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Biomedical subjects

B Leigh

Publications and source records attributed to B Leigh.

At least 19 recordsLinked to original sources

Squamous cell carcinoma of the anus and HIV infection.

We retrospectively reviewed six patients with squamous cell carcinoma of the anus (SCCA) and human immunodeficiency virus (HIV) infection treated between 1985 and 1988. All six patients were homosexual men. Five patients had AIDS and one was HIV-positive. The most common symptoms and signs were pain (n = 5), mass (n = 5), and bleeding (n = 5). The average tumor size was 3.2 cm with a range of 1-10 cm. Five tumors were located in the anal canal and one at the anodermal junction. One patient was treated with biopsy alone, one with local excision, one with wide local excision and radiation therapy, and two with diverting colostomy. The average follow-up was 8 months. Of the five AIDS patients, two died, one was transferred to a hospice facility, one was lost to follow-up, and one remains alive 1 year following treatment. The HIV-positive patient died secondary to metastatic SCCA. This group of patients raises the question of a possible association between HIV and SCCA.

Acquired Immunodeficiency Syndrome

Kaposi's sarcoma of the rectum in patients with the acquired immunodeficiency syndrome.

We retrospectively reviewed eight patients with biopsy-proven anorectal Kaposi's sarcoma (KS) treated between 1984 and 1989 at San Francisco General Hospital. All patients were homosexual men with the acquired immunodeficiency syndrome (AIDS). The average age was 34 years. Three patients had primary rectal KS without metastases. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients with advanced AIDS received no specific treatment for anorectal KS. Follow-up ranged from 1 month to 5 years. Three of the untreated patients and the three patients treated with chemotherapy or radiotherapy were alive 1 month to 5 years after diagnosis. Aggressive surgical treatment of anorectal KS is not indicated.

Acquired Immunodeficiency Syndrome

Neutron- and X-ray-induced mutations at the yellow, white, forked and vermilion loci of Drosophila melanogaster; a preliminary analysis.

Neutrons and X-rays were used to induce mutations at the yellow, white, vermilion and forked loci of Drosophila melanogaster by irradiation of spermatozoa in males. The mutations were characterized for the presence and location of simultaneously induced rearrangements and recessive lethal mutations. F1 females carrying induced visible mutations were identified, described and tested for fertility. The data are given in this paper. The proportions of mutants at the 4 loci, the ratios of whole-body: mosaic mutations, and the fertility of the mutant-carrying F1 females were similar for both types of radiation. Differences were observed between the frequencies of induced visible mutations and the rates of coincident visible and lethal induction. Although the analysis of the mutant chromosomes has not yet been completed, our data can be interpreted as providing confirmation that there are qualitative differences between the genetic effects of neutrons and X-rays.

Animals

Neutrons and X-rays, comparative studies with Drosophila melanogaster. 1. The viability and fertility of induced autosomal translocations.

Studies on the genetic effects of neutrons and X-rays have produced evidence that may be interpreted as indicating that neutrons induce clusters of closely linked genetic changes. According to this interpretation, it is to be expected that neutron-induced translocations will have a higher rate of associated recessive lethality, compared with translocations induced by low-LET radiation such as X-rays. The experiment reported here was designed to test whether this expectation is fulfilled. The dose--frequency response with neutrons for the induction of autosomal translocation was established by exposing males from the Oregon-K stock and then sampling treated mature sperm. From the data obtained, it was estimated that 10 Gy neutrons should induce about the same frequency of autosomal translocations as 27 Gy X-rays. These 2 doses were used to induce translocations in the spermatozoa of males carrying lethal-free autosomes, derived from the Oregon-K stock. Induced translocations were tested for homozygous viability and fertility. When these criteria were used, no qualitative difference was detected between the translocations induced by neutrons and X-rays.

Animals

Neutrons and X-rays, comparative studies with Drosophila melanogaster. 2. Sex-chromosome loss and partial loss, evidence for the induction of chromatid aberrations in spermatozoa.

Losses and duplications of BSY y+-chromosome markers were induced by irradiation of spermatozoa with either 0.5-MeV neutrons or 100-kV X-rays. These 2 types of radiation are known to induce significantly different ratios of double:single strand breaks in DNA. Exceptional progeny were grouped into 3 categories; no Y marker, one Y marker, and Y marker duplications + mosaics. The last combination consisted of exceptions derived from only chromatid-type rearrangements. All other classes of exceptions may be derived from either chromatid- or chromosome-type rearrangements. Doses of 15 Gy neutrons and 27 Gy X-rays induced identical frequencies of exceptional progeny, giving an RBE of 1.8. The ratios of the 3 classes of exceptions were similar for both types of radiation. This observation can be interpreted as indicating that, under the conditions used here, chromosome and chromatid rearrangements are not derived directly from double and single DNA strand breaks, respectively.

Animals

X-ray induced sex-chromosome loss, when ring-X chromosome males are irradiated and mated to females carrying mei-9, mei-41 or mei-218.

Radiation damage induced in the sperm nucleus is repaired after this nucleus has entered the oocyte. The yield of induced genetic damage is known to be dependent on maternal genotype and can also be modified by treatment of the females with metabolic inhibitors. The experiments reported here were designed to find out whether a more specific analysis of the interaction between male gamete and oocyte cytoplasm can be carried out using mutants that are known to affect repair processes. Males carrying ring-X chromosomes were exposed to X-ray doses up to 1000 R and mated to females homozygous for a repair-deficient mutant. The mutants used were mei-9a, mei-9L1, mei-41A10, and mei-41D5. In addition a yellow (y) X chromosome was used as a control and an attempt was made to obtain data using mei-21815, a mutant at a locus not thought to affect repair. With mei-9 mutants there is an enhancement of the spontaneous and induced rates of paternal sex-chromosome loss. The mei-41 mutants did not affect the rates of paternal sex-chromosome loss. Mei-218 females were difficult to work with because they gave very few progeny. From these data it can be argued that repair-deficient mutants will indeed be useful for an analysis of the fixation of radiation-induced genetic damage.

Animals

Inhibition of [3H]GABA binding to postsynaptic receptors in human cerebellar synaptic membranes by carboxyl and amino derivatives of GABA.

Fifty synthetic analogues of GABA were tested for their ability ot interact with GABA receptors, using [3H]GABA binding to human cerebellar membranes as an in vitro model. The most active compounds were found to be aliphatic and heterocyclic aminosulphonic acids. Compounds with highly substituted nitrogen atoms were only weakly active unless a long alkyl chain, which can interact with the postsynaptic membrane, was present. It was concluded that a pyramidal nitrogen atom is favoured fro binding of GABA analogues to human cerebellar membranes.

Cerebellum

Induced nondisjunction in drosophila oocytes.

Nondisjunction of the sex chromosomes and compound-second chromosomes was induced in Drosophila melanogaster by irradiation of immature oocytes and cold treatment of mature oocytes. These two treatments cause nondisjunction by different mechanisms. This results in a differential for stage sensitivity and the production of relatively different frequencies of the various exceptional progeny classes.

Animals

X-ray induction of autosomal translocations in spermatozoa of Drosophila melanogaster and maternal effects of X.Y-chromosomes.

Wild-type ORK Drosophila melanogaster males were given an exposure of 3000 R X-radiation. Mature sperm were then sampled by mating to X.Y/X.Y, X.Y/X, or X/X females that carried markers on the second and third chromosomes for the detection of induced autosomal translocations. Two pairs of maternal stocks were used and heterozygous X.Y/X females were obtained by making both reciprocal crosses. The highest frequencies of induced translocations were obtained with X/X females. In one series these frequencies are higher than those obtained with either X.Y/X or X.Y/X.Y females. In the other series a uniform frequency of translocations was obtained with all types of female, except for one of the two types of heterozygous female, which gave lower frequencies. The experiments have provided data which show that the addition of Y-chromosomes to the maternal genome does not have a specific effect on the recovery of induced paternal autosomal translocations. Maternal Y-chromosomes increased the proportions of fertile F1 males, this effect being consistent in direction but varying in degree.

Animals

Mechanisms of nondisjunction induction in drosophila oocytes.

Quantitative and qualitative studies on the induction of no-disjunction and related phenomena can be carried out using the germ cells of Drosophila. X-Irradiation breaks chromosomes and cold-shock disrupts spindles, these two treatments producing different spectra of nondisjunction in oocytes.

Animals

The formation and recovery of two-break chromosome rearrangements from irradiated spermatozoa of Drosophila melanogaster.

Chromosomes and chromatid-type rearrangements can be induced by exposure of spermatozoa of Drosophila to ionising radiation. A model, proposed to explain the formation and recovery of compound autosomes, has been extended to account for the induction of centric fragments capped by a duplication of paternal chromosome material. Three basic assumptions have been used; (1) that the sperm nucleus contains a haploid set of unreplicated chromosomes, (2) that the broken chromosome ends can be joined together before or after replication, and (3) that one of the first two cleavage nuclei may be lost and an adult organism derived from the other. The present paper reports a theoretical application of this combination of assumptions to the general case of the formation and recovery of two-break rearrangements. This has led to an elucidation of the relation between repeats, compounds, fragments, and deficiencies on the one hand and inversions and translocations on the other hand. Dicentric chromosomes and segmental aneuploidy can be simply explained. A selective screen is formed by the segregation of chromatid rearrangements and the aneuploidy tolerance levels of the early cleavage nuclei. Thus there is an alternative way of explaining observations which might indicate preferential breakage or joining.

Animals

The timing of the restitution of chromosome breaks induced by X-rays in the mature sperm of Drosophila melanogaster.

Drosophila melanogaster males with marked X and Y chromosomes were irradiated, and mature sperm sampled by mating the males to females carrying attached-X chromosomes. Induced loss and partial loss of the paternal sex chromosomes was studied. F1 females were scored according to their phenotype, and transmitted fragments were analyzed genetically. Half of the exceptional F1 females could be scored as "partial losses". Of the apparent total loss exceptions, which were tested, half were carrying detectable fragments. 21% of the transmissible fragments is an under-estimate because only 6 of the 10 chromosome tips were marked in such a way that duplications could be detected. In addition, the markers used were located near, but not at, the chromosome ends. These data are interpreted as indicating that a high proportion of the chromosome loss and partial loss, induced by irradiation of mature sperm, is a consequence of chromatid rearrangements arising from chromosome breaks which stay open until replication. It is suggested that, during the transition from sperm head to mature pronucleus, repair of breaks and chromosome replication are two processes that occur in overlapping time intervals. It is therefore possible for chromosome breaks induced in mature sperm to give rise to chromosome and chromatid rearrangements.

Animals

Concentration-effect studies with MMS, TEB, 2, 4, 6-TriCl-PDMT, and DEN on the induction of dominant and recessive lethals, chromosome loss and translocations in Drosophila sterm.

Comparative tests were made with four mutagens, treating male germ cells, particularly mature sperm, of Drosophila melanogaster. Dominant lethals, sex-linked recessive lethals, sex-chromosome loss and partial loss, and in one test translocations were used as genetic and points. The four mutagens, methanesulphonate (MMS), 2,3,5,6-tetraethyleneimino-I,4-benzoquinone (TEB), I(2,4,6-trichlorophenyl)-3,3-dimethyltriazene (2,4,6-triC1-PDMT), and diethyl nitrosamine (DEN) are known to differ in their chemical properties and mode of mutagenic action. An apparent relationship between dominant lethal induction and other genetic damage was found only with TEB. All four mutagens are efficient inducers of sex-linked recessive lethals. At low concentrations there was no direct concentration-frequency relationships. The two direct mutagens, MMS and TEB were effective in the chromosome loss tests. DEN does not induce translocations or any of the other types of damage studied which can be attributed to chromosome breakage. It is concluded that the sex-linked recessive lethal test is a simple and efficient way of preliminary screening chemical mutagens with Drosophila melanogaster.

Animals