Kinetics of cell-mediated cytotoxicity: Stochastic and deterministic multistage models

One of the body's major defenses against viral diseases and tumors is the killing of abnormal cells by host defense cells, such as T lymphocytes. The mechanism by which killing is accomplished is unknown. Here we develop both stochastic and deterministic models for the kinetics of killing in aggregates which contain a single lymphocyte and multiple target cells (LT_n conjugates), as might be seen early in an immune response, and in aggregates containing multiple lymphocytes and a single target cell (L_nT conjugates), which is characteristic of the late phase of a successful immune response. Comparing our models with data, we rule out the possibility of certain classes of lytic mechanisms and draw attention to the characteristics of likely mechanisms. Our stochastic model can be viewed as a specialized application of queueing theory to cell biology. For certain choices of arrival-time and service-time distributions, we find an exact correspondence between our stochastic and deterministic models.     

Locus determining the human sperm-specific lactate dehydrogenase,LDHC, is syntenic with LDHC

From the data presented in this report, the human LDHC gene locus is assigned to chromosome 11. Three genes determine lactate dehydrogenase (LDH) in man. LDHA and LDHB are expressed in most somatic tissues, while expression of LDHC is confined to the germinal epithelium of the testes. A human LDHC cDNA clone was used as a probe to analyze genomic DNA from rodent/human somatic cell hybrids. The pattern of bands with LDHC hybridization is easily distinguished from the pattern detected by LDHA hybridization, and the LDHC probe is specific for testis mRNA. The structural gene LDHA has been previously assigned to human chromosome 11, while LDHB maps to chromosome 12. Studies of pigeon LDH have shown tight linkage between LDHB and LDHC leading to the expectation that these genes would be syntenic in man. However, the data presented in this paper show conclusively that LDHC is syntenic with LDHA on human chromosome 11. The terminology for LDH genes LDHA, LDHB, and LDHC is equivalent to Ldhl, Ldh2, and Ldh3, respectively.     

Mobilization of cloned luciferase genes into Vibrio harveyi luminescence mutants

A recombinant plasmid which carried a 5 kb fragment of Vibrio harveyi DNA containing the luxA and luxB genes was mobilized from Escherichia coli into luminescence-deficient mutants of V. harveyi. The cloned genes complemented a temperature sensitive luciferase mutation, but failed to complement lesions in two different aldehyde deficient mutants. Expression of the cloned genes was not subject to autoinduction in either E. coli or in V. harveyi.     

Community patterns of nectivorous adult parasitoids (Diptera,Bombyliidae) on their resources

Summary Highly diverse assemblages of nectivorous bee flies (Diptera: bombyliidae) occur at desert sites in California presenting an opportunity to investigate the ecology of this little-known group. This study compared communities of adult bee flies visiting flowers at two sites, one in the Mojave Desert (Darwin Plateau) and one in the Great Basin (Mono Basin), during periods of higher and lower resource abundance. The range of resources used by single species varied inversely with the number of species present, with the greatest number of species and smallest niche breadths occurring at the Darwin Plateau. Adult bee flies did not visit flower resources at random. Rather the two major divisions of the family exhibited contrasting patterns of specialization on plant species. Results of this study support the hypothesis that resources were limiting for adult bee flies in the period of lower food abundance at the Darwin Plateau and not limiting at the Mono Basin during this study. Bee flies at the Mono Basin exhibited lower densities per flower (despite higher densities per unit area), lower frequency of feeding, a lower degree of specialization, and less pronounced phenological changes than bee flies at the Darwin Plateau. The data suggest that episodes of population regulation in the non-parasitic (i.e. adult) stage, due to short supply of the adults' food, contribute to determining the structure of parasitoid communities.     

Relationship of the replication and incompatibility genes of an IncFVI haemolysin plasmid with other F-like haemolysin plasmids

The replication and incompatibility region of the IncFVI plasmid pSU502 has been isolated by in vitro DNA manipulation as part of a 12.6 kb plasmid, denominated pSU503. Plasmid pSU503 was strongly incompatible with its parental plasmid, pSU1, but was fully compatible with the haemolytic plasmids pSU316 (IncFIII/IV), pHly152 (IncI2) and pSU233 (Inc-pSU233). Furthermore, the 6.9 kb EcoRI fragment of pSU503 which carries the replication and incompatibility determinants of pSU1 did not show any detectable homology (less than 70%) with any of the haemolysin-determining plasmids with which it is compatible. Thus, homologous haemolysin determinants have become linked to apparently unrelated replicons.     

Sexual differentiation of rat liver carbonic anhydrase III

Using radioimmunoassay, the concentration of carbonic anhydrase III in the livers of adult male rats was found to be approx. 30-times greater than that observed in mature females. Castration of male rats led to a marked reduction in liver carbonic anhydrase III concentrations which could be partially restored to control levels by testosterone replacement. Administration of testosterone to ovariectomised female rats induced about a 5-fold increase in liver carbonic anhydrase III concentration. Immunoprecipitation analysis of the products of liver mRNA translation in vitro with antiserum specific for carbonic anhydrase III showed that hormonal control of the levels of carbonic anhydrase III in liver is mediated by changes in the amount of translatable carbonic anhydrase III mRNA. Marked changes in liver carbonic anhydrase III concentrations were also observed in developing and ageing male rats.     

Postoperative Depression of Tumour-directed Cell-mediated Immunity in Patients with Malignant Disease

Leucocytes from 46 melanoma patients, 45 breast carcinoma patients, and 95 control donors were tested by the leucocyte migration test against the supernatants of homogenates of malignant melanomas, breast carcinomas, simple breast tumours, and breasts showing simple cystic disease. By comparison with controls inhibition of migration occurred significantly more frequently when tumour patients'' leucocytes were exposed to extracts of histogenetically similar tumours.Cell-mediated immunity to tumour-associated antigens was measured in 12 patients with breast carcinoma and 12 with malignant melanoma immediately before surgical operation and in the postoperative period. All patients tested before operation showed significant inhibition of migration on contact with extracts of histogenetically similar tumours. Postoperatively the degree of leucocyte migration inhibition was reduced in all patients with melanoma and breast carcinoma. Significant inhibition of leucocyte migration returned in most patients 6-22 days after operation.     

The behaviour of 14C profiles in Helianthus seedlings

Summary The log. ¹⁴C activity/distance profile in the stems of Helianthus seedlings consists of two main parts: region 1, the linear advancing front and region 2, which is also linear but with a less steep slope. As the front passes down the stem, the slope of region 1 remains constant but the amplitude of the front becomes attenuated. The attenuation increases with temperature. The apparent velocity of the profile, which can be derived from the position of the front, is also temperature dependent. Small amounts of ¹⁴C occur in the stem ahead of the profile; these amounts increase with a rise of temperature. Region 2 behaves differently: its slope decreases steadily with time but it is insensitive to temperature. The behaviour of this region is dependent on the movement of tracer into an immobile fraction as well as on the longitudinal movement of tracer in the translocation stream.     

SYNTHESIS OF RNA IN NEURONS OF THE HYPOGLOSSAL NERVE NUCLEUS, AFTER SECTION OF THE AXON, IN MICE

Synthesis of RNA in neurons of the hypoglossal nerve nucleus after axonal section was studied by means of [5-³H]uridine administration and radioautographic counting techniques in mice. The results of the experiments were evaluated by counts of silver grains over the nucleoplasm and cytoplasm of the neurons. RNA synthesis was greater in neurons after axonal section, and this increase was evident from 12 hr after the operation. The greatest increases in the operated side were observed in the 1st, 2nd and 3rd days after operation. In the 7th and 14th days RNA synthesis was still greater in the hypoglossal nucleus of the sectioned nerve but the difference in the control nucleus was not so striking. In the 30th day synthesis of RNA in left and right hypoglossal nuclei was comparable.