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Biomedical subjects

H Potter

Publications and source records attributed to H Potter.

At least 19 recordsLinked to original sources
PubMed1992

Magnetic resonance imaging in diagnosis of transient osteoporosis of the hip.

The results of magnetic resonance (MR) imaging in six patients with transient osteoporosis of the hip were reviewed. Short TR/TE (repetition time/echo time) images demonstrated diffusely decreased signal intensity in the femoral head and intracapsular region of the femoral neck. Increased signal intensity was noted with progressive T2 weighting. Bone biopsies were performed in four patients. Histologic findings were nonspecific and included fat necrosis, marrow edema, increased bone resorption, and reactive bone formation. Repeat MR scans in two patients, performed six and eight months after the initial scans, showed an almost complete return to normal marrow signal. All patients became asymptomatic without bony deformity. In the appropriate clinical setting, MR scanning can aid in the diagnosis of transient osteoporosis as the cause of a painful hip.

Acute Disease↗
PubMed1991

A system for assaying homologous recombination at the endogenous human thymidine kinase gene.

A system for assaying human interchromosomal recombination in vitro was developed, using a cell line containing two different mutant thymidine kinase genes (TK) on chromosomes 17. Heteroalleles were generated in the TK+/+ parent B-lymphoblast cell line WIL-2 by repeated exposure to the alkylating nitrogen mustard ICR-191, which preferentially causes +1 or -1 frameshifts. Resulting TK-/- mutants were selected in medium containing the toxic thymidine analog trifluorothymidine. Mutations were characterized by exon-specific polymerase chain reaction amplification and direct sequencing. In two lines, heterozygous frameshifts were located in exons 4 and 7 of the TK gene separated by approximately 8 kilobases. These lines undergo spontaneous reversion to TK+ at a frequency of less than 10(-7), and revertants can be selected in cytidine/hypoxanthine/aminopterin/thymidine medium. The nature and location of these heteroallelic mutations make large deletions, rearrangements, nondisjunction, and reduplication unlikely mechanisms for reversion to TK+. The mode of reversion to TK+ was specifically assessed by DNA sequencing, use of single-strand conformation polymorphisms, and analysis of various restriction fragment length polymorphisms (RFLPs) linked to the TK gene on chromosome 17. Our data suggest that a proportion of revertants has undergone recombination and gene conversion at the TK locus, with concomitant loss of frameshifts and allele loss at linked RFLPs. Models are presented for the origin of two recombinants.

Amino Acid Sequence↗
PubMed1991

A calcium-activated protease from Alzheimer's disease brain cleaves at the N-terminus of the amyloid beta-protein.

Alzheimer's disease, Down's syndrome, and to a far lesser extent, normal aged brains exhibit abnormal extracellular deposits of amyloid. The major component of brain amyloid is the beta-protein, a 4Kd fragment of the larger beta-protein precursor. The finding of the abnormally processed beta-protein and a protease inhibitor (alpha 1-antichymotrypsin) in the amyloid deposits prompted us to search for proteases which may generate the beta-protein from its precursor. We now report on the presence and partial purification of one such proteolytic activity from Alzheimer's brain. Normal physiologic C-terminal cleavage of the secreted form of the beta-protein precursor occurs in the middle of the beta-protein suggesting that the beta-protein accumulates due to an alternative degradation pathway. We propose here that the protease activity we describe participates in this abnormal pathway.

Alzheimer Disease↗
PubMed1989

The protease inhibitor, alpha 1-antichymotrypsin, is a component of the brain amyloid deposits in normal aging and Alzheimer's disease.

The purpose of this study was to characterize the nature and the origin of the Alzheimer's disease amyloid deposits. We used an amyloid antiserum to screen a human liver expression library. A positive clone was sequenced and found to code for the serine protease inhibitor alpha 1-antichymotrypsin, an acute phase serum protein. Thus, this protein is a second component of the brain amyloid in addition to the beta-protein. In order to determine whether the inhibitor originated from the serum or was made in the brain, we performed Northern blots on tissue from control and Alzheimer brain and found that alpha 1-antichymotrypsin RNA is present in the brain and that the diseased brain contained larger amounts than the controls. Immunocytochemistry and in situ hybridization show the astrocytes to produce the inhibitor, mainly around senile plaques, alpha 1-antichymotrypsin is only associated with the amyloid deposits of the beta-protein kind in normal aging of man and monkeys. Alzheimer's, Down's syndrome and hereditary cerebral hemorrhage with amyloidosis of Dutch origin, but not in primary and secondary amyloidosis or familial amyloidotic polyneuropathy. The specific association between alpha 1-antichymotrypsin and the beta-protein prompted us to suggest a role for this serine protease inhibitor in the proteolytic processing of the beta-protein precursor.

Aging↗
PubMed1989

Alpha 1-antichymotrypsin in brain aging and disease.

The recent finding (Abraham et al., 1988) that the serine protease inhibitor, alpha 1-antichymotrypsin, is tightly associated with the amyloid deposits of normal aged and Alzheimer's disease brains, suggests a role for this inhibitor in the amyloid deposition. We used immunohistochemistry to analyze the presence of alpha 1-antichymotrypsin in the similar brain amyloid which accumulates in monkeys with increasing age. The earliest alpha 1-antichymotrypsin immunoreactivity was found in cortical perivascular cells before the appearance of either thioflavin S-identifiable amyloid deposits or beta-protein reactivity in vessels. The cortical amyloid, both in senile plaques and vasculature, was seen only several years later, and could be stained for both beta-protein and alpha 1-antichymotrypsin. In addition, we analyzed the association of alpha 1-antichymotrypsin with the other types of amyloidoses. alpha 1-antichymotrypsin antibodies immunolabeled only amyloid deposits that have as their major component the beta-protein: normal aging, Alzheimer's disease, Down's syndrome and in the hereditary cerebral hemorrhage with amyloidosis of Dutch origin (HCHWA-D), but not in Creutzfeldt-Jakob disease, Familial Amyloidotic Neuropathy, primary amyloidosis, or secondary amyloidosis. Lastly, we used immunocytochemistry to identify cells that express alpha 1-antichymotrypsin during brain degeneration. Such immunoreactivity was found in astrocytes near areas of neuronal or tissue loss, in pericytes and in a few neurons, even in diseases with no alpha 1-antichymotrypsin-containing amyloid deposits. In summary, alpha 1-antichymotrypsin is found in three cell types in various brain diseases. In amyloid deposits it is found only in association with the beta-protein, further strengthening its possible role in the processing of the beta-protein precursor or the stability of the beta-protein amyloid deposits.

Aging↗
PubMed1979

Biochemical assay designed to detect formation of recombination intermediates in vitro.

A biochemical assay that is designed to detect recombination intermediates formed in vitro is described. The assay measures the fusion of two essentially homologous plasmids, one of which is radioactively labeled and the other of which carries several copies of the lac operator. The fusion product is radioactive and can be bound to a nitrocellulose filter by lac repressor. This assay for genome fusion is rapid and readily applicable to the many fractions that result during enzyme purification. The fused product is not destroyed in the assay and may be recovered from the filter for further analysis by electron microscopy. The product is then seen to consist of figure 8 structures that can be cleaved by the restriction enzyme EcoRI to give chi forms, structures similar to those recovered from recombination-proficient cells. It is expected that this assay will be useful in the purification of the "recombinase-type" activity detected in crude cell lysates. To demonstrate this point, the assay was applied to the protein fractions recovered from a molecular sieve column. The results indicate that the fusion activity has an apparent molecular weight of 50,000--100,000.

DNA Restriction Enzymes↗
PubMed1979

Continuities in the olfactory deficits of chronic alcoholics and alcoholics with the Korsakoff syndrome.

Olfactory dysfunction, a finding prevalent among alcoholic Korsakoff patients, was investigated in long-term alcoholics with Korsakoff's Syndrome. The results demonstrate that alcoholics are impaired on odor quality discrimination but performed normally on complex hue discriminations. These findings support the hypothesis that chronic alcoholics and alcoholic Korsakoff patients represent two points on a single continuum of cognitive deterioration associated with alcohol abuse.

Alcohol Amnestic Disorder↗
PubMed1978

In vitro system from Escherichia coli that catalyzes generalized genetic recombination.

This paper reports an in vitro system for studying generalized genetic recombination. The system uses extracts from Escherichia coli as a source of enzymes and plasmid DNA molecules as substrates. Unit-size plasmid DNA rings are converted into genomes fused at a region of DNA homology at a frequency of about 5-10% over a period of hours. That the fused structures are the result of recombination is supported by two lines of evidence. When two partially homologous plasmids of different sizes are used as substrates for the in vitro system, intermediates containing one plasmid of each size are obtained. Furthermore, fused structures are not formed with high efficiency in extracts from recombination-deficient (Rec A(-)) cells.DNA synthesis does not appear to be required for the formation of the recombination intermediates; it is possible to omit DNA precursors from the reaction mixture and, furthermore, to develop the fused structures even in the presence of chaintermininating dideoxynucleoside triphosphates. The structures formed in vitro have the basic properties of recombination intermediates previously recovered from intact cells. That is, two genomes are demonstrably fused at a region of homology. However, in one way the molecules formed in vitro have a property less frequently observed in vivo-the fused genomes often appear to be connected over an extended region of homology ranging up to several hundred base pairs in length. This extended region of pairing may indicate the presence of two crossover connections very close together and, as will be discussed, may provide an insight into the mechanism by which the recombination intermediate is formed.

Crossing Over, Genetic↗
PubMed1977

On the mechanism of genetic recombination: the maturation of recombination intermediates.

DNA molecules of the plasmid ColEl are normally recovered from wild-type cells as a set of monomer- and multimer-size rings. The data of this paper show that the multimer-size species are a product of genetic recombination. Multimer rings do not arise after transfection of purified monomers into bacterial host cells lacking a functional recA recombination system. Analogously, purified dimers, trimers, and tetramers, transfected into recA- cells, can replicate, but are constrained to remain in those conformations. Only upon transfection into rec+ cells can they regenerate the full spectrum of monomer- and multimer-size species. In this paper we trace the flow of genetic information from the monomer to the multimer state and back again under the guidance of the recA recombination system. The formation of multimer-size DNA rings is discussed as a natural consequence of the maturation of a Holliday recombination intermediate formed between two monomer plasmid genomes.

Chromosomes↗
PubMed1976

Response plasticity in hamster olfactory bulb: peripheral and central processes.

It is a well-established fact that prolonged odor stimulation leads to marked sensory adaptation. This study demonstrates comparable electrophysiological phenomena occurring at the level of the olfactory receptor and at more central olfactory structures. Recordings of overall receptor response and of olfactory bulb unit responses were made during repeated odor stimulation. During the course of a single, continuous odor presentation response decrements were seen in the EOG (at the olfactory receptors) and were mirrored at the mitral cell layer of the bulb. When brief periods without stimulation were introduced between such odor presentations, receptor responsiveness rebounded to its original level, but mitral cell responses did not. On the basis of this dissociation it is suggested that the pattern of response decrement within the bulb represents a case of stimulus-specific habituation in a simple cortical subsystem and is well worth future investigation as a model of neural plasticity. Surgical disconnection of the olfactory bulb from one or more of its centrifugal inputs results in hyperactive, hyperresponsive mitral cells, which habituate more rapidly and show longer recovery times than do those in the intact bulb. In addition, the synchronization of such units to the inhalation cycle is markedly reduced as compared with normal preparations. These facts together suggest that the habituation of mitral cell activity does not depend on centrifugal inputs, although one or more of such inputs act indirectly in an inhibitory fashion to modulate and tune mitral cell response characteristics.

Adaptation, Physiological↗
PubMed1976

On the mechanism of genetic recombination: electron microscopic observation of recombination intermediates.

This paper deals with the nature of recombination intermediates. Using the electron microscope to study the DNA of the plasmid colicin E1, we have observed more than 800 molecules that appear to represent intermediates in the process of recombination. Specifically, after isolating colicin DNA and linearizing it with the restriction enzyme EcoRI, we find crossed molecules with twice the normal colicin DNA content. These forms consist of two genome-length elements held together at a region of DNA homology. The molecules can be recovered from wild type and Rec B-C host cells but are not present among the colicin DNA forms isolated from recombination-deficient Rec A cells. We have termed the experimentally observed molecules "chi forms" and believe that they represent the recombination intermediate of the Holliday model.

Colicins↗