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A regulatory role is proposed for the antigen-responsive B cell, as suppressor-inducer of feedback control during the secondary response in vivo. In a double adoptive transfer of memory cells primed to a thymus-dependent antigen from one irradiated host to another, antigen-specific suppressors are generated after a critical time in the primary recipient, able to entirely ablate a secondary anti-hapten response. Positive cell selection in the fluorescence-activated cell sorter confirmed that suppression was mediated by an Lyt-2+ T cell; however, positively selected B cells were also inhibitory and able to induce suppressors in a carrier-specific manner: Bhapten induced suppressors in a carrier-primed population, and Bcarrier induced suppressors in a hapten-carrier population. At the peak of the antibody response in the primary host, memory B cells and their progeny were unable to differentiate further to plasma cells due to their intrinsic suppressor-inducer activity, but this autoregulatory circuit could be severed by adoptive transfer to carrier-primed, X-irradiated recipients.

H-2k-restricted T cell clones derived from CBA mice infected with X31 (H3N2) influenza virus, were shown to recognize distinct, nonoverlapping sequences within the HA1 subunit of the viral hemagglutinin (HA) using synthetic peptides. Three I-Ak-restricted T cell sequences were identified within HA1 68-83, 120-139, and 269-288, and two recognition sites presented in the context of the I-Ek molecule were mapped to HA1 sequences 226-245 and 246-265. T cell clones specific for these regions of HA1 demonstrated varying abilities to differentiate between natural variant viruses that had accumulated substitutions within their HA molecules as a result of antigenic drift. Clones that recognized sequences HA1 226-245 and HA1 246-265 failed to discriminate between natural variants and focused on conserved sequences within these epitopes. A majority of T cell clones were sensitive to amino acid substitutions that have featured in antigenic drift occurring within three major antigenic sites of the HA1 subunit; substitutions at HA1 residues 78 (V)/83(K) and 275(D)/278(I) within the HA1 subunit of mutant viruses correlated with a 75% reduction in the proliferative response for T cell clones specific for sequences HA1 68-83 and HA1 269-288, respectively. Furthermore, a clone that recognized HA1 120-139 was nonresponsive to a mutant virus HK/71, implicating amino acids at HA1 position 129(G) and/or 132(Q) within this sequence as crucial for recognition. Our data, together with the previous finding that sequence HA1 53-63 is also a major I-Ak-restricted T cell recognition site, demonstrate a level of diversity in the T cell recognition of influenza HA, within a single mouse haplotype hitherto unrecognized, and imply that the T cell repertoire diversity against foreign antigens may be greater than previously assumed. Furthermore, the frequency at which HA-specific T cells have been identified that focus on amino acids within the HA1 subunit of HA also featuring in antigenic drift, suggests that a failure of MHC class II-restricted T cells to recognize specific epitopes within mutant HA molecules may contribute significantly to the capacity of variant influenza viruses to evade immune recognition.

Female residents of King County, Washington state, aged 25-54 years, in whom breast cancer was diagnosed in 1981 and 1982 were interviewed regarding their reproductive histories. Their responses were compared with the responses of a sample of women from the same population, who were selected by random digit-dialing from the same county, so that their age distribution resembled that of the cases. Premenopausal women who had ever lactated had 0.49 times the risk of developing breast cancer, as compared to premenopausal women who had never lactated (95% confidence interval, 0.30-0.82). Among both premenopausal and postmenopausal women, risk of breast cancer decreased with increasing duration of lifetime lactation experience, although the effect was consistently stronger for premenopausal women. This protective effect persisted after adjustment for age, parity, and age at first full-term pregnancy. Other reproductive factors, and demographic factors such as income and education, did not confound the relationship. This study confirms other recent findings of a protective effect of lactation against the development of breast cancer in young women.

A population-based case-control study of bladder cancer was conducted in 10 geographic areas in the United States. Risk of bladder cancer was not related to overall alcohol intake, nor to amounts of wine, beer, or spirits consumed. Alcohol also did not interact with known or suspected bladder carcinogens to increase risk, and no evidence was found that indirect mechanisms associated with alcohol ingestion the risk of bladder cancer.

An increasing number of epidemiologic studies of rare diseases are being conducted as collaborative ventures among several institutions in different geographic areas. Geographic area must be accounted for in the analysis, along with age and other potential confounders. This paper shows that it may not be possible to accurately predict the distribution of persons with rare diseases by age and geographic area. Therefore, selecting controls by matching on age group and geographic area is more efficient than selecting controls in all age and geographic area strata based on prior estimates of expected numbers of cases.

Magnets play a large part in the study of elementary sub-nuclear particles. Advances in the technology of superconducting magnets suggest that these magnets will be an important factor in the design of future accelerators, and their associated experimental equipment.

Studies have been made on the oligosaccharide residues of the alkali-stable carbohydrate–protein linkage of sialoglycopeptides derived from human erythrocytes. Four glycopeptides were isolated after alkaline borohydride treatment and Pronase digestion of MN-active sialoglycopeptides. The structure of one of these glycopeptides (GPIV) has been studied by sequential hydrolysis with specific glycosidases. Glycopeptide GPIV contained (per mol): 1mol of fucose, 1mol of sialic acid, 3mol of galactose, 3mol of mannose, 4mol of acetylglucosamine, 1mol of aspartic acid and fractional amounts of threonine, serine and glycine. The molecular weight of the glycopeptide was estimated to be 2330 by gel filtration. On the basis of glycosidase-digestion results, a tentative structure is proposed for the oligosaccharide moiety of glycopeptide GPIV.

1. Mouse mast-cell tumours P815 Y and HC were shown to contain glycoprotein material composed of glucosamine, galactosamine, sialic acid, galactose and mannose. 2. The major amino acids released after acid hydrolysis of Pronase-treated digests of the glycoprotein are aspartic acid, glutamic acid, serine, threonine, proline, glycine and alanine. The Pronase-digested material is not degraded in alkaline solution. 3. On incubation of mast cells with [35S]sulphate, heparin is the major radioactive product. However, [1−14C]glucosamine and d-[14C]glucose are incorporated largely into the glycoprotein. 4. The fate of [35S]sulphate-labelled and [1−14C]glucosamine-labelled material was studied. In each case high-molecular-weight radioactive material is released from the cells into the culture medium. The t½ of [35S]sulphate-labelled material in cells is 70hr. and that of [1−14C]-glucosamine-labelled material in cells is 40hr. 5. About 60% of the [35S]sulphate-labelled material is present in the mitochondrial and granular fraction. [1−14C]-Glucosamine-labelled material is present in both microsomal and mitochondrial and granular fractions, [14C]sialic acid being concentrated in the microsomal fraction.

A controlled retrospective study of some short‐term and long‐term effects of elective induction of labour was conducted. There did not appear to be any increase in the incidence of maternal complications during labour, or of neonatal problems in the induced‐labour group compared with the remainder of the mothers in the hospital. In the follow‐up phase of the study, two treatment groups of children who were delivered after amniotomy and amniotomy plus the administration of oxytocin were compared with each other, and with a control group of children bom after spontaneous labour. The children were assessed at the age of five years on verbal and non‐verbal subtests of a standardized intelligence scale, tests of gross motor and fine motor coordination, and auditory and visual tests. A full physical examination was also performed. No statistically significant differences nor trends of clinical interest were found between the groups on any measure.

A model for antigenic variation is proposed on the basis of changes in the expression of blood group determinants during the cell cycle.

Heteroantisera were raised in rabbits against human thymocytes or Burkitt's lymphoma EBI cells. After suitable absorption, the sera were specific for thymocytes and T lymphoblasts, or B lymphoblasts and several lymphoblastoid cell lines. The specificity of the antisera was confirmed by preparing purified populations of T or B lymphocytes on immunoabsorbent columns, followed by mitogenic stimulation with phytohemagglutinin. The antisera did not react with normal resting lymphocytes.

1. The uptake and incorporation of [35S]sulphate into mucopolysaccharides by colon and duodenum in vitro are unaffected by the vitamin A status of the animals. 2. Uptake and incorporation in vivo are unaffected at 4hr. after injection of [35S]sulphate, but at later times are decreased in some tissues of vitamin A-deficient animals. 3. The rate of removal of 35S from blood, its rate of appearance in urine, the plasma concentration of sulphate and the uronic acid content of several tissues are not significantly altered in vitamin A deficiency. 4. These results, and direct measurement of 35S in mucopolysaccharides at various times after injection of [35S]sulphate, suggest that the synthesis of mucopolysaccharides is unaffected but that their turnover is increased in vitamin A deficiency. 5. Neither the growth rate of, nor the incorporation of [35S]sulphate into heparin by, P815Y and HC cultured neoplastic mast cells is decreased when the horse serum necessary for growth is treated with ultraviolet light or is replaced by serum from vitamin A-deficient rats. 6. The addition of citral is no more toxic to growth rate or to incorporation of 35S than is the addition of vitamin A itself. 7. It is concluded that neoplastic mast cells in culture do not require vitamin A for growth or for the synthesis of heparin. 8. None of these results is compatible with the view that vitamin A or a derivative is directly involved in the biosynthesis of sulphated mucopolysaccharides.

The cytostatic effects of puromycm, [6N]O2'-dibutyryl 3',5'-adenosine monophosphate, and adenosine on asynchronous and synchronous cultures of the murine mastocytoma, P815Y, have been studied. Cell growth was arrested after a minimum of one further division. A model is proposed for the inhibition of cell division in which the periods of inhibition and growth arrest are separated in time by one cell cycle.