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Biomedical subjects

H Green

Publications and source records attributed to H Green.

At least 37 records · Page 2Linked to original sources
PubMed2001

A comprehensive analysis of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer: confirmation of linkage to TCO1.

About 5% of nonmedullary thyroid cancer is familial. These familial nonmedullary thyroid cancer cases are characterized by an earlier age of onset, more aggressive phenotype, and in some families a high propensity to benign thyroid disease. Little is known about the genes conferring predisposition to nonmedullary thyroid cancer. Three loci have been identified through genetic linkage: MNG1 on 14q32, TCO1 on 19p13.2, and fPTC on 1p21. In addition to these putative genes, a number of loci represent candidate familial nonmedullary thyroid cancer predisposition genes by virtue of their involvement in sporadic disease (TRKA), their role in benign disease (TSHR), and because they underlie syndromes with a risk of nonmedullary thyroid cancer (PTEN). To evaluate the roles of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer, we have carried out a comprehensive mutation and linkage analysis of these genes in 22 families. One family was linked to chromosome 19q13.2, confirming that TCO1 underlies a subset of familial nonmedullary thyroid cancer. None of the families was linked to MNG1 or fPTC, and there was no evidence to support the roles of PTEN, TSHR, or TRKA. Familial nonmedullary thyroid cancer is an emerging clinical phenotype that is genetically heterogeneous, and none of the currently identified genes accounts for the majority of families.

Adult↗
PubMed2000

Targeted ablation of the murine involucrin gene.

Involucrin is synthesized in abundance during terminal differentiation of keratinocytes. Involucrin is a substrate for transglutaminase and one of the precursors of the cross-linked envelopes present in the corneocytes of the epidermis and other stratified squamous epithelia. These envelopes make an important contribution to the physical resistance of the epidermis. We have generated mice lacking involucrin from embryonic stem cells whose involucrin gene had been ablated by homologous recombination. These mice developed normally, possessed apparently normal epidermis and hair follicles, and made cornified envelopes that could not be distinguished from those of wild-type mice. No compensatory increase of mRNA for other envelope precursors was observed.

Animals↗
PubMed2000

Alternative subcellular locations of keratinocyte basonuclin.

Basonuclin is a zinc finger protein present in the basal cell layer of the epidermis and in hair follicles. Human basal epidermal cells are often heterogeneous with respect to a nuclear or cytoplasmic location of basonuclin and the protein may be concentrated in either compartment. In mouse and rat epidermis, although clusters of basonuclin may be seen in some basal cell nuclei, the protein is mainly concentrated in the cytoplasm. When epidermis whose basal cells contain predominantly cytoplasmic basonuclin is disaggregated and the cells are cultivated in the presence of supporting 3T3 cells, the basonuclin of the growing keratinocyte colonies is strongly concentrated in the cell nuclei. Transfer of the cells to culture medium without supporting 3T3 cells results in a predominantly cytoplasmic concentration of the basonuclin. This translocation is reversible, since addition of supporting 3T3 cells restores most basonuclin to the nucleus. The nuclear location is associated with more rapid cell growth. We conclude that different states of the keratinocyte require greater or less activity of basonuclin, and the subcellular location of the protein is probably related to the magnitude of its action on the cells.

3T3 Cells↗
PubMed2000

Identification of the familial cylindromatosis tumour-suppressor gene.

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

Amino Acid Sequence↗
PubMed2000

Fractures of the hyoid bone and laryngeal cartilages in suicidal hanging.

A prospective study of neck trauma associated with suicidal hanging was undertaken at the Forensic Science Centre, Adelaide over a 3-year period from July 1996 to June 1999. There were a total of 40 cases of suicidal hanging with an age range of 17-74 years (average = 35 years; M:F = 33:7). Fractures of neck structures were identified in 19 cases (47.5%) and were more common in older victims and males. Nine victims had only thyroid cartilage fractures (22.5%), four victims had only fractures of the hyoid bone (10%), and six victims had fractures of both the hyoid bone and thyroid cartilage (15%). No fractures of the cricoid cartilage or cervical spine were demonstrated. Potentially confusing issues encountered in the assessment of possible fractures of neck structures included cases where there was congenital absence of the greater horn of the thyroid cartilage, where accessory nodules of cartilage were present in the posterior margin of the thyrohyoid membrane, and where there had not yet been bony fusion of the cartilaginous joints between the greater horns and body of the hyoid bone.

Journal Article↗
PubMed2000

Effects of a 21-day expedition to 6,194 m on human skeletal muscle SR Ca2+-ATPase.

We investigated the effects of a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m) on selected Ca2+ sequestration properties of sarcoplasmic reticulum (SR) calcium pump in vastus lateralis muscle. Muscle samples were obtained by biopsy from 5 male climbers (peak oxygen consumption, VO2peak = 52.3 +/- 2.1 mL.kg(-1).min(-1)) approximately 7 days prior to (PRE) and 4 days following (POST) the expedition. A comparison of PRE versus POST measures of maximal Ca2+-ATPase activities (117 +/- 8.5 vs. 97.6 +/- 5.6 nmol.mg protein(-1).min(-1)) and Ca2+-uptake (204 +/- 15 vs. 161 +/- 11 nmol.mg protein(-1).min(-1)) measured in crude homogenates obtained from pre-exercised muscle, indicated only an effect (p < 0.05) of the expedition on Ca2+-uptake. The reduction in Ca2+-ATPase activity, representing 16.6%, was not significant (p = 0.089). The sarco endoplasmic reticulum calcium (SERCA)-ATPase isoforms, measured using Western blotting techniques, revealed a small reduction (p < 0.05) in SERCA 1 (-4.6 +/- 1.9%), but not in SERCA 2a (+2.0 +/- 1.4%). Prior to the expedition, both Ca2+-ATPase activity and Ca2+-uptake were reduced (p < 0.05) by approximately 34 and 18%, respectively, following 40 min of a two-step continuous cycling task (20 min at 59% VO2peak and 20 min at 74% VO2peak). The exercise-induced reduction in Ca2+-ATPase activity was independent of fiber type. Only in the case of Ca2+-uptake was a lower exercise response (p < 0.05) observed following the expedition, an effect that was due to the lower resting value. It is concluded that acclimatization as experienced during a mountaineering expedition induces changes in the properties of the SR Ca2+-pump, and particularly to Ca2+-sequestering function.

Acclimatization↗
PubMed2000

Pathologic features of childhood pedestrian fatalities.

A retrospective analysis of 68 cases of fatal childhood pedestrian accidents in South Australia that occurred over a 20-year period from January 1977 to December 1996 was undertaken. The age range was 12 months to 16 years (average, 7.6 years), with a male to female ratio of 41:27. The most common site of significant injury was the head (91.2%), followed by the abdomen (50%), chest (47.1%), and neck (38.2%). The most frequently encountered significant injury combinations involved the head, chest, and abdomen (14.7%); the head and chest (11.8%); and the head, neck, and abdomen (11.8%). Injuries were severe, consisting of extensive compound and comminuted skull fractures, neck fractures, and massive intraparenchymal brain and internal organ damage with avulsions and fragmentation. Non-life-threatening limb injuries occurred in 88% of cases. A distinct subgroup involved infants and younger children playing in driveways at home who were hit by reversing vehicles. The injuries were often of such a severe nature that death was instantaneous and with no possibility of successful medical intervention. More deaths occurred during the winter than summer months.

Abdominal Injuries↗
PubMed2000

Methadone maintenance programs--a two-edged sword?

Retrospective review was undertaken of all autopsies in which methadone was detected at the Forensic Science Centre, South Australia, during a 3-year period from July 1996 to June 1999. Thirty-five cases were found in which methadone had either caused or contributed to death (age range = 14-54 years; average = 31 years; M:F = 3.4:1). Ten victims were participating in a methadone maintenance program, of whom four died within a week of enrollment. Eight victims (23%) not enrolled in a methadone maintenance program were found who had died after the use of "diverted" methadone (i.e., prescribed for someone else) (age range = 14-34 years; average = 25 years; M:F = 6:2). Deaths were directly attributable to methadone toxicity in seven of the eight cases, with additional drugs or alcohol being found in seven cases. Prevention of ongoing deaths caused by methadone diversion could be achieved by allowing only daily releases of methadone, with the addict having to consume the drug under close supervision.

Adolescent↗
PubMed2000

Adaptations in skeletal muscle exercise metabolism to a sustained session of heavy intermittent exercise.

The purpose of this study was to investigate the hypothesis that a single, extended session of heavy exercise would be effective in inducing adaptations in energy metabolism during exercise in the absence of increases in oxidative potential. Ten healthy males [maximal aerobic power (VO(2 peak)) = 43.4 +/- 2.2 (SE) ml x kg(-1) x min(-1)] participated in a 16-h training session involving cycling for 6 min each hour at approximately 90% of maximal oxygen consumption. Measurements of metabolic changes were made on tissue extracted from the vastus lateralis during a two-stage standardized submaximal cycle protocol before (Pre) and 36-48 h after (Post) the training session. At Pre, creatine phosphate (PCr) declined (P < 0.05) by 32% from 0 to 3 min and then remained stable until 20 min of exercise at 60% VO(2 peak) before declining (P < 0.05) by a further 35% during 20 min of exercise at 75% VO(2 peak). Muscle lactate (mmol/kg dry wt) progressively increased (P < 0.05) from 4.59 +/- 0.64 at 0 min to 17.8 +/- 2.7 and 30.9 +/- 5.3 at 3 and 40 min, respectively, whereas muscle glycogen (mmol glucosyl units/kg dry wt) declined (P < 0.05) from a rest value of 360 +/- 24 to 276 +/- 31 and 178 +/- 36 at similar time points. During exercise after the training session, PCr and glycogen were not as depressed (P < 0.05), and increases in muscle lactate were blunted (P < 0.05). All of these changes occurred in the absence of increases in oxidative potential as measured by the maximal activities of citrate synthase and malate dehydrogenase. These findings are consistent with other studies, namely, that muscle metabolic adaptations to regular exercise are an early adaptive event that occurs before increases in oxidative potential.

Adaptation, Physiological↗
PubMed2000

Postcontractile force depression in humans is associated with an impairment in SR Ca(2+) pump function.

To investigate the hypothesis that intrinsic changes in sarcoplasmic reticulum (SR) Ca(2+)-sequestration function can be implicated in postcontractile depression (PCD) of force in humans, muscle tissue was obtained from the vastus lateralis and determinations of maximal Ca(2+) uptake and maximal Ca(2+)-ATPase activity were made on homogenates obtained before and after the induction of PCD. Eight untrained females, age 20.6+/-0.75 yr (mean +/- SE), performed a protocol consisting of 30 min of isometric exercise at 60% maximal voluntary contraction and at 50% duty cycle (5-s contraction and 5-s relaxation) to induce PCD. Muscle mechanical performance determined by evoked activation was measured before (0 min), during (15 and 30 min), and after (60 min) exercise. The fatiguing protocol resulted in a progressive reduction (P<0.05) in evoked force, which by 30 min amounted to 52% for low frequency (10 Hz) and 20% for high frequency (100 Hz). No force restoration occurred at either 10 or 100 Hz during a 60-min recovery period. Maximal SR Ca(2+)-ATPase activity (nmol x mg protein(-1) x min(-1)) and maximal SR Ca(2+) uptake (nmol. mg protein(-1) x min(-1)) were depressed (P<0.05) by 15 min of exercise [192+/-45 vs. 114+/-8.7 and 310+/-59 vs. 205+/-47, respectively; mean +/- SE] and remained depressed at 30 min of exercise. No recovery in either measure was observed during the 60-min recovery period. The coupling ratio between Ca(2+)-ATPase and Ca(2+) uptake was preserved throughout exercise and during recovery. These results illustrate that during PCD, Ca(2+) uptake is depressed and that the reduction in Ca(2+) uptake is due to intrinsic alterations in the Ca(2+) pump. The role of altered Ca(2+) sequestration in Ca(2) release, cytosolic-free calcium, and PCD remains to be determined.

Adult↗
PubMed2000

Human skeletal muscle exercise metabolism following an expedition to mount denali.

Chronic exposure to high altitude is known to result in changes in the mechanisms regulating O(2) delivery to the contracting muscle. However, the effects of acclimatization on metabolism in the contracting muscle cell remain unclear. In this study, we have investigated the hypothesis that acclimatization would result in a closer coupling between ATP utilization and ATP production and that the improved energy state would be accompanied by a reorganization of the metabolic pathways consisting of an increased oxidative and decreased glycolytic potential. Five men, mean age of 28 +/- 2 (SE) yr, performed a standardized, two-stage submaximal cycling task in normoxia for 20 min at each of 59 and 74% peak O(2) consumption before and 3-4 days after returning from a 21-day expedition to Mount Denali (6,194 m). Acclimatization was without effect in altering the resting values of the adenine nucleotides (ATP, ADP, AMP), inosine monophosphate (IMP), or phosphocreatine (PCr) in the vastus lateralis. During exercise (40 min) after acclimatization compared with preacclimatization, PCr was not as depressed (33.2 +/- 7.1 vs. 40.6 +/- 5.4 mmol/kg dry wt) and IMP (0.289 +/- 0.11 vs. 0. 131 +/- 0.03 mmol/kg dry wt) and lactate (26.1 +/- 6.2 vs. 18.6 +/- 8.8 mmol/kg dry wt) in contracting muscle were not as elevated (P < 0.05). Although no effect of acclimatization was observed for the maximal activity (mol. kg protein(-1). h(-1)) of citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.45), lactate dehydrogenase was increased by 13% (36.5 +/- 2.6 vs. 41.2 +/- 3.1, P < 0.05). It is concluded that acclimatization results in an improved energy state in the contracting muscle when tested under normoxic conditions; however, these effects are not associated with a higher oxidative potential or a lower glycolytic potential as hypothesized.

Acclimatization↗
PubMed2000

Downregulation in muscle Na(+)-K(+)-ATPase following a 21-day expedition to 6,194 m.

To investigate the hypothesis that acclimatization to altitude would result in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, tissue samples were obtained from the vastus lateralis muscle of six volunteers (5 males and 1 female), ranging in age from 24 to 35 yr, both before and within 3 days after a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m). Na(+)-K(+)-ATPase, measured by the [(3)H]ouabain-binding technique, decreased by 13.8% [348 +/- 12 vs. 300 +/- 7.6 (SE) pmol/g wet wt; P < 0.05]. No changes were found in the maximal activities (mol. kg protein(-1). h(-1)) of the mitochondrial enzymes, succinic dehydrogenase (3.63 +/- 0.20 vs. 3.25 +/- 0.23), citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.44), and malate dehydrogenase (12.6 +/- 1. 8 vs. 12.7 +/- 1.2). Similarly, the expedition had no effect on any of the histochemical properties examined, namely fiber-type distribution (types I, IIA, IIB, IC, IIC, IIAB), area, capillarization, and succinic dehydrogenase activity. Peak aerobic power (52.3 +/- 2.1 vs. 50.6 +/- 1.9 ml. kg(-1). min(-1)) and body mass (76.9 +/- 3.7 vs. 75.5 +/- 2.9 kg) were also unaffected. We concluded that acclimatization to altitude results in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, which occurs without changes in oxidative potential and other fiber-type histochemical properties.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

The ribosomal protein QM is expressed differentially during vertebrate endochondral bone development.

Endochondral ossification is a carefully coordinated developmental process that converts the cartilaginous model of the embryonic skeleton to bone with accompanying long bone growth. To identify genes that regulate this process we performed a complementary DNA (cDNA) subtractive hybridization of fetal bovine proliferative chondrocyte cDNA from epiphyseal cartilage cDNA. The subtracted product was used to screen a fetal bovine cartilage cDNA library. Ten percent of the clones identified encoded the bovine orthologue of the human ribosomal protein "QM." Northern and western blot analysis confirmed that QM was highly expressed by cells isolated from epiphyseal cartilage as opposed to proliferative chondrocytes. In contrast, no detectable difference in the expression of mRNA for the ribosomal protein S11 was detected. Immunohistochemical analysis of fetal bovine limb sections revealed that QM was not expressed by the majority of the epiphyseal chondrocytes but only by chondrocytes in close proximity to capillaries that had invaded the epiphyseal cartilage. Strongest QM expression was seen in osteoblasts in the diaphyseal region of the bone adjoining the growth plate, within the periosteum covering the growth plate and within secondary centers of ossification. Hypertrophic chondrocytes within the growth plate adjoining the periosteum also were positive for QM as were chondrocytes in the perichondrium adjoining the periosteum. In vitro investigation of the expression of QM revealed higher QM expression in nonmineralizing osteoblast and pericyte cultures as compared with mineralizing cultures. The in vivo and in vitro expression pattern of QM suggests that this protein may have a role in cell differentiation before mineralization.

Amino Acid Sequence↗
PubMed1999

Basonuclin, a zinc finger protein of keratinocytes and reproductive germ cells, binds to the rRNA gene promoter.

Basonuclin is a protein containing three pairs of C(2)H(2) zinc fingers. The protein has been found in the basal (germinal) cell layer of stratified squamous epithelia, such as the epidermis, and in germ cells of the testis and ovary. We show here that the human protein has specific affinity for a segment of the promoter of the gene for rRNA. Basonuclin interacts with two separate parts of the promoter, each possessing dyad symmetry. The upstream part, but not the downstream part, is known to bind UBF1, a transcription factor for rDNA. Basonuclin is likely to be a cell-type-specific regulatory protein for rDNA transcription.

DNA↗
PubMed1999

Medicolegal complications of pseudologia fantastica.

A 46-year-old woman allegedly on a witness protection scheme who died under unusual circumstances with a factitious history of two previous homicide attempts and multiple medical problems including paraplegia and lung carcinoma is presented to demonstrate difficulties that may arise in the medicolegal investigation of such cases. A diagnosis of pseudologia fantastica was made once no corroboration of the presenting history or medical illnesses could be made. Death was due to haemorrhage from a self-inflicted incised wound to the arm.

Journal Article↗
PubMed1999

Alterations in sarcoplasmic reticulum function in female vastus lateralis with eccentric exercise.

This study examined the alterations in sarcoplasmic reticulum (SR) Ca2+ sequestration function in homogenates during eccentric exercise and recovery and following additional eccentric exercise, and correlated these alterations with changes in force output. Eight healthy, untrained females, aged 20-25 years, cycled for a total of 60 min on an eccentric cycle ergometer (30 min at 66+/-3% VO2 peak and 30 min at 76+/-3% VO2 peak, determined during concentric exercise). Biopsies (extracted from the vastus lateralis) were taken before and after the exercise as well as on days 2, 6 and prior to and following identical exercise on day 14. Ca2+-uptake (nmol/min/mg protein) was unaffected (p > 0.05) following the first session of eccentric exercise; however, by day 2 a depression in uptake (p < 0.05) was observed which persisted throughout the remainder of the experiment. Maximal Ca2+-ATPase activity (nmol/min/mg protein) was elevated (p < 0.05) immediately following the first exercise session, remained elevated through day 2 and returned to pre-exercise levels by day 6 of recovery and increased again by day 14. No changes in either Ca2+-ATPase activity or Ca2+-uptake were observed with exercise on day 14. Both eccentric sessions, performed on days 0 and 14, resulted in similar depressions in force (p < 0.05) immediately following exercise. By day 2 force had recovered to pre-exercise levels. The results demonstrate that a prolonged alteration in SR Ca2+-uptake occurs following eccentric work that is unaccompanied by parallel changes in either SR Ca2+-ATPase activity or mechanical performance.

Adult↗
PubMed1999

Serial effects of high-resistance and prolonged endurance training on Na+-K+ pump concentration and enzymatic activities in human vastus lateralis.

The purpose of this study was to compare two contrasting training models, namely high-resistance training and prolonged submaximal training on the expression of Na+-K+ ATPase and changes in the potential of pathways involved in energy production in human vastus lateralis. The high-resistance training group (VO2peak = 45.3 +/- 1.9 mL kg(-1) min(-1), mean +/- SE, n = 9) performed three sets of six to eight repetitions maximal, each of squats, leg presses and leg extensions, three times per week for 12 weeks, while the prolonged submaximal training group (VO2peak = 44.4 +/- 6.6 mL kg(-1) min(-1), n = 7) cycled 5-6 times per week for 2 h day(-1) at 68% VO2peak for 11 weeks. In the HRT group, Na+-K+ ATPase (pmol g(-1) wet wt), measured with the 3H-ouabain binding technique, showed no change from 0 (289 +/- 22) to 4 weeks (283 +/- 15), increased (P < 0.05) by 16% at 7 weeks and remained stable until 12 weeks (319 +/- 19). For prolonged submaximal training, a 22% increase (P < 0.05) was observed from 0 (278 +/- 31) until 3 weeks (339 +/- 29) with no further changes observed at either 9 weeks (345 +/- 25) or 11 weeks (359 +/- 34). In contrast to high-resistance training, where a 15% increase (P < 0.05) was observed, only in the maximal activity of phosphorylase, prolonged submaximal training resulted in increases in malate dehydrogenase, beta-hydroxyl-CoA dehydrogenase, hexokinase and phosphofructokinase. In contrast to high-resistance training which failed to result in an increase in VO2peak, prolonged submaximal training increased VO2peak by approximately 15%. Only for prolonged exercise training was a relationship observed for VO2peak and Na+-K+-ATPase (r = 0.59; P < 0.05). Correlations between VO2peak and mitochondrial enzyme activities were not significant (P > 0.05) for either training programme. It is concluded that although both training programmes stimulate an up-regulation in Na+-K+ ATPase concentration, only the prolonged submaximal training programme enhances the potential for beta-oxidation, oxidative phosphorylation and glucose phosphorylation.

3-Hydroxyacyl CoA Dehydrogenases↗