Ultrastructural Morphometric Study of Follicular Center Lymphocytes: II. Analyses of Cleaved-Cell Populations Do Not Support the Lukes-Collins' Concept

Ultrastructural morphometric analysis was carried out on six cases of lymph node biopsies with reactive hyperplasia to establish the frequency and depth of invaginations in nuclear profiles situated in the mantle zones and follicular centers. The frequency distribution of the depth of invaginations was similar in nuclear profiles whether in the small lymphocytes of mantle zones or the small, partially transformed (centrocytes) and fully transformed (centroblasts) lymphocytes of follicular centers. Invaginated and cleaved lymphocytes were not confined to the partially transformed (centrocytic) lymphocytes of follicular centers, and nuclear profiles with invaginations bore no resemblance to those depicted in the Lukes-Collins model. A considerable proportion of mantle zone lymphocyte nuclear profiles had invaginations (ranging from 7.5% to 53.6%) and there was no difference between the frequency of deep indentations or clefts in mantle zone lymphocytes (8.1 ± 5.4%) and the small unstimulated (9.3 ± 5.3%) and partially transformed (8.4 ± 1.4%) lymphocytes in follicular centers. Computer modeling of stylized nuclei with conical indentations indicated that all lymphocytic nuclei likely have multiple invaginations or groove-like creases.     

Genetic homology between man and the chimpanzee: Syntenic relationships of genes for galactokinase and thymidine kinase and adenovirus-12-induced gaps using chimpanzee-mouse somatic cell hybrids

The induction by adenovirus-12 of a site-specific gap and assignment of the chimpanzee genes for thymidine kinase and galactokinase were studied by utilizing chimpanzee-mouse hybrid cells. It has been shown that adenovirus-12 induces a specific gap in the long arm of human chromosome 17 (HS 17); with chimpanzee-mouse hybrid cells the specific gap appears on the short arm of the chimpanzee homolog [PTR 19 (HS 17)] of HS 17. This result supports the proposed relationship of HS 17 to PTR 19 (HS 17) by means of a pericentric inversion. The chimpanzee thymidine kinase and galactokinase genes were assigned to PTR 19 (HS 17), further confirming the homology to HS 17. Other syntenic relationships and gene assignments were consistent with proposed homologies between chimpanzee and human chromosomes.     

Immunoassays and nucleic acid detection with a biosensor based on surface plasmon resonance

A technique based on surface plasmon resonance is described which can be used to detect changes of refractive index that occur when one partner of a molecular binding pair diffuses from solution to bind the other partner which is immobilised on a silver surface. Results for the molecular binding pairs; protein-antibody, hapten-antibody and DNA-DNA are described. Instrumentation necessary for implementation of the technique is detailed. Immunoassay of proteins and haptens is possible in less than one minute with a sensitivity of 10(-9) mol/l. Hybridisation of 10 fmoles of a 97 base target sequence on the 1 mm2 area of detection to an immobilised oligonucleotide probe can be detected in less than five minutes. Advantages of the technique include the ability to record the kinetics of binding reactions in "real time" and the lack of labels in this simple assay format. Methods of improving the sensitivity are discussed.     

Intraparenchymal pulmonary lymph node: case report and literature review

Summary A case of a 44-year-old woman with a solitary pulmonary coin lesion is presented. Histologic study of this nodule revealed a normal intraparenchymal pulmonary lymph node. A review of the literature discusses the incidence and characteristics of this entity.

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Nud lymphatique intrapulmonaire: revue de la littérature. A propos d'un cas

Résumé L'observation d'un cas de lésion nodulaire du poumon est rapportée chez une femme de 44 ans. L'étude histologique du nodule a révélé un nud lymphatique intrapulmonaire normal. La revue de la littérature apprécie l'incidence et les caractéristiques de cette localisation.

     

Mode of transmission and histology of M. leprae infection in nude mice

Athymic (nude) mice were experimentally infected with Mycobacterium leprae via the alimentary and respiratory tracts and through the skin. Animals were allowed to inhale aerosols of M. leprae or had bacilli instilled into the nostrils or directly into the lungs. Others were fed M. leprae by gastric tube or had bacilli placed on the tongue. Attempts were also made to transmit M. leprae from infected footpads by Aedes aegyptii mosquitoes. The most successful infections resulted from nasal instillations and from bacilli inoculated onto the tongue surface: in these cases heavy systemic infections occurred. M. leprae was also shown to survive passage through the alimentary tract and bacilli recovered from the faeces were capable of causing infection in recipient nude mice. The possible epidemiological significance of these findings for the transmission of leprosy in man is discussed.     

Airborne infection with Mycobacterium leprae in mice.

Although the portal of entry and mode of spread of M. leprae in human leprosy are still uncertain, it is widely held that direct person-to-person skin contact is important. This assumption has ignored the fact that patients with highly bacilliferous leprosy have nasal as well as dermal infection and that, since M. leprae is shed predominantly from the nose, leprosy might be an airborne infection. The present study was designed to investigate this possibility with mice exposed to airborne infection with M. leprae. The conditions are described in which thymectomised-irradiated CBA strain mice exposed to M. leprae aerosols sustained an immediate lung retention of 1 X 10(5) bacteria. Fourteen to 24 months later, 33% (10 of 30) of the mice had countable numbers of acid-fast bacilli (greater than 2 X 10(4)) with the characteristics of M. leprae in one or more homogenates prepared from ears, foot pads, nose or lungs. Evidence is presented from the distribution of M. leprae that the infection had arisen from systemic spresd of bacilli initially entering the lungs rather than from multiplication of organisms locally retained there, or in the nose, at the time of airborne infection. The relevance of these results to the possible route of infection of leprosy in man is discussed.     

The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Spatial heterogeneity of the effects of calcitonin gene-related peptide (CGRP) on the microvasculature of ligaments in the rabbit knee joint

1. Experiments were performed in anaesthetized rabbits to examine the effects of calcitonin gene-related peptide (CGRP) and the CGRP antagonist CGRP_8–37 on blood flow to the medial collateral ligament of the knee joint.
2. Topical application of CGRP (10⁻¹³ to 10⁻⁹  mol) to the exposed external surface of eight knee joints resulted in dose-dependent dilatation of vessels in both the ligament and the joint capsule. The magnitude of this response varied significantly in different regions of the medial collateral ligament, with the 10⁻⁹  mol dose of CGRP giving the maximum response (101.5±25.3% increase) at the femoral insertion site of the medial collateral ligament and lowest (23.1±8.8%) at the tibial insertion site.
3. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) produced dose-dependent constriction of vessels in the ligament and the joint capsule in five knees, with a trend towards the greatest effect occurring at the femoral insertion site (45.8±8.1% reduction in blood flow). With the 10  nmol dose, the vasoconstrictor response at the femoral insertion site differed significantly (P<0.05) from the responses obtained at the tibial insertion and joint capsule sites.
4. Topical application of CGRP_8–37 (0.1, 1 and 10  nmol) to four chronically denervated knees produced substantially smaller vasoconstrictor responses at all sites. At the femoral insertion site, where 10  nmol CGRP_8–37 normally produces a 45.8±8.1% reduction in blood flow (n=8), ten days following denervation this response was reduced to 6.5±6.1%, this difference being significant (P=0.01).
5. Adrenaline was applied topically to augment blood vessel tone, in order to establish how effectively co-administration of CGRP would offset this increase in tone. Adrenaline (10⁻¹⁰  mol) produced vasoconstriction at all sites (n=6). In the capsule this vasoconstriction was virtually abolished when CGRP (10⁻⁹  mol) was co-administered with adrenaline but in the ligament vasodilatation occurred at all sites. This vasodilatation was significantly greater at the femoral insertion site compared to the tibial insertion and mid ligament sites (P<0.05 for both) and the capsule (P<0.01).
6. Topical application of substance P (10⁻¹⁰ or 10⁻⁹  mol) failed to elicit dilatation of ligament blood vessels.
7. These results suggest that endogenous CGRP may play an important role in regulating blood flow to different structures in and around the knee joint.

     

Conducting qualitative research in the health sector: researcher issues and dilemmas.

This article contributes to bridging the gap between research activity and the practical implementation of management decision making in the health sector by reflecting upon some of the issues and dilemmas for researchers, whether academics or managers, in conducting qualitative research in this sector. The article presents the methodological issues addressed by a team of researchers engaged on a project about manager learning and development in an NHS Trust, and highlights concerns about ethical issues that emerged from the research process. The study had involved a series of interviews with senior managers and clinical staff, doctors, nurses and therapists, and it addressed issues surrounding change within the organization, the impact on individuals' jobs, and the resultant learning and development required and undertaken. The article emphasizes that engaging in reflection on the research process is valuable and suggests that it should become a mainstream part of such research. It concludes that there is an important role of qualitative management research in the health sector and that for it to be acceptable and valued, it must be operationally sensitive, ethically robust and methodologically rigorous.