Distribution of lung disease

Radiologists rely on imaging patterns to arrive at a diagnosis. The different morphological patterns in the lungs are well known, but less emphasis has traditionally been placed on the pattern of distribution. This important feature greatly assists in the differential diagnosis regarding many pulmonary diseases and is the focus of this article. Chest radiographs often result in a narrow differential if one understands the regional differences and microenvironments within the lung and takes into consideration the ancillary imaging findings. High-resolution computed tomography offers additional information at the level of the secondary pulmonary lobule to fine-tune the distribution pattern and, consequently, the differential diagnosis. Disease distribution is often as important as the morphologic appearance of the disorder. This article will approach pulmonary diseases from the perspective of distribution patterns, highlighting the more common patterns. The goal of this review article is to give radiologists a conceptual framework that may be applied in their daily work environment.     

Impact of Detergent on Biophysical Properties and Immune Response of the IpaDB Fusion Protein,a Candidate Subunit Vaccine against Shigella Species

Shigella spp. are causative agents of bacillary dysentery, a human illness with high global morbidity levels, particularly among elderly and infant populations. Shigella infects via the fecal-oral route, and its virulence is dependent upon a type III secretion system (T3SS). Two components of the exposed needle tip complex of the Shigella T3SS, invasion plasmid antigen D (IpaD) and IpaB, have been identified as broadly protective antigens in the mouse lethal pneumonia model. A recombinant fusion protein (DB fusion) was created by joining the coding sequences of IpaD and IpaB. The DB fusion is coexpressed with IpaB''s cognate chaperone, IpgC, for proper recombinant expression. The chaperone can then be removed by using the mild detergents octyl oligooxyethelene (OPOE) or N,N-dimethyldodecylamine N-oxide (LDAO). The DB fusion in OPOE or LDAO was used for biophysical characterization and subsequent construction of an empirical phase diagram (EPD). The EPD showed that the DB fusion in OPOE is most stable at neutral pH below 55°C. In contrast, the DB fusion in LDAO exhibited remarkable thermal plasticity, since this detergent prevents the loss of secondary and tertiary structures after thermal unfolding at 90°C, as well as preventing thermally induced aggregation. Moreover, the DB fusion in LDAO induced higher interleukin-17 secretion and provided a higher protective efficacy in a mouse challenge model than did the DB fusion in OPOE. These data indicate that LDAO might introduce plasticity to the protein, promoting thermal resilience and enhanced protective efficacy, which may be important in its use as a subunit vaccine.     

Rarity of CDK4 germline mutations in familial melanoma

To date, two genes have been implicated in melanoma pathogenesis. The first, CDKN2A, is a tumour suppressor gene with germline mutations detected in 20% of melanoma-prone families. The second, CDK4, is an oncogene with co-segregating germline mutations detected in only three kindreds worldwide. We examined 16 American melanoma-prone families for mutations in all coding exons of CDK4 and screened additional members of two previously reported families with the Arg24Cys germline CDK4 mutation to evaluate the penetrance of the mutation. No new CDK4 mutations were identified. In the two Arg24Cys families, the penetrance was estimated to be 63%. Overall, 12 out of 12 invasive melanoma patients, none out of one in situ melanoma patient, five out of 13 dysplastic naevi patients, two out of 15 unaffected family members, and none out of 10 spouses carried the Arg24Cys mutation. Dysplastic naevi did not strongly co-segregate with the Arg24Cys mutation. Thus the phenotype observed in melanoma-prone CDK4 families appears to be more complex than just the CDK4 mutation. Both genetic and environmental factors are likely to contribute to the occurrence of melanoma and dysplastic naevi in these families. In summary, although CDK4 is a melanoma susceptibility gene, it plays a minor role in hereditary melanoma.     

Serotonin depolarizes type A and C primary afferents: an intracellular study in bullfrog dorsal root ganglion

Intracellular recordings were obtained from the somata of type A and C primary afferents in the isolated bullfrog dorsal root ganglion (DRG) preparation. Bath application of serotonin (5-HT) in concentrations of 0.25-1.0 mM led to slow and fast depolarizing responses. Slow, maintained 5-HT depolarizations were observed in 47% of type A and 70% of type C neurons. These slow depolarizations were associated with an underlying increase in input resistance (Rin). In some type A neurons, the Rin increase was masked by a decrease in Rin due to depolarization-induced rectification. The slow 5-HT depolarization of type A, but not type C neurons showed pronounced tachyphylaxis to repeated 5-HT applications. In type C afferents, serotonin's slow action was often accompanied by spontaneous firing. Manganese decreased slow 5-HT depolarizations of both cell types. A slow depolarization and excitation of type C afferents by methysergide and cinanserin was also observed. Fast transient 5-HT depolarizations accompanied by a rapid decrease in Rin were observed in 7% of type A and 24% of type C neurons. In some DRG cells the fast and slow depolarizations combined to form a biphasic response. The actions of 5-HT reported here resemble in some ways 5-HT responses recorded extracellularly from the spinal terminations of primary afferents.     

Periodic Hematopoiesis in Human Cyclic Neutropenia

Human cyclic neutropenia is characterized by severe depression of blood neutrophil levels approximately every 21 days. To investigate the mechanism of cyclic neutropenia four patients were studied with daily complete blood counts, serial bone marrow examinations, marrow reserve testing, serum muramidase determinations, DF²²P granulocytokinetic studies, and, in one patient, in vivo [³H]TdR labeling. Periodogram analysis of the serial blood counts in the latter patient and visual inspection of multiple cycles in the others revealed periodic fluctuations in the levels of blood neutrophils, monocytes, lymphocytes, reticulocytes, and platelets. Rhythmic changes in the morphologic and radioisotopic studies as well as the marrow reserve tests and muramidase measurements were consonant with a mechanism of periodic failure of marrow production rather than peripheral destruction. Human cyclic neutropenia is analogous to cyclic neutropenia in the grey collie dog and may be viewed as the consequence of cyclic hematopoiesis.     

Bone morphogenesis in implants of residues of radioisotope labelled bone matrix

Bone matrix demineralized in 0.6 N HCl at 2° for 24 h and implanted in muscle in allogeneic rats possesses consistently reproducible bone morphogenetic activity. Experiments on implants of matrix, obtained from donors injected with³H-tyrosine or³H-tryptophan, or Na³⁵SO₄, suggest that bone morphogenetic property is a protein or apart of a protein that is (1) insoluble in buffer solutions, pH 3.6 and 5.0; (2) degraded in buffer solutions at pH 7.4 by an endogenous sulfhydryl-group neutral proteinase; (3) digested by trypsin at 15° within 8 h without solubilization of the helical regions, possibly even without degradation of the nonhelical ends of the bone collagen molecule, and without any loss of the periodic ultrastructure of the collagen fibrils; (4) degraded or removed by 0.1 N NaOH at 2° within 24 h without solubilization of collagen; (5) biologically active even after nitration of tyrosyl groups with tetranitromethane. The release of only one-third of the radioactivity with loss of nearly all yield of new bone by limited tryptic digestion of³H-borohydride-reduced matrix indicates that the bone morphogenetic response is the function of a non-collagenous component. Autoradiographs of implants of matrix with non-collagenous proteins labelled with³H-tryptophan,³H-tyrosine, or both³H-tyrosine and³H-phenyl-alanine demonstrate random dissemination of the radioactive constituents and no evidence of local transfer of labelled proteins or soluble protein derivatives. Hypothetically, the bone morphogenetic response is controlled by an insoluble acidic bone morphogenetic protein or polypeptide (BMP) and a soluble neutral proteinase (BMP-ase) resembling trypsin in activity except functionally more specific for BMP. Firmly bound but separable from bone collagen, BMP is one of many short-lived morphogenetic substances appearing and disappearing throughout embryonic development and persisting in postfetal life. Where the BMP receptor resides and how it activates cell mechanisms of differential repression and derepression of such genes as code for osteogenesis is unknown.     

Protective behaviours among young African American women with non-monogamous sexual partners

In the USA, partner non-monogamy is reported to be more common among African American women than White women and may contribute to African American women’s increased risk for HIV and other sexually transmitted infections (STIs). Few studies have explicitly and comprehensively described the protective behaviours that African American women employ with non-monogamous partners to reduce their HIV risk. We conducted interviews to examine protective behaviours among 11 African American women aged 18–24 years who perceived that a partner in the preceding 12 months had another sex partner. Participants described three types of partnerships with 29 non-monogamous men; these partnerships clustered into three categories. Narrative analysis revealed an overall paucity of protective behaviours with non-monogamous partners. Protective behaviours (i.e. communication and condom use) were informed by partnership type, rather than perceptions of non-monogamy. There were few instances in which partner non-monogamy motivated women to terminate sex partnerships. Rather, these decisions were often motivated by changes in other relationship dynamics. To address HIV/STI risk related to partner non-monogamy, HIV prevention strategies for young African American women should emphasise the importance of condom use in all non-marital partnership types. Interventions where testing is available may be effective for women who frequently test for HIV/STIs but do not use condoms.     

Reproductive Toxicity of Sulfamethazine in Swiss CD-1 Mice during Continuous Breeding

Sulfamethazine (SMZ) was evaluated for reproductive toxicityin Swiss CD-1 mice using a continuous breeding protocol. SMZwas administered in the diet at 0, 0.25, 0.5, or 1% (w/w), whichrepresented an average daily intake of 0, 313, 625, or 1250mg SMZ/kg/day, respectively. Exposure of F0 male and femalemice to 1% SMZ for 126 days resulted in a significant decreasein the mean number of live pups per litter and the number oflitters produced (task 2); the percentage pups born alive to1% SMZ females showed a nonsignificant decrease versus controlfemales. The effects on fertility were rapid to onset (1 to4 weeks) and cumulative in nature. F0 male and female body weightswere slightly depressed from 3 weeks to the end of the study.The crossover mating trial (task 3) revealed that the adverseeffect on ferility involved both treated partners in that littersize decreased when either 1% SMZ males were bred to controlfemales or 1% SMZ females were mated with control males. Afterapproximately 155 days of exposure of F0 mice to 1% SMZ, theterminal body weight of 1% SMZ females was significantly decreasedand that of 1% SMZ males showed a nonsignificant decrease. Inaddition, the liver weight to body weight ratio of the maleswas increased. Further, the prostate and seminal vesicle weightto body weight ratios were decreased in 1% SMZ males relativeto control males. No treatment-related gross or histopathologicallesions were noted for the pituitary or reproductive organsof either sex. Sperm assessment indicated no significant differencein the epididymal sperm concentration or percentage motile orabnormal sperm. In conclusion, SMZ was found to be a reproductivetoxicant in the male and female Swiss CD-1 mouse, albeit atrelatively high dietary intake (1250 mg/kg/day), and in thepresence of mild systemic toxicity.