Imaging macrophages and the apoptosis of granulocytes in a rodent model of subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V.

Monocytes/macrophages (Mphis), the predominant cell types in subacute and chronic inflammation, are attracted to and activated by monocyte chemotactic peptide-1 (MCP-1). Mphis promote the resolution of inflammation through the induction of apoptosis and phagocytosis of senescent (spent) and bystander (superfluous) granulocytes. We wished to determine whether MCP-1, which selectively binds to Mphis, could be used to image subacute and chronic inflammation. We also sought to image granulocyte apoptosis within these lesions with technetium-99m labeled annexin V, a marker of apoptotic cells. Sterile inflammation was induced in 45 12-week-old male Sprague-Dawley rats by deep intramuscular injection of turpentine into the right thigh. Groups of four to six animals were then imaged 1 h after tail vein injection of 37-148 MBq (1-4 mCi) of 99mTc-labeled MCP-1 or annexin V 1-14 days after turpentine treatment. Image analysis showed significantly greater activity of both MCP-1 and annexin V in inflamed thighs than in control thighs (165%-290% and 188%-313%, respectively; P<0.01) on days 1-5 after turpentine injection. Dual autoradiography in animals co-injected with iodine-125 labeled bovine serum albumin on days 1 and 4 showed specific location of MCP-1 to infiltrating Mphis while annexin V localized to focal zones of apoptosis within granulocytic infiltrates adjacent to abscess cavities. Scintillation well counting on day 5 demonstrated significantly higher (P<0.005) ratios of abscess to control thigh specific activities for MCP-1 (5.83+/-2.17) and annexin V (9.24 +/- 2.8) as compared to 125I-labeled bovine serum albumin (3.11 +/- 0.65). No significant increases in uptake were noted at imaging or ex vivo analyses on days 13 and 14, when lesions were predominately fibrotic. It is concluded that 99mTc-labeled MCP-1 and 99mTc-labeled annexin V both localize in zones of subacute inflammation, reflecting the density of Mphis and the incidence of apoptotic granulocytes, respectively. These agents may be useful in the characterization of subacute inflammation.

Respiratory symptoms and subcutaneous granuloma caused by mesocercariae: a case report.

A 38-year-old man with no history of pulmonary disease developed intermittent hives and bronchospasms shortly after returning from a hunting trip. Approximately one year later, examination of an excised subcutaneous nodule demonstrated infection with a mesocercaria (larval trematode). The morphology of the parasite was consistent with infection with a parasite of the Alaria spp. or Strigea spp. Eating undercooked wild goose meat during the hunting trip was the most likely source of infection. This appears to be the first report of human infection with mesocercariae acquired through the ingestion of wild goose meat.

Preliminary investigation of ultrasound scattering analysis to identify women at risk for later invasive cancer. I: Motivation and experimental technique for characterization of isolated breast tissue lobules.

A new experimental technique is described that allows the characterization of the angle-dependent ultrasonic scattering properties of isolated breast tissue lobules. A review of breast tissue micro-architecture is presented as background material. Measured estimates of the scatter angle-dependent differential scatter cross-sections (DSC) from 31 excised lobules (14 cancer in situ, 17 noncancer) were examined, and dominant trends described by statistical factors. Three factors were extracted, using principal component factor analysis, which collectively accounted for over 70% of the scatter angle-dependent variation exhibited by the measured data.

Preliminary investigation of ultrasound scattering analysis to identify women at risk for later invasive cancer. II: Extraction of dominant scattering angle-dependent trends from excised breast tissue.

Normalized estimates of the scattering angle-dependent differential scattering cross-section (DSC) at 1.0 MHz were measured from 278 samples of excised breast tissue taken from 66 women. A comparison of results for samples that contained tissue structures previously associated with an increased probability of developing breast cancer to those that did not contain high-risk structures showed that the average magnitude of DSC estimates was insufficient to identify samples with high-risk lesions. Principal component factor analysis (PCFA) was applied to extract scattering angle-dependent trends common to the entire data base. The normalized estimates of the measured DSCs (NDSC) from tissue samples are compared to estimates previously obtained from isolated breast tissue lobules as well as with results from the PCFA. Results are presented that indicate that the dominant angle-dependent trends in the NDSC results are independent of the age of the patient and are similar to trends extracted from isolated breast tissue lobules. The breast tissue structure common to all of these specimens is the terminal duct.

Preliminary results for shear wave speed of sound and attenuation coefficients from excised specimens of human breast tissue.

A pilot study involving 53 specimens of excised human female breast tissue was performed to provide preliminary estimates of the acoustic shear wave speed of sound and linear attenuation coefficient associated with high risk for development of invasive breast cancer. The measured shear wave properties were studied as a function of: 1. whether the tissue was presented as a 2.0 to 4.0 gram mass biopsy sample or a 2.0 to 4.0 gram mass subsample taken from a larger mastectomy source; 2. the time post-excision prior to shear wave characterization; 3. the risk factor associated with the number and types of lesions found in the specimen; and 4. the percent by volume of fat or collagen present in the sample. The shear speed of sound was found to range between 20 and 900 m/s with a tendency for lower speeds as a function of time post excision. The results for shear attenuation coefficients ranged from 300 to 9000 cm-1 and did not show a marked time dependence. Average results from mastectomy specimens differed from those for biopsies, but the difference may have been due to variations in tissue composition and time post excision before shear wave characterization.

Development and transformation of the ductal plate in the developing human liver.

The livers of 15 embryos and fetuses measuring from 0.5 cm to 21 cm in crown-rump length were examined. The liver of the smallest embryo showed a sheet of hepatocytes without any ductal plates or intrahepatic bile ducts. Transformation of the hepatocytes of a hilar ductal plate was first observed in a 1.8-cm embryo. A 10.0-cm fetus had ductal plates virtually throughout the liver. Focal transformation of the flattened cells of the ductal plates into tubules composed of columnar or cuboidal ductal cells was observed. Mature interlobular ducts were observed predominantly in the hilum whereas scattered primitive interlobular ducts were scattered throughout the parenchyma. The transformation of hepatocytes into interlobular bile ducts thus seemed to occur in two stages: in the first, the hepatocytes of the ductal plate became flattened and developed increased cytokeratin; in the second, these flattened cells became focally cuboidal or columnar, lost their carcinoembryonic antigen, became strongly positive for epithelial membrane antigen, and formed tubules and primitive interlobular bile ducts.

Cystic dysplasia of testis.

A rare developmental disorder, cystic dysplasia of the testis, encountered in a newborn infant, is described. The relationship to renal dysplasia and the recent literature are reviewed.

Pathology of renal and hepatic anomalies in Meckel syndrome.

We describe 9 cases of Meckel syndrome (dysencephalia splanchnocystica), ranging in gestational age from 17 to 39 weeks. Five were liveborn, and the longest survival was 30 hours. Six of the 9 had all 3 elements of the classically defined triad, namely occipital encephalocele, renal cystic dysplasia, and postaxial polydactyly. The remaining 3 cases had only 2 elements of the triad. The renal abnormalities in the 9 cases resembled one another closely, varying only slightly in severity. They consisted of renal cystic dysplasia with different degrees of nephronic differentiation. The 8 available livers all contained intrahepatic bile duct anomalies. Seven of them had the classic "ductal plate malformation," as defined by Jorgensen [1977]; the remaining case had a less severe form of this malformation. The livers of the Meckel syndrome fetuses were compared to those of age-matched control fetuses, and it was concluded that the hepatic abnormality represents an arrested development of the intrahepatic biliary system at the stage of biliary cylinders with varying degrees of reactive bile duct proliferation, bile duct dilatation, portal fibrosis, and portal fibrous vascular obliteration superimposed on the arrested pattern. The case showing the least severe hepatic lesion also had the least severe renal lesion. The anomalies that were present are listed. The relationship of the different lesions to each other is briefly discussed. It was concluded that the hepatic lesion appears to be a consistent manifestation in Meckel syndrome and is of diagnostic value as the renal lesion has previously been shown to be.

Factor XIIIa-catalyzed cross-linking of platelet and muscle actin. Regulation by nucleotides.

Actin from human blood platelets or rabbit skeletal muscle can serve as substrate for factor XIIIa. The latter catalyzes the incorporation of 1.5-2 mol monodansylcadaverine/mol rabbit actin and 0.5 mol/mol platelet actin. Highly cross-linked platelet and muscle actin polymers form in the absence of added amines, indicating the presence of both acceptor and donor sites. As expected, the cross-link was found to be a gamma-glutamyl-epsilon-lysine bone, with an average of 0.3-0.4 mol dipeptide/mol platelet actin. Both cross-linking and amine incorporation are prevented by ATP, ADP, GTP, CTP, but not by AMP and cyclic AMP. These nucleotides may have important regulatory role in muscle and non-muscle systems.