Reliability of ultrasonographic measurements of bovine sole structures in relation to sole horn thickness, measured by computed tomography, and sole horn hardness.

The goal of the present study was to determine the effect of sole horn thickness (SHT) and sole horn hardness (SHD) on ultrasonographic visualization of sole structures in the inner and outer claws of 150 Holstein-Friesian cows, and to evaluate different ultrasound frequencies for this purpose. Ultrasonographic views of the sole structure were considered complete when 3 echogenic lines, representing the ventral surface of the sole horn, the borders of the sole horn and soft-tissue layer, and the ventral surface of the distal phalanx, were seen. The proportion of complete ultrasonographic views of the sole structures, designated as the ultrasonographic visualization proportion (UVP), and the measurement errors of SHT were evaluated by comparing images from computed tomography (CT) and ultrasonography. The latter images were generated using 3 different probes, frequencies of 6.5 and 5.0 MHz, and 2 different ultrasound machines (#1 and #2) to assess the apex, middle, and heel regions of the claws. The UVP were 60.8 to 77.9% for the 6.5-MHz probe in ultrasound machine #1 (probe A), which were lower than those (>90%) for both the 5.0-MHz probe in ultrasound machine #1 (probe B) and the 5.0-MHz probe in ultrasound machine #2 (probe C). The UVP was significantly lower in claws with an SHD ≥50 units than in claws with an SHD <40 or 40 to <50 units (UVP: 77.1% compared with 93.7 and 91.4%, respectively) when measured with probe B. In claws with an SHT <10 mm, the UVP was significantly lower when SHD was ≥50 units compared with <40 or 40 to >50 units; the values were 69.0% versus 91.3 and 85.9%, respectively, for probe A, and 89.7% versus 100 and 100%, respectively, for probe B. When SHT were measured by either probes A or B in ultrasound machine #1, the proportions of claws in which ultrasonographic values were within a ±1 mm range compared with the values obtained by CT were 84.9 to 91.3% for CT-determined SHT <5 mm, 66.7 to 71.9% for CT-determined SHT 5 to <7 mm, 28.9 to 51.2% for CT-determined SHT 7 to <10 mm, and 6.2 to 19.7% for CT-determined SHT ≥10 mm. The data indicated that increased SHT was associated with a decrease in ultrasonographic measurement accuracy. In claws with an SHT <5 mm, the high proportion of ultrasonographic values that were accurate within a ±1 mm range suggests that this imaging modality would be useful in cows with thin soles.

Quantitative evaluation of the relationship between dorsal wall length, sole thickness, and rotation of the distal phalanx in the bovine claw using computed tomography.

Computed tomography (CT) was performed on 800 untrimmed claws (400 inner claws and 400 outer claws) of 200 pairs of bovine hindlimbs to investigate the relationships between dorsal wall length and sole thickness, and between dorsal wall length and the relative rotation angle of distal phalanx-to-sole surface (S-D angle). Sole thickness was 3.8 and 4.0 mm at the apex of the inner claws and outer claws, respectively, with dorsal wall lengths <70 mm. These sole thickness values were less than the critical limit of 5 mm, which is associated with a softer surface following thinning of the soles. A sole thickness of 5 mm at the apex was estimated to correlate with dorsal wall lengths of 72.1 and 72.7 mm for the inner and outer claws, respectively. Sole thickness was 6.1 and 6.4 mm at the apex of the inner and outer claws, respectively, with dorsal wall lengths of 75 mm. These sole thickness values were less than the recommended sole thickness of 7 mm based on the protective function of the soles. A sole thickness >7 mm at the apex was estimated to correlate with a dorsal wall length of 79.8 and 78.4mm for the inner and outer claws, respectively. The S-D angles were recorded as anteversions of 2.9° and 4.7° for the inner and outer claws, respectively, with a dorsal wall length of 75 mm. These values indicate that the distal phalanx is likely to have rotated naturally forward toward the sole surface. The distal phalanx rotated backward to the sole surface at 3.2° and 7.6° for inner claws with dorsal wall lengths of 90-99 and ≥100 mm, respectively; and at 3.5° for outer claws with a dorsal wall length ≥100 mm. Dorsal wall lengths of 85.7 and 97.2 mm were estimated to correlate with a parallel positional relationship of the distal phalanx to the sole surface in the inner and outer claws, respectively.

Quantitative evaluation of bone development of the distal phalanx of the cow hind limb using computed tomography.

Computed tomography (CT) was performed on 400 claws (200 inner and 200 outer claws) of 100 pairs of bovine hind limbs to investigate the etiological theory that an exacerbating factor for ulceration is exostosis of the tuberculum flexorium within the distal phalanx. A variety of morphological changes of the tuberculum flexorium of bovine hind limb claws was visualized by 3-dimensional CT, and the geometry of these claws suggested a growth pattern of bone development with respect to the assumed daily loading patterns. This growth occurs initially at the abaxial caudal aspect of the distal phalanx and is followed by horizontal progression toward the axial aspect. The length of downward bone development on the solar face of the distal phalanx was 2.73±1.32 mm in the outer claws, significantly greater than in the inner claws (2.38±0.96 mm). Ratios of downward (vertical) bone development to the thickness of the subcutis and the corium (VerBD ratios) did not differ between the outer and inner claws (36.7 vs. 38.3%, respectively). Ratios of horizontal bone development to the axial-to-abaxial line of the tuberculum flexorium (HorBD ratios) were approximately 60% for both outer and inner claws. These quantitative measures regarding horizontal and vertical bone development within the distal phalanx were positively correlated with age and VerBD ratios (r=0.53 and r=0.36 for the inner and outer claws, respectively). Correlations between claw width of the outer claw and length of vertical bone development (r=0.43), the HorBD ratio (r=0.51), and the VerBD ratio (r=0.42) suggested that the relative size difference between the inner and outer claws enhances bone development in the outer claw. Correlation coefficients between VerBD and HorBD ratios (r=0.52 and 0.63 for the inner and outer claws, respectively) suggested that horizontal and vertical bone development occurs as a synchronized process within the tuberculum flexorium. This age-related progress of bone development within the tuberculum flexorium is associated with increased exposure to several exacerbating factors and the laminitic process.

Exonic deletion of CASP10 in a patient presenting with systemic juvenile idiopathic arthritis, but not with autoimmune lymphoproliferative syndrome type IIa.

Systemic juvenile idiopathic arthritis (s-JIA) is a rare inflammatory disease classified as a subtype of chronic childhood arthritis, manifested by spiking fever, erythematous skin rash, pericarditis and hepatosplenomegaly. The genetic background underlying s-JIA remains poorly defined. To detect copy number variations, we performed single nucleotide polymorphism (SNP) array analysis in 50 patients with s-JIA. We found a 13-kb intragenic deletion of CASP10 in one patient. RT-PCR of the mRNA extracted from the patient's lymphoblastoid cells revealed that CASP10 mRNA was truncated. Sequencing the mRNA revealed that this deletion resulted in a frame shift with an early stop codon. CASP10 is known as a causative gene for autoimmune lymphoproliferative syndrome (ALPS) type IIa, another childhood syndrome of lymphadenopathy and splenomegaly associated with autoimmune haemolytic anaemia and thrombocytopenia. TCR αß(+) CD4/CD8 double-negative T cells in the peripheral blood as a diagnostic marker of ALPS were not high in this patient and lymphocyte apoptosis induced by anti-Fas antibody was normal, denying ALPS in the patient. The father and a sister of the patient showing no symptoms of ALPS or s-JIA, also had the same deletion. Furthermore, we found no other mutations of CASP10 in the other 49 s-JIA patients. These data suggest that the pathogenic significance of CASP10 mutations should be carefully evaluated in s-JIA or even ALPS type IIa in further studies.

Abnormal expression of the genes involved in cytokine networks and mitochondrial function in systemic juvenile idiopathic arthritis identified by DNA microarray analysis.

OBJECTIVES: Systemic juvenile idiopathic arthritis (sJIA) is a rheumatic disease in childhood characterised by systemic symptoms and a relatively poor prognosis. Peripheral leukocytes are thought to play a pathological role in sJIA although the exact cause of the disease is still obscure. In this study, we aimed to clarify cellular functional abnormalities in sJIA. METHODS: We analysed the gene expression profile in peripheral leukocytes from 51 patients with sJIA, 6 patients with polyarticular type JIA (polyJIA) and 8 healthy children utilising DNA microarrays. Gene ontology analysis and network analysis were performed on the genes differentially expressed in sJIA to clarify the cellular functional abnormalities. RESULT: A total of 3491 genes were differentially expressed in patients with sJIA compared to healthy individuals. They were functionally categorised mainly into a defence response group and a metabolism group according to gene ontology, suggesting the possible abnormalities in these functions. In the defence response group, molecules predominantly constituting interferon (IFN)gamma and tumour necrosis factor (TNF) network cascades were upregulated. In the metabolism group, oxidative phosphorylation-related genes were downregulated, suggesting a mitochondrial disorder. Expression of mitochondrial DNA-encoded genes including cytochrome c oxidase subunit 1(MT-CO1) and MT-CO2 were suppressed in patients with sJIA but not in patients with polyJIA or healthy children. However, nuclear DNA-encoded cytochrome c oxidases were intact. CONCLUSION: Our findings suggest that sJIA is not only an immunological disease but also a metabolic disease involving mitochondria disorder.

Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle.

The architecture of the junctional sarcoplasmic reticulum (SR) and transverse tubule (T tubule) membranes and the morphology of the two major proteins isolated from these membranes, the ryanodine receptor (or foot protein) and the dihydropyridine receptor, have been examined in detail. Evidence for a direct interaction between the foot protein and a protein component of the junctional T tubule membrane is presented. Comparisons between freeze-fracture images of the junctional SR and rotary-shadowed images of isolated triads and of the isolated foot protein, show that the foot protein has two domains. One is the large hydrophilic foot which spans the junctional gap and is composed of four subunits. The other is a hydrophobic domain which presumably forms the SR Ca2+-release channel and which also has a fourfold symmetry. Freeze-fracture images of the junctional T tubule membranes demonstrate the presence of diamond-shaped clusters of particles that correspond exactly in position to the subunits of the feet protein. These results suggest the presence of a large junctional complex spanning the two junctional membranes and intervening gap. This junctional complex is an ideal candidate for a mechanical coupling hypothesis of excitation-contraction coupling at the triadic junction.

Caffeine and taurine enhance endurance performance.

Caffeine enhances endurance performance; however, its effect on accumulated lactate remains unclear. Conversely, taurine, which also enhances endurance performance, decreases accumulated lactate. In this study, the effect of combination of caffeine and taurine on endurance performance was assessed. Mice ran on a treadmill, and the accumulated lactate was measured. In addition, muscle fibers from the gastrocnemius muscle of the mice were stained with ATPase and analyzed. The use of caffeine and taurine over a 2 week period enhanced endurance performance. Moreover, taurine significantly decreased the accumulated concentration of lactate over long running distances. However, the diameter of the cross-sections and ratios of Types I, IIA, and IIB muscle fibers were not affected.

Quantitative investigation and classification by MRI of residual cleft cysts in the pituitary glands of cows.

The application of MRI to 167 Holstein cows and 76 Japanese black cows made it possible to distinguish two types of residual cleft cysts (RCCs) in their pituitary glands on the basis of the differences in signal intensity: fluid-filled lesions with an intensity equal to that of cerebrospinal fluid (CSF) (hypointense on T1-weighted images and hyperintense on T2-weighted images); and solid lesions that were hypointense compared with cerebral parenchyma and isointense with CSF on T1-weighted images, and hypointense compared with cerebral parenchyma on T2-weighted images. Solid material was observed in lesions with a mean (sd) diameter of 2.09 (1.28) mm in 56 (33.5 per cent) of the Holstein cows, and in lesions with a mean diameter of 1.91 (0.89) mm in 20 (26.3 per cent) of the Japanese black cows. Four of the Holstein cows had RCCs more than 7 mm in diameter. Long-term development of the RCCs was suggested by histological findings of epithelial stratification and a structural shift from having a single to a stratified epithelial layer within the residual clefts of the affected pituitary glands.

[Inflammatory myofibroblastic tumor of the lung; report of a case].

A 24-year-old male admitted to our hospital with a pulmonary nodule detected by his chest X-ray and computed tomography (CT). His laboratory findings were within normal limits. Chest CT showed a 10 mm solitary nodule in the right lower lobe. Positron emission tomography showed moderately positive detection correspond to the nodule. We couldn't rule out a malignant tumor and performed partial resection of the right lower lobe. Pathological findings definitely revealed pulmonary inflammatory myofibroblastic tumor. This case was reported together with some reviews of the literature.

[Surgical treatment for pulmonary aspergillosis with hyper immunoglobulin-E syndrome; report of a case].

A 6-year-old girl who had been diagnosed as hyper immunoglobulin-E syndrome, was admitted to the department of pediatrics of our institute in May 2006, because of pulmonary aspergillosis. The chest X-ray showed bilateral cavities with niveau and fungus ball in the left middle lung field. In spite of medical treatment by antibiotics and antimycotics, the lesions did not improve. Therefore, bilateral lobectomy was done. After surgery, she needed re-operation twice, because of prolonged air leakage. There are few reports of lung surgery for the patient with the hyper immunoglobulin-E syndrome, and we present our case and review previous 2 case reports in the Japanese literature.

Photodynamic detection of canine mammary gland tumours after oral administration of 5-aminolevulinic acid.

5-Aminolevulinic acid (5-ALA) is widely used in photodynamic detection (PDD) and therapy. We evaluated the pharmacokinetics of 5-ALA-induced porphyrins and its effectiveness in PDD in dogs with mammary gland tumours (MGTs) following oral administration. Healthy dogs and those with MGTs (nine each) were orally administered 4 mg kg-1 5-ALA. Protoporphyrin IX (PpIX) was not detected in the plasma of healthy dogs but it peaked in dogs with MGT at 2 h after 5-ALA administration. In the PDD study, 16 dogs with MGT were orally administered 40 mg kg-1 5-ALA, and MGT but not normal tissue showed red fluorescence after 2-4 h. Photon counts were 6635-63 890 and 59-4011 (median, 19 943 and 919) for MGT and non-tumour tissues, respectively. Cell density strongly correlated with PpIX photon counts of MGT tissue of the dogs (R = 0.743, P = 0.0009). We suggest that 5-ALA-PDD might be an effective diagnostic tool for MGTs.

Glomerulonephritis in children with mixed connective tissue disease.

AIMS: Mixed connective tissue disease (MCTD) has overlapping clinical features with systemic lupus erythematosus (SLE). Renal biopsy is necessary for all children with SLE to evaluate the prognosis, because they are at a quite high risk of developing renal complications. Furthermore, lupus nephritis and hypocomplementemia usually precede the appearance of clinical manifestations. Immune complex-mediated nephritis is one of the major complications of MCTD. Juvenile MCTD is known to be associated with a higher risk of nephritis than adult MCTD. However, it is uncertain whether all children with MCTD should be subjected to a renal biopsy, and whether most of those with hypocomplementemia present nephropathy, as in patients with SLE. We examined the histopathological characteristics of juvenile MCTD nephritis, the importance of renal biopsy and the implications of hypocomplementemia in our patients and reported cases of MCTD. MATERIAL AND METHODS: We performed renal biopsy in 11 children with MCTD and found 6 patients with glomerulonephritis. In addition, we studied the frequency and the characteristics of glomerulonephritis in 71 cases of juvenile MCTD (our 11 patients and 60 reported cases). We also analyzed the relationship between hypocomplementemia and pathological features in 41 cases of MCTD nephritis (23 adults, 18 children). RESULTS: 6 of our 11 patients had glomerulonephritis, but of them four had no abnormality in urinalysis at the time of biopsy. In 5 patients renal biopsy showed normal findings. Review of 71 cases of juvenile MCTD showed that of them 28% presented latent asymptomatic nephritis at the time of biopsy. Membranous nephropathy (MN) and mesangial proliferative glomerulonephritis (MPG) were common in MCTD. Interestingly, hypocomplementemia was more frequently observed in patients with MN or mixed form of MN and MPG (MPG/MN) than simple MPG based on our review of 41 cases (p < 0.01). CONCLUSION: A more aggressive indication of renal biopsy should be considered in children with MCTD because of the high incidence of non-clinical nephritis. The hypocomplementemia observed in patients with MCTD suggests the high frequency of glomerulonephritis, including membranous lesions.

Expression of lactate dehydrogenase-A and -B messenger ribonucleic acids in chick glycogen body.

Glucose is a main metabolic substrate in the central nervous system (CNS). Recently, lactate has attracted renewed attention because it plays an important role in the CNS as a metabolic substrate between neurons and astrocytes. Lactate and lactate dehydrogenase (LDH), a key enzyme for lactate and pyruvate interconversion, have been investigated. The glycogen body (GB) is a gelatinous tissue in the dorsal area of the lumbosacral spinal cord in birds. It is composed of uniform cells with high glycogen storage and is thought to be in the astroglia lineage. In this article, we investigated the LDH enzyme activity in embryo GB (embryonic d 12, 14, 16, 17, and 18) and chickens. To detect the subtype of the LDH, mRNA expressions in GB were investigated and compared with those of cerebral cortex and spinal cord. By histochemical observations, LDH enzyme activity was detected in the cytoplasm of GB cells of all embryonic periods after embryonic d 12. In biochemical analysis, the enzymatic activities of the GB were higher than in the cerebral cortex. In the GB the subtype of LDH mRNA was LDM-B only, and in the cerebral cortex and spinal cord, the subtype of LDH mRNA was predominantly LDH-B, and a small amount of LDH-A was found in the chicken and embryo. The LDH-B mRNA expression in GB was detected during all periods of the study (after embryonic d 12). These observations suggest that GB expressed only LDH-B and that GB cells are not lactate-producing cells, like astrocyte, but rather are lactate-consuming cells, similar to neurons in CNS.

[Right atrial blood cyst; report of a case].

A 53-year-old female was admitted to our hospital for examination of an abnormal shadow on chest X-ray. Computed tomography (CT) revealed a large mass of 3 cm in diameter in the right atrium. The mass arose from the right atrial septum and was removed with the interatrial septum. Histological specimen showed a blood cyst contained serous effusion.

[Completion pneumonectomy for pulmonary aspergillosis with hyper immunoglobulin-E syndrome].

A 22-year-old man was admitted to the department of pediatrics of our institute in February 2005, because of pulmonary aspergillosis. He had been diagnosed as hyper immunoglobulin-E syndrome in infancy, and repeated pulmonary infectious desease, such as pulmonary aspergillosis. He received art of right upper lobectomy by pulmonary aspergillosis at the age of 17. In February 2005, he had hemosputum and the chest X-ray showed a giant cavity with niveau in the right lung. In spite of medical treatment by antibiotics and antimycotics, the lesion rapidly increased in size. Therefore, right completion pneumonectomy and omentopexy around the bronchial stump was done. His postoperative course was uneventful.

Involvement of transient receptor potential A1 channel in algesic and analgesic actions of the organic compound limonene.

BACKGROUND: TRPA1 is a Ca-permeable nonselective cation channel expressed in sensory neurons and acts as a nocisensor. Recent reports show that some monoterpenes, a group of naturally occurring organic compounds, modulate TRP channel activity. Here, we report that limonene, being contained in citrus fruits and mushrooms, shows a unique bimodal action on TRPA1 channel. METHODS: We examine the effects of limonene on sensory neurons from wild-type, TRPV1- and TRPA1-gene-deficient mice and on heterologously expressed channels in vitro. Molecular determinants were identified with using mutated channels. Cellular excitability is monitored with ratiometric Ca imaging. Nociceptive and analgesic actions of limonene are also examined in vivo. RESULTS: In wild-type mouse sensory neurons, limonene increased the intracellular Ca(2+) concentration ([Ca(2+) ]i ), which was inhibited by selective inhibitors of TRPA1 but not TRPV1. Limonene-responsive neurons highly corresponded to TRPA1 agonist-sensitive ones. Limonene failed to stimulate sensory neurons from the TRPA1 (-/-) mouse. Heterologously expressed mouse TRPA1 was activated by limonene. Intraplantar injection of limonene elicited acute pain, which was significantly less in TRPA1 (-/-) mice. Systemic administration of limonene reduced nociceptive behaviours evoked by H2 O2 . In both heterologously and endogenously expressed TRPA1, a low concentration of limonene significantly inhibited H2 O2 -induced TRPA1 activation. TRPA1 activation by limonene was abolished in H2 O2 -insensitive cysteine-mutated channels. CONCLUSIONS: Topically applied limonene stimulates TRPA1, resulting in elicitation of acute pain, but its systemic application inhibits nociception induced by oxidative stress. Because limonene is a safe compound, it may be utilized for pain control due to its inhibition of TRPA1 channels. What does this study add: Limonene, a monoterpene in essential oils of various plants, has been known for its antitumor and anti-inflammatory properties. However, molecular basis of their actions has not been identified. This study shows that limonene activates nociceptive TRPA1 and elicits acute pain, when it is topically applied. In addition, systemic application of limonene exerts inhibitory effects on nociception induced by an oxidative stress-induced TRPA1 activation.

Purified ryanodine receptor from rabbit skeletal muscle is the calcium-release channel of sarcoplasmic reticulum.

The ryanodine receptor of rabbit skeletal muscle sarcoplasmic reticulum was purified as a single 450,000-dalton polypeptide from CHAPS-solubilized triads using immunoaffinity chromatography. The purified receptor had a [3H]ryanodine-binding capacity (Bmax) of 490 pmol/mg and a binding affinity (Kd) of 7.0 nM. Using planar bilayer recording techniques, we show that the purified receptor forms cationic channels selective for divalent ions. Ryanodine receptor channels were identical to the Ca-release channels described in native sarcoplasmic reticulum using the same techniques. In the present work, four criteria were used to establish this identity: (a) activation of channels by micromolar Ca and millimolar ATP and inhibition by micromolar ruthenium red, (b) a main channel conductance of 110 +/- 10 pS in 54 mM trans Ca, (c) a long-term open state of lower unitary conductance induced by ryanodine concentrations as low as 20 nM, and (d) a permeability ratio PCa/PTris approximately equal to 14. In addition, we show that the purified ryanodine receptor channel displays a saturable conductance in both monovalent and divalent cation solutions (gamma max for K and Ca = 1 nS and 172 pS, respectively). In the absence of Ca, channels had a broad selectivity for monovalent cations, but in the presence of Ca, they were selectively permeable to Ca against K by a permeability ratio PCa/PK approximately equal to 6. Receptor channels displayed several equivalent conductance levels, which suggest an oligomeric pore structure. We conclude that the 450,000-dalton polypeptide ryanodine receptor is the Ca-release channel of the sarcoplasmic reticulum and is the target site of ruthenium red and ryanodine.

Distribution of PCBs, HCHs and DDTs, and their ecotoxicological implications in Bay of Bengal, India.

Analyses of environmentally persistent pollutants like polychlorinated biphenyls (PCBs), hexachlorocyclohexane (HCH) isomers, and dichlorodiphenyltrichloroethane (DDT) and its metabolites in seawater and sediment samples collected from six locations along the east coast of India were carried out using High-Resolution Gas Chromatograph with High-Resolution Mass Spectrometer (HRGC-HRMS). Sediment and water from Chennai harbour and Cuddalore fishing harbour contained higher concentration of all the compounds. The highest concentration (6570 pg/g dry weight) of total PCB was found in sediment from Chennai harbour followed by sediments sampled in Chennai (opposite to Cooum River mouth) (505 pg/g), Cuddalore fishing harbour (335 pg/g) and Mandapam (251 pg/g). Concentrations in other locations were two orders of magnitude lower than Chennai harbour. A distinct PCB distribution pattern in sediment was observed between harbours and other locations. Greater concentrations of tetra-, penta- and hexachlorobiphenyls were observed in sediments of harbours and opposite to Cooum river mouth, but in other locations lower chlorinated biphenyls (di, tri and tetra-) were more. In seawater, HCH concentration was greater than DDT, but it was quite opposite in sediments. Elevated levels of DDT in sediment were observed only at highly populated urban locations, reflecting the local usage and input of this pesticide. Based on sediment/water quality criteria/guidelines, some coastal locations of the Bay of Bengal could be designated as being polluted by DDTs and gamma-HCH (lindane), but not by PCBs. This investigation reveals the declining trend on the environmental burden of persistent pesticides in Indian marine environment. Data on the organochlorine concentrations found in this survey can be used as reference levels for future POPs monitoring programme.

[Intraoperative frozen section diiagnosis of small peripheral lung adenocarcinoma for limited operation].

Sixty-two cases of peripheral lung adenocarcinoma 2 cm or less in diameter were diagnosed as type A, B, or C according to Noguchi classifications by intraoperative frozen section diagnosis. Four of 19 type A were changed finally to type B by postoperative pathologic examination. Likewise 10 of 34 type B were changed finally to 1 type A, 8 type C, and 1 type D. Three of 9 type C were changed finally to 2 type B and 1 type D. Frozen section diagnosis for small peripheral lung adenocarcinoma has some special problems and limitations. Only cases of type A diagnosed by frozen section diagnosis should be permitted to undergo limited surgical resection.

On the mechanism of protection of distal joints after local gene transfer in collagen-induced arthritis.

Considerable interest has been generated by the observation that adenovirus-mediated gene delivery to a single arthritic joint results in suppression of arthritis in distal joints associated with the presence of small numbers of transduced cells in distal joints. It has been proposed that this is mediated by trafficking of transduced cells from the injected to distal joints. There are, however, alternative explanations that have not been explored, including the possibility that transgene protein or infectious virions circulate to distal sites. To investigate these possibilities, a replication-incompetent adenovirus encoding viral IL-10 (vIL-10) was administered to naive mice and to mice with collagen-induced arthritis by intraarticular, periarticular, or intravenous injection. In all cases, the ability to protect distal joints correlated with serum levels of vIL-10 protein. After intraarticular or intravenous injection, vIL-10 cDNA could be detected not only in distal joints, but also in the liver, which is the major target of circulating adenovirus, demonstrating that adenovirus circulating through the bloodstream is taken up by the joint tissue. Periarticular administration of adenovirus, which resulted in lower serum levels of vIL-10, protected only the injected paws and failed to induce trafficking immunoregulatory cells capable of suppressing distal disease. These observations suggest that circulating vIL-10 protein is the major mediator of distal protection. The presence of small numbers of transduced cells at distal sites can be accounted for by transduction of distal synovium after entry of adenovirus virions into the circulation.