A 90-year-old woman presenting with hip pain.
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Acetabulum↗
Biomedical subjects
P Johnston
Publications and source records attributed to P Johnston.
On the trail of Leonardo.
A night course taken almost 25 years ago sparked an interest in Leonardo da Vinci that has become a passion for a London, Ont., neurosurgeon. Dr. Rolando Del Maestro now boasts one of the largest collections of da Vinci artifacts in North America.
Anatomy, Artistic↗
Speech modifications algorithms used for training language learning-impaired children.
In this paper, the details of processing algorithms used in a training program with language learning-impaired children (LLI's) are described. The training program utilized computer games, speech/language training exercises, books-on-tape and educational CD-ROM's. Speech tracks in these materials were processed using these algorithms. During a four week training period, recognition of both processed and normal speech in these children continually increased to near age-appropriate levels. We conclude that this form of processed speech is subject to profound perceptual learning effects and exhibits widespread generalization to normal speech. This form of learning and generalization contributes to the rehabilitation of temporal processing deficits and language comprehension in this subject population.
Algorithms↗
Effects of short-term calcium depletion and repletion on biochemical markers of bone turnover in young adult women.
The skeletal responses to calcium depletion and repletion in rodents have been well characterized, but those in humans are poorly understood. The present study sought to evaluate the effects of short term dietary calcium depletion and repletion on biochemical markers of bone turnover in 15 young Caucasian women (age, 21-30 yr). The study contained 3 phases: 1) 5 days of a regular diet containing more than 800 mg/day calcium to establish baseline values (baseline phase), 2) 22 days of a restricted diet containing less than 300 mg/day calcium (depletion phase), and 3) 7 days of a normal diet containing more than 800 mg/day calcium (repletion phase). Serum and urine samples were obtained from each subject during the baseline phase; on the first, second, and last days of the depletion phase; and on the third and last days of the repletion phase. Serum levels of calcium, PTH, 1,25-dihydroxyvitamin D3, osteocalcin, and C-terminal type I procollagen peptide (PICP) and urinary levels of calcium and deoxypyridinoline were determined. Serum and urinary calcium levels were significantly reduced, and serum PTH and 1,25-dihydroxyvitamin D3 levels were markedly increased during depletion. These changes were completely reversed after 1 week of repletion. Depletion also rapidly and significantly increased the urinary deoxypyridinoline level, indicating increased bone resorption. The increase also returned rapidly to baseline upon repletion. Calcium depletion had contrasting effects on bone formation markers; whereas depletion significantly reduced the serum PICP level, it significantly increased serum osteocalcin level. Past histomorphometric studies in rodents indicated that the number of mature but inactive osteoblasts was increased during depletion despite an inhibition of bone formation. Thus, it is speculated that although the reduction in serum PICP reflected the depletion-associated inhibition of bone formation, the increase in serum osteocalcin could represent this depletion-related increase in osteoblast number. During repletion, serum osteocalcin remained elevated above baseline. PICP recovered from its depressed level and increased above baseline, a finding consistent with past histomorphometric findings of increased bone formation during repletion. In summary, this study confirms that 1) a short calcium depletion period produces calcium stress in young women, which leads to rapid stimulation of bone resorption and inhibition of bone formation; and 2) a subsequent calcium repletion period could lead to a compensatory increase in bone formation. In conclusion, the skeletal responses to calcium depletion/ repletion in young women may be similar to those in rodents.
Adult↗
Anatomy training for surgeons--a personal viewpoint.
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Anatomy↗
Misleading serum free thyroxine results during low molecular weight heparin treatment.
Measured free thyroxine concentrations in serum increase markedly after intravenous heparin administration, but the effect of heparin administered subcutaneously has not been adequately documented. We found in vitro increases of up to 63% in measured FT4 after a single dose of subcutaneous heparin (enoxaparin, 2000 units) in nine healthy volunteers, and the magnitude of these increases was correlated with initial serum triglyceride concentrations (r = 0.93, P <0.005) and in vitro free fatty acid release (r = 0.88, P <0.005). In 10 cardiac inpatients receiving repeated doses of enoxaparin (2000 units twice daily), measured FT4 increased by up to 171% in specimens taken 2-6 h after injection. When specimens were obtained 10 h after injection, the effect appeared to be minimized, with in vitro increases of <40%, but such increases may still be sufficient to cause interpretative errors. If FT4 estimation is absolutely necessary in patients receiving enoxaparin, specimens should be taken > or =10 h postdose and analyzed within 24 h.
Adult↗
Scatter factor/hepatocyte growth factor expression enhances human glioblastoma tumorigenicity and growth.
We have shown previously that the multifunctional cytokine scatter factor/hepatocyte growth factor (SF/HGF) is elevated in human malignant gliomas. In this study we investigated how human SF/HGF expression affects the malignancy of the U373 human glioblastoma cell line in vivo and in vitro. Human SF/HGF gene transfer increased U373 glioblastoma tumorigenicity by > or = 20-fold and enhanced the growth rate of intracerebral U373 xenografts by 3- to 8-fold. SF/HGF expression had no effect on the proliferation of glioblastoma cell monolayers but increased their anchorage-independent colony formation in soft agar by 5- to 8-fold. These results are the first to show that SF/HGF expression by human glioblastoma cells enhances their growth dysregulation in vitro and malignancy in vivo.
Animals↗
Protection against oral and gastrointestinal diseases: importance of dietary nitrate intake, oral nitrate reduction and enterosalivary nitrate circulation.
Over the last 20 years, dietary nitrate has been implicated in the formation of methemoglobin and carcinogenic nitrosamines in humans. This has led to restrictions of nitrate and nitrite levels in food and drinking water. However, there is no epidemiological evidence for an increased risk of gastric and intestinal cancer in population groups with high dietary vegetable or nitrate intake. A reevaluation of our currently very negative perception of dietary nitrates comes from recent research into the metabolism and enterosalivary circulation of nitrate in mammals. These studies showed that nitrate is converted to nitrite in the oral cavity that then "fuels" an important mammalian resistance mechanism against infectious diseases. Moreover, there is now evidence that the conversion of nitrate into oxides of nitrogen prevents the formation carcinogenic nitrosamines.
Animals↗
Nitrate-reducing bacteria on rat tongues.
Nitrite-producing bacteria (NPB) were isolated from tongues of laboratory rats. The most commonly found nitrite-producing organism was Staphylococcus sciuri, followed by Staphylococcus intermedius, Pasteurella spp., and finally Streptococcus spp. Both morphometric quantification of bacteria on tongue sections and enumeration of culturable bacteria (CFU) showed an increase in the density of bacteria towards the posterior tongue. Up to 65% of bacteria were located in the deep clefts on the posterior tongue. The proportion of culturable NPB in the total culturable microbial population increased from 6% (10(5) CFU cm-2) on the anterior tongue to 65% (10(7) CFU cm-2) on the posterior tongue. Different species compositions of NPB were found on different tongue sections with S. intermedius populations decreasing and S. sciuri and Pasteurella populations increasing towards the posterior tongue. Nitrite production was sensitive to oxygen, and significant nitrite production was only detected on the posterior tongue where the majority of bacteria are situated in deep clefts in the tongue surface. This study suggests the importance of bacteria in nitrite production, from nitrate, on the tongue. Nitrite produced on the tongue may subsequently form nitric oxide in the acidic environment of the stomach. Because of the antimicrobial properties of nitric oxide, a key role for nitrate-reducing tongue bacteria in host animal defense against food-borne pathogens in proposed.
Animals↗
Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo.
Scatter factor (SF), also known as hepatocyte growth factor, is angiogenic in systemic tissue, and SF titers correlate with the malignancy and metastatic phenotype of certain systemic cancers. Human gliomas express SF and its receptor c-met, but their role in the malignant progression of these tumors has not been defined. To examine this, 9L glioma cells that express c-met but not SF were transfected with human SF cDNA, and their behavior in vitro and in vivo was examined. SF gene expression was detected in conditioned medium of 9L-SF but not in control 9L-neo-transfected cell lines, by reverse transcriptase-PCR, immunoblot, ELISA, and scatter activity assays. Gliomas derived from 9L-SF and control 9L-neo cell lines implanted in the caudate/putamen of Fisher 344 rats (intracranially) and in the flanks of SCID/Beige mice (subcutaneously) were examined. Extracts from intracranial (i.c.) gliomas contained elevated levels of SF protein as determined by ELISA (1 to 5.5 ng SF/mg protein), whereas no SF was detected in control tumors. Reverse transcriptase-PCR of RNA from i.c. gliomas revealed that only 9L-SF gliomas expressed SF and both 9L-neo and 9L-SF gliomas expressed the c-met SF receptor. By postimplantation Day 14, 9L-SF i.c. gliomas were approximately 5-fold larger than 9L-neo control tumors (p < 0.001). Subcutaneous 9L-SF glioma growth was also greater than that in controls, although the differences were more variable. SF-producing i.c. gliomas contained elevated levels of 48-kd urokinase (3.5-fold) and 92-kd type IV collagenase (2.8-fold), both enzymes that correlate with the malignant progression of human gliomas (p < 0.001). SF-producing and control 9L cell lines did not differ in rates of proliferation, thymidine incorporation, or adhesion-independent growth in vitro. Conditioned medium from 9L-SF cells stimulated thymidine incorporation into microvessel brain endothelial cells 3- to 4-fold higher than did CM from 9L-neo controls (p < 0.001). Intracranial 9L-SF gliomas were more angiogenic than controls based on elevated peak (2.25-fold; p < 0.005) and mean (1.7-fold; p < 0.008) blood vessel densities. These results suggest that SF production by glioma cells enhances glioma malignancy in vivo, in part, by paracrine mechanisms involving glioma-associated angiogenesis.
Animals↗
Endothelial cell-based cytokine gene delivery inhibits 9L glioma growth in vivo.
Malignant brain neoplasms present great therapeutic challenges due to their extremely aggressive behavior and relative isolation by the blood-brain and blood-tumor barriers. Endothelial cells may be versatile platforms for delivering genes to solid tumors by virtue of their location at blood-tissue interfaces and their proliferation in response to endothelial mitogens produced by tumors. Immortalized rat brain endothelial cells that express the E. coli lacZ reporter gene and the gene for murine interleukin-2 (RBEZ-IL2) were co-inoculated with 9L glioma cells to Fisher rats to examine the effects of endothelial cell-based cytokine delivery on glioma growth in vivo. 9L glioma growth was not affected by the implantation of control RBEZ cells. The growth of subcutaneous and intracranial 9L gliomas was significantly inhibited by RBEZ-IL2 cells (P < 0.005 and P < 0.01, respectively) when compared to control transfected RBEZ cells. Rats receiving intracranial 9L glioma cells with RBEZ-IL2 cells showed increased survival (P < 0.001). Histologic and immunohistologic analysis showed enhanced activation of microglia/macrophages and CD8-positive T lymphocytes and/or natural killer cells within brain at sites of 9L inoculation with RBEZ-IL2 cells. This report establishes that immortalized endothelial cells can be used for cytokine gene delivery and to activate anti-tumor host responses to experimental gliomas within the central nervous system.
Animals↗
Expression of HIV-1 envelope glycoprotein alters cellular calmodulin.
Removal of parts of a known calmodulin binding site at the C-terminus of HIV-1 envelope glycoprotein, gp160, can result in diminished infectivity. We investigated whether expression of full length gp160 would result in changes in intracellular calmodulin compared to expression of gp160 truncated to remove both known calmodulin binding sites. Both Western and Northern blots demonstrated that expression of gp160 led to increased calmodulin when compared to expression of truncated gp160. The induced calmodulin was associated preferentially with a particulate subcellular fraction. Confocal immunomicroscopy confirmed the increase in calmodulin and also showed that there was enhanced colocalization of calmodulin with gp160. Understanding of the role of calmodulin in the viral life-cycle may lead to new therapeutics.
Binding Sites↗
Temporal processing deficits of language-learning impaired children ameliorated by training.
Children with language-based learning impairments (LLIs) have major deficits in their recognition of some rapidly successive phonetic elements and nonspeech sound stimuli. In the current study, LLI children were engaged in adaptive training exercises mounted as computer "games" designed to drive improvements in their "temporal processing" skills. With 8 to 16 hours of training during a 20-day period, LLI children improved markedly in their abilities to recognize brief and fast sequences of nonspeech and speech stimuli.
Child↗
Cytodiagnosis of Hashimoto's thyroiditis associated with a metastatic adenocarcinoma.
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Adenocarcinoma↗
Delivery of human fibroblast growth factor-1 gene to brain by modified rat brain endothelial cells.
Fibroblast growth factor (FGF) is an endothelial cell mitogen and serves as a mitogen and/or differentiating factor that can be neuroprotective for other cell types within the CNS. We established brain microvascular endothelial cell lines that secrete FGF-1 with the ultimate goal of examining their usefulness as a cellular platform for FGF gene delivery to brain. A chimeric gene consisting of the secretory sequence of FGF-4 linked at the 5' end of human FGF-1 (sp-hst/KS3:FGF-1) was transfected into rat microvascular endothelial cells previously altered to express the lacZ reporter gene (RBEZ), and numerous clones were found to secrete FGF-1 (RBEZ-FGF). Immunoblotting of conditioned medium demonstrated an 18-kDa protein corresponding to FGF-1. Conditioned medium from RBEZ-FGF cells enhanced [3H]thymidine incorporation in BALB/c3T3 fibroblasts by up to sevenfold when compared with conditioned medium of control cell lines, corresponding to as much as 110 ng of active FGF-1/mg of cell protein/24 h. RBEZ-FGF cell lines remained contact-inhibited and proliferated independent of exogenous endothelial mitogens, in contrast to control lines that are mitogen-dependent. Incubation of PC12 cells with RBEZ-FGF cells or their conditioned medium induced neurite outgrowth by PC12 cells. RBEZ-FGF cells survived following implantation to neonatal and adult rat caudate-putamen for at least 21 days based on 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside (X-gal) histochemistry, and FGF-1 gene expression by these cells in vivo was demonstrated by in situ hybridization and reverse transcriptase-PCR. These findings suggest that endothelial cells may be useful for FGF gene delivery to the CNS.
Animals↗
Karyotype and nuclear DNA content of the Australian lungfish, Neoceratodus forsteri (Ceratodidae: Dipnoi).
The karyotype of the lungfish, Neoceratodus forsteri, is described as 2n = 54, comprising 3 pairs of very large metacentrics, 1 pair of large submetacentrics, 13 pairs of smaller acrocentrics, and 10 pairs of microchromosomes. In addition to centromeric constitutive heterochromatin, C-bands were located on the arms of almost all of the macrochromosomes. The nuclear DNA content of N. forsteri was confirmed as being high (98.6-111.9 pg/nucleus).
Animals↗
Graduate university course another sign of continuing interest in medical history.
Whether the interest is shown through a new graduate course in medical history at the University of Toronto or membership in history-of-medicine clubs, physicians continue to show a keen curiosity about their profession's past. "Other countries have well-established medical-history museums and large permanent collections," explains one museum curator, "and Canada should not neglect her own medical past." Unfortunately, difficult economic times mean universities and hospitals often have a hard time giving priority to medical history.
Curriculum↗
BC's "Island of death" marked a sad chapter in Canada's medical history.
Although the first case of leprosy in Canada was detected in 1815 in New Brunswick, the saddest chapter concerning the disease's history in Canada did not open until the late 1800s when leprosy was discovered among Chinese migrant workers on Canada's West Coast--a chapter that was not closed until 1957. Penelope Johnston relates the story of British Columbia's "Island of Death," where lepers used to be quarantined.
British Columbia↗