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Biomedical subjects

L A Hansen

Publications and source records attributed to L A Hansen.

At least 127 records · Page 7Linked to original sources
PubMed1989

Synthetic lipid second messenger sn-1,2-didecanoylglycerol: a complete tumor promoter in mouse skin.

sn-1,2-Didecanoylglycerol, a synthetic lipid second messenger and model diacylglycerol, was evaluated as a complete skin tumor promoter in CD-1 mice. In addition, sn-1,2-dioctanoylglycerol, sn-1,2-didecanoylglycerol, the second stage tumor promoter mezerein, and the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined for their ability to stimulate epidermal protein kinase C activity in vitro. All four compounds stimulated epidermal protein kinase C activity utilizing lysine-rich histone as the phosphate acceptor substrate. sn-1,2-Dioctanoylglycerol and sn-1,2-didecanoylglycerol stimulated epidermal protein kinase C activity to a maximum velocity similar to that obtained when the enzyme was stimulated with TPA; however, about 1000 times greater concentration of the sn-1,2-diacylglycerols was required. sn-1,2-Didecanoylglycerol was evaluated as a complete skin tumor promoter in CD-1 mice utilizing a dosing regimen demonstrated to produce epidermal hyperplasia. Mice were initiated with 200 nmol 7,12-dimethylbenz[a]anthracene. One week later the mice received twice daily topical applications of 1 nmol TPA, 2 mumol sn-1,2-didecanoylglycerol or 5 mumol sn-1,2-didecanoylglycerol, 5 days/week. Additional initiated mice received twice weekly topical applications of 2 or 5 nmol TPA. Initiated mice treated with 5 nmol TPA twice weekly or with 1 nmol TPA twice daily for 5 days/week (cumulative weekly doses of 10 nmol TPA) responded similarly, based on the tumor incidence and the average number of tumors per mouse. Initiated mice treated with 2 or 5 mumol sn-1,2-didecanoylglycerol twice daily developed tumors in a dose-dependent manner. Initiated mice treated with 5 mumol sn-1,2-didecanoylglycerol twice daily developed many tumors, and at 20 weeks there was a 74% tumor incidence and an average of 6.0 tumors/mouse. At 20 weeks, 24% of the initiated mice treated with 2 mumol sn-1,2-didecanoylglycerol twice daily developed tumors, with an average of 1.1 tumors/mouse. Mice which were not initiated but treated twice daily with 5 mumol sn-1,2-didecanoylglycerol for 20 weeks did not develop any tumors. These data demonstrate that the representative synthetic lipid second messenger sn-1,2-didecanoylglycerol, like TPA, is a complete tumor promoter in DMBA-initiated mouse skin.

Animals↗
PubMed1989

A neuropathological subset of Alzheimer's disease with concomitant Lewy body disease and spongiform change.

The neuropathological heterogeneity of Alzheimer's disease (AD) is increasingly recognized. Diffuse Lewy body disease, for example, most frequently occurs in cases fulfilling histopathological criteria for AD, and these patients usually present with dementia rather than parkinsonism. We report five cases of concomitant AD and diffuse Lewy body disease with still another coexistent neuropathological feature: localized and stereotyped spongiform change in the neuropil. This spongiform change was most striking in the superior and inferior temporal, entorhinal, and insular cortex and the amygdala and was virtually indistinguishable from that seen in Creutzfeldt-Jakob disease. Electron microscopic study on one case revealed membrane-containing vacuoles in close association with neuritic plaques and plaired helical filament-filled processes. Immunocytochemistry using antibodies to prion proteins (PrPsc or PrP27-30) failed to label plaque or vascular amyloid in the five cases. Four primates inoculated with brain tissue from one case have not evidenced neurological disease in the 3 years since the transmission experiment. We conclude that these cases represent a neuropathological subset of AD with relatively widespread Lewy bodies and a localized spongiform change, predominantly involving the medial temporal region. Despite the light and electron microscopic commonality with Creutzfeldt-Jakob disease, there is no clear evidence that these cases represent a form of transmissible spongiform encephalopathy.

Aged↗
PubMed1989

Hypothermia due to an ascending impairment of shivering in hyperacute experimental allergic encephalomyelitis in the Lewis rat.

Severe hypothermia and an ascending impairment of shivering are previously undescribed clinical signs in hyperacute experimental allergic encephalomyelitis (EAE) in the Lewis rat. These occurred in hyperacute EAE induced by inoculation with guinea pig spinal cord homogenate and heat-killed Bordetella pertussis. Hypothermia was first detected on day 6-7 post-inoculation, within 12-24 h of the onset of neurological signs, and became more severe as the disease progressed. Rectal temperatures less than or equal to 30 degrees C were common at ambient temperatures of 19-22 degrees C. Shivering was assessed by palpation and by cold tremor electromyography. Shivering was absent in the tail by day 6-7 post-inoculation. The impairment then progressed to affect the hindlimbs, thorax and occasionally the forelimbs. Shivering was absent in hindlimbs with only mild or moderate weakness. Histological studies revealed perivascular inflammation with polymorphonuclear and mononuclear cells, oedema, fibrin deposition, haemorrhage, primary demyelination and axonal degeneration in the spinal cord, dorsal root ganglia and spinal roots. The brainstem was also involved but the cerebral hemispheres, including the hypothalamus, were spared. The close relationship between the severity of hypothermia and the extent of shivering impairment indicates that reduced shivering is an important cause of hypothermia in hyperacute EAE. It is concluded that this impairment of shivering is due not to hypothalamic damage but to lesions elsewhere in the central and peripheral nervous systems.

Animals↗
PubMed1989

Substance P and somatostatin coexist within neuritic plaques: implications for the pathogenesis of Alzheimer's disease.

In recent years the present authors and others have sought to determine the neurochemical composition of the dilated neuronal processes found within neuritic plaques of patients with Alzheimer's disease. To date a number of neurotransmitter and neuropeptide systems have been observed within different plaques, yet at present it is unclear whether individual human plaques contain more than one transmitter substance. In the present study a highly sensitive dual-immunolabeling procedure was employed and it was demonstrated that substance P and somatostatin-immunoreactive profiles coexist within single senile plaques of patients with Alzheimer's disease. Coexistence of somatostatin and substance P immunoreactivity within plaques was observed in the hippocampus and amygdala but not in the neocortex, although the latter region contained plaques within which somatostatin and substance P existed alone. The frequency with which we observed one or more neuropeptide within plaques was relatively low and in fact most plaques contained neither substance P nor somatostatin immunoreactivity. In addition, a large number of swollen peptidergic processes were observed outside of plaques. The significance of these observations with respect to the pathogenesis of Alzheimer's disease is discussed.

Aged↗
PubMed1989

Pulmonary lymphoma in Sjögren's syndrome.

Sjögren's syndrome (SS) is an immunologic disease characterized by progressive destruction of the exocrine glands that causes mucosal and conjunctival dryness. In addition to the common pulmonary complications of diffuse interstitial lung disease, airways obstruction, desiccation of the upper respiratory tract, localized parenchymal nodules, recurrent tracheobronchitis, bronchiectasis, interstitial pneumonitis, and pleural effusion, patients with SS have a high risk of developing non-Hodgkin's lymphoma that may affect the lungs. Among 50 patients with SS and associated lymphoma, 10 had pulmonary involvement by lymphoma. The mean age of these 10 patients was 59.7 years, and 8 were women. The mean duration of SS was 7.2 years, and the mean interval between the onset of SS and lymphoma was 5.4 years. Cough and slowly progressive dyspnea were the most common pulmonary symptoms, and chest roentgenographic findings varied. Lung biopsies revealed a spectrum of low-to high-grade lymphomas, and high-grade lymphomas were associated with increased mortality. Of the 10 patients, 4 died from 8 to 48 months after lymphoma was diagnosed. We conclude that pulmonary involvement is common in patients with lymphoma associated with SS; thus, lymphoma should be considered in the differential diagnosis of pulmonary lesions in patients with SS.

Adult↗
PubMed1989

Pulmonary complications in diabetes mellitus.

Diabetes mellitus produces serious complications in several major organ systems. The pulmonary complications, although uncommon and not well recognized, may be life-threatening. We describe a 20-year-old patient with diabetic ketoacidosis in whom pulmonary zygomycosis developed. This condition was complicated by stenosis of the left upper lobe bronchus despite successful treatment of the zygomycosis. Bronchial obstruction has become a well-recognized complication of pulmonary zygomycosis. In addition to infections caused by Zygomycetes, mycobacteria, viruses, and bacteria, the pulmonary complications described in patients with diabetes include pulmonary edema, disordered breathing during sleep, and reductions in elastic recoil of the lungs, diffusing capacity of the lungs for carbon monoxide, and bronchomotor tone. Other reported complications are respiratory alkalosis, cardiorespiratory arrest, pneumothorax, pneumomediastinum, plugging of the airways with mucus, and aspiration pneumonia attributable to diabetic gastroparesis.

Adult↗
PubMed1989

Development of two isogenic sweet corn hybrids differing for glycinebetaine content.

A hybrid of sweet corn, Zea mays L. (;1720'; Rogers Brothers Seed Co.), was found to be comprised of glycinebetaine-positive and glycinebetaine-deficient individuals in a 1:1 mixture. This phenomenon was traced to segregation for a single, nuclear, dominant gene determining leaf glycinebetaine content within the female inbred parent of this hybrid. Selection for homozygous recessive (glycinebetaine-deficient) and homozygous dominant (glycinebetaine-positive) genotypes of the female inbred parent enabled production of two isogenic versions of hybrid ;1720' differing with respect to a single copy of the dominant allele, by mating these female parent selections with the common homozygous recessive (glycinebetaine-deficient) male parent. These two isogenic hybrids are shown to differ by a factor of 300- to 400-fold in glycinebetaine titer of young expanding leaves of salinized plants, but exhibit no striking differences in the levels of free amino acids or the level of N-methylnicotinic acid (nicotinic acid betaine; trigonelline). The only significant difference between the two hybrids in terms of amino acid composition was found to be in the level of alanine under nonsalinized conditions. The betaine-deficient hybrid exhibited a 14% lower alanine level than the betaine-positive hybrid. Betaine deficiency was not associated with altered stress-induced accumulation of amino acids such as proline, serine, and asparagine plus aspartate, attesting to the high specificity of the genetic difference between these isogenic hybrids with respect to betaine accumulation. This germplasm offers unique opportunities to test whether a single dominant allele determining stress-induced betaine accumulation capacity influences stress resistance in maize.

Journal Article↗
PubMed1989

Eikenella corrodens: an unusual cause of endocarditis in a patient with silent mitral valve prolapse.

A 69-year old man with clinically silent mitral valve prolapse developed infective endocarditis secondary to Eikenella corrodens after dental work. The patient required surgical removal of abscessed teeth and long-term antibiotic therapy. E. corrodens is a gram-negative coccobacillus which normally inhabits the oropharynx, gastrointestinal tract, and upper respiratory tract. The organism can cause cutaneous and abdominal abscesses, meningitis, osteomyelitis, and endocarditis. Patients with mitral valve prolapse and a pre-existent systolic murmur or Doppler echocardiographic evidence of mitral regurgitation should receive prophylactic antibiotics for any procedure associated with a bacteremia. An infection caused by E. corrodens should be considered in patients with fever after dental manipulation or in patients with "culture-negative" endocarditis.

Aged↗
PubMed1988

Decreased levels of protein kinase C in Alzheimer brain.

Protein kinase C (PK-C) levels were determined using [3H]phorbol-12,13-dibutyrate (PDB) binding and the in vitro phosphorylation of histone H I (III-S), in autopsied human frontal cortex of age- and postmortem time-matched normal and Alzheimer patients. PK-C levels in Alzheimer particulate fractions determined by both methods were about 50% of those in controls. PK-C levels in Alzheimer cytosol fractions were not significantly different from those in controls. In a parallel study, we measured the phosphorylation of a Mr 86,000 protein (P86), the major protein kinase C substrate in the cytosol fraction prepared from Alzheimer frontal cortex, and found it to be reduced to 43% of that in control brains. This reduction in P86 protein phosphorylation compared to controls was not detected in brain samples prepared from demented patients without Alzheimer's disease. We considered 3 extraneous factors (postmortem delay, age and sex) which may have affected the extent of P86 phosphorylation and concluded that the reduced P86 phosphorylation in the Alzheimer samples is not due to any of them. Reduced PK-C levels and Mr 86,000 protein phosphorylation may reflect a biochemical deficit related specifically to the pathogenesis of Alzheimer's disease.

Aged↗
PubMed1988

Increased Mr 60,000 protein phosphorylation is correlated with neocortical neurofibrillary tangles in Alzheimer's disease.

Increased Mr 60,000 protein phosphorylation has been found in the cytosol fraction of brain tissue from Alzheimer's disease patients. A correlation between this biochemical change and the morphologic abnormalities found in Alzheimer's disease was sought. Three neuropathologic features were studied: neurofibrillary tangles and neuritic plaques, findings characteristic of Alzheimer's disease, and gliosis, a non-specific change. The number of tangles correlated well with the extent of Mr 60,000 protein phosphorylation (p less than 0.001); but the number of plaques did not. To investigate the possibility that gliosis causes the increased Mr 60,000 protein phosphorylation, cases of Pick's disease and multi-infarct dementia were also studied. The levels of Mr 60,000 protein phosphorylation in these cases were comparable to those seen in normal controls. These findings suggest that the increased Mr 60,000 protein phosphorylation is closely related to diseased, tangle-bearing neurons and is not directly related to neuritic plaque formation or secondary gliosis.

Alzheimer Disease↗
PubMed1988

Neocortical morphometry, lesion counts, and choline acetyltransferase levels in the age spectrum of Alzheimer's disease.

We studied neocortical morphometry (cortical thickness, neurons, and glia), lesion counts (plaques and tangles), and choline acetyltransferase levels in up to 113 Alzheimer brains and 48 controls. Comparisons between young (under 65) and old (over 70) Alzheimer cases revealed more tangles in the former, but no other statistically significant differences in the measured variables. Differences in these parameters between young Alzheimer cases and young controls were similar to the differences found between old Alzheimer cases and old controls. Linear regression analyses correlating some of these variables with age in Alzheimer's disease, considered together with the effects of normal aging on the same parameters, reveal in Alzheimer's disease a spectrum of graded pathologic severity inversely proportional to age. Nevertheless, even in advanced old age (80 to 100), significant differences persist in these parameters between very elderly Alzheimer brains and controls.

Aged↗
PubMed1988

Neocortical morphometry and cholinergic neurochemistry in Pick's disease.

With a computerized image-analysis apparatus for neocortical morphometry and chemical methods for evaluation of the cholinergic system, five brain specimens of Pick's disease (PD) were studied and the results compared to those from specimens of age-matched normal subjects and Alzheimer's disease (AD). The PD specimens showed major reductions in brain weight, frontal and temporal cortical thickness, and large neuron populations, compared with controls. Lesser reductions were seen in small neurons and thickness of the inferior parietal cortex. The authors found no relationship between age of onset or disease duration and either the degree of cortical thinning or neuron loss or the number of Pick bodies in the neocortex and hippocampus. PD specimens were more atrophic than AD brains, having lower brain weights and more fronto-temporal thinning. Large neurons were comparably reduced in the two conditions in the frontal and temporal lobes, but small neuron losses were greater in the PD midfrontal area. Only the AD cases showed loss of large neurons in the inferior parietal region. Levels of choline acetyltransferase were normal in PD and reduced in AD, whereas muscarinic receptor binding was decreased in both.

Aged↗
PubMed1987

Neocortical cell counts in normal human adult aging.

Fifty-one brains from clinically and neuropathologically normal individuals ranging in age from 24 to 100 years were studied to determine what changes occur in neocortical neuroectodermal cell populations as a function of normal aging. Twenty-mu-thick sections from the midfrontal, superior temporal, and inferior parietal areas were examined with an image-analysis apparatus with combined manual and automatic editing capacity. Neuroectodermal cells were counted, measured, and assigned to one of ten categories, which were later summarized in three: large neurons (greater than 90 mu 2), small neurons (41 to 90 mu 2), and glia (5 to 40 mu 2). Determinations were also made of brain weight, cortical thickness, neuronal density, neuron-glia ratio, and percentage of cell area. The results showed statistically significant age-related decrements in the following values: brain weight, cortical thickness in the midfrontal and superior temporal areas, large neurons in all three areas, and the neuron-glia ratio in the midfrontal and inferior parietal areas. The total number of neurons, neuronal density, and percentage of cell area were all unchanged. Increasing with age were the number of small neurons in the midfrontal cortex and glia in the midfrontal and superior temporal areas. The following conclusions were drawn: Aging affects the frontal and temporal lobes more than the parietal; the salient change is shrinkage of large neurons with consequently increasing numbers of small neurons; constant neuronal density coupled with diminished cortical volume (decreased brain weight and cortical thinning) indicate that there is some neuronal loss with age, but it is of much lesser magnitude than previously supposed; and the number of glia increases with age.

Adult↗
PubMed1987

Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles.

Senile dementia of the Alzheimer type (SDAT) is typified pathologically by neuritic plaques (NP) and neurofibrillary tangles (NFT) in the neocortex and hippocampus. However, in a large series of cases (60) over age 74 a significant minority (30%) lacked neocortical tangles. In order to determine if these latter cases (Group B) otherwise differ from the majority which have both neocortical plaques and tangles (Group A), various clinical and neuropathological parameters were measured for both groups and the results compared. The following indices were examined: degree of dementia, rate of progression of dementia, age at death, brain weight, cerebral hemispheric weight, cortical cell counts from the frontal, temporal, and parietal lobes, the number of neocortical NP, the number of hippocampal NP and NFT, and the levels of neocortical choline acetyltransferase and somatostatin. The two groups showed no statistically significant differences in any of these categories except for increased numbers of neocortical NP in Group A in midfrontal and superior temporal regions. However, cases in Group A showed greater pathologic abnormality in nearly every parameter, albeit without attaining statistical significance. We conclude that SDAT with neocortical NFT is the same disease as SDAT without them, although the presence of such tangles is associated with a tendency towards greater severity.

Aged↗
PubMed1987

9-(1-3-Dihydroxy-2-propoxymethyl)guanine prevents death but not immunity in murine cytomegalovirus-infected normal and immunosuppressed BALB/c mice.

Immunosuppressed (from treatment with cortisone acetate and anti-thymocyte globulin) and control adult female BALB/c mice, latently infected with murine cytomegalovirus (MCMV) or lethally challenged (10(6) PFU) with MCMV intraperitoneally, were treated with 9-(1-3-dihydroxy-2-propoxymethyl)guanine (DHPG) intraperitoneally. A dose of 3 mg/kg reduced mortality by 50% in lethally challenged normal mice; 10 mg/kg was required in immunosuppressed mice. When 15 mg/kg was given, the onset of treatment could be delayed for 64 h after lethal challenge. DHPG did not prevent the establishment of latent MCMV infection or immunosuppression-induced reactivation. The antibody titer to MCMV in DHPG-treated mice which survived lethal challenge was 41 (reciprocal of geometric mean) 4 to 5 weeks after inoculation; such mice survived a second lethal challenge. When antiserum treatment was begun 64 h and DHPG was begun 72 h after a lethal challenge, most mice survived; most did not when either treatment alone was begun at those times. In summary, DHPG effectively treated lethal MCMV infection even in immunosuppressed mice and even when treatment onset was delayed for 64 h. Treatment did not alter the establishment or reactivation of latent infections or the induction of effective immunity. The administration of DHPG coupled with antiserum treatment may be even more effective than the administration of either alone.

Acyclovir↗