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Biomedical subjects

P H Fitzgerald

Publications and source records attributed to P H Fitzgerald.

At least 73 records · Page 4Linked to original sources

Cytogenetic studies of acute promyelocytic leukemia.

Translocation t(15;17) is reported in bone marrow cells from six of seven patients with active acute promyelocytic leukemia (APL). One patient who showed t(15;17) at final relapse did not show it in directly prepared or cultured cells taken from a previous relapse. Bone marrow samples from two patients showed only cells with a normal karyotype in the direct preparation, whereas more than 60% of cells cultured for 24 hr showed t(15;17). R-Banding, G-banding, and an attempt at high-resolution banding indicated the break points t(15;17)(q24;21) for one of our patients.

Adult↗

The incidence and epidemiology of retinoblastoma in New Zealand: A 30-year survey.

One hundred cases of retinoblastoma were diagnosed in New Zealand-born children between 1948 and 1977 inclusive. Five patients had an affected parent, and of the remaining sporadic cases 25 had bilateral and 70 unilateral tumours. The frequency of retinoblastoma, 1 in 17,500 births, was similar to that reported for most other countries. There was no evidence of an increase in the incidence of all cases of sporadic retinoblastoma during the 30-year period studied, nor was there any significant fluctuation in their incidence with space and time. There was an excess of bilateral sporadic cases in the southern-most districts of New Zealand, but this was of marginal significance. There was no significance evidence for any environmental influence on the occurrence of retinoblastoma.

Age Factors↗

Acute promyelocytic leukemia: cytogenetics and bone-marrow culture.

Six patients were diagnosed as having acute promyelocytic leukemia (APL) according to FAB criteria. One patient conformed to the M3 variant. Informative cytogenetic results (G-banding) on five of the patients showed that three of them, including the M3 variant, had the 15;17 translocation in bone-marrow or blood cells. Cells with the translocation were accompanied by cells with a normal karyotype in all patients and no other chromosomal abnormality was present. This first report of the 15;17 translocation from the South Pacific region is relevant to the uneven geographical distribution of APL patients with the translocation. Five of the six patients including the M3 variant, showed a distinctive pattern of cell growth in agar culture characterized by a profusion of small, uniform clusters containing 6-20 cells with the appearance of promyelocytes. The remaining patient had a pattern of cell growth more typical of M2 acute leukemia. This cell growth pattern may be useful in diagnosing and monitoring the course of APL.

Aged↗

The wound fibroblast and macrophage. II: Their origin studied in a human after bone marrow transplantation.

The origin of the wound fibroblast and macrophage was studied in a patient following bone marrow transplantation, using sex chromosome markers. Fibroblast-like cells emigrating from explants of a 5-day-old skin wound had the host karyotype, whereas macrophages had donor markers. These results suggest that the wound fibroblast in man is of local tissue origin, whereas wound macrophages are derived from haemopoietic tissue.

Bone Marrow Transplantation↗

A complex Ph1 translocation in a patient with primary thrombocythaemia.

Routine blood examination of a 27-year-old female revealed a platelet count of 2000 X 10(9)/l. Bone marrow cells showed the Philadelphia chromosome which was one product of a complex rearrangement of chromosomes 9, 22 and X. Her platelet count was lowered by plateletphoresis and chemotherapy. She remains in good health 19 months later, but her thrombocythaemia is considered to be an early manifestation of chronic myeloid leukaemia.

Adult↗

Normal sister chromatid exchange and cell cycle progression in cultured lymphocytes from patients with malignant lymphoma.

Twenty patients with malignant lymphoma were examined; all but 2 were untreated or had not recently received therapy. Sister chromatid exchange (SCE) and cell progression through to the third mitotic cycle after phytohemagglutinin stimulation did not differ according to lymphoma type or disease stage, and the lymphoma group as a whole did not differ from 20 normal controls. These findings are contrary to other recent studies of SCE in malignant lymphoma. The only patient who had received recent chemotherapy had the highest SCE score and a greatly accelerated cell cycle response.

Adolescent↗

Transient leukemoid proliferation of the cytogenetically unbalanced +21 cell line of a constitutional mosaic boy.

A newborn without any signs of Down's syndrome was found to have an acute proliferation that remitted without drug therapy. Chromosomal analysis of blood, bone marrow, and skin cells revealed that the child was a constitutional mosaic with normal cells and a low number of cells in which one no. 21 chromosome was replaced by a probably isochromosome for the no. 21 long arm: 46,XY/46,XY,i(21q). The abnormal cell line of the mosaic appeared to be selectively involved in this proliferation.

Acute Disease↗

Richter's syndrome with identification of marker chromosomes.

A case is presented of a man with Richter's syndrome with diffuse histiocytic lymphoma following a ten-year history of untreated chronic lymphatic leukemia. He did not respond to therapy. The lymphoma cells had 61 chromosomes with aneuploidy of 13 chromosomes and 11 structurally altered chromosomes. Only chromosomes 8, 9, 12, 14, and 18 were diploid and without abnormality. Significantly, part of chromsome 1q was duplicated as in the partial trisomy of 1q reported to characterize a number of hematologic neoplasms. A large marker chromosome with subterminal centromere was a tandem duplication of chromosome 4q.

Aneuploidy↗

Elimination of an abnormal cell line from blood lymphocytes during post-natal growth.

A cell line carrying an additional metacentric chromosome of unknown origin was present in PHA-stimulated blood lymphocytes from a newborn female. The child had no marked physical or developmental abnormality but was small. The abnormal cell line, present in 20 % of blood cells at birth, progressively decreased and was absent by 16 months. Loss of the cell line appeared to involve a process of elimination rather than a chance event.

Cell Line↗

Non-random association of mitotic cells from cultured human lymphocyte suspensions.

By using chromosome markers in two separate cell lines of a human dispermic chimera, it was shown that 4.9% of metaphases in suspensions of PHA-cultured lymphocytes were paired because of non-random factors. A similar amount of metaphase pairing occurred in cultured lymphocytes of normal donors, and evidence from the relative mitotic cycles of the paired cells indicated that some of this pairing was non-random. Such non-random pairing could be a source of bias in cell kinetic and other studies involving metaphase cells in lymphocyte cultures.

Cells, Cultured↗

A true hermaphrodite dispermic chimera with 46,XX and 46,XY karyotypes.

A 16-year-old male with hypospadias and gynaecomastia had a rudimentary uterus with a right Fallopian tube and ovary; the left gonad was a functioning testis. Cytogenetic studies showed cells with 46,XX and 46,XY sex chromosomes in cultured blood, skin and gonadal tissues. Cells with the 46,XX constitution predominated in all tissues. Extensive investigations failed to demonstrate blood cell and serum chimerism, but there was little genetic variation of these characters between family members. Cytogenetic studies demonstrated that the father had contributed different marker chromosomes to the 46,XY and 46,XX cell lines of the propositus, whereas the mother had contributed the same two informative markers to both cell lines. The patient was a chimera with two diploid cell lines of different sex that had developed from the products of two separate acts of syngamy. Dispermy was demonstrated, and, whereas there was no evidence of different maternal contributions to the chimeric cell lines, uncertainty remains that these were identical.

Adolescent↗

Sister chromatid exchange and cell cycle progression in cultured lymphocytes from patients with chronic lymphatic leukemia.

Sister chromatid exchange (SCE) was significantly increased in patients who had chronic lymphatic leukemia (CLL) and who had received therapy compared with untreated patients and normal controls. Elevated SCE appeared to be a function of the therapy and not the leukemia. Differential chromatid staining was used to identify successive cell reproduction cycles. In comparison to normal lymphocytes, the cells responding to phytohemagglutinin in CLL cultures showed no evidence of retarded progression through successive cell cycles.

Aged↗

Mitogenic proteins of pokeweed. I. Purification, characterization and mitogenic activity of two proteins from pokeweed (Phytolacca octandra).

Saline extracts from the roots of the pokeweed species. Phytolacca octandra were separated by ion-exchange chromatography into three fractions, Po-1, Po-2 and Po-3. Po-1 contained two monomeric proteins with molecular weights of 36,000 and 29,000 and these were partially purified by gel filtration. Po-2 was purified as a single polymeric protein composed of approximately ten 14,000 mol. wt polypeptides and is a new pokeweed mitogen. Po-3 was purified as a single polymeric protein composed of approximately four 31,000 mol. wt subunits, and apart from its polymeric structure closely resembles commercial pokeweed mitogen (PWM). Po-2 and Po-3 were mitogenic for unseparated human peripheral blood lymphocytes but the degree of mitogenic activity in Po-2 preparations was dependent on storage following purification. Purified B cells were not stimulated by either mitogen. Po-3 was a potent mitogen for T cells but preparations of Po-2 required storage before they stimulated T cells. Higher responses were observed in co-cultures of B and T cells than in separated B and T cell cultures. It is suggested that human B and T lymphocytes show synergy in their responses to Po-2 and Po-3.

Amino Acids↗

Mitogenic proteins of pokeweed. II. The differentiation of human peripheral blood B lymphocytes stimulated with purified pokeweed mitogens (Po-2 and Po-6) from pokeweed, Phytolacca octandra.

Purified pokeweed mitogens, Po-2 and Po-3, extracted from Phytolacca octandra, stimulated plasma cell formation in cultures of human peripheral blood lymphocytes. Plasma cell formation did not occur in cultures of purified B cells but was dependent on T-cell help. High T-cell numbers, however, suppressed plasma cell formation in mixed B- and T-cell cultures stimulated with Po-2. T-cell helper function was exerted across a major histocompatibility barrier and was not dependent on T-cell proliferation. Soluble helper factor(s) from activated T cells were not demonstrated. Po-3 was an effective B-cell stimulant only at concentrations between 0.1 and 1.0 micrograms/ml. In contrast, relatively high concentrations of Po-2 (50--100 micrograms/ml) were required to induce B-cell differentiation. More plasma cells were generated in Po-2-stimulated cultures than in Po-3-stimulated cultures and this was thought to reflect the more aggregated state of Po-2.

B-Lymphocytes↗

Total aneuploidy and age-related sex chromosome aneuploidy in cultured lymphocytes of normal men and women.

In PHA-cultured lymphocytes, about 8% of metaphases from 32 women were aneuploid compared to 4% of metaphases from 35 men. A significant part of this aneuploidy was characterized by sex chromosome involvement: in women, the loss of gain of X chromosomes; in men, the gain of X chromosomes and the loss or gain of Y chromosomes. The incidence of this aneuploidy was positively age-related for both sexes. Premature division of the X-chromosome centromere was closely associated with X-chromosome aneuploidy in women and men, and appeared to be the mechanism of non disjunction causing this aneuploidy. Premature centromere division (PCD) indicated a dysfunction of the X-chromosome centromere with aging, and this dysfunction was the basic cause of age-related aneuploidy. A similar mechanism of nondisjunction may operate for the Y chromosome of men, but could not be clearly demonstrated because of the low incidence of Y-chromosome aneuploidy. The balance of the aneuploidy was characterized by chromosome loss and the involvement of all chromosome groups. It was consistent with chromosome loss from metaphase cells damaged during preparation for cytogenetic examination.

Adolescent↗