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Biomedical subjects

P Russell

Publications and source records attributed to P Russell.

At least 19 recordsLinked to original sources

Pyp3 PTPase acts as a mitotic inducer in fission yeast.

The p34cdc2 M-phase kinase is regulated by inhibitory phosphorylation of Tyr15, largely through the actions of the p107wee1 tyrosine kinase and p80cdc25 protein tyrosine phosphatase (PTPase). In this study we demonstrate that a second PTPase, encoded by pyp3, also contributes to tyrosyl dephosphorylation of p34cdc2. Pyp3 was identified as a high copy suppressor of a cdc25- mutation. The pyp3 gene encodes a 33 kDa PTPase that is more closely related to human PTP1B and fission yeast pyp1 and pyp2 PTPases than to cdc25. Pyp3 does not share an essential overlapping function with pyp1 or pyp2. We demonstrate that disruption of pyp3 causes a mitotic delay that is greatly exacerbated in cells that are partially defective for cdc25 function and that pyp3 function is essential in cdc25-disruption wee1- strains. Pyp3 PTPase effectively dephosphorylates and activates the p34cdc2 kinase in vitro. We conclude that the pyp3 PTPase acts cooperatively with p80cdc25 to dephosphorylate Tyr15 of p34cdc2.

Alleles

Negative regulation of mitosis by two functionally overlapping PTPases in fission yeast.

We have identified a third protein tyrosine phosphatase (PTPase) gene in fission yeast, pyp2, encoding an 85 kDa protein. Disruption of pyp2 has no impact on cell viability, but pyp2 is essential in strains lacking the 60 kDa pyp1 PTPase. The two pyp PTPases are approximately 42% identical in their C-terminal catalytic domains and share weak homology in their N-terminal regions. Both genes play a role in inhibiting the onset of mitosis. Disruption of either gene rescues the G2 arrest caused by mutation of the cdc25 mitotic inducer, though the effect of pyp1-disruption is more pronounced. Disruption of pyp1 advances mitosis, suppresses overexpression of the tyrosine kinase encoded by the wee1 mitotic inhibitor, and causes lethal mitotic catastrophe in cdc25 overproducer cells. Cells bearing inactive wee1 are unresponsive to disruption of pyp1. Overexpression of pyp1 or pyp2 delays the onset of mitosis by a wee1-dependent mechanism. These data reveal an unexpected second role for protein tyrosine phosphorylation in the mitotic control that acts by promoting the inhibitory wee1 pathway.

Amino Acid Sequence

Chromosome condensation caused by loss of RCC1 function requires the cdc25C protein that is located in the cytoplasm.

We cloned the hamster cdc25C cDNA by using the human cdc25C cDNA as a probe and prepared an antibody to Escherichia coli-produced hamster cdc25C protein that is specific to the human cdc25C protein. The microinjected antibody inhibited a chromosome condensation induced by tsBN2 mutation, indicating that the cdc25C protein is required for an activation of p34cdc2 kinase caused by loss of RCC1 function. The hamster cdc25C protein located in the cytoplasm, prominently in a periphery of the nuclei of cells arrested with hydroxyurea, and seemed to move into the nuclei by loss of RCC1 function. Also, we found a molecular shift of the cdc25C protein in cells showing premature chromosome condensation (PCC), in addition to normal mitotic cells. This molecular-shift appeared depending on an activation of p34cdc2 kinase.

Amino Acid Sequence

Evaluation of an in vitro invasion assay for use on solid tissue samples and cultured cells.

An invasion assay, developed for monitoring the in vitro penetration of reconstituted basement membrane, matrigel, was modified and successfully applied to solid tumours, normal tissues as well as a variety of normal and tumour cell lines. However, we found that some normal fibroblasts were capable of in vitro invasion whilst some malignant cell lines with invasive capacity in vivo did not penetrate the matrigel. Nevertheless, this method can distinguish invasive capacity within a tumour model, and as a consequence may be used to elucidate some of the biochemical mechanisms in the invasion process comparing cells grown both in vitro and in vivo. Since the method does not always correlate with invasion in vivo the results must be interpreted with caution.

3T3 Cells

Pulmonary infection with Petriellidium boydii.

A 52-year-old woman with pulmonary involvement with Petriellidium boydii in a bronchiectatic lung segment is described. Pulmonary involvement with this organism has been most frequently described in patients with underlying systemic diseases or compromised immune systems. This patient apparently had neither problem and was normal in all other aspects. Surgical resection was done to avoid local pulmonary parenchymal invasion or dissemination of this fungus. The patient is now in good health two years after operation.

Ascomycota

Characteristics of a retrovirus associated with a hamster melanoma.

The continuous culture of a hamster melanoma cell line has led to the spontaneous appearance of a retrovirus (HaRV) with typical type-C characteristics. The virus differs from all other known hamster viruses in its ability to transform murine as well as rat and hamster cells with apparent one-hit kinetics. Guinea pig, human and feline cells were not transformed although reverse transcriptase activity was detected in the supernatant from infected human cells. HaRV-transformed hamster embryo cells produced solid tumours (all non-pigmented) in 4 out of 35 animals when injected into hamsters while HaRV-transformed murine cells produced no tumours in mice. Injection of HaRV alone in hamsters, mice and rabbits did not induce tumours. HaRV possesses a 70S RNA which dissociates to 35S in DMSO and has a reverse transcriptase which utilizes the 70S virus RNA as a template. The size, morphology and density (1.15 g/ml) are similar to other known type-C viruses. Polyacrylamide gel electrophoresis indicates the presence of polypeptides analogous to those found in other type-C viruses.

Animals

Biochemical and immunological properties of the reverse transcriptase associated with a hamster retrovirus.

Several properties of an RNA-directed DNA polymerase associated with a hamster retrovirus (HaRV) were examined and found to be similar to other polymerases from mammalian type-C viruses in that the enzyme (i) is more active with Mn2+ than Mg2+, (ii) uses the reverse transcriptase-specific poly(rCm).oligo(dG) template, (iii) possesses substantial endogenous polymerase activity and (iv) is strongly inhibited by homologous antisera and moderately inhibited by antisera directed against other type-C viruses. In contrast to previous reports of polymerases from other hamster viruses, HaRV polymerase is active in endogenous assays and the activity is associated with a 70,000 mol. wt. polypeptide in highly purified virions and with 70,000 and 85,000 mol. wt. polypeptides in fresh, unpurified virus. Only one major peak of polymerase activity eluted from DEAE-cellulose while subsequent elution of this peak from phosphocellulose produced two major peaks of polymerase activity. The mol. wt. of these two peaks were 70,000 and 85,000 by glycerol density-gradient sedimentation. The HaRV reverse transcriptase and p30 were found to be most closely related antigenically to other rodent retrovirus proteins.

Animals

Sclerosing stromal tumours of the ovary.

Sclerosing stromal tumours of the ovary have recently been described as a histologically and clinically distinct subgroup within the thecoma-fibroma spectrum of benign ovarian sex cord stromal tumours. Reported cases occurred predominantly in young women and only occasional tumours showed evidence of hormonal activity. The present series of five cases expands the spectra of both histological patterns and clinical presentations and suggests that the entity of sclerosing stromal tumours may not be as clearly circumscribed as has been previously reported.

Adolescent

Proliferating ovarian "epithelial" tumours: a clinico-pathological analysis of 144 cases.

In a 25-year period, 144 patients with proliferating epithelial ovarian tumours were treated at the King George V Memorial Hospital. These tumours were classified according to the World Health Organisation (WHO) Histological Classification of Ovarian Tumours and subsequently divided into 4 grades of proliferation, again on histological criteria. The tumours were staged at laparotomy in accord with the recommendations of the International Federation of Gynecology and Obstetrics (FIGO). Follow-up data, analysed by a life-table method, were correlated against histological type of tumour, histological grade of proliferation, clinical/laparotomy stage, and mode of surgical therapy. Stage 1 proliferating tumours may be treated by surgery alone, including unilateral salpingo-oophorectomy in selected cases. Stage 2 and Stage 3 tumours should be treated similarly to invasive ovarian carcinomas of the same stage, despite their overall favourable prognosis.

Castration

A new gene involved in expression of fructose-1,6-diphosphate aldolase activity in Escherichia coli.

A new gene, fdaB, has been mapped by transduction and partial diploid analyses and located adjacent to argA at 59.9 min on the Escherichia coli recalibrated linkage map. This gene is involved in expression of fructose-1,6-diphosphate aldolase activity and indirectly in ribosomal RNA synthesis. The temperature-sensitive mutant strain AA-157, containing the defective gene product of of fdaB, accumulates high concentrations of fructose 1,6-diphosphate at the nonpermissive temperature.

Chromosome Mapping

The pathological assessment of ovarian neoplasms. III: The malignant "epithelial" tumours.

One thousand common "epithelial" tumours of the ovary were encountered in a 25-yr study period at the King George V Memorial Hospital. These tumours were classified according to the World Health Organisation (W.H.O.) Histological Classification of Ovarian Tumours. In this report a detailed histological assessment of the 298 malignant "epithelial" tumours is presented, including criteria for histological grading and typing. Evidence for the multifocal tumorigenesis of serous tumours and the pathological correlates of endometrioid carcinoma are stressed.

Adenocarcinoma

Extrauterine mesodermal (müllerian) adenosarcoma. A case report.

Extrauterine mesodermal (müllerian) adenosarcomas have only recently been described, and this is the first reported case from Australia. These tumours fall within the category of common epithelial tumours' in the World Health Organisation (W.H.O.) classification of ovarian tumours and comprise benign looking epithelial structures (glands, papillae) in association with sarcomatous stroma. They are thus distinct from malignant mesodermal mixed tumours in which both epithelial and stromal elements are cytologically malignant.

Adult

The pathological assessment of ovarian neoplasms. II: The proliferating 'epithelial' tumours.

All neoplasms of the ovary encountered in a 25-year study period at the King George V Memorial Hospital were classified according to the World Health Organisation Histological Classification of Ovarian Tumours. Of these, one thousand fell into the category designated as 'common epithelial tumours'. In this report a detailed histological assessment of the 144 proliferating epithelial tumours is presented, including the criteria for distinguishing them from their benign and malignant counterparts and for histological typing and grading of these tumours.

Cell Division

The pathological assessment of ovarian neoplasms. I: Introduction to the common 'epithelial' tumours and analysis of benign 'epithelial' tumours.

All neoplasms of the ovary encountered in a 25-year study period at the King George V Memorial Hospital were classified according to the World Health Organisation Histological Classification of Ovarian Tumours. Of these, one thousand fell into the category designated as 'common epithelial tumours'. In this report, the major clinical and pathological correlates and survival data of epithelial tumours as a whole are analysed and criteria are explained for the histological grading of the proliferating and malignant tumours. A detailed histological assessment of the 558 benign epithelial tumours is then presented.

Adolescent