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Biomedical subjects

J Pringle

Publications and source records attributed to J Pringle.

At least 19 recordsLinked to original sources
PubMed1999

Spinal growth and a histologic evaluation of the Risser grade in idiopathic scoliosis.

STUDY DESIGN: Thirty-four patients with idiopathic scoliosis who underwent anterior spinal surgery as part of the correction of spinal deformity were studied prospectively. Superior and inferior endplates were harvested and examined histologically for evidence of residual growth activity. This was then correlated with Risser grades, chronologic age, and pubertal status. OBJECTIVES: To clarify the correlation between Risser grade and vertebral endplate growth potential in patients with idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: The importance of longitudinal spinal growth in patients with idiopathic scoliosis and its correlation with curve progression and the crankshaft phenomenon after posterior fusion are well recognized. The Risser grade, which shows the extent of excursion of the iliac apophysis on serial plain radiographs, is commonly used to estimate residual spinal growth. However, the correlation between the Risser grade and vertebral endplate growth potential in patients with idiopathic scoliosis remains unclear. METHODS: Superior and inferior endplates were harvested from these patients and examined histologically for evidence of residual growth. This was correlated with Risser grade, chronologic age, and pubertal status. RESULTS: Risser Grade 5 was found to be the only indicator of cessation of vertebral growth in idiopathic scoliosis. Of the 14 patients with Risser Grade 4, 10 showed significant growth activity in the vertebral endplates. The reliability of Risser Grade 4 increases when combined with chronologic age and time since menarche in female patients. CONCLUSIONS: The crankshaft phenomenon is reported to occur only in patients with Risser Grade 2 or less, particularly those with open triradiate cartilages. Our findings of significant endplate growth activity, even in patients with Risser Grade 4, make it unlikely that the crankshaft phenomenon is caused purely by longitudinal spinal growth.

Adolescent↗
PubMed1999

Spinal osteoblastoma: CT and MR imaging with pathological correlation.

OBJECTIVES: To illustrate the CT and MRI features of spinal osteoblastomas and correlate the imaging with histological findings. DESIGN: In a retrospective review the CT and MRI features of spinal osteoblastomas with respect to mineralisation, signal intensity (SI), adjacent reactive changes, enhancement following gadolinium-DTPA (5 cases) and adjacent soft tissue masses were compared and correlated with the histological findings including the degree of osteoid formation and matrix mineralisation, vascularity and surrounding reactive changes in bone and soft tissue. PATIENTS: Eleven patients (7 males and 4 females; age range 8-43 years, mean age 19.5 years) with 12 osteoblastomas (1 patient suffered a recurrence) were studied. RESULTS: All lesions showed classical features on CT with varying degrees of matrix mineralisation, whereas MRI identified mineralisation in only eight of 12 cases. MRI showed low signal intensity of the lesion on both T1- and T2-weighted sequences in several cases in the absence of heavy mineralisation. In these cases, histological examination revealed diffuse osteoid production by the tumour. All patients given gadolinium showed enhancement within the tumour on MRI. Reactive bone marrow changes were identified on MRI in 10 cases, and in five of these the changes were at multiple levels. An adjacent soft tissue mass was demonstrated in five cases, but extraosseous tumour was present histologically in only two of these. CONCLUSIONS: The MRI appearances of spinal osteoblastomas are varied and show no characteristic features. MRI may also overestimate the extent of the lesion due to extensive reactive changes and adjacent soft tissue masses. CT should continue to be the investigation of choice for the characterisation and local staging of suspected spinal osteoblastomas.

Adolescent↗
PubMed1998

P-glycoprotein and metallothionein expression and resistance to chemotherapy in osteosarcoma.

The expression of the drug resistance (DR) mediators P-glycoprotein (P-gp) and the metallothioneins (MT) was assessed immunohistochemically in biopsy material from patients with high-grade malignant osteosarcoma (OS). No significant difference was found in survival rate between expressors of both P-gp and MT and non-expressors. Thus, it was concluded that lack of expression of these two drug resistance-related proteins does not appear to confer any advantage in terms of patient survival in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Radiological and clinical recurrence of giant-cell tumour of bone after the use of cement.

We have reviewed 13 operations on 11 patients using curettage and polymethylmethacrylate cement for giant-cell tumour of bone (GCT) to assess the value of radiology in the early detection of recurrence. There were four recurrences, the most specific radiological sign on plain radiography was lysis of 5 mm or more at the cement-bone interface. This preceded clinical signs by a mean of four months and was identified at a mean of 3.75 months after operation. There was not always a complete sclerotic margin around the cement, but when it was present, there was never evidence of recurrence. MRI was helpful in assessing cases with evidence of recurrence. Frequent surveillance with plain radiography should continue for one year after operation irrespective of clinical signs of recurrence. When the appearance of the plain radiographs suggests recurrence, MRI should be performed and followed by image-guided needle biopsy.

Adult↗
PubMed1994

Doxorubicin and cisplatin with granulocyte colony-stimulating factor as adjuvant chemotherapy for osteosarcoma: phase II trial of the European Osteosarcoma Intergroup.

PURPOSE: This report describes the toxicity and feasibility of administering doxorubicin (DOX) and cisplatin (CDDP) at 2-week intervals with granulocyte colony-stimulating factor (G-CSF) to patients with osteosarcoma and the compatibility of this regimen with endoprosthetic surgery performed after three cycles. PATIENTS AND METHODS: Twenty-four patients with biopsy-proven osteosarcoma were treated with three preoperative cycles of DOX 25 mg/m2/d on days 1 to 3 and CDDP 100 mg/m2 on day 1 with G-CSF 5 micrograms/kg/d on days 4 to 14. Surgery was scheduled at week 6 to be followed by three further cycles of chemotherapy at 2-week intervals. RESULTS: Two-week chemotherapy was feasible, but delays and dose reductions only allowed 74% and 78% of the intended dose-intensity of DOX and CDDP to be administered. Thrombocytopenia accounted for 50% of delays. Significant toxicity included neutropenic sepsis, severe mucositis, prolonged nausea and vomiting, and electrolyte disturbances. Twenty-one limb-salvage procedures and one amputation were performed. There were eight episodes of excessive perioperative bleeding. CONCLUSION: Intensive 2-week chemotherapy with intercurrent surgery is feasible and allows a greater dose-intensity of chemotherapy to be administered compared with the same regimen administered at 3-week intervals without G-CSF. The toxicity is considerable, but manageable.

Adolescent↗
PubMed1993

Induction of myelin genes during peripheral nerve remyelination requires a continuous signal from the ingrowing axon.

The effect of a permanent transection on myelin gene expression in a regenerating sciatic nerve and in an adult sciatic nerve was compared to establish the degree of axonal control exerted upon Schwann cells in each population. First, the adult sciatic nerve was crushed, and the distal segment allowed to regenerate. At 12 days post-crush, the sciatic nerve was transected distal to the site of crush to disrupt the Schwann cell-axonal contacts that had reformed. Messenger RNA (mRNA) levels coding for five myelin proteins were assayed in the distal segment of the crush-transected nerve after 9 days and were compared to corresponding levels in the distal segments of sciatic nerves at 21 days post-crush and 21 days post-transection using Northern blot and slot-blot analysis. Levels of mRNAs found in the distal segment of the transected and crush-transected nerve suggested that Schwann cells in the regenerating nerve and in the mature adult nerve are equally responsive to axonal influences. The crush-transected model allowed the genes that were studied to be classified according to their response to Schwann cell-axonal contact. The levels of mRNAs were 1) down-regulated to basal levels (P0 and MBP mRNAs), 2) down-regulated to undetectable levels (myelin-associated glycoprotein mRNAs), 3) upregulated (mRNAs encoding 2'3'-cyclic nucleotide phosphodiesterase and beta-actin), or 4) not stringently controlled by the removal of Schwann cell-axonal contact (proteolipid protein mRNAs). This novel experimental model has thus provided evidence that the expression of some of the important myelin genes during peripheral nerve regeneration is dependent on continuous signals from the ingrowing axons.

Animals↗
PubMed1993

Chemotherapy of malignant fibrous histiocytoma of bone.

BACKGROUND: Malignant fibrous histiocytoma of bone (MFHB) is a rare tumour with a 3 year survival of 30%-40% when treated with surgery alone. A small number of patients have previously been treated with pre-operative chemotherapy and responses observed. The aim of the present study was to further determine the response of MFHB to pre-operative chemotherapy. PATIENTS AND METHODS: A non-randomised study of 18 patients with MFHB. Twelve had localised disease and 6 had pulmonary metastases. In 14 patients pre-operative treatment consisted of methotrexate 8 g/m2 on day 1, ifosfamide 3 g/m2 and doxorubicin 60 mg/m2 on day 10. This regimen was given twice and twice post-operatively. A further 4 patients received cisplatin 100 mg/m2 on day 1 and doxorubicin 25 mg/m2 on days 1, 2, 3. Three cycles were given pre- and post-operatively. RESULTS: 15 patients had surgery after chemotherapy. Tumour necrosis was present in all resection specimens and ranged from 50%-100%. 7/15 had > 90% necrosis. Disease free survival is 82% for those patients with a greater than 2 year follow-up. CONCLUSION: This study confirms previous reports that MFHB is a chemosensitive tumour. In view of its rarity collaborative trials are needed to establish the optimum drug treatment including drug selection dose and duration.

Adolescent↗
PubMed1992

A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains.

Cell polarization requires that a cellular axis or cell-surface site be chosen and that the cytoskeleton be organized with respect to it. Details of the link between the cytoskeleton and the chosen axis or site are not clear. Cells of the yeast Saccharomyces cerevisiae exhibit cell polarization in two phases of their life cycle, during vegetative growth and during mating, which reflects responses to intracellular and extracellular signals, respectively. Here we describe the isolation of two mutants defective specifically in cell polarization in response to peptide mating pheromones. The mutants carry special alleles (denoted bem1-s) of the BEM1 gene required for cell polarization during vegetative growth. Unlike other bem1 mutants, the bem1-s mutants are normal for vegetative growth. Complete deletion of BEM1 leads to the defect in polarization of vegetative cells seen in bem1 mutants. The predicted sequence of the BEM1 protein (Bem1p) reveals two copies of a domain (denoted SH3) that is found in many proteins associated with the cortical cytoskeleton and which may mediate binding to actin or some other component of the cell cortex. The sequence of Bem1p and the properties of mutants defective in this protein indicate that it may link the cytoskeleton to morphogenetic determinants on the cell surface.

Adaptor Proteins, Signal Transducing↗
PubMed1992

Regulation of 2',3'-cyclic nucleotide phosphodiesterase gene expression in experimental peripheral neuropathies.

2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme associated with central nervous system myelination. Although present in the mammalian peripheral nerve, it is not clear what its role is during myelination nor how the expression of this gene is regulated in the PNS. In this study, CNPase gene expression was studied in the crushed and permanently transected rat sciatic nerve, two models of peripheral nerve neuropathy. The Schwann cells of the crushed nerve initially demyelinate, remain in a non-myelinating condition until active regeneration induces remyelination (10-21 days after injury), whereas those of the permanently transected nerve remain in a quiescent, non-myelinating state after the initial demyelination. An increase of CNPase mRNA levels is observed during degeneration and remains high whether the peripheral nerve is regenerating or not, suggesting transcriptional activation of CNPase mRNA and/or increased CNPase mRNA stability as a response to nerve injury. In contrast, the steady state level of CNPase protein did not increase during degeneration or regeneration suggesting either negative translational regulation of CNPase gene expression or a higher turnover of this protein in the injured peripheral nerve. Furthermore, CNPase activity dropped sharply during early degeneration and remained low in the quiescent cells of the permanently transected nerve while it increased in the regenerating nerve. The results suggest that although transcriptional or post-transcriptional regulation of CNPase gene expression is not dependent on Schwann cell-axonal contact, the activity of CNPase appears to be dependent on myelination and indirectly dependent on the presence of axons in the peripheral nerve.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1992

Ewing sarcoma: MR imaging of chemotherapy-induced changes with histologic correlation.

In a study group of 18 consecutive patients with Ewing sarcoma proved by means of biopsy, the signal intensity characteristics of tumor on magnetic resonance (MR) images were assessed before and after chemotherapy. Sixteen patients underwent MR imaging at 1.5 T before chemotherapy; all 18 patients underwent MR imaging at 1.5 T within 10 days after chemotherapy. Standard spin-echo sequences were used with T1 and T2 weighting in all patients. The primary tumor was visualized in all 16 patients who underwent MR imaging before chemotherapy. Histologic correlation, obtained in 14 patients, showed that areas of high T2-weighted signal intensity on MR images obtained after chemotherapy may represent tumor necrosis, cystic hemorrhagic areas, and fibroblastic repair tissue. In 10 patients (71%), microscopic clusters of viable tumor cells were depicted in areas of both low and high signal intensity after treatment. It is concluded that MR imaging is unreliable for exclusion of active disease, although a pattern of change in signal intensity is qualitative evidence of chemotherapeutic effect.

Adolescent↗
PubMed1991

A suppressor of a yeast splicing mutation (prp8-1) encodes a putative ATP-dependent RNA helicase.

Five small nuclear RNAs (snRNAs) are required for nuclear pre-messenger RNA splicing: U1, U2, U4, U5 and U6. The yeast U1 and U2 snRNAs base-pair to the 5' splice site and branch-point sequences of introns respectively. The role of the U5 and U4/U6 small nuclear ribonucleoprotein particles (snRNPs) in splicing is not clear, though a catalytic role for the U6 snRNA has been proposed. Less is known about yeast splicing factors, but the availability of genetic techniques in Saccharomyces cerevisiae has led to the identification of mutants deficient in nuclear pre-mRNA splicing (prp2-prp27). Several PRP genes have now been cloned and their protein products characterized. The PRP8 protein is a component of the U5 snRNP and associates with the U4/U6 snRNAs/snRNP to form a multi-snRNP particle believed to be important for spliceosome assembly. We have isolated extragenic suppressors of the prp8-1 mutation of S. cerevisiae and present here the preliminary characterization of one of these suppressors, spp81. The predicted amino-acid sequence of the SPP81 protein shows extensive similarity to a recently identified family of proteins thought to possess ATP-dependent RNA helicase activity. The possible role of this putative helicase in nuclear pre-mRNA splicing is discussed.

Adenosine Triphosphate↗
PubMed1991

Immunocytochemical localization of follicle regulatory-protein (FRP) in testis.

Follicle regulatory protein (FRP) can exert paracrine control over follicular development. It is synthesized by the granulosa cells of the developing follicles and was localized in the cytoplasm of the mural cells by immunocytochemistry. When administered to male dogs and rats, FRP causes impairment of spermatogenesis. In the intact male rat, it has been postulated that FRP manifests its effects at a stage prior to the conversion of testosterone to dihydrotestosterone. Sertoli cells of the seminiferous tubules are implicated in testosterone metabolism. Furthermore, Sertoli cells in male gonads are regarded as the counterpart of granulosa cells in ovaries. The exact source of FRP in the male is not known. Therefore, it was of interest to study the localization of FRP in the male gonads. Testicular sections of the pig, dog, cat, rat, mouse, monkey, and man were immunocytochemically stained with monoclonal antibody to porcine FRP of ovarian origin. Sections of pig ovaries were used as controls throughout the study. Specificity of immunocytochemical localization was established by preabsorption. FRP antibody predominantly localized to the interstitial compartment of the pig testis. In the seminiferous tubules, FRP localization was limited to basal spermatogonia and Sertoli cells of tubules at few specific stages of spermatogenesis. The study also showed that the monoclonal antibody against porcine FRP is species-specific. Antibody binding was found only in pig testis, whereas tissues from the cat, dog, mouse, rat, monkey, and man did not display any immunocytochemical reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Myelin basic protein-mRNA used to monitor trimethyltin neurotoxicity in rats.

Trimethyltin (TMT) is an alkyltin that targets neurons of the limbic system. A gene probe (i.e., mRNA) for myelin basic protein (MBP), a major component of central nervous system myelin, was used to monitor this toxic neuropathy in Sprague-Dawley rats. Animals were administered a single intraperitoneal injection of TMT-hydroxide at a neuropathic (8.0 mg/kg/body wt) or nonneuropathic (0.8 mg/kg/body wt) dose and sampled at 1, 3, or 7 days postexposure to correlate the progression of hippocampal neuropathology with probe (i.e., MBP-mRNA) levels. Microscopic examination of the brain showed only moderate but progressive damage over the 7-day postexposure period in animals treated with the neuropathic dose. Neuronal loss was first observed in the dendate gyrus and CA4 at 1 day postexposure, and progressed to the CA3c sector at 3 and 7 days postexposure. Elsewhere in the brain, minimal involvement of the entorhinal cortex neurons occurred 3 days postexposure and intensified by 7 days. No histological damage was seen at the nonneuropathic (0.8 mg/kg) dose. For gene probe analysis, the brain was divided into anterior and posterior halves. In rats treated with the neuropathic dose of TMT, the anterior brain showed progressive depressions of MBP-mRNA levels over the 1-, 3-, and 7-day postexposure period that correlated with increasing hippocampal neuropathology. The posterior brain showed no significant changes in MBP-mRNA levels with respect to that of controls over the same time period. At the nonneuropathic dose (0.8 mg/kg) a significant depression of MBP-mRNA levels occurred in the anterior brain at 7 days postexposure in the absence of overt histological damage.

Animals↗
PubMed1991

Levels of proteolipid protein mRNAs in peripheral nerve are not under stringent axonal control.

The proteolipid protein (PLP) is the major protein in the myelin sheath of the CNS. It was recently reported that PLP coding transcripts are also found in the PNS, although the protein was not detectable in peripheral nerve myelin. In the present investigation, levels of mRNA for PLP in sciatic nerve were studied during development and following transection and crush injury. Results were compared to those for P0, the major PNS myelin protein, and the myelin-associated glycoprotein (MAG). PLP transcript levels were very low at 21 days in sciatic nerve and remained unchanged in the adult sciatic nerve. This contrasts markedly with P0 and MAG mRNAs, which are expressed at high levels during development and decrease in content significantly by adulthood. The level of PLP messages was reduced approximately 40% in the quiescent Schwann cells in the distal segment of the sciatic nerve at 21 days after permanent transection, yet P0 mRNA levels were very low, and MAG mRNAs were undetectable in this tissue. The distal segment of the crush-injured sciatic nerve is characterized by transient demyelination followed by rapid myelination. PLP mRNA levels remained comparatively unaffected in the 3-week period following crush injury. RNase protection experiments using two antisense riboprobes confirmed that levels of PLP-derived protected fragments, corresponding to PLP and DM-20 messages, remained unchanged in the developing and adult sciatic nerve. These results indicate that myelin-specific P0 and MAG genes are tightly controlled at the level of transcription through Schwann cell-axonal interactions, whereas PLP transcription in the peripheral nerve remains nearly dissociated from axonal influences.

Animals↗
PubMed1991

The prognostic significance of pretreatment serum lactate dehydrogenase in patients with small-cell lung cancer.

Pretreatment serum lactate dehydrogenase (LDH) levels were assayed in 288 patients presenting with small-cell lung cancer (SCLC) between 1976 and 1985. Patients were routinely staged by physical examination, chest x-ray, bone, brain, and liver scans, and bone marrow evaluation. Clinical response and survival were assessed following treatment with combination chemotherapy as part of four clinical trials. Patients with extensive disease (ED) presented with a higher incidence (108 of 147, 73%) of abnormally elevated LDH (greater than 193 IU/L) than those (65 of 141, 46%) with limited disease (LD) (P = 2 x 10(-6)). Forty percent of patients had an initial normal LDH level and a higher response rate (89 of 108, 82%; complete response [CR], 47%) than those with elevated values of LDH (119 of 156, 76%; CR, 29%). The CR rate varied inversely with the level of LDH in patients with LD (P = .026) but not in those with ED (P = .300). The median survival time and 1-year and 2-year survival rates for patients with elevated LDH were 39 weeks and 33% and 6%, respectively, whereas for those with a normal LDH level these were 53 weeks and 54% and 16%, respectively. Patients with LD and elevated levels of LDH manifested a higher relative death rate (1.63:1) when compared with patients with LD and LDH in the normal range (P = .0083). The survival of patients with ED did not differ between those with normal and elevated levels of LDH (P = .273). A significant survival advantage persisted for patients with LDH in the normal range following adjustments for extent of disease, performance status (PS), and treatment protocol (P = .044, log-rank analysis). In conclusion, serum LDH appears to be a significant independent pretreatment prognostic factor in patients with SCLC that correlates with stage of disease, response to treatment, and survival.

Adult↗
PubMed1991

Myelin basic protein-messenger RNA (MBP-mRNA) expression during triethyltin-induced myelin edema.

Triethyltin (TET) is a neurotoxicant that produces severe but transient cerebral edema, characterized ultrastructurally by vacuolation of the intraperiod line of central nervous system (CNS) myelin. TET has been reported to depress levels of myelin basic protein (MBP), a protein thought to play a critical role in myelin compaction. In the present study, the genomic expression (i.e., mRNA) of MBP was monitored throughout the pathogenesis of TET-induced myelin edema and recovery in Sprague-Dawley rats given a single injection of a neuropathic (8.0 mg/kg) or non-neuropathic (0.8 mg/kg) dose of TET-bromide. Levels of MBP-mRNA from the anterior and posterior brain were collected 1 hr, 3 hr, 2d, and 7d, postexposure. The optic nerve and caudal brainstem, representing anterior and posterior brain sites, respectively, were examined at the same time-points for ultrastructural evidence of edema and recovery. Our data indicate that neuropathic doses (8.0 mg/kg) of TET significantly stimulated MBP transcript throughout the brain at all exposure time-points. The magnitude and time-course of this stimulation differed in the anterior and posterior brain, with the latter region showing higher levels of MBP-mRNA. In the posterior brain, the highest levels of mRNA correlated with the appearance of edema in the caudal brainstem. In the anterior brain, MBP-mRNA levels were only marginally increased over controls. Ultrastructural evidence of myelin edema was confined to the brainstem in rats treated with neuropathic dose of TET. Intralamellar vacuolation appeared at 3 hr and 2d postexposure and could be correlated with peak levels of MBP transcript, whereas, recompacted myelin, which appeared by 7d postexposure, was associated with declining levels of the mRNA. Ultrastructural changes in the oligodendroglia were suggestive of metabolic stimulation and correlated with high MBP-mRNA levels. In summary, these data indicate that an initial genomic event in TET-induced myelin edema is stimulation of MBP transcript.

Animals↗