The cytologic diagnosis of malignant neoplasms in pleural and peritoneal effusions

This study presents data on 3,011 pleural and peritoneal effusion specimens that were examined over a three-year period (1982 to 1984). Totals of 812 (44%) of 1,846 pleural and 423 (36%) of 1,165 peritoneal specimens were positive for malignant cells. While 535 patients had malignant pleural effusions, 254 patients had malignant peritoneal effusions, and 57 had both malignant pleural and peritoneal effusions. The most common primary neoplasms causing malignant pleural effusions were carcinomas of breast (24%) and lung (19%) and lymphoreticular neoplasms (16%). The most common primary neoplasms causing malignant peritoneal effusions were carcinomas of ovary (32%) and breast (13%) and lymphoreticular neoplasms (7%). There was an average interval of more than 30 months between the histologic diagnosis of the primary neoplasm and the diagnosis of malignant effusions in patients with carcinoma of breast, lymphoreticular neoplasm and malignant melanoma. The average time until death following the diagnosis of a malignant effusions was five months or less, except for patients with carcinoma of the breast and carcinoma of the ovary. One hundred twenty-five patients (15%) presented with malignant effusions caused by neoplasms of unknown primary sites. The most common primary neoplasms that were later diagnosed were, in decreasing order of frequency, carcinoma of the ovary, carcinoma of the lung and lymphoreticular neoplasms.     

Polymorphism of murine major histocompatibility Class I antigen: assignment of putative allodeterminants to distinct positions of the amino acid sequence within the first external domain of the antigen

Forty-five new monoclonal antibodies reacting with the mouse H-2Dd antigen have been established. The specificities of 34 of these antibodies were mapped into the first external domain (N) of the Dd antigen by testing reactivities with the products of mosaic H-2 genes in which the coding sequences of the first and/or the second external domains of the H-2Dd genes were recombined in vitro with the remaining portion of the H-2Ld gene. These antibodies reacted with at least 13 distinct allodeterminants located in the N domain, composed of 91 amino acids, as judged from panel tests carried out on various H-2 haplotypes. To assign possible positions of antigenic determinants of these and other anti-H-2Dd antibodies, we compared primary sequences of seven H-2 antigens and searched for correspondence between the pattern of amino acid substitutions in the N domain, allowing 15 positions to be assigned for the antigenic sites. These putative antigenic determinants were assessed for possible relationships with several parameters of protein secondary structure postulated according to predictive methods. Many of these sites appear to be associated with greatest local hydrophilicity, known to correlate with sites of antibody binding in various proteins. We therefore propose that some of the correspondences found in this work represent structural correlates of allodeterminants.     

75 deaths in asthmatics prescribed home nebulisers.

The circumstances surrounding the deaths of 75 asthmatic patients who had been prescribed a domiciliary nebuliser driven by an air compressor pump for administration of high dose beta sympathomimetic drugs were investigated as part of the New Zealand national asthma mortality study. Death was judged unavoidable in 19 patients who seemed to have precipitous attacks despite apparently good long term management. Delays in seeking medical help because of overreliance on beta agonist delivered by nebuliser were evident in 12 cases and possible in a further 11, but these represented only 8% of the 271 verified deaths from asthma in New Zealanders aged under 70 during the period. Evidence for direct toxicity of high dose beta agonist was not found. Nevertheless, the absence of serum potassium and theophylline concentrations and of electrocardiographic monitoring in the period immediately preceding death precluded firm conclusions whether arrhythmias might have occurred due to these factors rather than to hypoxia alone. In most patients prescribed domiciliary nebulisers death was associated with deficiencies in long term and short term care similar to those seen in patients without nebulisers. Discretion in prescribing home nebulisers, greater use of other appropriate drugs, including adequate corticosteroids, and careful supervision and instruction of patients taking beta agonist by nebuliser should help to reduce the mortality from asthma.     

Effects of pH and temperature on the interaction of an impermeant probe with surface proteins of the human red blood cell.

The conformation of the outer surface of the human red cell membrane has been studied under various conditions using the impermeant probe [125I]diazodiiodosulfanilic acid. At least seven polypeptides were labeled by the reagent, including the three extractable glycoproteins separable by the electrophoretic method employed. The Mr = 43,000 protein band was shown to contain two labeled species, one a glycoprotein, in addition to its major constituent, red cell actin. The extent and pattern of labeling were very sensitive to changes in pH and temperature. Total labeling increased with increasing pH and was greater at 4 degrees C than 37 degrees C. Binding of the probe to the Mr = 90,000 polypeptide and the major glycoprotein were relatively increased with increasing pH and temperature while opposite effects were observed for the Mr = 43,000 peptide(s). The pH effects on external membrane labeling were rapidly reversible. Results were similar in cells of different densities, suggesting that the pH and temperature effects were not related to cell age. The data presented emphasize the lability of membrane conformation and reactivity and thus the necessity to consider carefully the conditions of labeling in interpretation of studies using impermeant probes.     

Biochemical evidence for a separate,MHC-linked locus encoding H-2.28 antigens

In comparing the tryptic peptide maps of the H-2L and H-2D glycoprotein antigens isolated from NP-40 lysates of RADA1 (H-2 ^a ) leukemic cells, no more than 37% of the observed arginine-containing tryptic peptides are found to be homologous. Thus, the primary amino-acid sequences of these two antigens are probably less than 90% homologous. This constitutes the strongest evidence to date that the MHC-linkedH-2L region encodes H-2L antigens separately from theH-2D region, even though H-2L antigens bear D-end-associated antigenic determinants of the H-2.28 family. The anti-H-2.28 alloantiserum (k×r anti h2) used to precipitate H-2L antigens in this investigation was the NIH contract antiserum D28b. As the tryptic peptide maps also surprisingly revealed, D28b precipitates H-2D antigens as well and, thus, anti-H-2.4 immunoadsorbants were employed to isolate H-2L free of H-2D antigens. In light of the dual specificity of D28b, its reactivity with BALB/c-H-2 ^dm2 mutant cells was re-examined. Even though mutant lymphocytes, which lack H-2L but not H-2D antigens, are not cytotoxically lysed by D28b (as are parental H-2^d cells), D28b appears to precipitate H-2D antigens from NP-40 extracts of mutant splenocytes.     

A specific increase in chloroplast gene mutations following growth of Chlamydomonas in 5-fluorodeoxyuridine.

Summary Growth of Chlamydomonas in the thymidine analog 5-fluorodeoxyuridine (FdUrd) leads to a reduction in the amount of chloroplast DNA and also alters the pattern of chloroplast gene transmission in crosses (Wurtz et al., 1977). We have now found that growth of Chlamydomonas in FdUrd also increases at least 10 to 20 fold the frequency of cells expressing antibiotic resistant or non-photosynthetic mutations in the chloroplast genome with no concomitant increase in nuclear gene mutations with similar phenotypes. Clearly this effect is not locus specific since the non-photosynthetic chloroplast mutations thus far isolated comprise 9 recombinationally separate loci in the chloroplast genome (Shepherd et al., 1977, 1979). Only with the use of FdUrd has isolation of this important class of non-photosynthetic mutations been possible. The efficiency of recovery of chloroplast gene mutations rises as FdUrd concentration increases from 0.1 to 1.0 mM. At higher concentrations of FdUrd, growth rates and mutant yields are reduced. We propose the analog increases the yield of chloroplast mutations by a two-step process in which mutations are first induced as a result of thymidine starvation and then become expressed because the chloroplast DNA has been greatly reduced in ploidy and possibly damaged. FdUrd has its maximal effect on both recovery of chloroplast gene mutations and chloroplast gene transmission in crosses after cells grown in the presence of the analog for several generations remain at stationary phase for about 24 h. These observations suggest that chloroplast DNA metabolism is very active in non-dividing stationary phase cells of Chlamydomonas.     

A dynamic partnership: celebrating our gut flora

Emerging data indicate that humans enjoy health through a productive collaboration with their colonizing flora, the majority of whom reside in the colon. This minireview provides a perspective on recent data and the exciting scientific challenges ahead.     

Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.     

Constraints on the morphological evolution of marsupial shoulder girdles

Throughout their evolutionary histories, marsupial mammals have been taxonomically and morphologically less diverse than their sister taxa the placentals. Because of this, it has been proposed that the evolution of marsupials has been constrained by the functional requirements of their mode of reproduction. Marsupials give birth after short gestation times to immature neonates that immediately crawl, under the power of their precociously developed shoulder girdles, to the teat where they attach and complete their early development. Using a novel approach incorporating adult and embryological morphological data, this study is the first to both: (1) statistically support adult patterns of morphological divergence consistent with the constraint hypothesis, and (2) identify ontogenetic patterns of morphological change that demonstrate that the constraint was responsible, at least in part, for their formation. As predicted by the marsupial constraint, the shoulder girdles of adult marsupials are less diverse than those of adult placentals, and adult marsupial scapulae are less morphologically diverse than adult marsupial pelves. Furthermore, marsupials that complete an extensive crawl to the teat are restricted to a common pattern of ontogenetic scapular shape change, strongly supporting the hypothesis that the morphological development of the marsupial scapula has been limited evolutionarily by its obligate role in the crawl to the teat. Because this study establishes that ontogenetic and evolutionary morphological change is correlated within mammalian scapulae, it is probable that the marsupial constraint also restricted the morphological divergence of the scapula over evolutionary time by limiting ontogenetic change in the scapula. These findings, coupled with the importance of the shoulder girdle in mammalian locomotor specialization, support the conclusion that the low morphological diversity of marsupial forms over evolutionary time could be directly due to the constraint on marsupial morphological evolution caused by the functional requirements of the crawl to the teat.