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Biomedical subjects

M Freire

Publications and source records attributed to M Freire.

At least 19 recordsLinked to original sources

Immunohistochemical detection of parathyroid hormone-related protein in a cutaneous squamous cell carcinoma causing humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy is a cancer-related hypercalcemia caused by production of humoral factors by malignant cells in patients without bone metastases. Squamous cell carcinomas are the tumors most frequently associated with humoral hypercalcemia of malignancy, and parathyroid hormone-related protein is the main humoral factor implicated. In spite of the fact that normal keratinocytes produce parathyroid hormone-related protein, it is highly unusual for patients with squamous cell carcinomas of the skin to present with humoral hypercalcemia of malignancy. We present a well-documented case of cutaneous squamous cell carcinoma complicated by hypercalcemia in a patient with high levels of plasma parathyroid hormone-related protein and immunohistochemical evidence of high parathyroid hormone-related protein production by the tumoral cells.

Aged↗

Studies on control of visceral leishmaniasis: impact of dog control on canine and human visceral leishmaniasis in Jacobina, Bahia, Brazil.

To assess the effect of removing leishmania-infected dogs on the incidence of visceral leishmaniasis, a controlled intervention study was performed in northeast Brazil. The attempted elimination of seropositive dogs resulted in an initial significant decrease in the annual incidence of seroconversion among dogs from 36% to 6% over the first two years. In the following two years, the incidence increased to 11% and 14%, respectively. In a control area in which dogs were surveyed but seropositive dogs were not removed, the cumulative incidence did not vary significantly from year to year, ranging from 16% to 27%. In the intervention area, the prevalence of dog seropositivity decreased from 36% before the intervention to 10% and remained stable. These findings suggest that attempting to remove seropositive dogs is insufficient as a measure for eradicating visceral leishmaniasis in dogs. However, the force of transmission of infection among dogs can be reduced by such programs. Also, when the number of human cases before and after the start of the intervention was calculated, a significant decrease in incidence of disease in the intervention area was observed among children less than 15 years of age (P < 0.01). The results of this intervention study suggest that the elimination of the majority of seropositive dogs may affect the cumulative incidence of seroconversion in dogs temporarily and may also diminish the incidence of human cases of visceral leishmaniasis.

Adolescent↗

[Serum levels of soluble interleukin-2 receptor in alcoholic patients].

OBJECTIVES: Contribution of cellular immunity to the onset and perpetuation of alcohol-induced liver damage remains controversial. The aim of this work was to know whether T-cells participate in the pathogenesis of alcoholic liver injury by measuring the serum levels of sIL-2R in alcoholic patients with different degree of hepatic damage. PATIENTS AND METHODS: Fifty two patients and eighteen healthy subjects (Control group) were included. All patients were active drinkers of at least 100 grams/day of ethanol over a ten-years period. Serum sIL-2R was determined by ELISA. Liver biopsy was performed in all patients and liver function tests, serum immunoglobulins and complement proteins C3 and C4 were measured in all participants. The relationship between the sIL-2R and the severity of liver disease was studied. RESULTS: Circulating sIL-2R was higher in the group of patients than in the control (2.388 +/- 275.7 U/ml vs. 795.7 +/- 48.7 IU/mL; p < 0.001). There were not increased circulating sIL2R in those patients with alcoholic hepatitis. However, patients with cirrhosis showed increased serum sIL-2R regardless of the presence of alcoholic hepatitis. Furthermore, serum levels of sIL-2R inversely correlated with hepatic function test (r = -0.69; p < 0.001 for serum albumin; and r = -0.73; p < 0.001 for the prothrombin time) and were highest in those patients of the Child-Turcotte's class C. CONCLUSIONS: Circulating sIL-2R increases in alcoholic cirrhosis. However, our data do not support a contributory role of the cellular immunity, as assessed by circulating sIL-2R levels to the alcoholic liver damage. The increased serum sIL-2R in cirrhosis may result from defective heptic clearance of this molecule.

Alcoholism↗

A 180-kDa protein kinase seems to be responsible for the phosphorylation of prothymosin alpha observed in proliferating cells.

Prothymosin alpha (ProTalpha) is an acidic protein involved in cell proliferation. Its phosphorylation status is correlated with proliferative activity. Here we report the isolation and characterization of a ProTalpha-phosphorylating kinase (ProTalphaK) from mouse splenocytes that seems to be responsible for the in vivo phosphorylation of ProTalpha and that differs from other protein kinases reported to date. This enzyme, mainly located in the cytosol, has an molecular mass of 180 kDa and appears to be made up of two proteins of 64 and 60 kDa. Its activity was markedly enhanced by mitogenic activation of cells. The ProTalpha residues phosphorylated by the enzyme in vitro are a Thr at position 7 and another Thr at positions 12 or 13, both located within casein kinase 2 (CK-2) consensus motifs; these are the same residues as are phosphorylated in vivo. The new enzyme shows a number of clear structural and catalytic differences from CK-2. It phosphorylates histones H2B and H3, although with weaker activity than ProTalpha. An enzyme with the same characteristics was also found in other murine tissues and cell lines.

Animals↗

Prothymosin alpha binds histones in vitro and shows activity in nucleosome assembly assay.

Prothymosin alpha (Pro Talpha) is a polypeptide which appears to be involved in cell proliferation, though its precise function has yet to be identified. Here, we report experiments which show that calf Pro Talpha selectively binds to core histones and histone H1 in vitro. Characterization of these interactions by various procedures (including affinity chromatography on Pro T alpha-Sepharose columns, immunoblotting assay and investigation of the behaviour of mixtures of Pro T alpha and histones in solution) indicated that Pro T alpha has higher affinity for core histones (particularly H3 and H4) than for H1. Similarities between the histone-binding patterns of Pro T alpha and of poly(glutamic acid) suggest that the observed histone-binding capacity resides largely in the acidic central region of Pro T alpha. However, all five histones were also bound by T alpha 1 (a peptide corresponding to the first 28 amino acids of Pro T alpha); histone binding by the N-terminal region of Pro T alpha thus cannot be ruled out. Phosphorylation of Pro T alpha does not appear to affect these interactions. In accordance with the observed capacity for histone binding, Pro T alpha (in conjunction with ATP and some Pro T alpha-binding factor/s in a thymocyte extract) was able to induce in vitro nucleosome assembly. We discuss the possibility that Pro T alpha plays a role in chromatin remodelling.

Amino Acid Sequence↗

rK39: a cloned antigen of Leishmania chagasi that predicts active visceral leishmaniasis.

The diagnosis of visceral leishmaniasis (VL), a serious and often fatal parasitic disease caused by members of the Leishmania donovani complex, remains problematic. Current methods rely on clinical criteria, parasite identification in aspirate material, and serology. The latter methods use crude antigen preparations lacking in specificity. A previously described cloned antigen, rK39, of Leishmania specific for all members of the L. donovani complex (L. chagasi, L. donovani, L. infantum) was very useful in the serodiagnosis by ELISA of both human and canine VL. The present study demonstrated that rK39 seroreactivity correlated with active disease. The sera from early or self-healing infected subjects reacted with leishmanial lysate and were generally nonreactive with rK39. These data demonstrate the utility of rK39 in the serodiagnosis of VL and as an indicator of active disease.

Animals↗

Idiopathic eosinophilic synovitis. Case report and review of the literature.

Eosinophilia of synovial fluid is an uncommon condition. The majority of the reported cases are associated to diseases such as rheumatoid arthritis, parasitic disease, hypereosinophilic syndrome, Lyme disease, and allergic processes as well as hemarthrosis and arthrography. Presently there are only four cases of eosinophilic synovitis with unknown cause. We are reporting a patient with oligoarthritis of the knees, massive eosinophilia, and Charcot-Leyden crystals in synovial fluid without associated cause. We review the clinical and biological features of eosinophilic synovitis and discuss its pathogenesis.

Adolescent↗

The prothymosin alpha gene is specifically expressed in ectodermal and mesodermal regions during early postimplantation mouse embryogenesis.

Prothymosin alpha (ProT alpha) is a highly acidic nuclear protein, once believed to have an extracellular immunoregulatory role but more recently implicated in cell proliferation and/or differentiation. Several recent studies have revealed that ProT alpha mRNA is present during embryogenesis. However, these studies did not investigate the spatial distribution of ProT alpha mRNA in the embryo. Here we present a detailed study of the spatial distribution of ProT alpha mRNA during the early stages of postimplantation development (6.5-12.5 dpc) of the mouse. Three findings are of particular interest. First, ProT alpha mRNA levels increase during the early postimplantation stages (6.5-8.5 dpc) of mouse embryogenesis. Second, ProT alpha mRNA is not uniformly distributed in the mouse embryo, but is present in a spatially specific manner. Third, we have observed that the mouse ProT alpha gene is expressed almost exclusively in ectodermal and mesoderm-derived structures, and not in cells which give rise to the definitive endoderm.

Animals↗

Stereoscopic and biplanar microphotography of Golgi-impregnated neurons: a correlative study using conventional and real-time, direct-image confocal microscopies.

A correlative study of neuronal reconstruction methods was made using both conventional (non-confocal) and real-time confocal microscopies. Simple and sophisticated (totally automated) methods are described for making both biplanar microphotographs using conventional transmitted light, and stereoscopic microphotographs using real-time confocal microscopy of Golgi-impregnated neurons. Confocal microscopy discriminates against out-of-focus layers to produce optical sections which can be summed on photographic film to obtain neuronal reconstructions. Biplanar images are obtained by fusion, using a stereo-viewer, of two adjacent optical sections obtained with a conventional transmitted light microscope. Stereoscopic and biplanar microphotographs of 3-day-old chick neurons are presented.

Animals↗

Markers of T-cell differentiation and maturation in C57BL/6 and BALB/c mice and in the calf: a comparative study.

No significant differences were found between C57BL/6 and BALB/c mice in the levels of Thy 1.2 antigen (a T-cell marker) or the activities of the T-cell maturation-related enzymes adenosine deaminase (ADA, EC 3.5.4.4), serine-esterase (SE, EC 3.4.21), N-acetyl-beta-D-glucosaminidase (NABG, EC 3.2.1.30) and beta-glucuronidase (BG, EC 3.1.1.1), in either unfractionated lymphoid cells or T-lymphocyte-enriched fractions. ADA, SE, NABG and BG activities were much higher (P < 0.01) in the calf than in the corresponding populations in mice. However, the distributions of these activities among thymocyte subpopulations were very similar in mice and the calf. These results provide indirect evidence to suggest that the course of T-cell maturation is similar in mice and the calf.

Acetylglucosaminidase↗

Comparison of the polymerase chain reaction and serology for the detection of canine visceral leishmaniasis.

The polymerase chain reaction (PCR) and serology was evaluated for the diagnosis of canine visceral leishmaniasis in Bahia, Brazil in a study of 125 dogs. The PCR was 100% sensitive in 25 dogs that had Leishmania demonstrated by either culture or hamster inoculation. It was 100% specific for 35 dogs from the northeastern United States, all were PCR negative. However, 22 of 54 Brazilian dogs that were culture-hamster inoculation-negative were positive by PCR. The nature of the PCR product was identified by hybridization with specific Leishmania probes. Whereas the sensitivity of serology in relationship to infection, as determined by hamster or culture assay was more than 80%, sensitivity of serology was only 63% when compared with PCR. These results raise questions about the use of serology to detect Leishmania infection in dogs, and suggest that the PCR might serve as a better gold standard to define Leishmania infection than culture or hamster inoculation.

Animals↗

[Colonic ulcer in HIV (+) patients].

UNLABELLED: A characteristic rectocolonic endoscopic finding is the presence of ulcers, which may correspond to different diagnosis. Between January, 1989 and May, 1993, we performed 28 colonoscopies and 12 rectoscopies in patients with HIV (+). In all cases, histologic, parasitologic, bacteriologic, virologic, and micrologic studies were practised on tissue biopsies. Eighteen of them presented rectocolonic ulcers (we are not including anal and terminal ileum ulcers). The studies involved 16 males and 2 females, with an average age of 31, 21 years old (20-47), 14 of which were male homosexuals, 2 intravenous drug abusers, 1 hemophilic and an heterosexual female. Symptoms were as follows: 15 with hematochezia, 7 with proctorrhagia, 6 with enterorrhagia and 2 with both manifestations. All the rest, presented chronic diarrhea, loss of weight, anal secretion, asthenia, fever, constipation and anemia in isolated cases. Diagnosis were 6 rectocolonic cytomegalovirus (all occurred during the current year). Other related opportunistic pathogens included an intestinal TBC, a rectal Herpes and a Burkitt's lymphoma. Related etiological agents were not found in 9 patients, in spite of systematic quest. Opportunistics found in three of the cases revealed AIDS in those patients. COMMENTS: 1-The indexes of male homosexuals are strikingly higher than the rest of our HIV endoscopy statistics. 2-We observed prevailing idiopathic lesions. 3-The relationship between "CU like" pictures, already described, and the immunocomponents of the idiopathic CU is unknown. 4-All our CMV cases are recent. 5-Hematochezia was the most frequent symptom. 6- Herpetic ulcers correspond to HSV type 1. 7-Diffuse ulcers may correspond to lymphoma.

Adult↗

Prothymosin alpha and factors from calf thymic cells decrease expression of Thy 1.2 antigen among small thymocytes from C57BL/6 mice.

In this work we studied the effect of Prothymosin alpha (ProT alpha) and other thymic factors on the expression of Thy 1.2 antigen (a T-cell marker) and the activities of adenosine deaminase (ADA, E.C. 3.5.4.4), N-acetyl-beta-D-glucosaminidase (NABG, E.C. 3.2.1.30), beta-glucuronidase (BG, E.C. 3.1.1.1) and serine-esterase (SE, E.C. 3.4.21)., the levels of which change during the T-cell differentiation process among small thymocytes obtained from C57BL/6 mice. Incubation of small thymocytes in the presence of ProT alpha, Thymus Extracts (TE) or supernatants prepared from thymic stromal cells (TSCS) or thymocytes (TS) reduced the proportion of cells killed by anti-Thy 1.2 monoclonal antibodies but did not affect the enzymatic activities studied. This is the first evidence that ProT alpha affects Thy 1.2 expression in vitro.

Acetylglucosaminidase↗

Characterization of T cell responses to purified leishmania antigens in subjects infected with Leishmania chagasi.

T cell responses to lipophosphoglycan-associated protein (LPG-AP) and the rgp63 antigens were studied in subjects with either asymptomatic L. chagasi infection or cured visceral leishmaniasis. The [3H]-thymidine uptake of lymphocytes stimulated with LPG-AP and rgp63 (mean +/- SD) was 14275 +/- 5048 and 3523 +/- 1678 cpm, respectively, for subjects with asymptomatic L. chagasi infection and 20046 +/- 5102 and 5086 +/- 3500 cpm, respectively, for subjects cured of visceral leishmaniasis. The responses to LPG-AP in both asymptomatic and cured visceral leishmaniasis were higher (P < 0.01) than those observed with rpg63. LPG-AP induced IFN-gamma production in all subjects studied, while rgp63 did not induce lymphocyte proliferation or IFN-gamma production in the majority of the subjects tested. IFN-gamma levels in cultures stimulated with LPG-AP were 103 +/- 81 pg/ml in individuals with asymptomatic L. chagasi infection and 127 +/- 123 pg/ml in subjects cured of visceral leishmaniasis. IFN-gamma levels in cultures stimulated with LPG-AP from subjects with asymptomatic L. chagasi infection were comparable to those observed in subjects cured of visceral leishmaniasis (P > 0.05). These data indicate that LPG-AP is recognized and induces T cell proliferation and IFN-gamma production in subjects with protective immune response against Leishmania chagasi.

Adolescent↗