Intrinsic healing capacity and tearing process of torn supraspinatus tendons: In situ hybridization study of α1(I) procollagen mRNA

To determine the healing potential and healing process of torn supraspinatus tendons, in situ hybridization was used to localize cells containing α1 type-I procollagen mRNA. Biopsy specimens of torn supraspinatus tendons from 19 patients with complete-thickness tears and 13 patients with incomplete-thickness tears were obtained during surgery. Four macroscopically normal supraspinatus tendons were obtained to serve as normal controls. Specimens were fixed in 10% buffered formalin and embedded in paraffin. A 22-mer oligonucleotide probe was labeled with digoxigenin and used as an in situ marker. The labeled cells were mainly composed of tenocytes and undifferentiated mesenchymal cells. In complete-thickness tears, the labeled cells at the proximal tendon stumps in the specimens that were obtained less than 4 months after trauma were significantly more abundant than in the specimens obtained 4 months or more after trauma. However, the number of labeled cells was maintained at the torn portion even in long-standing incomplete-thickness tears. The labeled cells at the margins of concomitant intratendinous extensions of the tears were detected even in the long-standing tears. The intratendinous extensions exhibited more labeled cell than were bursal-side or joint-side layers of the tendon substance in the incomplete-thickness tears (p < 0.05). The torn supraspinatus tendon may possess an intrinsic healing capability in the intermediate and late phases of tendon healing. Incomplete-thickness tears and concomitant intratendinous extensions can continue to rupture after the initial injury.     

Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Previous studies using transgenic mice and rabbits have demonstrated that high level of LPL activity in adipose and skeletal muscle protects against diet-induced hypercholesterolemia and subsequently prevents aortic atherosclerosis. However, it is unknown, per se, whether increased LPL activity itself is antiatherogenic, or whether the antiatherogenic effect of LPL is dependent upon the LPL lipid-lowering effect. To address this issue, we fed LPL transgenic and littermate rabbits diets containing different amounts of cholesterol (0.3-0.6%) adjusted to maintain their plasma cholesterol concentrations at similarly high levels for 16 weeks. We analyzed their lipoprotein profiles and compared their susceptibility to atherosclerosis. The results showed that the overexpression of LPL in transgenic rabbits reduced remnant lipoproteins (beta-VLDL, d<1.006 g/ml) but concomitantly led to a significant increase of the large (d=1.02-1.04 g/ml) and small LDLs (d=1.04-1.06 g/ml) compared to the amounts in control rabbits. Furthermore, we found that with equally high hypercholesterolemia, transgenic rabbits developed 1.8-fold more extensive aortic atherosclerosis than control rabbits. To examine the hypothesis that altered lipoprotein profiles may be responsible for the enhanced atherosclerosis in transgenic rabbits, we studied the atherogenic properties of apoB-containing lipoproteins in vitro. These studies revealed that small-sized LDLs of transgenic rabbits were more susceptible to copper-induced oxidation and had higher affinity to biglycan than large remnant lipoproteins. We conclude, therefore, that LPL exerts a dual function in terms of its atherogenicity, namely antiatherogenicity, through enhancing receptor-mediated remnant lipoprotein catabolism and proatherogenicity via the generation of a large amount of small-sized LDLs. At an equal atherogenic-cholesterol level, small and dense LDLs are more atherogenic than large remnant lipoproteins.     

Feline CD 4 molecules expressed on feline non-lymphoid cell lines are not enough for productive infection of highly lymphotropic feline immunodeficiency virus isolates

Summary To investigate whether the feline CD 4 (fCD 4) molecules are involved in infections of highly lymphotropic feline immunodeficiency virus (FIV) isolates, we expressed fCD 4 stably on Crandell feline kidney cells andFelis catus whole foetus 4 cells by transfection of a cDNA encoding the fCD 4 glycoprotein, and then infected them with TM 1 and TM 2 strains of FIV, which are unable to infect these cells productively. In spite of fCD 4 being expressed on these cells, no virus production was observed. This result indicates that fCD 4 expression alone cannot induce a productive infection of the FIV TM 1 and TM 2 strains.     

Nuclear abnormalities in Pelger-Huet anomaly; progress in blood cell morphology

Gene abnormalities responsible for familial Pelger-Huet anomaly have been recently discovered. Abnormalities in sequence of Lamin B Receptor(LBR) gene results in a lack of LBR protein that is essential for chromatin-binding to nuclear membrane. In neutrophils lacking LBR protein shows abnormal bilobular or monolobular nuclear forms and hyper-condensed chromatin-aggregation. We re-analyzed distribution of such Pelger-Huet anomaly in other cell lineages; we found that not only neutrophils but erythroblasts, monocytes, lymphocytes, plasma cells, eosinophils and basophils are also carrying chromatin-hypercondensation. One third of megakaryocytes are also binucleated like neutrophils. We compared neutrophil morphology between familial Pelger-Huet anomaly and so called pseudo-Pelger-Huet anomaly observed in patients with myelodysplastic syndromes(MDS) and acute myeloid leukemia(AML). The neutrophils in MDS were much similar to those of the familial anomaly, but neutrophils of AML, such as t (8;21) M2-AML and t (15;17) M3-AML, showed more heterogeneous pattern in lobulation and chromatin-hypercondensation. Especially in M3, differentiation-induction by all-trans retinoic acid induced a marked neutrophilia with pseudo-Pelger-Huet anomaly without chromatin-hypercondensation. Lack of LBR protein in familial Pelger-Huet anomaly results in hypolobulation and chromatin-hypercondensation in neutrophils, but in other cells such as erythroblasts and lymphocytes only chromatin-hypercondensation can be observed. In contrast pseudo-Pelger-Huet anomaly are more heterogeneous in morphology compared to the familial anomaly. The lack of leukemic or MDS transformation in the familial anomaly is a sharp contrast to the neoplastic nature of the pseudo-Pelger-Huet anomaly. In conclusion, our morphological recognition of certain abnormality of cells shows an marked progression when genetic abnormality responsible for some of them are discovered, and often make us recognize a further heterogeneity in them. We, hematologists and technicians, must be well prepared to report our own observation of an un-explained morphological abnormality.     

Giant fusiform aneurysm of the basilar artery: consideration of its pathogenesis

BACKGROUND: We tried to determine the pathogenesis of a fusiform aneurysm of the basilar artery based on the findings of two patients who had pontine infarctions due to thrombosis within the aneurysm. CASE REPORT: The patients were female, aged 75 and 62 years. At autopsy of the first case, the dilated basilar artery was filled with fresh and old thrombus. The wall was extremely thin on the left side, where a fresh red thrombus was evident, and thick on the right side, where an old white thrombus appeared. The thick wall had a thickened and hyalinized intima, and a deposition of atheromatous plaque disrupted both the internal elastic lamina and muscle layer. The left vertebral artery was atherosclerotic and its lumen was severely compromised, but the right vertebral artery was hypoplastic. On angiogram of the second case, the dilated basilar artery presumably was filled with thrombus on the left side, contralateral to the dilated and tortuous vertebral artery. The left vertebral artery was hypoplastic. CONCLUSION: Atherosclerosis may be the essential factor in the pathogenesis of a fusiform aneurysm of the basilar artery in elderly patients. The disrupted internal elastic lamina and muscle layer may be susceptible to mechanical injury by hemodynamic strain, causing progressive attenuation of the arterial wall. Stenosis of the vertebral artery on the dominant side probably produces a jet stream within the basilar artery on the stenotic side and a stagnant zone on the opposite side, promoting the initial thrombus formation.     

High establishment efficiency of lymph node stromal cells which spontaneously produce multiple cytokines derived from adult T-cell leukemia/lymphoma patients

Stromal cells isolated from lymph nodes of adult T-cell leukemia/lymphoma (ATL) patients were cultured. Such lymph node stromal cells (LNSC) could be maintained for more than one year, whereas LNSC from other lymphoproliferative disorders ceased to proliferate within months. The rate of human T lymphotropic virus type I (HTLV-I) integration in these LNSC was examined by nested polymerase chain reaction (PCR) and estimated to be about 1 genome per 100 cells. These LNSC showed the same combination of cytokine production irrespective of the patient origin, granulocyte-macrophage (GM)-CSF, G-CSF, interleukin (IL)-1 beta, IL-6, interferon (IFN)-gamma and IL-8, being positive but not M-CSF, IL-1 alpha, IFN-alpha, tumor necrosis factor (TNF)-alpha, IL-2, LD78 and the IL-1 receptor antagonist (IL-1ra). The results show that LNSC from ATL patients have pronounced proliferation activity and constitutively secrete various cytokines. They therefore provide useful models for studying the microenvironment of lymph nodes in vitro, and especially the growth mechanism of ATL cells.     

Neurofibrillary tangles and Lewy bodies in the locus ceruleus neurons of the aged brain

Summary The presence of Lewy body and neurofibrillary tangle in the locus ceruleus neurons of aged brain is described. Ultrastructural study revealed that in some Lewy bodies the presence of twisted tubules or paired helical filaments amongst the filaments of the Lewy body. A quantitative analysis of serial sections of locus ceruleus from aged brain, incidences of the Lewy body and neurofibrillary change were 0.07% (9/11,515) and 6.6% (15/11,515), respectively. The incidence of neurons containing both structures was 0.008% (1/11,515).