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Biomedical subjects

I T Lott

Publications and source records attributed to I T Lott.

At least 37 records · Page 2Linked to original sources
PubMed1986

Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease.

We examined the distribution and density of N-methyl-D-aspartate (NMDA) displaceable L-[3H]glutamate binding sites in human hippocampal samples obtained postmortem from Alzheimer's disease (AD) patients and from age-matched controls. Binding to NMDA receptors was stable for at least 72 h postmortem, and the pharmacological profile corresponded to that described using electrophysiology. NMDA receptors were concentrated in the terminal fields of major hippocampal pathways including the perforant path, Schaffer collaterals and the hippocampal output to the subiculum, all of which are proposed to use an excitatory amino acid transmitter. Little if any change in hippocampal receptor density was observed in AD patients compared to age-matched controls except in one case where major hippocampal cell loss occurred. The distribution of NMDA receptors did, however, correspond to the predilection for neuritic plaques and neurofibrillary tangles in hippocampal subfields.

Aged↗
PubMed1986

Cerebral cortical contributions to sensory evoked potentials: hydranencephaly.

The contribution of the cerebral cortex to the generation of sensory evoked potentials was studied in an infant with hydranencephaly. On CT scan no tissue above the thalamus was noted. Long-latency potentials to auditory stimuli were absent whereas the short-latency or brain-stem auditory evoked potentials and some of the components of the middle latency auditory evoked potentials (No and Po) were present. To visual stimulation only the electroretinogram was detected. To somatosensory stimulation only the spinal cord potentials could be detected. The absence of long-latency components in each of the sensory modalities supports the concept that these potentials require intact cerebral hemispheres in man.

Anencephaly↗
PubMed1985

Plasticity of hippocampal circuitry in Alzheimer's disease.

Two markers of neuronal plasticity were used to compare the response of the human central nervous system to neuronal loss resulting from Alzheimer's disease with the response of rats to a similar neuronal loss induced by lesions. In rats that had received lesions of the entorhinal cortex, axon sprouting of commissural and associational fibers into the denervated molecular layer of the dentate gyrus was paralleled by a spread in the distribution of tritiated kainic acid-binding sites. A similar expansion of kainic acid receptor distribution was observed in hippocampal samples obtained postmortem from patients with Alzheimer's disease. An enhancement of acetylcholinesterase activity in the dentate gyrus molecular layer, indicative of septal afferent sprouting, was also observed in those patients with a minimal loss of cholinergic neurons. These results are evidence that the central nervous system is capable of a plastic response in Alzheimer's disease. Adaptive growth responses occur along with the degenerative events.

Acetylcholinesterase↗
PubMed1985

Retinoic acid embryopathy.

Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5). Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.

Abnormalities, Drug-Induced↗
PubMed1985

Long-term follow-up of infants and children treated with extracorporeal membrane oxygenation (ECMO): a preliminary report.

Extracorporeal Membrane Oxygenation (ECMO) has been used clinically as a life-saving treatment modality in infants and children who are dying of respiratory insufficiency. From 1973 to 1980 47 children less than 10 years of age were treated in a study to determine the feasibility and effectiveness of ECMO in the pediatric population. Despite a predicted mortality of 90% or greater, 24 patients survived. Eighteen of those patients have been seen in long-term follow-up. Thirteen patients (72%) demonstrate basically normal growth and development. Five patients (28%) have definite handicaps which are severe in two. Despite ligation of one common carotid artery and systemic heparinization, the risk of intracranial hemorrhage and/or neurodevelopmental problems appears to be no higher in this ECMO group and may even be lower than in the high-risk population treated with conventional therapy. The incidence of chronic respiratory problems, especially bronchopulmonary dysplasia, is zero in this group of patients. Only one patient (4%) has a defect that lateralizes to the right hemisphere which may have been affected by ligation of the carotid artery. Further study is required; however, it appears that ECMO offers life-saving intervention without increasing morbidity in select children with severe respiratory insufficiency.

Adolescent↗
PubMed1984

Communicating hydrocephalus and lysosomal inclusions in mannosidosis.

A 32-year-old man with mannosidosis had a gait disorder develop that was associated with communicating hydrocephalus. The gait disorder improved with ventriculoperitoneal shunting, but proximal muscle weakness remained. Biopsy specimens of muscle and nerve disclosed typical lysosomal inclusions in both tissues, as well as selective loss of unmyelinated axons.

Adult↗
PubMed1983

Pancytopenia in mannosidosis.

A case of autoimmune pancytopenia is described in a patient with mannosidosis who developed anti-platelet and anti-neutrophil antibodies and a low haptoglobin level. Bone marrow biopsy and 111InCl3 bone marrow scanning demonstrated hypoplasia of the marrow with a paucity of "storage cells." Pathogenic mechanisms and implications for other inborn errors of metabolism are discussed.

Adult↗
PubMed1982

Dementia in Down's syndrome: observations from a neurology clinic.

Clinical manifestations of dementia were reviewed in 15 Down's syndrome (DS) patients referred to a neurological clinic over a 24-month period for mental deterioration. The ages ranged from 32-64 years. One hundred percent showed personality changes and loss of independent daily living skills, the presenting symptoms in two-thirds of the cases. Other manifestations included seizures (53%), gait deterioration (73%), sphincteric incontinence (40%), and pathological release reflexes (67%). All 7 patients with CT-scans showed moderate or severe central and peripheral cortical atrophy. Detailed clinical information is presented for two patients, one of whom showed a temporary remission with imipramine. A characteristic dementia syndrome appears to be present in a subpopulation of aging DA patients with radiographic findings of Alzheimer's disease.

Activities of Daily Living↗
PubMed1982

Down's syndrome, aging, and Alzheimer's disease: a clinical review.

This review has been directed towards those aspects of DS which bear upon pathological aging. Clinical dementia in DS has heretofore been studied largely by retrospective methods with variable findings. A prospective study utilizing techniques designed to measure cognitive performance in a poorly verbal, retarded population is badly needed. There is definitive evidence for Alzheimer's disease changes in the brains of DS patients with some suggestion of altered topography compared to the general population. Immunological studies have established a T-cell deficiency in DS that may be linked to precocious aging of thymic-dependent processes. Both antiviral and nonantiviral effects of interferon are accentuated in cell culture systems utilizing DS tissue, presumably as a consequence of the localization of the interferon gene(s) on chromosome 21. Multiple endocrine studies confirm the high frequency of autoimmune disease, an abnormality that may be related to the problems of immune surveillance in DS. Precocious aging has been noted in regards to measures of skin elasticity, fenestration of cardiac valves, and premature cataracts. The 21st chromosome has been implicated in the elevated activity of superoxide dismutase, a finding of significance in regard to potential intracellular damage from increased levels of peroxide. Several studies have suggested a compensatory increase in glutathione peroxidase.

Adolescent↗
PubMed1981

Mannosidosis: isolation and comparison of mannose-containing oligosaccharides from gingiva and urine.

Excessive gingival hyperplasia with storage of mannose-rich oligosaccharides appears to be a unique feature present in a 31-year-old mannosidosis patient. Fractionation and analysis of the gingiva established the presence of (Man)2GlcNAc (2.2 mumol/g), (Man)3GlcNAc (3.5 mumol/g), (Man)4GlcNAc (2.8 mumol/g) and higher oligomers (Man)5GlcNAc--(Man)8GlcNAc (0.5 mumol/g); (Man, mannose; GlcNAc, N-acetylglucosamine). Eight characteristic oligosaccharides were isolated from the patient's urine by thin-layer chromatography. The most abundant was (Man)2GlcNAc (161--558 mumol/l); decreasing amounts of higher homologues up to a dekasaccharide, (Man)9GlcNAc (1--4 mumol/l) were also present. In contrast to urine, in which the trisaccharide was predominant, tetrasaccharides and pentasaccharides were more abundant in gingiva.

Acetylglucosamine↗
PubMed1981

Serum and urinary trisaccharides in mannosidosis.

A trisaccharide, Man2glcNAc, was the most abundant urinary oligosaccharide (161-558 mumol per liter) in a patient with mannosidosis. By means of a newly developed high-performance liquid chromatography (HPLC) procedure, we were able to measure low levels of serum trisaccharide (0.1--0.4 nmol per milliliter). This is the first report of the measurements of serum oligosaccharides in mannosidosis. Our observations on the disparate relationship between serum and urinary concentrations of this trisaccharide suggest that a facilitated renal clearance of oligosaccharides may be related to the nonprogressive aspect of this disorder.

Adult↗
PubMed1980

A light and electron microscopic study of mannosidosis.

The present work investigated the light and electron microscopic changes in hypertrophied gingiva in a patient with mannosidosis. The biopsy specimens studied covered a period of 20 months; biopsy specimens were taken before and after a therapeutic trial with oral and local zinc sulfate. The intensity of the disease was progressive, in spite of the zinc, and was characterized by marked hyperplasia of the epithelium and severe inflammation of the stroma. Many of the cells in the inflammatory infiltrate, as well as cells indigenous to the gingiva, showed a striking vacuolation of their cytoplasm. Histiocytes were most numerous and also were most heavily vacuolated, but fibroblasts, endothelial cells, plasma cells, and epithelial cells also manifested the vacuolar change. In the histiocytes, the vacuoles occupied most of the cytoplasm, ranged widely in size, and were contiguous, molded, and intercommunicating. The vacuoles were bound by a single membrane and were filled predominantly by a finely granular material of medium density but also by varying amounts of coarser, darker granules, fragmented membranes, myelin-like figures, lipid droplets, and small vesicles. The vacuoles were interpreted as being consistent with secondary lysosomes that contained excessively stored substrate, similar to what has been observed in the mucopolysaccharidoses, in which the vacuoles have also been demonstrated histochemically and cytochemically to contain acid phosphatase, a known lysosomal marker.

Adult↗
PubMed1980

Response-contingent taste-aversion in treating chronic ruminative vomiting of institutionalised profoundly retarded children.

Two case studies are presented describing the use of response-contingent taste-aversion procedures to treat chronic ruminative vomiting of profoundly retarded children. Each treatment programme was designed to be carried out by para-professional staff in an institutional setting. Each programme eliminated rumination, with effects maintained one to nine months following treatment. For one subject who exhibited major weight-loss prior to intervention, substantial weight-gain was also demonstrated.

Adolescent↗
PubMed1980

Liver in the cerebro-hepato-renal syndrome: defective bile acid synthesis and abnormal mitochondria.

Two infants with the cerebro-hepato-renal syndrome (Zellweger's disease) exhibited cholestasis and progressive liver damage. Because abnormalities of mitochondrial structure and function have been reported in this condition, we examined the bile acids for evidence of defects in the mitochondrial phase of bile acid synthesis, namely, oxidation of the cholesterol side chain to form C-24 bile acids. The presence of increased amounts of the C-27 bile acid intermediates (trihydroxycoprostanic acid, varanic acid, and dihydroxycoprostanic acid) were noted and identified by gas-liquid chromatography-mass spectrosocopy confirming that a defect in the mitochondrial pathways for bile acid side chain cleavage is involved in this entity. The clinical course, liver histopathology, and hepatocyte ultrastructural abnormalities suggest that these bile acids may reflect an underlying mitochondrial dysfunction in this disease and possibly may contribute to the progressive hepatic lobular fibrosis observed in these patients.

Abnormalities, Multiple↗
PubMed1979

Abnormal copper metabolism in Menke's steely-hair syndrome.

Copper (Cu) metabolism was selectively studied in seven infants with Menke's steely-hair syndrome (SHS). A daily oral regimen of CuSO4 (584 microgram Cu/kg) and L-histidine (100 mg/kg) in three infants produced an increase in serum Cu concentrations ranging from 33-95% of normal, but without the formation of ceruloplasmin. Cohn serum protein fractionation after oral Cu/L-histidine loading showed a disproportionate accumulation of Cu in the albumin fraction (V). The electron spin resonance spectrum of fraction V showed a heightened signal for the SHS patients, suggesting that an increased concentration of a radical Cu species is present after oral loading. The Sephadex G-150 chromatographic profile of serum fraction V in SHS did not differ significantly from controls. These results suggest that, in SHS, Cu absorbed in the presence of L-histidine is in an abnormal complex involving albumin, which does not allow for holoceruloplasmin biosynthesis. Cu and ceruloplasmin concentrations in the cord blood specimen of an infant who went on to develop SHS were normal, a finding which may account for the transient period of seemingly normal development after birth in SHS patients. An almost 6-fold difference in mean Cu concentration was observed in SHS fibroblasts compared to controls. Fibroblast Cu concentration was elevated in one to two possible maternal heterozygotes, a finding which may permit diagnosis of the carrier state for some SHS heterozygotes.

Blood Proteins↗