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Biomedical subjects

M R Pinto

Publications and source records attributed to M R Pinto.

At least 55 records · Page 3Linked to original sources

A unique dicentric X;Y translocation with Xq and Yp breakpoints: cytogenetic and molecular studies.

A 32-year-old woman presented with secondary amenorrhea and infertility. She was of normal height and her breasts were well developed, but she had streak gonads; there were no signs of virilization, and she showed no somatic stigmata of Turner syndrome. Chromosome analysis revealed a dicentric X;Y translocation with Xq and Yp breakpoints. Centromeric banding demonstrated a Y centromere and a "suppressed" X centromere. The karyotype of the patient was interpreted as 46,X,t(X;Y)(q22;p11). The Yp breakpoint was confirmed by DNA-hybridization studies with six probes detecting Y-specific sequences. These DNA-hybridization studies were consistent with the presence of the long arm, centromere, and much of the proximal short arm of the Y. The Y-DNA studies of this female also revealed the absence of the distal short arm of the Y chromosome, to which the testis-determining factor has previously been localized.

Adult↗

The relationship between reactivities to lepromin A (Fernandez and Mitsuda) and a soluble protein antigen of Mycobacterium leprae.

Three methods of evaluation were used to investigate the relationship between skin test reactions elicited by different antigens of Mycobacterium leprae. The latter were the Fernandez and Mitsuda reactions to lepromin, and that to a Soluble Protein Antigen (SPA) of M. leprae. All three methods of evaluation demonstrated some degree of relationship though not as high as would be expected. The closest correlation was between Mitsuda and SPA reactions; while Fernandez and Mitsuda, and Fernandez and SPA reactions showed more or less similar coefficients of correlation.

Adolescent↗

Possible effects of hormonal contraceptives on human mitotic chromosomes.

Chromosome breakage, as an indicator of genetic damage, was assessed in peripheral blood lymphocytes of 44 women using different types of hormonal contraceptives (HC) for various periods of time, as well as on 44 matched controls. The selection of individuals for this study was preceded by the completion of a questionnaire to avoid, as far as possible, all cases subjected to known clastogenic agents. 48-h cultures were established by standard techniques and every sample from each "study" individual and her own matched "control" were simultaneously and similarly processed. The use of HC was found to be associated with a highly significant increase of chromosome aberrations in this in vivo study (p less than 0.001). The likelihood that the association found is a causal one is suggested and the theoretical clinical implications of these findings are discussed.

Adolescent↗

The volume of distribution of ceftazidime and albumin in normal, immature and infected bone.

The penetration of ceftazidime into bone was determined by measuring the volume of distribution of 14C-ceftazidime in infected and non-infected bone of adult mongrel dogs. The volume of distribution in non-infected cortical bone was 0.114 +/- 0.011 l/kg (mean +/- S.E.M.) and increased significantly in non-infected immature callus to 0.484 +/- 0.13 l/kg (P less than 0.05). In the presence of infection, the volume of distribution in non-infected cortical bone was 0.144 +/- 0.05 l/kg, and significantly higher in infected reactive cortical bone, 0.453 +/- 0.07 (P less than 0.05). We conclude that ceftazidime penetrates infected and non-infected bone and that this penetration is greater into immature bone.

Animals↗

Segregation patterns and phenotypes of unbalanced offspring in a large family with (10;18) chromosome translocation.

We describe a large family in whom a balanced 10;18 chromosome translocation is segregating through five generations. Six severely mentally retarded relatives and an abnormal fetus further define the phenotypic expression of dup (18q21----qter). Other segregants detected prenatally included a fetus with deletion 18q21----qter and two fetuses with dup(18pter----q21) owing to tertiary trisomy. One of the latter also had an extra X chromosome; this might be another example of possible nonhomologous pairing in man.

Chromosome Aberrations↗

The PLC/PRF/5 human hepatoma cell line. I. Reevaluation of the karyotype.

The karyotype of the PLC/PRF/5 (Alexander) human hepatoma cell line was identified at passage +/- 110, prior to attempting in situ hybridization studies to determine the chromosomal localization of the hepatitis B virus (HBV) DNA integration sites. The karyotype was established by means of G-, Q-, and sequential C-banding techniques. Multiple consistent numerical and structural abnormalities were detected. These were compared with the original published unbanded karyotype of this cell line (at passage less than 25) and also with a previously published banded karyotype (at passages 60-90). Despite minor differences in the compared banded karyotypes (which are probably interpretational), the concordance in modal number and morphological karyotypic similarities over the course of 10 years indicate that this cell line is stable in vitro.

Carcinoma, Hepatocellular↗

The PLC/PRF/5 human hepatoma cell line. II. Chromosomal assignment of hepatitis B virus integration sites.

The chromosomal sites at which hepatitis B virus (HBV) DNA is integrated into the genome of the hepatocellular carcinoma (HCC) cell line, PLC/PRF/5 were investigated in an attempt to understand the mechanisms by which hepatitis B virus may induce malignant transformation. In situ hybridization of an HBV DNA probe to metaphase chromosomes of the PLC/PRF/5 cell line, followed by statistical analysis, identified three integration sites; these were 15q22-q23, 11q22, and 18q12. In particular, hybridization to chromosome #15, which is present in four copies in complete metaphases of this cell line, was highly significant (p much less than 0.0005).

Adult↗

Acute megakaryoblastic leukaemia with 3q inversion and elevated thrombopoietin (TSF): an autocrine role for TSF?

A patient with acute megakaryoblastic leukaemia is described in whom exactly the same paracentric inversion of 3q was detected as in three previously documented cases. The patient's serum thrombopoietin (TSF) was significantly raised. Based on these findings we postulate a role for a gene (? oncogene) on chromosome 3q in thrombopoietin production. Abnormalities of 3q may assist in delineating a subgroup of acute nonlymphocytic leukaemia, namely acute megakaryoblastic leukaemia.

Bone Marrow↗

Amniotic band syndrome and conditions simulating disruption malformations.

Twelve cases of fetal malformation due to the amniotic band syndrome (ABS) or disruption sequence were reviewed; these included craniofacial malformations, limb defects and gastroschisis. No one case was similar to another. The initial diagnosis was correct in 5 of the 12 cases, mainly those involving limb defects. All 4 cases in which major malformations were present were initially diagnosed incorrectly. The importance of correct diagnosis mainly concerns counselling regarding the future risk of recurrence--the probability of familial recurrence of ABS is very low, whereas the risk of recurrence of a familial neural tube defect is about 5%.

Amniotic Band Syndrome↗

Age-related changes in bone in the dog: fluid spaces and their potassium content.

We measured erythrocyte, plasma, osteocyte, extravascular extracellular, and total water fluid spaces and calculated their K content in cortical bone of dogs of various age. Total and exchangeable K were measured by atomic absorption spectroscopy and by volume of distribution techniques, respectively. All fluid spaces in bone decreased with increasing age of the dogs. The total and exchangeable K contents of cortical bone and the K content calculated from the fluid spaces were within the same range in each age group. These values all fell with increasing age.

Aging↗

Non-random in vitro 7;14 translocations detected in a routine cytogenetic series. 12 examples and their possible significance.

This study describes 12 examples of translocations between chromosomes 7 and 14 in short-term peripheral blood lymphocyte cultures from 10 patients investigated in a routine cytogenetic series. Only one constant breakpoint was found on 14q, and chromosome 7 had two constant breakpoints, one on 7p and the other on 7q. The cause and true significance of such nonrandom in vitro chromosome translocations is not known at present, but one may speculate as to their possible indication of heterozygosity for a chromosome instability syndrome and thus a predilection for the development of lymphoid or other malignancy.

Adult↗

Sperm binding to eggs of Ciona intestinalis. Role of Ca2+.

In this paper we show that in the ascidia Ciona intestinalis extracellular Ca2+ is required for the binding of the spermatozoa to the vitelline coat (VC) glycerol-treated eggs and for fertilization to occur. Divalent cations, Mg2+ and Mn2+, cannot replace Ca2+. Once bound, the spermatozoa cannot be detached from the vitelline coat by adding of EGTA. Verapamil does not interfere with the binding of spermatozoa to the vitelline coat, whereas it blocks the Ca2+ ionophore A23187-induced sperm activation and acrosome reaction. Fertilization too was inhibited by the presence of this drug.

Acrosome↗

The incidence, type, and subsequent evolution of 14 variant Ph1 translocations in 180 South African patients with Ph1-positive chronic myeloid leukemia.

A Philadelphia (Ph1) chromosome translocation was found in 180 of 198 cases of chronic myeloid leukemia (CML). A standard t(9;22) was present in 166 patients, 83 of whom were black, 79 white, and 4 of "mixed" ancestry; whereas a variant Ph1 translocation was detected in 14 patients (7.8%), 11 of whom were black and only 3 white. There was a higher frequency of a variant Ph1 among black patients compared with whites. The significantly higher frequency of a variant among our patients compared with surveys from elsewhere could be due to differing environmental agents. Simple variants were detected in four patients. Complex variants were found in eight cases; in one of these patients, only chromosomes #9 and #22 were involved, but a complex rearrangement of chromosome #9 had occurred. A "masked" Ph1 translocation was detected in two cases, both of which showed monosomy #22 because the Ph1 chromosome was incorporated or interchanged with chromosome #9. Karyotypic evolution of the Ph1-positive cell line was observed more frequently in the variant group (71.4%) than the standard group (29.5%). This difference was significant (p less than 0.005). There was no difference in the type of clonal changes seen in standard and variant groups. The majority of clonal changes were observed during the acute stage in both groups. In the variant group, there was no obvious correlation between the type of variant, type of clonal change, blast morphology, or survival. Their initial survival pattern resembled that of Ph1-negative cases, but those patients who survived longer than 1 year showed a survival trend similar to standard Ph1-positive cases. Possible explanations for the specificity of chromosome #22 involvement and the constancy of the 22q11 breakpoint in all these variant translocations are discussed.

Adult↗

Chromosome patterns in 26 South African children with acute nonlymphocytic leukemia (ANLL).

Of 46 black leukemic children 52% had acute nonlymphocytic leukemia (ANLL), whereas only 11% of 62 white leukemic children had the disease. An abnormal karyotype was found in 73% of the 26 children with ANLL, and the majority of abnormal karyotypes were pseudodiploid. "Balanced" translocations were noted in 10 children, of whom four had t(8;21) associated with M2 ANLL, two had t(15;17) and M3 ANLL, two had a t(9;22), one child with M5 ANLL had t(10p;11q), and an infant with congenital M5 ANLL had t(8;16). Monosomy #7 was detected in two preleukemic children who subsequently developed M4 ANLL. Hyperdiploidy was present in only three cases. These patterns were compared with those of other published series, confirming the increased frequency of chromosome abnormalities in children with ANLL. The differing ratio of ANLL:ALL, some of the distinctive clinical features, and the high frequency of detectable chromosome abnormalities in black children may be reflections of a particular oncogenic agent(s) within their environmental background that could be responsible for the initiation of the leukemic process.

Adolescent↗

"Masked" Ph1 chromosome abnormalities in CML: a report of two unique cases.

Two patients with chronic myeloid leukemia (CML) showed previously undescribed variants of a "masked" Ph1 abnormality. The first patient had the karyotype 46,XY, + 21, -9, -22, +mar9,mar18 at presentation in the chronic phase. The dicentric marker 9 was interpreted as representing the usual translocation of 22q11 to 9q34, followed by translocation of the Ph1 chromosome (the deleted 22) to 9p and probable translocation of 9p to the distal long arm of the marker. The patient developed clones containing 2 and 3 copies of the "Ph1-containing" marker 9 concomitant with the metamorphosis of his disease to a more aggressive phase. The second case presented with the karyotype 46,XY,-9,-22,+two D-group markers. A complex rearrangement of chromosomes 9 and 22 is postulated, with interstitial insertion of either 9p or distal 9q into chromosome 22q11. This patient is still in the chronic phase of his disease 9 mo after presentation. The common denominator in these unusual "masked" cases is the 22q11 breakpoint. The paucity of published reports of duplication of 9q + without concurrent duplication of the Ph1 chromosome, supported by the findings in our first case, leads us to conclude that the amplification of genes on the Ph1 chromosome are more important for the evolution of the abnormal stem cell in CML than the chromosome 9 derivative.

Adult↗