-myc oncogene as well as Ig and TcR genes were in germline configurations. The presence of the rearranged N-myc in the reported case could imply an alternative mechanism of mutation of this oncogene in the pathogenesis of hematological malignancies.

Aged↗

[Multiple endocrine neoplasia II A syndrome: relationship between age of the patient, levels of basal calcitonin and size of the thyroid tumor].

This paper presents our experience in four families having the multiple endocrine neoplasia (MEN) II-A syndrome, with a total of 19 affected patients. All had medullary thyroid carcinoma (MTC), 6 also had pheochromocytoma (PH) and 3 had hyperparathyroidism. The screening of the members of the families to measure basal and pentagastrin response calcitonin (CT) serum levels allowed an early diagnosis of medullary thyroid carcinoma, when lesions were only 1 mm in diameter. Measurement of vanillymandelic acid, catecholamines and metanephrines in 24-hour urine collections allowed the diagnosis of pheochromocytoma in patients, some of whom were asymptomatic. A clear relationship was found between the age of the patients, the basal serum calcitonin level and size of the MTC.

Adolescent↗

A fully automated method for mononuclear bone marrow cell concentration.

We describe our experience in processing 40 bone marrow aspirates harvested for autotransplantation from patients with several hematological diseases using the CS-3000 blood cell separator. The bone marrow of the first 30 patients was processed by a semiautomated method, and a fully automated procedure was used for the remaining 10 cases. Both procedures were developed in our laboratory and yielded a similar average mononuclear cell recovery of 87.78% and 86.98%, respectively, and similar nucleated cell recovery (27.39% and 27.11%). The cloning efficiency of hematopoietic progenitor cells, measured as the total CFU-GM colony recovery in the in vitro cultures, did not differ between processed and recovered mononuclear cells. On the other hand, all the patients with transplants showed complete hematologic recovery, and the time to engraftment was similar to that described for other procedures. The automated procedure resulted in an average red cell removal of 97.81%, similar to the semiautomated procedure (94.19%), though with a narrower range (96.31-98.6% vs. 80.34-98.34%). The time taken to process a similar amount of bone marrow cell suspension was very different for each method: 1 hour for the fully automated vs. 2 1/2 hours for the semiautomated method to process 1,000 ml. Furthermore, the semiautomated procedure required the addition of homologous or irradiated plasma in a laminar air flow chamber, while the automated method is performed in a closed sterile system. We conclude that our procedure using the CS-3000 processor is an efficient method for fully automated large-scale processing of human bone marrow cells.

Adolescent↗

Genes homologous to ubiquitin-conjugating proteins and eukaryotic transcription factor SII in African swine fever virus.

The nucleotide sequence of the 6004-bp EcoRI I fragment of African swine fever virus DNA has been determined. Translation of the sequence revealed eight closely spaced open reading frames (ORFs), three of them reading rightward and five leftward. Northern blot hybridization analysis indicated that ORFs I73R and I78R were transcribed early in infection, whereas ORFs I177L, I196L, and I329L were expressed at late times. Transcripts for ORFs I215L, I226R, and I243L were detected at low levels in early RNA and at higher levels in late RNA. The intergenic regions between genes I73R/I329L and I78R/I215L were characterized by the presence of direct repeats in tandem. Direct repetitions were also found within ORF I196L. The protein encoded by ORF I329L contained a putative cleavable signal peptide and an internal transmembrane domain, and that encoded by ORF I177L had an amino-terminal hydrophobic region with the characteristics of a "start-stop" sequence. ORF I243L encoded a protein similar to the eukaryotic elongation factor SII. The protein encoded by ORF I215L was homologous to the family of ubiquitin-conjugating proteins.

African Swine Fever Virus↗

Effect of oxidants on proteases of the fibrinolytic system: possible role for methionine residues in the interaction between tissue type plasminogen activator and fibrin.

Evidence has recently been presented that activated macrophages (M phi) express both urinary (u-PA) and tissue type (t-PA) plasminogen activator. Major cell products of M phi and polymorphonuclear neutrophils (PMN) are reactive oxidants of the HOCl/chloramine type. Since PMN and M phi are involved in inflammatory and fibrinolytic processes, we were interested in the interaction of u-PA, t-PA, and plasmin with oxidants of the leukocyte type. The enzymes were treated with chloramine-T, which at pH 8.5 is a selective oxidant for methionine residues. Oxidation by chloramine-T of t-PA abolishes about 40% of both stimulation susceptibility of t-PA by fibrinogen degradation products (FDP) and affinity of t-PA to FDP. However, the plasminogenolytic and amidolytic activity of unstimulated t-PA as well as the plasminogenolytic activity of u-PA and the amidolytic activity of plasmin are not impaired. Identification of the amino acid residues in the t-PA responsible for the interaction with fibrin might be of great importance in order to understand the mechanism of the clot- selectivity of t-PA. The present study gives evidence that fibrin specificity of t-PA partly depends on chloramine oxidizable amino acids, presumably methionine residues. Hence, experimental data on the interaction between t-PA and fibrin, using oxidized and labelled t-PA should be interpreted with caution. It may be suggested that oxidants of the leukocyte type might regulate t-PA activity and selectivity for fibrin.

Chloramines↗

Single chain-urokinase binds to oxidized fibrin(ogen) derivatives.

Single chain- urokinase (scu-PA), in contrast to two chain urokinase, is a physiological plasminogen activator of fibrin selectivity. The mechanism of selective fibrinolysis of scu- PA has not been clarified up to now. This study has shown that fibrin selectivity might involve oxidative processes. Binding studies with immobilized oxidized fibrinogen degradation products (FDP) demonstrated higher affinity of scu-PA to oxidized than to unmodified FDP. The fibrin(ogen) domain responsible for this oxidant mediated increase of scu-PA affinity is localized in the D-subunit of fibrin(ogen). Thus, experimental data upon the interaction of scu-PA with fibrin(ogen) using oxidized and I- labelled fibrin(ogen) might be interpreted with caution: the oxidized product may behave in a distinct manner than the unoxidized, native, one. Activated leukocytes release large amounts of scu-PA and of oxidants of the chloramine type. The oxidants could contribute significantly to fibrinolysis and proteolysis in areas of inflammation, preparing fibrin for its specific degradation. The present data support the concept of an involvement of oxidative processes in the fibrinolytic pathway.

Fibrin Fibrinogen Degradation Products↗

Concentrations of cefmetazole in plasma and tissue resulting from peri-incisional administration before appendectomy.

The levels of cefmetazole in plasma and tissue were determined after injection of a dose of 30 mg/kg into the zone of the wound of each of 15 patients undergoing appendectomy. The mean plasma levels of cefmetazole at the start and end of surgery (8.9 +/- 2.4 and 31.7 +/- 6.4 min after dosage) were 21.1 and 59.0 micrograms/ml, respectively; concentrations of the drug were 14.6 and 4,486.9 micrograms/g in skin, 9,165.0 and 1,756.4 micrograms/g in subcutaneous tissue, and 8,669.6 and 2,022.9 micrograms/g in muscle.

Administration, Topical↗

Familial lupus erythematosus.

The child of a woman with discoid lupus erythematosus (DLE) had lesions of DLE develop at the age of 2 months. The original lesions persisted and new lesions continued to develop to date; the child is now 28 months old. In a second child, now 11 months old, a probable lupus erythematosus rash developed at 1 week of age.

Adult↗

Multiple myeloma with cutaneous involvement.

A 49-year-old man with multiple myeloma, IgA type, contracted cutaneous plasmocytomas. No deposits of immunoglobulin were found in the cutaneous tumor by direct immunofluorescence. The case is an unusual manifestation occurring in multiple myeloma.

Fluorescent Antibody Technique↗