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Biomedical subjects

L Hansen

Publications and source records attributed to L Hansen.

At least 181 records · Page 10Linked to original sources
PubMed1990

The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity.

Thirty-six clinically diagnosed and pathologically confirmed Alzheimer's disease (AD) patients included 13 with cortical and subcortical Lewy bodies (LBs). The patients with LBs appeared to constitute a distinct neuropathologic and clinical subset of AD, the Lewy body variant (LBV). The LBV group showed gross pallor of the substantia nigra, greater neuron loss in the locus ceruleus, substantia nigra, and substantia innominata, lower neocortical ChAT levels, and fewer midfrontal tangles than did the pure AD group, along with a high incidence of medial temporal lobe spongiform vacuolization. Analysis of neuropsychological tests from 9 LBV subjects and 9 AD patients matched for age and degree of dementia revealed greater deficits in attention, fluency, and visuospatial processing in the LBV group. Similar comparisons of neurologic examinations showed a significant increase in masked facies; in addition there was an increase in essential tremor, bradykinesia, mild neck rigidity, and slowing of rapid alternating movements in the LBV group. Extremity rigidity, flexed posture, resting tremor, or other classic parkinsonian features were not characteristic of the LBV patient. In some cases, it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological features.

Aged↗
PubMed1990

Differential involvement of protein kinase C isozymes in Alzheimer's disease.

Decreased levels of protein kinase C (PKC) and a reduction in the in vitro phosphorylation of a Mr 86,000 protein (P86), the major PKC substrate, are biochemical characteristics of brain tissue from patients with Alzheimer's disease (AD) (Cole et al., 1988). In the current study, we utilized antibodies against individual isozymes of PKC to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC(beta II) was lower in particulate fractions prepared from AD hippocampal and cortical tissue than in controls and higher in AD cytosol fractions from the cortex than in controls. Immunohistochemical studies in AD neocortex revealed reduced numbers of anti-PKC(beta II)-immunopositive neurons and diminished staining intensity. In contrast, AD hippocampal neurons in CA3-CA4 were more intensely stained with anti-PKC(beta II) antiserum than were controls. The concentration of PKC(beta I) was lower in particulate fractions prepared from AD hippocampus than in controls and was higher in soluble fractions prepared from AD cortex than in controls. The concentration of PKC(alpha) was lower in AD particulate fractions than in controls in the hippocampus. Immunohistochemistry with PKC(alpha) antiserum revealed moderately intense neuron staining and an intense staining of glial cells in AD neocortex. The concentrations and histochemical distributions of PKC(gamma) were not altered in the disease. PKC immunoreactivity was also found in neuritic plaques. The staining patterns of neuritic plaques with different isoform antibodies varied considerably. Anti-PKC(alpha) faintly stained entire plaques and surrounding glial cells; anti-PKC(beta I) stained dystrophic plaque neurites; and anti-PKC(beta II) stained the amyloid-containing portions of plaques.

Aged↗
PubMed1989

Growth kinetics of four human breast carcinomas grown in nude mice.

The immune-deficient nude mouse with human tumor xenografts is an appropriate model system for performing detailed growth kinetic examinations. In the present study one estrogen and progesterone receptor-negative (T60) and three receptor-positive (Br-10, MCF-7, T61) human breast cancer xenografts in nude mice were investigated. The proliferative tumor characteristics were examined by growth curves, thymidine labelling technique, and flow cytometric DNA analysis performed on fine-needle aspirations. The results showed that the tumors had growth kinetics comparable to other human tumor types with cell generation times of 42 to 60 hours. The three receptor-positive tumors had slower growth rate, larger tumor volume doubling time, and smaller growth fraction and labelling index than the receptor-negative tumor. However, no single proliferation parameter was sufficient to characterize the growth kinetics of individual tumors or to describe proliferative differences between the tumors.

Animals↗
PubMed1989

Cutaneous-delayed hypersensitivity in nursing home and geriatric clinic patients. Implications for the tuberculin test.

Cutaneous-delayed hypersensitivity was studied by one and two-step Mantoux-type skin tests to four standard antigens in 33 elderly nursing home residents, 34 geriatric clinic patients, and 20 healthy young adult controls. Demographic and anthropometric data were collected to determine the effects of nutrition and other variables on cutaneous-delayed hypersensitivity. Anergy (a lack of response greater than 5 mm of induration when read at 48 hours) to any of the four antigens occurred in 34% of nursing home residents, 17% of geriatric clinic patients, and none of the healthy young adults. Mean and maximal responses were less in the nursing home residents than the clinic patients or controls, even if anergic individuals were excluded from analysis, suggesting both a qualitative and quantitative decline in cell-mediated immune function in this elderly population. Repeat testing with each antigen for which there was a negative initial response revealed a "booster" affect of 7 to 19% and occurred as commonly in the healthy young adults as in the nursing home residents or geriatric clinic patients. The mumps antigen elicited strong responses in the healthy young adults, but weak reactions in the nursing home residents. An unexpectedly high prevalence of positive tuberculin (PPD) responses occurred in the nursing home residents, suggesting recent exposure. Analysis of anthropometric and demographic characteristics show that neither nutritional status nor age alone can account for differences in cutaneous-delayed hypersensitivity observed between populations. Cutaneous-delayed hypersensitivity may vary widely between elderly populations and have important practical implications for the tuberculin test.

Adult↗
PubMed1988

Functional effects of asparagine-linked oligosaccharide on natural and variant human tissue-type plasminogen activator.

The role of Asn-linked oligosaccharide in the functional properties of both human tissue-type plasminogen activator (t-PA) and a genetic variant of t-PA was studied. Nonglycosylated and glycosylated wild-type t-PA were produced in mammalian cells which express recombinant t-PA. These proteins were compared in fibrin binding and 125I-labeled fibrin clot lysis assays, using purified components. The nonglycosylated form showed higher fibrin binding, as well as higher fibrinolytic potency than the glycosylated form. Subsequently, prevention of glycosylation of a t-PA variant which lacked the finger and epidermal growth factor domains (delta FE), was carried out in an attempt to enhance its fibrinolytic activity. Glycosylation was prevented by changing Asn to Gln; at Asn-117 to produce delta FE1X t-PA, and at Asn-117, -184, and -448 to produce delta FE3X t-PA. All variants were similar to wild-type t-PA in their catalytic dependence on fibrinogen fragments, fibrinolytic activity in fibrin autography analysis, and plasminogen activator activity. In a clot lysis assay, using citrated human plasma, the fibrinolytic potency of the variants were comparable to that of wild-type t-PA at activator concentrations of 17-51 nM (approximately 1-3 micrograms/ml). At 0.5-5.1 nM (approximately 0.03-0.3 micrograms/ml), however, the variant proteins had lower fibrinolytic potency than wild-type t-PA. Fifty percent lysis in 1.5 h for wild-type, delta FE, delta FE1X, and delta FE3X t-PA, required 2.5, 10, 7.5, and 5.5 nM t-PA, respectively. The fibrinogenolytic activity in human plasma was measured for wild-type, delta FE, delta FE1X, and delta FE3X t-PA, and showed significant fibrinogen depletion after 3 h of incubation at 51 nM, decreasing to 11, 11, 50, and 72% of basal levels, respectively. These data indicate that partial or total nonglycosylated t-PA variants have a higher fibrinolytic versus fibrinogenolytic ratio than their fully glycosylated counterparts.

Asparagine↗
PubMed1988

Irritation of the upper airways from mixtures of cumene and n-propanol. Mechanisms and their consequences for setting industrial exposure limits.

The immediate irritation response induced by mixtures of vapours of cumene (isopropyl benzene) and n-propanol was evaluated in mice according to the standard method (Designation: E 981-84) from The American Society for Testing and Materials. The animal model allows prediction of the irritation response in humans. Analyses of the results from the initial periods of the experiments leads to the hypothesis that competitive agonism exists between the two substances. Extrapolation of the results to TLV concentration levels taking into account the apparent dissociation constants leads further to expectation of additivity of the effects of mixtures of vapours. Following the initial response there is a fading or a desensitization stage. After desensitization, the responses were close to those of cumene alone. This may suggest that the receptor contains different binding sites which desensitize to a different extent.

1-Propanol↗
PubMed1988

Pulsed multigated Doppler ultrasonography in the diagnosis of carotid artery disease.

To evaluate the accuracy of a pulsed multigated Doppler system, 128 carotid arteries were examined. The spectral broadening index was calculated from the power spectrum of a small sample volume located in the center of the stream according to the flow profile and was related to the degree of stenosis as determined by contrast angiography. Even minor wall irregularities seen on the angiogram were classified as disease. The ability of the system to discriminate between normal and diseased vessels reached a sensitivity of 94% and a specificity of 91%. Classification of greater than 50% or less than 50% stenosis could be performed with a sensitivity of 90% and a specificity of 85%. Pulsed multigated Doppler ultrasonography allows identification of even minor degrees of stenosis of the carotid artery and provides an alternative to duplex scanning. Furthermore, the blood flow profile provided by a multigated Doppler system may add valuable information concerning blood flow characteristics not obtainable by single-gated systems.

Adult↗
PubMed1988

Comparison of estimates of ruminal protein degradation by in vitro and in situ methods.

Ruminal degradation of eight soluble proteins and 10 protein meals was determined using three methods: 1) an inhibitor in vitro system (IIV), to which inhibitors are added to prevent metabolism of protein degradation products, 2) in situ incubations in nylon bags and 3) in vitro NH3 production in typical ruminal inoculum. In vitro NH3 production rate from different proteins was not related to in situ or IIV degradation rate. Degradation rates for soluble proteins by IIV ranged from .103 to .813/h, yielding estimated extents of degradation that ranged from 73 to 94% (assuming ruminal passage of .05/h). For seven of the protein meals, degradation rates measured by IIV were threefold greater than in situ rates. However, mean degraded fractions estimated from zero-time intercepts were twofold greater using the in situ method, and calculated extents of degradation averaged 83% of IIV values. Extents of degradation estimated (assuming ruminal passage of .05/h) for fish meal, soybean meal, linseed meal, sunflower meal, rapeseed meal, copra meal and meat and bone meal were, respectively; 55, 79, 84, 59, 75, 54 and 58% (IIV) and 46, 63, 69, 51, 52, 43 and 55% (in situ). These values were generally similar to those reported in the literature. The extent of degradation of feather meal was 28% by in situ determination. Neither the IIV nor in situ method gave significant regressions for blood meal; neither method yields reliable data for very slowly degraded proteins. The IIV procedure has the advantage over the in situ method because it can yield degradation estimates for soluble as well as insoluble proteins.

Animals↗
PubMed1988

Follow-up after radical surgery for colorectal cancer. Design of a randomized study.

The value of different follow-up examinations after radical surgery for colorectal cancer has not been proven. The risk of such programmes, including invasive examinations, may invalidate the possible benefit from early diagnosis of recurrent and metachronous cancer. The present trial is a randomized study, evaluating possible benefit from a very detailed programme compared to that of virtually no follow-up. The design is presented, but so far no more than 207 of the 600 patients wanted for trial, have been included. Differences in mortality rates, survival and morbidity will be evaluated and the influence of repeated polypectomy upon risk of metachronous colorectal cancer will also be estimated.

Clinical Trials as Topic↗
PubMed1988

Technetium-99m MAG3 kit formulation: preliminary results in normal volunteers and patients with renal failure.

Previous studies have shown that [99mTc]mercaptoacetyltriglycine (MAG3) purified by high performance liquid chromatography (HPLC) is a very promising new renal imaging agent which has characteristics very similar to [131I]orthoiodohippurate. An easily prepared kit formulation has been developed and evaluated in ten normal volunteers and three patients on hemodialysis. The average radiochemical purity was 96.6%. There were no adverse reactions. In the volunteers, the relative uptake +/- 1 s.d. was 49.1% +/- 2.6% for the right kidney and 50.9% +/- 2.6% or the left kidney. Urine activity was 71.4% +/- 6.4% of the injected dose at 30 min and 94.4% +/- 2.2% at 180 min. The 60-min plasma clearance was 340.0 +/- 79.0 ml/min and the volume of distribution was 5.15 +/- 1.1I. Approximately 0.5% of the injected dose was present in the gallbladder at 30-60 min postinjection. Gut activity was not present 30-60 min postinjection but reached 1% of the injected dose by 3 hr. In the hemodialysis patients, approximately 1% of the injected dose was present in the gallbladder and 0.5% in the gut at 30-60 min; gut activity increased to approximately 5% at 3 hr. In summary, results using the kit formulation compare favorably to previously published data using the HPLC purified material. Based on these preliminary results, the kit formulation is expected to have widespread clinical utility.

Adult↗
PubMed1987

The clinical use of objective quantification of flow disturbance in carotid artery disease: correlation between spectral broadening index and arteriography.

In order to assess the accuracy of objective quantification of carotid flow disturbance, 147 carotid arteries were examined with continuous wave (CW) Doppler technique. The systolic spectral broadening index (SBI), determined as (maximum-mean)/maximum frequency, was calculated from the power spectrum and together with the peak frequency related to the angiographic degree of stenosis. Receiver operating characteristics curves were calculated and the SBI predicted disease with a specificity of 94%. On the other hand, the ability of the SBI to discriminate minor disease was not satisfactory. Both the SBI and the peak frequency were accurate in discriminating between greater or less than 50% stenosis. The study concludes that using CW Doppler the SBI can reliably predict carotid artery stenoses. For exclusion of minor lesions an additional test should be performed, e.g., pulsed Doppler spectral analysis.

Angiography↗
PubMed1987

Animal evaluation of technetium-99m triamide mercaptide complexes as potential renal imaging agents.

Technetium-99m mercaptoacetylglycylglycylglycine (MAG3), a [99mTc]triamide mercaptide (N3S) compound has been synthesized in an attempt to obviate the stereochemistry problems associated with the diamide dimercaptide (N2S2) ligands. Because initial studies have been promising, the terminal glycine on the MAG3 compound has been varied to create a new series of N3S compounds. Twelve new N3S complexes were initially screened in mice and the more promising complexes, 99mTc mercaptoacetylgylcylglycyl-glycine [( 99mTc]MAG3), 99mTc mercaptoacetylgylcylglycyl-L-alanine [( 99mTc]MAG2-Ala), and both complexes of 99mTc mercaptoeacetylglycylglycyl-L-asparagine [( 99mTc]MAG2-Asn) and 99mTc mercaptoacetylglycylglycyl-L-glutamine [( 99mTc]MAG2-Gln), were further evaluated in rats utilizing constant infusion blood clearances, extraction efficiencies and protein binding assays. The renal excretion of all these complexes compared favorably with simultaneously administered [131I]OIH and [125I]iothalamate. The triamide mercaptide complexes represent a new ligand class for 99mTc, which may provide a variety of complexes for the evaluation of renal tubular function.

Animals↗