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Biomedical subjects

R B Cumming

Publications and source records attributed to R B Cumming.

At least 37 records · Page 2Linked to original sources

Genetics of formamidase-5 (brain formamidase) in the mouse: localization of the structural gene on chromosome 14.

A single formamidase, which is different from the formamidases found in other tissues occurs in the brains of mice. This enzyme is here called formamidase-5 and the gene symbol is designated For-5. Two alleles are recognized on the basis of their differential heat sensitivity:For-5b is relatively heat stable and is present in strain C57BL/6J, while For-5d is relatively heat sensitive and is present in strain DBA/2J. The heat sensitivity of formamidase-5 in 44 other inbred strains and substrains was tested and found to resemble that of C57BL/6J or DBA/2J. Thirty-six recombinant inbred strains derived from progenitors that differed at For-5 were studies to test for single-gene inheritance and linkage with other loci. Complete concordance was found with the esterase-10 locus (Es-10), indicating close linkage. The 99% upper confidence limit of the distance between For-5 and Es-10 is 3.7 centimorgans (cM). Es-10 is located on chromosome 14 about 19 cM from the centromere. An independent demonstration of linkage of For-5 with Es-10 and another chromosome 14 marker, hairless (hr), is provided by the finding that the HRS/J strain, which has been sibmated for 60 generations with forced heterozygosity at the hr locus, is cosegregating at For-5 and Es-10. A survey of 32 inbred strains and substrains revealed that the For-5d allele is associated with the Es-10b allele, and that the For-5b allele is associated with Es-10a and Es-10c. Formamidase-5 segregates as expected in the F2 generation of crosses between strains bearing For-5b and For-5d alleles. It is possible that this unique formamidase of the brain is involved in the metabolism of a neurotransmitter substance.

Alleles↗

An autoradiographic study of unscheduled DNA synthesis in the germ cells of male mice treated with X-rays and methyl methanesulfonate.

Unscheduled DNA synthesis (UDS) in the germ cells of male mice after in vivo treatment with X-rays or methyl methanesulfonate (MMS) was assayed by use of a quantitative autoradiographic procedure. MMS induced UDS in meiotic through type III elongating spermatid stages, whereas X-rays induced UDS in meiotic through round spermatid stages. No UDS was detected in the most mature spermatid stages present in the testis with either MMS or X-rays. Taking into account differences in DNA content of the various germ-cell stages studied, we concluded that X-rays induced a maximum UDS response in spermatocytes at diakinesis--metaphase I. The level of UDS induced by MMS was about the same in all the stages capable of repair. Chromosome damage and UDS were measured simultaneously in the same spermatocytes at diakinesis 90 min after X-irradiation or MMS treatment. The level of UDS in most of the X-irradiated cells paralleled the extent of chromosome damage induced. A statistical analysis of these results revealed a positive correlation. As expected, MMS induced no chromosome aberrations above control levels. Therefore no correlation was determined between UDS and chromosome damage in this case. The distribution of UDS over the chromosomes treated at diakinesis with MMS or X-rays was studied. It was found that UDS occurred in clusters in the irradiated cells, whereas it was uniformly distributed in the MMS-treated cells.

Animals↗

The influence of vitamin A status on the response of chickens to aflatoxin B1 and changes in liver lipid metabolism associated with aflatoxicosis.

1 A series of experiments were conducted to investigate the effects of dietary retinol status on chickens ingesting aflatoxin B1. The effects of dietary supplementation with biotin and alpha-tocopherol were also examined. 2. Aflatoxin B1 levels greater than 1 mg/kg diet had a detrimental effect on 'liveability', body-weight gain, food intake and food conversion efficiency. When fed for more than 2 weeks aflatoxin increased relative liver weight and liver lipid concentration. These effects were less pronounced with avitaminotic A chickens. 3. A synergistic effect on hydropericardium development was observed between aflatoxin B1 and retinol. This effect was not observed when the dietary level of alpha-tocopherol was increased tenfold. 4. The specific activities of certain hepatic lipogenic and amino acid-metabolizing enzymes were influenced by aflatoxin ingestion. A reduction in lipogenic enzyme activity was observed before a reduction in the activities of amino acid-metabolizing enzymes. 5. Liver fatty acid composition was significantly influenced by aflatoxin B1. The extent of these changes was reduced by the inclusion of additional dietary biotin.

Aflatoxins↗

Effect of environmental temperature on susceptibility of young chickens to Salmonella typhimurium.

Day-old chickens kept in a cold environment (18 degrees to 22 degrees C) were more susceptible to a low and moderate challenge of Salmonella typhimurium than chickens similarly challenged and kept in a warm environment (32 degrees to 36 degrees C). Cold stress at 10 degrees C for 24 h when applied to 12-day-old chickens effectively increased the number of birds shedding organisms. However a similar cold stress on 20-day-old chickens resulted in a less dramatic increase in the number of birds shedding organisms. Of the 60 birds previously challenged with S. typhimurium and then subjected to cold stress, 16 birds recommenced shedding and 7 birds with no previous history of shedding began to shed organisms.

Animals↗

The effect of ovariectomy on liver metabolism and maintenance energy requirement of hens.

Six pullets from each of an egg-producing and meat-producing strain were ovariectomised at 12 weeks of age. Ovarian regrowth occurred in two of the egg-producing and four of the meat-producing strain. 2. Measurements of heat production and energy balance were made after peak lay with ovariectomised and sham-operated laying pullets of both strains. Measurements on the ovariectomised pullets were made before and after implantation with oestrogen pellets. 3. Within each strain the ME requirements for maintenance (per kg W0.75), determined by linear regression analysis, were similar whether or not the starvation heat production data were included. 4. The ME requirements for maintenance decreased substantially after ovariectomy but subsequent implantation with oestrogen pellets did not increase these requirements. 5. Studies of hepatic enzyme activities indicated that the major influence of the mature ovary was on hepatic lipid metabolism. This was exerted through a specific stimulation of lipogenesis rather than a general increase in metabolism.

Animals↗

A biochemical explanation for the fatty liver and kidney syndrome of broilers: its alleviation by the short-term use of dietary fat.

1. Fatty livers and kidney syndrome (FLKS) was induced in young broiler chickens by giving them a diet composed principally of wheat and meat meal. 2. FLKS resulted in reduced growth and increased liver weight; fasting for 18 h increased mortality, liver lipid and the specific activity of hepatic ATP-citrate lyase compared with birds fed on a commercial diet. The specific activities of hepatic fructose-1,6-diphosphate-1-phosphohydrolase and pyruvate carboxylase were reduced in birds suffering from FLKS and fasted for 18 h. 3. Feeding of the FLKS-inducing diet supplemented with 150 g animal tallow/kg for 54 h considerably reduced mortality while restoring liver composition and enzyme activities towards those observed in birds fed a commercial diet. Investigations indicated that the glycerol component of the fat was not responsible for the observed responses. 4. The present results suggest that in FLKS insufficiencies of biotin are induced in specific enzyme systems, but the syndrome may be alleviated without the use of supplementary biotin. 5. The evidence indicates that, when stressed, birds affected by FLKS diet from the hypoglycaemia occurring as a result of a reduced capacity for gluconeogenesis.

ATP Citrate (pro-S)-Lyase↗

Studies of fatty liver and kidney syndrome in chickens: dynamics of glucose metabolism.

1. Fatty liver and kidney syndrome (FLKS) was induced in a proportion of a group of 4-week-old chickens by giving a diet of meat meal and wheat; inclusion in the diet of animal tallow for 54 h substantially reduced the occurrence of FLKS. 2. Measurements of dynamic aspects of glucose metabolism were made with single injections of [2-3H]glucose which indicated that birds given the 'FLKS-inducing' diet and showing physical symptoms of FLKS had significantly lower rates of synthesis of glucose than birds given either the same diet supplemented with tallow or a commercial diet. 3. In a second series of experiments glucose metabolism was studied in birds (1) with or without physical symptoms that were given the 'FLKS-inducing' diet and (2) birds given the same diet supplemented with tallow or biotin. Affected birds fed the 'FLKS-inducing' diet had significantly lower plasma glucose concentrations, pool sizes and synthesis rates than birds fed the same diet and not showing symptoms, or birds fed the supplemented diets. 4. It is suggested that the cause of death in birds with FLKS is a low rate of gluconeogenesis during periods without feed which results in a lack of glucose to meet essential functions.

Animals↗

Prevention of Salmonella typhimurium infection inpoultry by pretreatment of chickens and poults with intestinal extracts.

Day-old chickens or turkey poults when pretreated with an oral dose of intestinal fluid froma healthy adult bird, were considerably more resistant to the subsequent establishment of Salmonella typhimurium in their intestinal tract than were non-treated chickens or turkey poults. Caecal fluid was more effective as a pretreatment than were washings taken from other parts of the gastro-intestinal tract of a healthy adult bird. This increased resistance of pretreated chickens or poults is thought to result from the rapid establishment of a conventional indigenous microflora which inhabits establishment and growth by the invading enteric pathogen.

Animals↗

Studies on DNA repair in early spermatid stages of male mice after in vivo treatment with methyl-, ethyl-, propyl-, and isopropyl methanesulfonate.

In vivo DNA repair occurring in early spermatid stages of the mouse has been studied with four mutagens that are chemical homologs: MMS, EMS, PMS and IMS. Using the well-studied sequence of events that occurs during spermatogenesis and spermiogenesis in the mouse, aatids was measured by the unscheduled incorporation of [3H]dT into these germ cells which were recovered from the caudal epididymides 16 days after chemical treatment. Purification of the caudal sperm DNA at this time verified that the [3H]dT was incorporated into the DNA. For each chemical mutagen a study was made on the level of DNA repair occurring in early spermatids as a function of the administered, in vivo dose. Within experimental errors, all four chemicals produced a linear increase in DNA repair in early spermatids with increasing dose. Only the highest dose of MMS (100 mg/kg) produced a greater repair response than expected for a linear curve. At equimolar doses the most effective chemical in inducing DNA repair was MMS, followed by EMS, IMS and PMS. When testicular injections of [3H]dT were given at the same time as the intraperitoneal injections of the mutagens, the amount of unscheduled incorporation of [3H]dT into the DNA of early spermatids was maximized. Since [3H]dT has been shown to be available for incorporation into germ-cell DNA for only approximately 1 h after injection, all four mutagens must reach the DNA of early spermatids and begin producing "repairable" lesions within 1 h after treatment. The amount of DNA repair occurring at later times after chemical treatment of early spermatids was studied by testicular injections of [3H]dT 1/2, 1, 2 and 3 days after chemical treatment. Repair was still occurring in the early spermatids at 3 days post-treatment; this repair is most likely a manifestation of the finite rate of the repair process rather than resulting from newly alkylated DNA. For MMS and EMS there was a rapid decrease in the level of DNA repair in the first 1/2 day following treatment. This was followed by a much slower, exponential decrease in the level of repair out to 3 days post-treatment. The curves suggest that the amount of repair is proportional to the number of repairable lesions still present in the DNA. For PMS and IMS the level of repair decreases rapidly in the first 1/2 day after treatment and thereafter remains relatively constant through 3 days post-treatment. With all four mutagens, DNA repair in early spermatids was detectable at doses 5 to 10 times lower than those required to observe other genetic end points such as dominant lethals, translocations and specific-locus mutations in any germ-cell stage. The sensitivity of detection of in vivo DNA repair in the germ cells of male mice makes such a system a useful adjunct to other genetic tests for studying chemical mutagenesis in mammals.

1-Propanol↗

Some immunological aspects of a recent Australian isolate of infectious bronchitis virus.

An infectious bronchitis virus, designated G48, isolated from birds during an outbreak of nephritis in a previously vaccinated broiler flock, overcame the resistance induced in birds vaccinated with 2 commercially available vaccines. Birds vaccinated with the A isolate of infectious bronchitis resisted challenge with this new virus. Cross neutralisation studies revealed that the new virus was serologically distinct from the 4 viruses tested. Homologous antiserum to G48 did not neutralise the other viruses and only antiserum to the A virus completely neutralised the new virus.

Animals↗

Induction of translocations by cyclophosphamide in different germ cell stages of male mice: cytological characterization and transmission.

Cytological and fertility tests were performed in F1 male mice derived from different germ-cell stages of male parents treated with cyclophosphamide (350 mg/kg body weight). The objectives of the present experiment were: (I) to determine the sensitivity of the male germ-cell stages to the induction of translocations by the compound, and (2) to characterize translocation configurations in F1 and F2 males, in order to obtain information about the pattern of chromosome breakage induced and its transmission to subsequent generations. Of 508 F1 males studied, 39 were partially sterile. The group of males conceived 8-21 days after treatment contained by far the highest proportion of partially sterile animals (30%). It was also the only group in which totally sterile animals (11%) were found. Of 25 semisterile males from this group, 24 gave evidence of translocations when spermatocytes were scored at diakinesis. The translocation frequencies in F1 derived from treated spermatozoa and spermatocytes were 14 and 1%, respectively. No translocations were detected cytologically in 6 semisterile males derived from treated spermatogonial stages. These results indicate that spermatid stages are especially sensitive to the mutagenic action of cyclophosphamide. In 21 of the 31 semisterile translocation males (68%), the majority of the spermatocytes contained 18 bivalents plus a ring-of-four configuration, indicating that both breakpoints were relatively centrally located; and in several of these males, the frequency of cells with rings was close to 100%. In another 9 F1 males (29%) the predominant multivalent configuration was a chain-of-four, indicating one of the breakpoints to be relatively more terminally located; and in one male (3%), the majority of cells had two unequal bivalents, indicating both breakpoints to be fairly close to the ends of the chromosomes involved. Determination of centromere positions by the use of C-banding showed that chain-of-four configurations in any one male were predominantly of a given type..

Animals↗

Surveys of Australian feedstuffs for toxigenic strains of Aspergillus flavus and for aflaxtoxin.

Because of the high prevalence of toxigenic A. flavus in commercial feed sources it is suggested that there is a danger of aflatoxin contamination if conditions are conducive to fungal growth. Under climatic conditions such as those experienced in the unusually wet summer of 1973-74 in many parts of Australia or where storage conditions are unsuitable, growth of A. flavus and elaboration of aflatoxin can be expected on a range of feed commodities from a wide geographical distribution. The results demonstrate the actual and potential danger of aflatoxin contamination in Australia feedstuffs. From these feed samples fungal species predominantly from the genera Aspergillus and Penicillium were also isolated, some of which are known to produce mycotoxins other than aflatoxin. The possibility of contamination of feeds by other mycotoxins cannot therefore be excluded.

Aflatoxins↗

Deamination of amino acids in the small intestine of chickens fed meat meal.

The loss of amino acids by bacterial deamination in the small intestine of chicks fed heated and unheated meat meal was studied by incubating the intestinal contents in vitro. The loss of amino acids by bacterial deamination was found to take place mainly in the lower small intestine. Deamination of amino acids was significantly higher in the contents of the small intestine of chicks fed a meat meal compared to the freeze-dried raw materials, and this deamination was reduced by the addition of 50 p.p.m. penicillin to the meat meal.

Amino Acids↗