Spectral histopathology of the lung: A review of two large studies

This paper summarizes results from two large lung cancer studies comprising over 700 samples that demonstrate the ability of spectral histopathology (SHP) to distinguish cancerous tissue regions from normal tissue, to differentiate benign lesions from normal tissue and cancerous lesions, and to classify lung cancer types. Furthermore, malignancy‐associated changes can be identified in cancer‐adjacent normal tissue. The ability to differentiate a multitude of normal cells and tissue types allow SHP to identify tumor margins and immune cell infiltration. Finally, SHP easily distinguishes small cell lung cancer (SCLC) from non‐SCLC (NSCLC) and provides a further differentiation of NSCLC into adenocarcinomas and squamous cell carcinomas with an accuracy comparable of classical histopathology combined with immunohistochemistry. Case studies are presented that demonstrates that SHP can resolve interobserver discrepancies in standard histopathology.     

Human disease classification in the postgenomic era: A complex systems approach to human pathobiology

Contemporary classification of human disease derives from observational correlation between pathological analysis and clinical syndromes. Characterizing disease in this way established a nosology that has served clinicians well to the current time, and depends on observational skills and simple laboratory tools to define the syndromic phenotype. Yet, this time-honored diagnostic strategy has significant shortcomings that reflect both a lack of sensitivity in identifying preclinical disease, and a lack of specificity in defining disease unequivocally. In this paper, we focus on the latter limitation, viewing it as a reflection both of the different clinical presentations of many diseases (variable phenotypic expression), and of the excessive reliance on Cartesian reductionism in establishing diagnoses. The purpose of this perspective is to provide a logical basis for a new approach to classifying human disease that uses conventional reductionism and incorporates the non-reductionist approach of systems biomedicine.     

Antileishmanial activity and ultrastructural changes of sesquiterpene lactones isolated from Calea pinnatifida (Asteraceae)

Bioactivity-guided fractionation of antileishmanial active CH₂Cl₂ phase of MeOH extract from leaves of Calea pinnatifida led to isolation of two sesquiterpene lactones calein C (1) and calealactone C (2), which structures were stablished on the basis of spectroscopic analysis. Compounds 1 and 2 displayed potent activity against Leishmania amazonensis promastigotes with EC₅₀ of 1.7 and 4.6 µg mL⁻¹, respectively. Compound 2 presented low cytotoxicity for J774 macrophages and displayed activity against amastigote forms of L. amazonensis similar to miltefosine with CC₅₀ values of 31.73 and 27.18 µg mL⁻¹, respectively. Additionally, compounds 1 and 2 caused ultrastructural changes in promastigotes leading to a loss of their classical structural morphology, as evidenced by electron microscopy. Also compound 2 decreased the mitochondria membrane potential. To the best of our knowledge, this is the first occurrence of 1 and 2 in C. pinnatifida. The results obtained highlighted the importance of studying sesquiterpene lactones isolated from Calea pinnatifida in terms of antileishmanial activity, in order to understand the mechanism of action of the isolated compounds in promastigotes forms of L. amazonensis.     

Osteopathy of the pectoral and pelvic limbs including pentadactyly in a young Kestrel (Falco t. tinnunculus)

Summary A five and a half weeks old female Kestrel exhibiting osteopathy of the pectoral and pelvic limbs, including symmetrical hyperdactyly, was investigated in order to clarify the pattern of the involved anatomical alterations and the possible causes of this developmental malformation. In the pectoral limb it consisted of a triplication of the alular digit, in the pelvic limb of a duplication of digit I. The live young Kestrel was observed for a period of two weeks to ascertain that it was unable to fly or procure prey on its own. After its death radiographs were taken and, apart from an eidonomic inspection including the wing claws, a detailed macroscopic dissection of the musculature of the pectoral and pelvic limbs was carried out using the in-water-method. Consecutive dissection steps were documented by a series of photographic slides. The relevant musculature, particularly that of the supernumerary digits, was recorded in proportional drawings. Subsequent to maceration of the limbs the isolated bones were reassembled according to the radiographs and also documented by means of photographs and drawings. This anatomical approach produced a reliable reconstruction of the skeletomuscular apparatus of the hyperdactylous limb parts. The eidonomic inspection revealed that at least young Kestrels may have two (alular and major digit) or even three wing claws per side. The proximal skeletal elements of both pectoral and pelvic limb were more sturdily built than in a typical Kestrel of comparable age. The proximal elements of the pelvic limb, the tarsometatarsus in particular, were shorter than in a typical Kestrel. In addition, the long axis of the tarsometatarsus was laterally bent in the transverse plane so that its proximal articular surfaces were medially inclined. Duplication of the cutaneous and osseous elements in the foot was accompanied by a duplication of some of the muscular and/or tendinous elements supplying digit I proper and the accessory digit I'. There were left-to-right asymmetries of the pedal musculature concerned. In contrast, the two accessory alular digits of each wing were almost completely devoid of musculature. Apart from atypical points of origin or insertion of the remaining distal musculture, left-to-right asymmetries and the two accessory alulae per wing, presumably, affected aerodynamic properties and resulted in flightlessness.A juvenile Kestrel of similar age and without hyperdactyly was dissected for comparison. In addition, the external appearance of the carpometacarpal region of two female Silkies, an obligatory pentadactylous breed of domestic fowl, was inspected and the skeletal parts of their pectoral and pelvic limbs compared with those of the hyperdactylous Kestrel. Our results and a literature review suggest that the symmetrical hyperdactyly in the Kestrel bears striking similarities to the hereditary hyperdactyly observed in certain breeds of domestic fowl. In addition, there is a striking resemblance between the hyperdactyly of the young Kestrel and certain forms of hyperdactyly induced by molecular genetical experiments of other authors on chicks. Comparison with these results taken from the literature suggest that the symmetrical hyperdactyly in the young Kestrel, including the alterations of the proximal skeletal elements, is caused by an unusually early expression of the Hoxd-11 gene group during embryological development. Most likely, this gene group is situated on the 2^nd chromosome in birds just as it is in mammals.

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Osteopathie der Vorder - und Hinterextremitäten, verbunden mit einer symmetrischen Hyperdactylie bei einem jungen Turmfalken (Falco tinnunculus)

Zusammenfassung Ein fünfeinhalb Wochen alter weiblicher Turmfalke mit einer Osteopathie der Vorder- und Hinterextremitäten, verbunden mit einer symmetrischen Hyperdactylie, wurde untersucht, um das Muster der beteiligten anatomischen Veränderungen und die möglichen Ursachen dieser Mißbildung zu erkennen. An der Vorderextremität bestand sie aus einer Verdreifachung des Alula-Fingers, an der Hinterextremität aus einer Verdoppelung der Zehe I. Die Beobachtung des lebenden jungen Turmfalken während eines Zeitraumes von zwei Wochen ergab, dass er flugunfähig war und keine Beute schlagen konnte.Nach seinem Tod und einer Inspektion der Eidonomie, einschließlich der Flügelkrallen, wurden Röntgenaufnahmen angefertigt. Danach folgte eine detaillierte makroskopische Präparation der Flügel- und Beinmuskulatur unter Verwendung der In-Wasser-Methode. Die einzelnen Präparationsschritte wurden anhand von Dia-Serien dokumentiert. Die relevante Muskulatur, insbesondere die der überzähligen Digiti, wurde in proportionsgetreuen Zeichnungen festgehalten. Nach Mazeration der Extremitäten wurden die Einzelknochen, entsprechend den Röntgenbildern, wieder zusammengesetzt und ebenfalls mit Fotografien und Zeichnungen dokumentiert. Dieser anatomische Ansatz lieferte eine zuverlässige Rekonstruktion des Skelett-Muskel-Apparates der hyperdactylen Extremitätenanteile.Die eidonomische Inspektion ergab, dass zumindest junge Turmfalken zwei (Digitus alularis und majoris) oder sogar drei Flügelkrallen haben können. Die proximalen Skelettelemente der Vorder- und Hinterextremität waren deutlich robuster gebaut als bei einem typischen Turmfalken vergleichbaren Alters. Die proximalen Elemente der Hinterextremität, insbesondere der Tarsometatarsus, waren kürzer als bei einem typischen Turmfalken. Darüberhinaus war die Längsachse des Tarsometatarsus in der Transversalebene laterad gekrümmt, so dass sich seine proximalen Gelenkflächen schräg mediad richteten. Entsprechend der kutanen und knöchernen Doppelbildungen des Fußes waren auch einige der Muskeln und Sehnen doppelt vorhanden, welche die eigentliche erste Zehe und die akzessorische erste Zehe versorgten. Es traten Rechts-/Links-Asymmetrien der betreffenden Muskulatur auf. Im Gegensatz dazu waren die beiden akzessorischen Alula-Finger jedes Flügels fast vollständig ohne Muskulatur. Abgesehen von atypischen Ursprungs- und Insertionspunkten der verbleibenden distalen Muskulatur, beeinträchtigten Rechts-/Links-Asymmetrien und die beiden akzessorischen Alulae pro Flügel vermutlich die aerodynamischen Eigenschaften und führten zur Flugunfähigkeit.Ein junger Turmfalke ähnlichen Alters ohne Hyperdactylie wurde zum Vergleich präpariert. Zusätzlich wurde die äußere Erscheinung der Carpometacarpal-Region zweier Seidenhühner, einer obligatorisch pentadactylen Hühnerrasse, inspiziert und die Skelettelemente ihrer Vorder- und Hinterextremitäten mit denen des hyperdactylen Turmfalken verglichen. Unsere Ergebnisse und ein Überblick der Literatur lassen auffallende Übereinstimmungen zwischen der symmetrischen Hyperdactylie des jungen Turmfalken und der erblichen Hyperdactylie bestimmter Hühnerrassen erkennen. Darüberhinaus besteht eine auffallende übereinstimmung zwischen der Hyperdactylie des jungen Turmfalken und bestimmten Formen der Hyperdactylie, welche von anderen Autoren durch molekulargenetische Experimente an Hühnerküken induziert wurden. Ein Vergleich mit diesen Ergebnissen aus der Literatur legt nahe, dass die symmetrische Hyperdactylie des jungen Turmfalken, einschließlich der Veränderungen der proximalen Skelettelemente, durch eine ungewöhnlich frühe Expression der Hoxd-11 Gengruppe im Laufe der Embryonalentwicklung verursacht wurde. Sehr wahrscheinlich ist diese Gengruppe bei Vögeln auf dem zweiten Chromosom lokalisiert — ebenso wie bei Säugetieren.

     

Development of strategies for the incorporation of biological pesticides into the integrated management of locusts and grasshoppers

• 1 Effective biological pesticides based on oil formulation of deuteromycete fungal spores have been developed for use against locusts and grasshoppers. The isolate IMI 330189 of Metarhizium anisopliae (flavoviride) var. acridum has been registered, extensively field tested and its operating characteristics explored. It should form an powerful component technology in the integrated management of locust and grasshopper pests.
• 2 The particular advantages of Metarhizium anisopliae were found to be efficacy and persistence, low vertebrate toxicity, little environmental impact, conservation of natural enemies and potential for recycling. Additional socio-economic advantages include the possibility of local production, ease of disposal and versatility in use. The principal disadvantages relate to operating characteristics such as slower speed of kill and slightly greater lability in storage than chemical pesticides.
• 3 Strategies are being developed to integrate biological control agents into locust and grasshopper management schemes; for Metarhizium the accent is placed on: (i) treating the pest before it invades crops and (ii) situations with a high premium on environmental issues.
• 4 For some pest situations, fast-acting chemical pesticides will still be necessary for crop protection.
• 5 A cheaper biological agent, such as Nosema locustae, with the capacity to persist in the pest insect population would be useful. Research is recommended on the long-term impact of Nosema in Africa.
• 6 An evaluation of the utility of the manual destruction of egg pods leads to the conclusion that we should consider the possibility of importing egg parasitoids, such as Scelio parvicornis from Australia, into Africa.
• 7 Further development work is needed to clarify the economics and politics of locust and grasshopper control; to improve the regulatory framework for biopesticides; to inform key decision makers of the availability and potential of Metarhizium; and to implement the bio-intensive IPM strategies described.

     

Button osteoma: its etiology and pathophysiology

The present study investigates a circumscribed bony overgrowth on the cranial vault, known as button osteoma (BtO) and referred to here as button lesion (BtL). We discuss its anthropological implications. Data on its histology, location, and population distribution (by age, race, and gender) are provided. Microscopically, BtL is composed of well-organized dense lamellated bone which is poorly vascularized and with very few osteocytes. It forms a dome-shaped roof over an underlying diploeized area which includes the ectocranial table. The frequency of BtL is similar in modern (37.6%) and archaeological (41.1%) populations, in blacks, whites, males, and females, and correlates with age. It is rare in nonhuman primates. Fifty-five percent of the human skulls studied by us had BtL only on the parietal, 23.6% on the frontal, and 3.6% on the occipital bones. Fifteen percent had BtL on both the frontal and parietal bones. No lateral preference was found. Most skulls with BtL (64.1%) had only one lesion, 20.4% had two BtL, and 15.4% demonstrated multiple BtL. The average number of button osteomas on an affected skull was 1.97. The frequency of large osteomas (0.5-1.0 cm) was similar in young and old age groups. The demographic characteristics of BtL, mainly its high frequency among ancient and modern populations, its independence of sex and race, its scarcity in other primates, and the fact that its macro- and microstruture are indicative of an hamartoma (and not an osteoma or exostosis) suggest an evolutionary background to the phenomenon.     

Dental and general health in a population of wild ring-tailed lemurs: a life history approach

Data are presented on dental and general health for seven groups of wild ring-tailed lemurs, Lemur catta, from the Beza Mahafaly Reserve, in southern Madagascar. As part of a study of population demography, adults were captured, collared, and tagged, and biometric measurements, dental casts, and analyses of dental and general health were made. Results indicate that patterns of dental health vary by individual, age, sex, and habitat. Prime adults show more dental attrition than young adults. Prime males living in more marginal habitats show greater mean attrition than those living in richer habitats. Dental damage, specifically to the toothcomb, indicates that mechanical stresses to this region may include the initial harvesting of foods, in addition to grooming. Males exhibit more evidence of past trauma, including scars and chipped teeth. These results indicate that environmental as well as social factors, such as female dominance, may lead to sex differences in health patterns among lemurs.     

Image processing,diagnostic information extraction and quantitative assessment in pathology

As we enter the information age we hold strong beliefs in the benefits of digital technology applied to pathology: numerical representation offers objectivity . Digital knowledge may indeed lead to significant information discovery, and, processing systems might be designed to allow a true evolution of capabilities. Questions arise whether the methodology underlying quantitative analysis provides the information that we need and whether it is appropriate for some of the problems encountered in diagnostic and prognostic histopathology. While one certainly would not dispute the value of statistical procedures, the clinical needs call for individual patient targeted prognosis.     

Chronopathological aspects of disease incidence in rice (Oryza sativa L.)

Rice seedlings maintained under uncontrolled glasshouse conditions were inoculated with conidial suspensions of a fungal pathogen, Helminthosporium oryzae, at various times during the 24 h. Significant increase in the percent germination and germ tube length of conidia were observed in the rice samples inoculated at 02:00 and 06:00h. The 24 h temporal variation in leaf temperature was positively correlated with variation in stomatal movements. The results indicate a 24 h rhythm in the behavior of the fungal pathogen on the host in relation to the conditions of the growing environment. In all the inoculated seedlings, the appearance of a large number of brown leaf spots was confined to the light span. Among the plants inoculated, earlier initiation of brown leaf spot appearance, maximum number of leaf spots, and highest disease severity were observed when plants were inoculated at 02:00h. There was a positive correlation between disease severity of the host and in vivo values of percent germination of conidia and germ tube length of the pathogen in plants inoculated between 02:00 and 06:00h. The findings of this study implicate that light intensity and temperature could play a predominant role in controlling disease susceptibility rhythms in plants.