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K S Crowley

Publications and source records attributed to K S Crowley.

9 recordsLinked to original sources
PubMed1998

Ribosome binding to mitochondria is regulated by GTP and the transit peptide.

The association between ribosomes and the pore proteins at the endoplasmic reticulum membrane is important to co-translational translocation. To determine if a similar association occurs between the ribosome and mitochondrial membrane protein(s) during protein import in higher eukaryotes, we examined ribosome-mitochondria binding. By using spectral measurements, analysis of mitochondrial associated RNA, and electron microscopy, we demonstrated that ribosomes stably bind to purified rat liver mitochondria in vitro. Binding of ribosomes to mitochondria was markedly reduced by GTP and nearly abolished by the non-hydrolyzable GTP analogue, guanosine-5'-[thio]-triphosphate (GTPgammaS), but was only modestly reduced by GDP or ATP and unaffected by CTP. The initial rate of GTP hydrolysis by mitochondria was increased by ribosomes, whereas the rate of ATP hydrolysis by mitochondria was not affected. Ribosomes programmed with mRNA for 92 amino acids of the N terminus of mitochondrial malate dehydrogenase bound to mitochondria, but unlike unprogrammed rat liver ribosomes, neither GTP nor GDP disrupted binding; however, GTPgammaS did. These data show that receptors specific for ribosomes are present on the mitochondrial membrane, and a GTP-dependent process mediates this binding. The presence of a nascent chain alters these binding characteristics. These findings support the hypothesis that a co-translational translocation pathway exists for import of proteins into mitochondria.

Animals↗
PubMed1994

Secretory proteins move through the endoplasmic reticulum membrane via an aqueous, gated pore.

The environment of secretory proteins undergoing translocation across the ER membrane was determined by incorporating fluorescent probes into nascent chains during translation. Dyes were positioned at various locations across the entire bilayer and inside the ribosome, and in each case the probes were in an aqueous milieu, as shown both by their fluorescence lifetimes and by collisional quenching of their fluorescence by iodide ions introduced into the ER lumen. The nascent chain therefore occupies an aqueous pore that spans the entire membrane. Since the pore is sealed off from the cytoplasm, cotranslational translocation is effected topographically. This pore is not open to the lumen after targeting is completed; it opens only after the nascent chain length reaches about 70 residues.

Animals↗
PubMed1993

The signal sequence moves through a ribosomal tunnel into a noncytoplasmic aqueous environment at the ER membrane early in translocation.

The signal sequence is in an aqueous milieu at an early stage in the translocation of a nascent secretory protein across the endoplasmic reticulum membrane. This was determined using fluorescent probes incorporated into the signal sequence of fully assembled ribosome-nascent chain-membrane complexes: the fluorescence lifetimes revealed that the probes were in an aqueous environment rather than buried in the nonpolar core of the membrane. Since these membrane-bound probes were not susceptible to collisional quenching by iodide ions, the space containing the signal sequence is sealed off from the cytoplasm by a tight ribosome-membrane junction. The nascent chain inside the ribosome is also not exposed to the cytoplasm and apparently passes through an aqueous tunnel in the ribosome.

Animals↗
PubMed1988

Diffuse histiocytic lymphoma: the 20-year experience of an Australian teaching hospital.

There is a paucity of information regarding the natural history and treatment outcome of diffuse histiocytic lymphoma (DHL) in Australia. Case records from 80 patients treated for DHL at the Royal Adelaide Hospital between 1965 and 1985 were reviewed to determine treatment outcome and prognostic information. Pathological review of biopsy specimens confirmed the correct diagnosis in 78 patients. The Ann Arbor staging criteria were unsatisfactory for prognostic purposes. We identified three prognostic groups: Localised disease (82% five-year survival), Advanced disease marrow negative (36% five-year survival), and Advanced disease marrow positive (11% five-year survival). An elevated plasma lactate dehydrogenase (LDH) and calcium (Ca++) predicted a poorer outcome; no patient with a LDH greater than 500 IU achieved longterm survival (p less than 0.001). Survival was identical for patients reclassified histologically as intermediate grade or high grade (Working Formulation). Localised disease was associated with a good prognosis (82% five-year survival) regardless of treatment modality. The outcome of patients with advanced disease has markedly improved over the last two decades, particularly with the introduction of combination chemotherapy containing doxorubicin in 1974 (p less than 0.005). Using these regimens, complete remission was achieved in 65% of patients, with a 39% five-year survival.

Adult↗
PubMed1988

Use of morphometry in cytological preparations for diagnosing follicular non-Hodgkin's lymphomas.

Morphometric techniques were applied to cytocentrifuge smears from 27 patients with histologically confirmed follicular non-Hodgkin's lymphoma to determine the usefulness of this method in diagnosis. Analysis of quantitative data confirmed that most subtypes were classified correctly on the basis of the proportion of large cells, small cleaved, and large non-cleaved cells, and nuclear, nucleolar, and cytoplasmic features. Morphometry is a more objective and reproducible technique than manual cell counting methods, and the use of cytocentrifuge smears has several advantages compared with conventional histological sectioning. Data derived with the aid of morphometry may be of value in follow up clinicopathological studies.

Cell Count↗
PubMed1987

Does the interchromatin compartment contain actin?

Transient blockage of transcription in chick liver by alpha-amanitin results in a temporary clearing of nucleoplasmic regions in affected nuclei and concurrent exposure in situ of a discrete interchromatin framework. This is accompanied by sharp decreases in total nuclear RNA (approximately 28%) and nonhistone protein content (approximately 18%). Electrophoretic analysis of matrix fraction proteins from such highly denuded nuclei shows a marked relative enrichment in actin and RNP-derived polypeptides. These observations suggest that actin is a real constituent of the interchromatin region and supports various reports that this protein may have a basic structural role in nuclei.

Actins↗
PubMed1983

Lymph node biopsy.

The lymph node biopsy may well be the most important surgical operation that the patient ever has. Recent advances in the immunological characterization of human lymphocyte sub-populations, and the use of selected cytochemistry techniques have enabled increased understanding of the pathogenesis of malignant lymphomas, as well as providing more precise categorization of the cell of origin of many of these tumours. The fact is, however, that the vast majority of diagnoses of lymph node biopsies are made on morphological features observed at light microscopy level. The diagnosis and differential diagnosis of lymphomas, and particularly their distinction from benign conditions, are among the most frequent and most difficult problems in diagnostic histopathology. Whilst many of the principles enumerated in the text apply to all areas of surgical pathology, meticulous attention to detail is essential at all phases in the preparation of a satisfactory lymph node biopsy.

Biopsy↗
PubMed1982

Primary gastrointestinal tract lymphoma--a clinico-pathological study of 28 cases.

A retrospective study of 28 patients with primary gastrointestinal tract lymphoma is presented. There were 27 cases of non-Hodgkin's lymphoma and one case of Hodgkin's disease. The patients with non Hodgkin's lymphoma of the gastrointestinal tract represented 10% of all non-Hodgkin's lymphoma cases seen at the Royal Adelaide Hospital/Institute of Medical and Veterinary Science complex over the six year survey period, 1972-1977. Of the patients with non-Hodgkin's lymphoma, 26 cases were diffuse type, and one case was nodular type. There was a M/F sex preponderance of 2 . 8/1, and 70% of cases were aged between 40 and 69 years. The commonest site was the stomach (19 cases), followed by small intestine (7 cases), and one case involved large intestine. At initial presentation, the disease was confined to the affected viscus (Stage IE) in seven patients (25%), and in 12 patients (43%) the disease involved viscus and regional lymph nodes (State IIE). The one patient with Hodgkin's disease had involvement of the large intestine, abdominal lymph nodes and bone marrow (Stage IV). This study was retrospective, and a management protocol was not employed. However, of the seven patients presenting with Stage IE disease, six cases had diffuse poorly differentiated lymphocytic lymphoma. Five of these patients were treated by surgical resection alone, and were in complete remission at follow-up of 66 to 103 months. In order to compare realistically the survival of different groups of patients with primary gastrointestinal lymphoma, we consider that a prospective multicentre clinical trial with comprehensive staging procedures, uniform histological classification and accepted management protocol is warranted.

Adult↗