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Biomedical subjects

M Perlin

Publications and source records attributed to M Perlin.

13 recordsLinked to original sources
PubMed1994

Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map.

High-resolution genetic linkage maps are indispensable for positional cloning of disease genes. Current procedures for map construction, although aided considerably by many existing computer programs, require extensive user-intervention at each of many repetitive steps. This is time consuming, labour intensive and increases the chance of error. We have developed an expert system computer program, MultiMap, which automates this step-by-step procedure. MultiMap is based on a novel map construction algorithm and allows investigator control of marker locus characteristics, such as informativeness, scorability or distance to nearest neighbours. We used MultiMap to construct a human genetic map at an average resolution of 6 cM, using published genotypes at 1266 microsatellite markers, and further extended this map by adding 397 VNTR and polymorphic gene markers.

Algorithms↗
PubMed1993

Efficient construction of high-resolution physical maps from yeast artificial chromosomes using radiation hybrids: inner product mapping.

For the positional cloning of genes and other novel types of genetic experiments, in humans and other organisms, there is a crucial need for techniques with which genome-wide high-resolution ordered clone maps can be rapidly constructed. Current best methods, such as sequence-tagged site (STS) content mapping, entail a large number of experiments and, in practice, require large low-resolution yeast artificial chromosome (YAC) clones and very many STSs. In this paper, we introduce a new approach, inner product mapping (IPM), that overcomes these limitations. IPM uses radiation hybrids (RHs) to provide localizing signatures for YACs. Two independent data tables that compare YACs against RHs and RHs against STSs are obtained; these tables are combined to produce a computed map of the YACs against ordered STSs. IPM maps each YAC independently, requires relatively few RH comparisons to map a YAC, and can work with small (or large) YACs and few (or many) STSs. This paper describes IPM and presents computer simulations supporting the efficiency of IPM over that of competing methods.

Chromosome Mapping↗
PubMed1993

MultiMap: an expert system for automated genetic linkage mapping.

With the advent of the Human Genome Project, the ability to rapidly construct comprehensive and accurate linkage maps based on genetic marker data from family studies is an absolute necessity. In addition to their usefulness in localizing genes for both simple and complex disorders, linkage maps are invaluable tools for genetic counseling using linked marker genes. Several computer program packages are publicly available which aid in the construction of linkage maps by computing multipoint likelihoods for specified locus orders. However, these programs work in a step-by-step fashion, requiring intensive user-intervention and analysis at each step. Such a repetitive process is amenable to computerized automation. We have developed and tested an expert system computer program, MultiMap, for automated genetic linkage mapping. This program greatly reduces the amount of user-computer interaction, increasing the accuracy and speed with which a map can be constructed. In addition, because the total mapping time is greatly reduced through automation, it is now feasible to explore and compare various mapping heuristics and mapping criteria in order to develop the most appropriate approach, or set of approaches, for genetic linkage mapping. MultiMap need not be restricted to the construction of genetic maps, but could be adapted to aid in the automated construction of physical maps as well.

Automation↗
PubMed1992

Maintenance and killing efficiency of conditional lethal constructs in Pseudomonas putida.

Conditional lethal (suicidal) genetic constructs were designed and employed in strains of Pseudomonads as models for containment of genetically-engineered microbes that may be deliberately released into the environment. A strain of Pseudomonas putida was formed with a suicide vector designated pBAP24h that was constructed by cloning the host killing gene (hok) into the RSF1010 plasmid pVDtac24 and placing it under the control of the tac promoter. After hok induction in P. putida only 40% of surviving cells continued to bear the hok sequences within 4 h of induction; in contrast, 100% of the cells in uninduced controls bore hok. A few survivors that demonstrated resistance to hok-induced killing developed in P. putida, which may have been due to a mutation or physiological adaptation that rendered the membrane 'resistant' to hok. Conditional lethal strains of P. putida also were formed by inserting gef (a chromosomal homolog of hok) under the control of the tac promoter into the chromosome using a transposon. Constructs with chromosomal gef, as well as an RK2-derived plasmid construct containing gef, were only marginally more stable than the hok constructs; they were effective in killing P. putida when induced and within 2 h post-induction killing from either gef construct resulted in a 10(3)-10(5)-fold reduction in viable cell count compared to uninduced controls.

Cloning, Molecular↗
PubMed1991

Detection of Giardia cysts by using the polymerase chain reaction and distinguishing live from dead cysts.

A method was developed for the detection of Giardia cysts by using the polymerase chain reaction (PCR) and the giardin gene as the target. DNA amplification by PCR, using giardin DNA as the target, resulted in detection of both live and dead cysts. When giardin mRNA was used as the target, the ability to amplify cDNA by PCR depended on the mode of killing. Cysts killed by freezing were not detected by PCR when giardin mRNA was the target. Cysts killed by heating or exposure to monochloramine, however, gave positive detection signals for both DNA and giardin mRNA targets. The amount of giardin mRNA and total RNA was significantly increased in live cysts following the induction of excystation. Cysts killed by freezing, heating, or exposure to monochloramine did not show a change in RNA content. The detection of the giardin gene by PCR permits a sensitive and specific diagnosis for Giardia spp. Discrimination between live and dead cysts can be made by measuring the amounts of RNA or PCR-amplified product from the giardin mRNA target before and after the induction of excystation.

Animals↗
PubMed1991

Cis-platinum chemotherapy for ocular basal cell carcinoma.

We have used intravenous cis-platinum chemotherapy in the treatment of three patients with basal cell carcinoma of the lid extending into the orbit. Cis-platinum chemotherapy caused a reduction in tumour size and thereby delayed surgery in all cases. It allowed for local resection in one case, appeared to delay a patient's exenteration in a second case, and was used prior to radiotherapy in a third case. While not curative, cis-platinum may be useful as an adjuvant to decrease tumour mass prior to local excision and for patients who refuse or must delay exenteration.

Aged↗
PubMed1987

Photodynamic inactivation of influenza and herpes viruses by hematoporphyrin.

Hematoporphyrin (HP), at concentrations as low as 0.5 microgram/ml, was found to inhibit the in vitro replication of influenza A and herpes simplex viruses, but not of several other viruses. The effect required exposure of the viruses or cells to visible light and was demonstrable when HP was administered shortly before virus inoculation or during the infection. In studies on the mechanism of action of HP, we found that in the presence of light, HP caused decomposition of GMP but not of various other nucleosides. It caused breakdown of yeast tRNA and inhibited polymerization of RNA and DNA by influenza virus and HSV-1-specific polymerases as well as some other polymerases isolated from bacterial and mammalian sources. Protective effects of HP and light were demonstrable in embryonated eggs infected with the WSN and PR8 strains of influenza A virus and in mice infected with the WSN strain. HSV-1-induced keratitis in rabbits and HSV-2-induced dermatitis in mice were not responsive to HP treatment.

Animals↗
PubMed1982

Increased erythrocyte osmotic fragility in pregnancy.

An unexpected increase in erythrocyte osmotic fragility during pregnancy in two healthy women prompted a study of the effects of pregnancy on osmotic fragility. The incubated glycerol lysis time, a rapid, sensitive measure of osmotic fragility, was determined in 100 pregnant women and 50 nonpregnant control subjects. Twenty-two of the pregnant women (22%) showed abnormal results when compared to normal nonpregnant women (p less than 0.0005). Increased erythrocyte fragility was observed primarily in the last trimester of pregnancy. Twenty-one of 65 women in the last trimester (32.3%) had abnormal incubated glycerol lysis time values, but only one of 34 (2.9%) showed increased fragility during early pregnancy. Physiologic shifts in erythrocyte osmotic fragility may create a problem in the diagnosis of hereditary spherocytosis during the last trimester of pregnancy.

Adult↗
PubMed1980

Initial experience with a "code-no code" resuscitation system in cancer patients.

A "code-no code" resuscitation classification was recently instituted at Memorial Sloan Kettering Cancer Center. Physician compliance was voluntary. Of 48 subsequent cardiopulmonary arrests, 7 patients (14.6%) were discharged from hospital. They included 4 of 17 patients (23.5%) previously assigned "code" status and 1 of 27 patients (3%) whose resuscitation status had not been designated. Reluctance on the part of the primary physician to withhold resuscitation was clearly evident in this group, of whom more than half had widespread malignancy. Stage of disease did not influence the 50% rate of successful resuscitations but no patient with metastatic or uncontrolled cancer left hospital. The discharge rate among arrest patients with recently diagnosed or localized cancer was 32%. These observations justify continued efforts to restrict cardiopulmonary resuscitation (CPR) to those with a reasonable prognosis for worthwhile palliation or cure.

Adolescent↗
PubMed1971

Effect of acid pH on macromolecular synthesis in L cells.

Eagle's medium adjusted to pH 6 was found to inhibit the rate of RNA and protein syntheses in monolayer cultures of L cells. Incubation of the cells at pH 6 decreased the rate of incorporation of amino acids into nascent peptide chains and caused a disaggregation of polyribosomes. Messenger RNA seemed to persist during the exposure of the cells to medium adjusted to pH 6, since protein synthesis resumed when the cells were transferred to recovery medium containing actinomycin D. The inhibitory effects of pH 6 on macromolecular synthesis were reversible and the viability of the cells exposed to pH 6 did not decrease. The permeability of the cells was not altered by the exposure to pH 6.

Amino Acids↗