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Biomedical subjects

P Hansen

Publications and source records attributed to P Hansen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats.

Many lines of evidence implicate oxidative damage in aging. Possible pathways include reactions that modify aromatic amino acid residues on proteins. o-Tyrosine is a stable marker for oxidation of protein-bound phenylalanine by hydroxyl radical, whereas 3-nitrotyrosine is a marker for oxidation of protein-bound tyrosine by reactive nitrogen species. To test the hypothesis that proteins damaged by hydroxyl radical and reactive nitrogen accumulate with aging, we used isotope dilution gas chromatography-mass spectrometry to measure levels of o-tyrosine and 3-nitrotyrosine in heart, skeletal muscle, and liver from young adult (9 mo) and old (24 mo) female Long-Evans/Wistar hybrid rats. We also measured these markers in young adult and old rats that received antioxidant supplements (alpha-tocopherol, beta-carotene, butylated hydroxytoluene, and ascorbic acid) from the age of 5 mo. We found that aging did not significantly increase levels of protein-bound o-tyrosine or 3-nitrotyrosine in any of the tissues. Antioxidant supplementation had no effect on the levels of protein-bound o-tyrosine and 3-nitrotyrosine in either young or old animals. These observations indicate that the o-tyrosine and 3-nitrotyrosine do not increase significantly in heart, skeletal muscle, and liver in old rats, suggesting that proteins damaged by hydroxyl radical and reactive nitrogen species do not accumulate in these tissues with advancing age.

Aging↗
PubMed1998

Family conferences as forums for decision making in hospital settings.

Social workers in hospitals are often involved in family conferences where patient, family members and hospital personnel meet together to exchange information about the patient's condition and to plan for the future. In this paper the complexities of these meetings as decision making arenas are discussed and an outline of the three phases of family conferences--preparation, the conference meeting and follow up--is presented. The final section reports on an exploratory review of recent conferences as perceived by social workers from an acute and rehabilitation teaching hospital. The social workers' comments indicate that the conferences achieve the desired outcomes, especially for hospital staff. In this hospital the conferences are more often used for providing family members with information, and for collective decision making about the patient's future care, than for providing information to the patients about their illness and treatment.

Attitude of Health Personnel↗
PubMed1997

Carbohydrate and peptide specificity of MHC class II-restricted T cell hybridomas raised against an O-glycosylated self peptide.

MHC class II E(k)-restricted, IL-2 secreting T cell hybridomas were raised against the synthetic glycopeptide Hb(67-76)-alpha-GalNAc, (T72(Tn)), in CBA/J mice (H-2(k)). The fine specificity of the hybridomas against the glycan moiety was investigated by testing their response against a panel of Hb(67-76)-derived glycopeptides, all with a glycan attached to serine or threonine at the position 72 in the peptide, but with different glycans. The hybridomas showed a high degree of specificity for the alpha-GalNAc moiety with few and faint cross-responses to the glycopeptides having other glycans attached even though some of these were structurally very similar to alpha-GalNAc. The fine specificity of the hybridomas for the peptide moiety was investigated by testing their responses to a panel of Hb(67-76)-alpha-GalNAc glycopeptides with alanine substitutions at all positions except at the two MHC binding anchor positions, I68 and K76, and the T72 to which the alpha-GalNAc was attached. Glycopeptides substituted with alanine at positions where the amino acid side chain pointed toward the TCR did not stimulate the hybridomas, whereas glycopeptides substituted with alanine at positions orientated down into the MHC binding groove stimulated many of the hybridomas. These results indicate that the glycan attached to the peptide as well as solvent-accessible parts of the peptide are recognized with a high degree of specificity by the T cells, whereas the parts of the peptide buried in the MHC binding site are less important or totally ignored by the T cells.

Animals↗
PubMed1997

Mft52, an acid-bristle protein in the cytosol that delivers precursor proteins to yeast mitochondria.

We have identified a novel protein, Mft52, in the cytosol of yeast cells. Mft52 has a two-domain structure that includes a receptor-like carboxyl-terminal "acid-bristle" domain, which binds basic, amphipathic mitochondrial targeting sequences. Native Mft52, purified from the cytosol of yeast cells, is found as a large particle eluting in the void volume of a Superose 6 gel filtration column. Fusion proteins, consisting of mitochondrial targeting sequences fused to nonmitochondrial passenger proteins, are targeted to mitochondria in wild-type yeast cells, but defects in the gene encoding Mft52 drastically reduce the delivery of these proteins to the mitochondria. We propose that Mft52 is a subunit of a particle that is part of a system of targeting factors and molecular chaperones mediating the earliest stages of protein targeting to the mitochondria.

Amino Acid Sequence↗
PubMed1997

Laparoscopic total esophagectomy.

OBJECTIVE: To evaluate early results with laparoscopic total esophagectomy for benign and malignant disease of the esophagus. DESIGN: Case series involving 9 patients with mean follow-up of 13 months. SETTING: An advanced endoscopic surgery unit at a tertiary referral teaching hospital. PATIENTS: Between December 12, 1993, and December 1, 1996, 9 patients with a mean age of 61 years underwent laparoscopic esophagectomy. Indications were adenocarcinoma in 5, squamous cell carcinoma in 1, dysplastic Barrett esophagus in 2, and refractory stricture with severe shortening in 1. INTERVENTIONS: Gastroduodenal mobilization, transhiatal wide esophageal dissection, gastric tube formation (8 cases), pyloromyotomy (2 cases), cervical anastomosis (8 cases), and laparoscopic jejunal feeding tube placement (8 cases). OUTCOME MEASURES: Operative time, amount of blood loss, operative complications, length of hospital stay, postoperative complications, dysphagia rates, and survival. RESULTS: All procedures were completed endoscopically. Operative time was 6.5 hours (range, 4 3/4 to 9 1/4). Average blood loss was 290 mL. One patient required a right thoracoscopy for an intrathoracic anastomosis because of questionable viability of the gastric tube. Mean hospital stay was 6.4 days (range, 4-9 days). Hospital complications included subclavian vein thrombosis (1 patient), dysphonia (6 patients), and atelectasis (5 patients). There were no anastomotic leaks. Three patients subsequently died: 2 of distant metastatic cancer (at 13 months and 33 months) and 1 of cardiac failure at 10 months. The 6 surviving patients were cancer free at a mean follow-up of 13 months. One patient had left vocal cord paralysis. All patients were doing well and had Visick scores of I or II. CONCLUSIONS: Laparoscopic esophagectomy is a technically feasible but difficult procedure. Despite the long operative times, patients do well and benefit from a shorter hospital stay and more rapid recovery compared with open esophagectomy. Its role as a curative cancer procedure remains unknown, but it may have a place on the basis of its palliative superiority.

Adult↗
PubMed1997

Laparoscopic adrenalectomy: history, indications, and current techniques for a minimally invasive approach to adrenal pathology.

Refinements in the field of laparoscopic general surgery have not only made the performance of laparoscopic adrenalectomy technically feasible, but have even made it the preferred method of treatment for benign adrenal pathology. The advantage of the laparoscopic approach lies in the fact that it allows precise, hemostatic dissection of the gland in a minimally invasive fashion. We present here the results of published reports of laparoscopic adrenalectomy as well as our own experience, and compare these data with reports from open procedures. The indications for the surgical removal of the adrenal gland have not changed, and include: endocrine active tumors, suspected malignancies, adrenal masses larger than 6 cm, and masses that have been followed and observed to be growing. Laparoscopic adrenalectomy can be accomplished with one of three approaches: anterior, lateral and posterior. Each approach has advantages and limitations, and our preferences are discussed. The general techniques are briefly described. The findings from many studies show that the blood loss, operative complications, hospital stay and recovery period are significantly reduced with the laparoscopic approach. Based on our experience with 19 laparoscopic adrenalectomies and a review of the current literature, laparoscopic adrenalectomy can be fairly described as the current "gold standard" treatment for benign adrenal disease. Patients benefit from short hospital stays, lower morbidity, and a more rapid recovery. The only question that remains is the appropriateness of laparoscopic adrenalectomy in the treatment of adrenal malignancy, and the answer to this will depend on the results of long-term outcome studies.

Adrenal Gland Diseases↗
PubMed1997

Novel insulinoma cell lines produced by iterative engineering of GLUT2, glucokinase, and human insulin expression.

Cellular engineering studies in our group are directed at creating insulin-secreting cell lines that simulate the performance of the normal islet beta-cell. The strategy described in this article involves the stepwise stable introduction of genes relevant to beta-cell performance into the RIN 1046-38 insulinoma cell line, a process that we term "iterative engineering." RIN cells stably engineered to contain multiple copies of the human insulin gene exhibit a large increase in insulin content, such that they approach the content of human islets assayed in parallel. Analysis by high-performance liquid chromatography demonstrates that these engineered cell lines process human proinsulin to mature insulin with high efficiency. Cell lines that are further engineered to express the GLUT2 and glucokinase genes demonstrate stable expression of the three transgenes for the full lifetime of the lines produced to date (6 months to 1 year in continuous culture). Transplantation of the engineered cell lines into nude rats reveals that stably integrated genes are expressed at constant levels in the in vivo environment over the full duration of experiments performed (48 days). Several endogenous genes expressed in normal beta-cells, including rat insulin, amylin, sulfonylurea receptor, and glucokinase, are stably expressed in the insulinoma lines during these in vivo studies. Endogenous GLUT2 expression, in contrast, is rapidly extinguished during in vivo passage. The loss of GLUT2 is overcome in engineered cell ines in which transporter expression is provided by a stably transfected transgene. These results suggest that a potential advantage of the iterative engineering approach may be to preserve stability of function and phenotype, particularly in the in vivo setting.

Animals↗
PubMed1997

Prolymphocytic leukemia: diagnosis and treatment. A case report.

A patient with B-cell prolymphocytic leukemia (PLL) who has had a prolonged survival is presented. The patient was diagnosed incidentally while asymptomatic, but later developed progressive disease. He was refractory to alkylating agents and fludarabine, but responded to treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone. This patient's prolonged survival may be due partly to his diagnosis at an indolent phase, possibly representing the early phase of the natural course of the disease. Diagnosis, clinical course, and treatment options for PLL are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Purification of cysteine-containing synthetic peptides via selective binding of the alpha-amino group to immobilised Cu2+ and Ni2+ ions.

Peptides containing a cysteine residue but lacking histidine and tryptophan were synthesised by the solid-phase method. Their retention behaviour on Cu2+ - and Ni2+ -loaded immobilised metal ion affinity chromatography (IMAC) supports at pH 5-11 was studied and compared with that observed for the corresponding compounds without the free alpha-amino group and/or the thiol function. Unexpectedly, it was found that neither a cysteine side-chain nor a cysteine disulphide affects the retention of the peptides. A free alpha-amino group is required for binding; no retention is observed in its absence. At pH 9 substantial amounts of metal ions were transferred from the chromatographic support to an alpha-amino-protected cysteine-containing peptide. However, at pH 7 no such transfer occurred. Therefore, the lack of retention observed for peptides with a blocked alpha-amino function over the entire pH range is not solely caused by metal ion scavenging by the thiol group. Partial dimerisation may occur upon chromatography; the dimers formed are retained strongly due to the presence of two free alpha-amino groups. It seems that IMAC on a Cu2+ - or Ni2+ -loaded support can be used for the purification of cysteine-containing peptides synthesised by the solid-phase method. Inclusion of a capping protocol in the synthesis ensures that a free alpha-amino group, which can be used as an affinity handle, will be present only on the target peptide.

Amino Acid Sequence↗
PubMed1995

Importance of the alpha-amino group in the selective purification of synthetic histidine peptides by immobilised metal ion affinity chromatography.

The retention behaviour of some histidine containing peptides on Cu2(+)- and Ni2(+)-loaded immobilised metal ion affinity chromatography (IMAC) supports has been investigated and compared with that observed for the corresponding compounds lacking the free alpha-amino group and/or the imidazole function. On immobilised Cu2+ all histidine-containing peptides, including those with a blocked alpha-amino function, were strongly retained above pH 5. The presence of a free alpha-amino group increased the retention marginally. On immobilised Ni2+ histidine peptides with a free alpha-amino group were strongly bound with a maximal retention at pH 8.5. Blocking of the amino group or removal of the imidazole moiety reduced the maximal retention by a factor 5 to 10, with no retention observed for peptides lacking both histidine and a free alpha-amino group. These observations indicate the involvement of two equipotent attachment points in the binding. It seems that IMAC on a Ni2(+)-loaded support can be used for the purification of histidine containing peptides synthesised by the solid-phase method. Inclusion of a capping protocol in the synthesis ensures that a free alpha-amino group, which can be used as an affinity handle, will be present only on the target peptide.

Amino Acid Sequence↗
PubMed1995

Heterotopic brain tissue in the scalp.

A posterior midline cutaneous lesion in the scalp of a 15-month-old child was excised. Clinical examination, extensive investigations and finally surgery revealed no intracranial connection. Histologically, the lesion was composed of well differentiated meningeal, glial and cerebral tissues, establishing it to be heterotopic brain tissue. Even when all preoperative procedures exclude the diagnosis of cephaloceles, surgeons should keep in mind the possibility of an intracranial connection of any midline scalp lesion in a child and the subsequent risk of meningitis.

Brain↗
PubMed1995

The cost-effectiveness of compulsory bicycle helmets in New Zealand.

This paper examines the cost-effectiveness for primary school children (age 5-12 years), secondary school children (13-18 years) and adults (over 18 years) of the legislation enacted on 1 January 1994 requiring road-cyclists in New Zealand to wear helmets. The cost to cyclists not in possession of a helmet before they became compulsory of either obtaining one or quitting cycling was compared with the number of deaths and hospitalisations expected to be prevented over the average life of a helmet. Corresponding to Victorian and United States estimates of the efficacy of cycle helmets at preventing serious head injuries, the cost per life saved was $88 379 to $113 744 for primary school children, $694 013 to $817 874 for secondary school children, and $890 041 to $1 014 850 for adults (New Zealand dollars = approximately 0.95 Australian dollars). The cost per hospitalisation avoided was $3304 to $4252, $17 207 to $20 278, and $49 143 to $56 035 respectively. These estimates are extremely sensitive to the estimated efficacy of helmets at protecting cyclists. Mainly anecdotal evidence for New Zealand suggests that they are not to be very effective at preventing serious head injuries; future research into the change in injury patterns as a result of the helmet regulation would be valuable. Nonetheless, the ranking of the abovementioned estimates does not contradict the policy in some parts of the world requiring helmets for children and/or teenagers, but not adults.

Adolescent↗
PubMed1995

Experiences of meaning in life: a combined qualitative and quantitative approach.

The present study investigates the relation of aspects of meaning in life with indices of psychological well-being by means of a combined qualitative and quantitative design. Content analysis of subjects' answers to open questions about personal experiences with meaning in life showed findings that are in line with phenomena that are reported in the literature. Meaningfulness was found to be strongly associated with contact with self, others and the world, whereas meaninglessness was associated with a state of alienation from self, others and the world. The Life Regard Index (LRI), an instrument designed to measure the construct of positive life regard, was found to be strongly associated with the interpersonal dimension of well-being. The exchange of both positive and negative feelings was associated with positive life regard. As predicted, effective coping with stressful life events in the past was associated with a current sense of meaningfulness as measured with the LRI. The findings support the clinical significance of the construct of meaning in life and add to the validity of the LRI. The strength and weakness of a combined qualitative and quantitative research approach are discussed.

Adaptation, Psychological↗
PubMed1995

Kinetics of 2-deoxyglucose transport in skeletal muscle: effects of insulin and contractions.

There is some controversy regarding whether insulin or contractile activity alters the affinity of skeletal muscle glucose transporters for glucose and its analogues. The effects of insulin and contractions on the kinetics of glucose transport were therefore reexamined in isolated rat skeletal muscles. Concentration-dependent rates of 2-deoxyglucose (2-DG) transport were measured in the absence or presence of insulin (2 mU/ml) in the epitrochlearis and split soleus muscles. The apparent half-maximal saturating substrate concentration (Km) for basal 2-DG transport (approximately 12 mM) was similar for the split soleus and epitrochlearis, and the apparent Km was not changed by insulin in either muscle type. The presence of 2 mU/ml insulin increased the maximal transport velocity (Vmax) approximately fourfold in the epitrochlearis and approximately eightfold in the split soleus. In the epitrochlearis, in vitro muscle contractions also resulted in an approximately fourfold increases in Vmax with no change in apparent Km. The combined effects of insulin and contractions on Vmax were completely additive, but the apparent Km was not different from insulin alone. The apparent Km values for basal and insulin-stimulated glucose transport were further characterized in the epitrochlearis isolated from transgenic mice overexpressing the GLUT-1 isoform in the sarcolemma and their nontransgenic littermates. The apparent Km for basal 2-DG transport in the transgenic muscle (9 mM) was not significantly different from the apparent Km for insulin-stimulated transport in the control muscle (10 mM). The present study provides evidence that insulin and contractions, either alone or in combination, increase glucose transport activity in skeletal muscle by increasing Vmax, with no significant change in Km. Our results also suggest that, in intact skeletal muscle, the Km for basal glucose transport (a process mediated primarily by GLUT-1) is similar to the Km values for stimulated transport, mediated predominantly by GLUT-4.

Animals↗
PubMed1994

[Resection of the ulnar head in post-traumatic wrist pain].

In a retrospective study, the effect of distal ulnar resection using the Darrach procedure was evaluated in 42 patients with post-traumatic distal radio-ulnar disability. Thirty women and 12 men, mean age 43 years were seen an average of seven years after the operation. In 57% of the cases the primary trauma was a Colles fracture. The main indication for operation was pain radiating from the distal radio-ulnar joint (83%), but seven patients were without substantial pain. 79% of the patients felt relief of pain after the operation, but 62% still suffered from occasional wrist pain. Twenty-six patients had a supination and a pronation of > or = 150 degrees postoperatively. Thirty-three patients had a dynamic handpower of > 60% of the opposite hand postoperatively. Ten patients stopped working or changed to less physically demanding jobs after the primary trauma. Three patients from this group could after the operation return to their primary physically demanding jobs. Radiographs showed no progress of radiocarpal osteoarthritis during the follow-up period. The Darrach procedure could relieve post-traumatic distal radioulnar pain conditions without adverse effect on radiocarpal function and alignment. Patients who only had mild pain symptoms preoperatively presented unsatisfactory postoperative results.

Adolescent↗