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Biomedical subjects

J Lynch

Publications and source records attributed to J Lynch.

At least 235 records · Page 13Linked to original sources

Familial colon cancer in the Tel-Aviv area and the influence of ethnic origin.

The family history of colon cancer was investigated in 38,823 individuals (2,129 families) who comprised a control and an oncology patient series from Tel-Aviv and nearby areas. A significant increased risk for colon cancer was observed among first-degree relatives of colon cancer patients when compared to controls. When the patient sample was divided into two groups based on country and continent of birth--European (Ashkenazim) and other (nonAshkenazim)--the relatives of the nonAshkenazi subjects showed a greater relative risk for colon cancer (P less than 0.05). Colon cancer was found to be less frequent in nonAshkenazim than in Ashkenazim controls. These findings suggest that although the colon cancer frequency in the nonAshkenazi group is lower, the genetic component may be more important than for the Ashkenazi sample. The nonAshkenazi Jews may represent distinct subgroups that differ with respect to either primary genetic susceptibility to colorectal cancer and/or they may have been subjected to peculiar, environmental carcinogenic exposures when compared to their Ashkenazim brethren.

Adult↗

Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor.

Epidermal regeneration following middermal injuries to skin requires both proliferation and migration of keratinocytes. Epidermal growth factor (EGF) stimulates the proliferation of keratinocytes in culture, and topical administration of EGF accelerates epidermal regeneration of partial thickness burns or split-thickness incisions in vivo. Transforming growth factor-alpha (TGF-alpha) and vaccinia growth factor (VGF) have substantial sequence homology with EGF, and all appear to bind to the same receptor protein. Whether TGF-alpha or VGF can affect epidermal wound healing in vivo is not known. The present studies show that topical administration of TGF-alpha or VGF in antibiotic cream to partial thickness burns (second degree) accelerated epidermal regeneration in comparison with untreated or vehicle-treated burns. Low levels of both TGF-alpha and VGF (0.1 microgram per milliliter) appeared to be more effective than EGF in stimulating epidermal regeneration. Regenerated epithelium from burns treated with TGF-alpha or VGF appeared normal histologically. This finding suggests that topical application of selected growth factors may be useful in accelerating healing of partial thickness injuries.

Animals↗

Genetic predictability and minimal cancer clues in Lynch syndrome II.

Increasing attention has been given to hereditary nonpolyposis colorectal cancer (HNPCC), a disorder which occurs four or five times more frequently than its hereditary counterpart, familial multiple adenomatous polyposis coli (FPC). Because of the lack of premonitory physical signs in HNPCC, its diagnosis must encompass pertinent family cancer history. This report describes a kindred with a subtype of HNPCC, the cancer family syndrome also referred to as Lynch syndrome II. Emphasis has been given to the temporal evolution of this disorder and the manner in which minimal clinical-genetic clues might best be employed for its diagnosis.

Colonic Polyps↗

Cloning and characterization of an abundant Plasmodium knowlesi antigen which cross reacts with Gambian sera.

A 110 kDa Plasmodium knowlesi antigen, termed PK110, has been identified on the basis of messenger RNA abundance in late schizonts. Most Plasmodium genes previously cloned have been identified by immune sera, which have selected immunodominant antigens composed of repeating epitopes. Although PK110 was not selected by immune sera, it also contains amino acid repeats, indicating that this structure may be a common feature of malarial proteins. Determination of 296 codons in the PK110 gene revealed the presence of thirteen tandem repeats of twelve amino acids whose consensus sequence is E E T Q K T V E P E Q T. A termination codon interrupts the fourteenth repeat, indicating that these repeats are at the C-terminus of the protein. Indirect immunofluorescence experiments with sera raised against the lambda gt11 fusion protein indicate that PK110 is present in intra-erythrocytic late schizonts. Cloned PK110 is recognized by Gambian sera, and shares epitopes with Plasmodium ovale. PK110 does not cross react immunologically or by DNA hybridization with Plasmodium falciparum.

Amino Acid Sequence↗

Salinity reduces membrane-associated calcium in corn root protoplasts.

Calcium is an important factor in the ability of plants to resist salt stress, possibly because of its role in maintaining membrane integrity. We studied the effects of NaCl stress on membrane-associated Ca in corn root protoplasts (Zea mays L. cv Pioneer 3377) using the fluorescent Ca probe chlorotetracycline (CTC). Protoplasts were isolated from the cortex of primary roots of corn seedlings (Gronwald and Leonard, Plant Physiol 1982 70: 1391-1395). After a 30 minute incubation in 50 micromolar CTC, the protoplasts were exposed to isosmotic treatment solutions containing various concentrations of NaCl just before fluorimetric analysis. Increasing NaCl concentrations caused a progressive reduction in net CTC fluorescence, to 50% of control values at 150 mm NaCl. NaCl did not displace CTC from the cells, nor did it directly interfere with Ca-CTC binding. Tests with CsCl, RbCl, KCl, LiCl, Na(2)SO(4), NaNO(3), and NaBr indicated that the reduction in CTC fluorescence was not specific to either Na or Cl, but may have been due to increased ionic strength of the treatment solutions. Like CTC fluorescence, root growth of intact corn seedlings was not specifically sensitive to Na, but was inhibited by several monovalent cations in the order Li > Cs >> Rb > Na > K. CTC fluorescence at 100 mm NaCl was restored to unstressed levels by increasing Ca concentrations. Since our salt treatments were isosmotic, we conclude that the ionic component of salt stress displaces Ca from membranes of corn root cells.

Journal Article↗

Influx of na, k, and ca into roots of salt-stressed cotton seedlings : effects of supplemental ca.

High Na(+) concentrations may disrupt K(+) and Ca(2+) transport and interfere with growth of many plant species, cotton (Gossypium hirsutum L.) included. Elevated Ca(2+) levels often counteract these consequences of salinity. The effect of supplemental Ca(2+) on influx of Ca(2+), K(+), and Na(+) in roots of intact, salt-stressed cotton seedlings was therefore investigated. Eight-day-old seedlings were exposed to treatments ranging from 0 to 250 millimolar NaCl in the presence of nutrient solutions containing 0.4 or 10 millimolar Ca(2+). Sodium influx increased proportionally to increasing salinity. At high external Ca(2+), Na(+) influx was less than at low Ca(2+). Calcium influx was complex and exhibited two different responses to salinity. At low salt concentrations, influx decreased curvilinearly with increasing salt concentration. At 150 to 250 millimolar NaCl, (45)Ca(2+) influx increased in proportion to salt concentrations, especially with high Ca(2+). Potassium influx declined significantly with increasing salinity, but was unaffected by external Ca(2+). The rate of K(+) uptake was dependent upon root weight, although influx was normalized for root weight. We conclude that the protection of root growth from salt stress by supplemental Ca(2+) is related to improved Ca-status and maintenance of K(+)/Na(+) selectivity.

Journal Article↗

Laboratory and clinical evaluation of isolation media for Campylobacter jejuni.

Six selective isolation media were evaluated for their ability to support the growth of Campylobacter jejuni. Colony counts of 70 isolated strains of C. jejuni and recovery studies on these strains in simulated positive feces samples demonstrated that Bolton and Hutchinson' charcoal, cefoperazone, deoxycholate agar and Karmali's charcoal-based selective medium produced the highest recovery rates with the greatest suppression of other fecal flora. C. jejuni colonies were more easily recognized on charcoal-based selective medium. A clinical evaluation performed on 2,780 human, animal, and avian feces specimens confirmed the results of the laboratory investigation. From human samples, 4 more strains of C. jejuni were isolated on charcoal-based selective medium than were isolated on Skirrow medium, and 19 more strains of C. jejuni or C. coli were isolated on charcoal-based selective medium from animal specimens. Suppression of normal fecal flora was also greater on charcoal-based selective medium.

Animals↗

Antiarrhythmic vs. antifibrillatory activity of the basic diphenylhydantoin derivative 3-[3-(4-phenyl-1-piperidyl)propyl]-5-(4-methoxyphenyl)-5-phenylhydantoin hydrochloride.

The effects of 3-[3-(4-phenyl-1-piperidyl)propyl]-5-(4-methoxyphenyl)-5-phenylhydantoin hydrochloride (TR 2985), a basic diphenylhydantoin derivative, were studied in four canine models of experimental cardiac dysrhythmias. In conscious dogs, 48 h after myocardial infarction, TR 2985 significantly reduced the frequency of spontaneous ventricular arrhythmias. However, in anesthetized dogs, TR 2985 produced only a slight and insignificant increase in the ventricular fibrillation threshold. In conscious dogs, 4 to 7 days after myocardial infarction, TR 2985 failed to prevent the electrical induction of reentrant ventricular tachycardia, and failed to protect against the development of ventricular fibrillation in response to ischemia at a site distant from the previous infarction. These results indicate that TR 2985 may be effective in preventing arrhythmias of a non-reentrant nature, but may be relatively ineffective in preventing reentrant ventricular tachycardia or ventricular fibrillation.

Anesthesia, General↗

Familial embryonal carcinoma in a cancer-prone kindred.

Familial testicular cancer is rare. This report describes a family with an unusual cancer spectrum that included the infantile form of embryonal carcinoma of the testis in the son of a cancer-free but putative obligate gene carrier mother, and the adult form of embryonal carcinoma in this women's maternal half-brother (their mutual mother had malignant melanoma and urinary bladder carcinoma). Hereditary syndrome designation remains elusive. Priority attention to biomarker research in families of this type for elucidation of cause and control is discussed.

Adult↗

Effect of thymosin alpha one on specific antibody response and susceptibility to infection in young and aged mice.

The antibody response to a variety of antigens has been shown to diminish with age. We investigated the capacity for Thymosin Alpha One (T alpha 1) treatment to augment antibody production in tetanus toxoid (TT) and pneumococcal capsular polysaccharide (PN) inoculated young and old mice. We also measured survival of these immunized mice after aerosol exposure to Streptococcus pneumoniae. As predicted antibody response to TT, but not PN, was significantly reduced in the old animals and T alpha 1 augmented antitetanus antibody in both young and old mice. T alpha 1 did not have an effect on anti pneumococcal antibody production. All mice that had received PN did have an antibody response, yet survival after exposure to the organism was strikingly less in the old animals. Our data support the contention that antibody response to T-dependent antigens (such as tetanus toxoid) falls with aging but can be reconstituted somewhat by thymic factors. Furthermore, for T-independent antigen (such as pneumococcal capsular antigens) the age-related changes are less evident. In the latter situation, the presence of a brisk antibody response after vaccination was not sufficient to prevent pneumonia and death in old animals.

Aerosols↗

Structure elucidation of platelet activating factor derived from human neutrophils.

Platelet activating factor (PAF) synthesized by human neutrophils challenged by opsonized zymosan or calcium ionophore was isolated from cells and buffer using Bligh and Dyer extraction following the addition of tracer amounts of tritiated-PAF. The extract was subjected to TLC separation of phospholipid classes, followed by reverse phase HPLC for molecular species separation. All fractions were measured for radioactivity, biological activity and fast atom bombardment mass spectrometry. While the radioactive tracer PAF could be separated into three molecular species, PAF biological activity eluted as a single component which was characterized as 1-O-hexadecyl-2-acetyl-glycero-3-phosphocholine. The lack of molecular species heterogeneity of PAF produced in response to stimuli implies a higher degree of control of biosynthesis than previously suspected.

Adult↗

Influx and efflux of p in roots of intact maize plants : double-labeling with p and p.

Rates of P influx and efflux were determined in whole plants at ambient P concentrations comparable to those found in soil solutions. Maize (Zea mays L. var NC+59) seedlings were trimmed (endosperm and adventitious roots removed) and grown in a greenhouse in solution cultures at P concentrations of approximately 0.4 and 1.8 micromolar. Roots of intact plants previously exposed to (32)P-labeled solutions at 0.2 and 2.0 micromolar P for 48 hours were rinsed 10 minutes in P-free solution and exposed to (33)P solutions at 0.2 and 2.0 micromolar for 10 minutes. Net depletion of (33)P from and appearance of (32)P in the ambient solution were used to measure influx and efflux. The ration of (32)P efflux to (33)P influx was about 0.68 at 0.2 micromolar and 0.08 at 2.0 micromolar. When plants were allowed to deplete P from solutions, the P concentration in the medium dropped to about 0.15 micromolar within 24 hours and 0.05 micromolar within 60 hours. Results indicate that P efflux is a substantial component of net P accumulation at P concentrations normally found in soil solutions.

Journal Article↗

Paravertebral malignant rhabdoid tumor in infancy. In vitro studies of a familial tumor.

Two female siblings died within three months after presenting with paravertebral tumors in the first year of life. The pathology of the two tumors was identical and characteristic of a malignant rhabdoid tumor. There were no identifiable tumor patterns within the kindred which have been associated with any hereditary cancer or precancer syndromes. Fibroblasts were cultured from skin biopsies obtained from the second patient and both parents. Assays of growth kinetics associated with cellular transformation revealed that fibroblasts from the affected sibling can be distinguished from those of the parents and age-matched controls by increased in vitro occurrence of tetraploidy. Such evidence suggests that increased in vitro tetraploidy occurring spontaneously in cultured fibroblasts is an expression of a cancer-prone gene. Increased in vitro tetraploidy has previously been demonstrated in some kindreds with heritable colon cancer syndromes, and may extend our understanding of the genetic etiology of some childhood cancers.

Biopsy↗