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Biomedical subjects

A C Smith

Publications and source records attributed to A C Smith.

At least 109 records · Page 6Linked to original sources
PubMed1994

The effect of transient temperatures on the growth of Salmonella typhimurium LT2. I: Cycling within the growth region.

The effect of fluctuating temperatures on microbial growth is important in the passage of foods through the food chain. Suspensions of Salmonella typhimurium were subjected to sinusoidally time-varying temperatures of periods from 40 to 480 min within their growth temperature range. The change in the numbers of viable bacteria was measured with time and the experimental growth curves and average generation times compared with predictions based on isothermal growth data. The experimental average generation times exceeded the predictions by less than 30%, although the discrepancy increased with cycle frequency. Instantaneous growth rates obtained for the 480 min cycles were in agreement with those predicted from isothermal behaviour.

Hot Temperature↗
PubMed1994

Iatrogenic bismuth poisoning. Case report.

A case of bismuth intoxication following the intraoral use of BIPP-impregnated gauze packs is presented. This report illustrates the need for caution when using potentially toxic compounds in the oral cavity where significant quantities can be absorbed to produce symptoms of poisoning.

Absorption↗
PubMed1994

Biopsy of inoperable pancreatic tumors does not adversely influence patient survival time.

PURPOSE: To determine the influence of pancreatic biopsy on the survival times of patients with inoperable tumors of the pancreas. MATERIALS AND METHODS: One hundred seventy patients were examined; results of histologic analysis confirmed pancreatic malignancy in 119. The biopsy and nonbiopsy groups were comparable for age, sex, the presence of liver metastases, and nodal status. RESULTS: No statistically significant difference was demonstrated between the survival time for the biopsy group (median, 23 weeks) and that for the nonbiopsy group (median, 22 weeks). The estimated relative risk for death (biopsy group compared with nonbiopsy group) was 0.85 (95% confidence limits = 0.61, 1.18). CONCLUSION: Pancreatic biopsy does not appear to adversely influence survival time for patients with inoperable pancreatic tumors. Because histologic examination aids clinical management, biopsy should be part of the diagnostic work-up for patients with suspected inoperable pancreatic carcinoma.

Aged↗
PubMed1993

Transgenic animal models for Alzheimer's disease.

The neuropathology of Alzheimer's disease is characterized by the deposition of abnormal protein aggregates. The main constituent of the deposition is beta-amyloid protein. A seminal role of this protein is supported by the discovery of point mutations in the gene of its precursor protein in certain forms of familial Alzheimer's disease. In vitro (cultured neuronal cells), overexpression of the precursor protein or a part of the precursor leads to degeneration of neurons, suggesting neurotoxicity of its derivatives. At this time, all of the reported transgenic mice bearing DNA construct for the precursor or a part of the precursor, however, have not developed convincing pathological changes similar to what is observed in patients with Alzheimer's disease. This interesting discrepancy between in vitro and in vivo suggests suppressors in vivo which ameliorate beta-amyloid precursor protein derivative-mediated neurotoxicity.

Alzheimer Disease↗
PubMed1993

Natural history of the recombinant (8) syndrome.

The recombinant 8[Rec(8)] syndrome [rec(8), (8qter-->8q22.1::8p23.1-->8qter] is due to a parental inv(8)(8pter-->8p23.1::8q22.1-->8p23.1::8q22+ ++.1-->8qter). All inv(8) parents we have studied were of Hispanic origin. The Rec(8) phenotype consists of a characteristic set of minor facial anomalies, cardiovascular and other major malformations, and moderate to severe mental retardation. The clinical phenotype is relatively consistent in all published cases; however the natural history of the condition has remained unknown. Retrospective and prospective information on 42 propositi, spanning a period from 5 days to 23 years, allowed us to define the natural history of this syndrome, tabulate the frequency and the evolution of phenotypic abnormalities, and share our experience with different therapeutic approaches.

Abnormalities, Multiple↗
PubMed1993

Selective neurotoxicity of COOH-terminal fragments of the beta-amyloid precursor protein.

The primary component of amyloid deposits found in the brains of patients with Alzheimer's disease is the beta-amyloid protein, a derivative of a much larger precursor protein (beta PP). We have previously reported that overexpression of carboxyl (COOH)-terminal fragments of beta PP from an integrated DNA construct leads to degeneration of neuronally differentiating mouse embryonic stem cells and that the neuronal degeneration is related to approximately 14- and 15-kDa COOH-terminal fragments of the precursor protein. We here demonstrate that these putative cytotoxic fragments contain intact beta-amyloid protein. When such transformed cell lines are treated with dimethyl sulfoxide to induce differentiation into muscle cells, however, the resulting muscle cells remain viable (as do control non-transformed cells), despite the production of comparable amounts of the 14- and 15-kDa fragments. These results are consistent with the hypothesis that particular COOH-terminal fragments of beta PP are amyloidogenic and neurotoxic.

Amyloid beta-Protein Precursor↗
PubMed1993

Chloroquinoxaline sulfonamide: a sulfanilamide antitumor agent entering clinical trials.

Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It does not appear to inhibit folate metabolism as does the structurally similar sulfaquinoxaline. Preclinical toxicology studies in dogs and rats have shown that CQS is toxic to lymphoid organs, bone marrow, gastrointestinal tract, pancreas, CNS, adrenal glands and testes. Toxicity was generally reversible with the exception of testicular atrophy in dogs and rats which occurred late and was not reversible within the study time frame. The pharmacokinetic data indicate that CQS binds to serum proteins in a dose and species specific manner. Terminal half-lives appear to vary between species from 60 hours in mice, 15 hours in rats, and 45-132 hours in dogs. Preliminary data indicate a longer terminal half-life in humans. Two phase I trials are ongoing using a 60 min infusion schedule once every 28 days. The starting dose for each trial was 18 mg/m2.

Animals↗
PubMed1993

CPITN, DMFT, and treatment requirements in a Nicaraguan population.

WHO basic methods were used to assess CPITN, DMFT, and treatment requirements in a population of 178 persons aged 12-64 yr living in urban and rural areas of Nicaragua. Two groups were examined: individuals presenting for dental treatment at health clinics (30%) and subjects chosen randomly at other locations (70%). Mean ages of both groups were similar although females were found in higher percentages among those presenting for dental care. With the exception of one young individual, all subjects had calculus in at least one sextant. About 26% of the subjects who presented for treatment had a > or = 6 millimeter pocket compared to about 14% of the remainder of subjects. The mean DMFT for health clinic subjects was 16.1 compared to 10.3 for subjects from other locations. Subjects presenting for treatment had twice as many missing teeth and a mean of 0.5 filled teeth compared to 2.4 filled teeth for other subjects. Subjects at the clinics were in greater need of restorative care and extractions, while subjects from other locations were found to have more teeth that did not require any treatment. Health clinic subjects reported more visits to the dentist in the last year than other subjects. Only 80% of those presenting for treatment owned a toothbrush compared to 97% of those examined in other locations, and the latter group reported brushing their teeth more frequently. Attrition was a commonly encountered tooth disorder with 53% of all subjects exhibiting this condition.

Adolescent↗
PubMed1993

Training in human genetics in the United States.

A national study of existing and future human resource needs in the field of human genetics has never been conducted. Published figures of the existing levels of human genetics training are not available. This report reviews the current status of graduate training in human genetics in the US. Issues of certification, accreditation, enrollment and recommendations for future training needs are also discussed. As of 1989, 109 US programs offered training at the graduate or postgraduate level in human genetics. Sixty-seven percent were degree-granting programs. A 20% increase in the number of programs occurred between 1985 and 1989. In contrast, the number of graduates increased by only 10.5%. Reasons for this decreased level of training productivity remain undefined.

Accreditation↗
PubMed1993

Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (COL3A1) allele produces Ehlers-Danlos syndrome type IV in the heterozygous offspring.

Ehlers-Danlos syndrome (EDS) type IV is a dominantly inherited disorder that results from mutations in the type III collagen gene (COL3A1). We studied the structure of the COL3A1 gene of an individual with EDS type IV and that of her phenotypically normal parents. The proband was heterozygous for a 2-kb deletion in COL3A1, while her father was mosaic for the same deletion in somatic and germ cells. In fibroblasts from the father, approximately two-fifths of the COL3A1 alleles carried the deletion, but only 10% of the COL3A1 alleles in white blood cells were of the mutant species. The deletion in the mutant allele extended from intron 7 into intron 11. There was a 12-bp direct repeat in intron 7 and intron 11, the latter about 60 bp 5' to the junction. At the breakpoint there was a duplication of 10 bp from intron 11 separated by an insertion of 4 bp contained within the duplicated sequence. The father was mosaic for the deletion so that the gene rearrangement occurred during his early embryonic development prior to lineage allocation. These findings suggest that at least some of the deletions seen in human genes may occur during replication, rather than as a consequence of meiotic crossing-over, and that they thus have a risk for recurrence when observed de novo.

Adult↗
PubMed1992

Monozygotic twin girls with congenital malformations resembling fanconi anemia.

Monozygotic (MZ) twin girls, diagnosed at birth to have Fanconi anemia (FA) on the basis of multiple anomalies and an apparently increased baseline chromosomal breakage frequency in one twin, have been followed prospectively for 13 years. They have not developed aplastic anemia or other hematologic manifestations of FA. There was no evidence for increased baseline or diepoxybutane (DEB)-induced chromosomal breakage in either twin when the studies were repeated in Denver as well as in New York. Since the cellular phenotype must be considered in establishing the diagnosis of FA, these MZ twins should not be classified as affected with FA. Using the scoring system for FA diagnosis developed by Auerbach et al. [1989], the probability coefficients of their having FA based solely on clinical findings, prior to DEB testing, were .75 and .92, respectively. When the combination of their anomalies are taken together, their FA probability coefficient is .98. Through the International FA Registry, 15 additional patients have been identified with an FA probability score of .75 or greater, but who have not developed aplastic anemia and who are DEB negative. These patients, as well as the twins described in this report, are most likely a heterogeneous group and may represent other syndromes like Holt-Oram, VATER, VACTERL and IVIC, with genetic as well as nongenetic etiologies. These cases demonstrate the importance of testing with DEB or other DNA crosslinking agent in order to discriminate between FA and other syndromes with a similar phenotype.

Abnormalities, Multiple↗
PubMed1992

Overexpression of amyloid precursor protein alters its normal processing and is associated with neurotoxicity.

The recent discovery that point mutations in the beta/A4 amyloid precursor protein may be the cause of certain forms of familial Alzheimer's disease provides strong support for the view that a thorough understanding of the metabolism of this protein may elucidate the pathogenesis of most forms of the disease and thus serve as a basis for rational prevention and therapy. Here we show that overexpression of a portion of the amyloid precursor protein molecule produces at least four distinct fragments of the COOH-terminus of amyloid precursor protein, suggesting altered proteolysis of amyloid precursor protein, and that such overexpression is associated with cytotoxicity. The degree of toxicity in the P19 cell culture model (differentiating mouse embryonal carcinoma cells) is shown to be related to the two larger novel COOH-terminal protein fragments (16 and 14 kilodalton), as well as to levels of expression of these two fragments. The toxicity is manifested in several differentiated cell lineages, including neuronal cells.

Amyloid beta-Protein Precursor↗
PubMed1992

Expression of a carboxy-terminal region of the beta-amyloid precursor protein in a heterogeneous culture of neuroblastoma cells: evidence for altered processing and selective neurotoxicity.

Six independent clonal isolates from a morphologically heterogeneous human neuroblastoma cell line stably expressed several products of the human amyloid precursor protein (APP) from an introduced DNA construct; the "substrate-adherent" phenotype (fibroblast-like cells) predominated in all 6; these displayed immunoreactivity of vimentin, but little to no reactivity of neuron-specific enolase. A stably transfected isolate which did not show any expression from the identical construct (presumably because of a position effect) exhibited the predominantly neuronal phenotype of the parental cells (neuron-specific enolase positive). These results suggest selective neurotoxicity of the expressed products. Two of the 6 stably expressing cell lines showed a decrease of native mRNA for APP to levels that were 1/4-1/3 that of the parental cells and a decrease of their growth rates to half that of the parental cells; these decreased growth rates were improved by conditioned medium from the parental cell line. Western blot analysis revealed at least four distinct fragments of the COOH-terminus of APP in the isolate which expressed protein and mRNA in greatest abundance, suggesting that overexpression of APP in a human neural cell line leads to aberrant cleavage of APP.

Amyloid beta-Protein Precursor↗
PubMed1992

Desmoplastic malignant melanoma: rare and difficult to diagnose.

BACKGROUND: We review our experience with a recent cluster of three cases of rare desmoplastic malignant melanoma (DMM). OBJECTIVE: Our purpose is to alert clinicians to this rare tumor and the difficulty in clinical and histopathologic diagnosis. METHODS: The clinical presentation and steps necessary to establish diagnosis are outlined. A literature review on diagnosis, treatment, and prognosis is presented. RESULTS: Two thirds of DMM are amelanotic and may appear only as a dermal nodule or thickening. Diagnosis can be made with the combination of light microscopy and immunopathology. Treatment consists of surgical excision. Lymph node dissection should be considered only when histologically positive regional nodes are present. CONCLUSION: The diagnosis of DMM may be difficult when based only on clinical expectation of melanoma and light microscopy findings. A strong clinical suspicion of DMM coupled with immunologic studies will establish the diagnosis.

Aged↗
PubMed1992

Paraneoplastic pemphigus, cicatricial conjunctivitis, and acanthosis nigricans with pachydermatoglyphy in a patient with bronchogenic squamous cell carcinoma.

A 77-year-old man with chronic conjunctivitis, acanthosis nigricans with pachydermatoglyphy, and pemphigus-like mucocutaneous lesions was found to have a well-differentiated bronchogenic squamous cell carcinoma. Histopathologic and immunofluorescence studies confirmed the diagnosis of paraneoplastic pemphigus. Skin lesions resolved with oral prednisone and azathioprine therapy, but the conjunctivitis and mucous membrane erosions persisted. The conjunctiva later became scarred with foreshortening of the fornices and development of symblepharon. External beam irradiation arrested the growth of the tumor but did not have any effect on the diseased conjunctiva and other mucous membranes. This case demonstrates that cicatrizing conjunctivitis with bullous mucocutaneous lesions may be a clinical sign associated with an occult neoplasm.

Acanthosis Nigricans↗