Microfilamentous type VI collagen in the hyalinized stroma of the hypertrophied ligamentum flavum

Summary Thickened ligamenta flava obtained from 14 patients with spinal canal stenosis were examined with special reference to type VI collagen. The characteristic histological finding in the thickened area was rupture of normal elastic fibre meshwork with resultant fibrosis which usually appeared hyaline. Using an immunohistological method, collagen types VI, I and III were found to be present in the hyaline matrix. Ultrastructural study revealed many microfilamentous structures of type VI collagen admixed in loosely packed, banded collagen fibres. With differential salt precipitation of pepsin-extracted collagen the existence of type VI collagen was confirmed by SDS-polyacrylamide gel electrophoresis analysis and Western blotting analysis using anti-type VI collagen antibody. Quantification of type VI collagen in pepsin-extracted crude collagen samples by an inhibition enzyme-linked immunosorbent assay showed an increasing amount of type VI collagen in the thickened ligamenta flava compared to the normal ligaments. Thus, increase of type VI collagen is the main contribution to the thickening of the ligamentum flavum. This may represent an adaptational and reparative process associated with disruption of elastic fibres.     

Bruceine B, A Potent Inhibitor of Leukocyte-Endothelial Cell Adhesion

Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 g/ml; 0.44 M) inhibited human neutrophil or T cell adhesion to tumor necrosis factor- (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.     

ISOLATED ADRENOCORTICOTROPIC HORMONE (ACTH) DEFICIENCY

The case to be reported is that of a 72-year-old woman with isolated adrenocorticotropic hormone (ACTH) deficiency, who complained of anorexia and generalized malaise. The secretions of human growth hormone(HGH), prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) were all within normal limit. In spite of the extremely low level of Cortisol, the plasma level of AGTH would not rise sufficiently, but a marked response of Cortisol to AGTH stimulation was recognizaed. The postmortem examination revealed a decrease In basophilic or PAS-positive cells of the anterior pituitary gland which also showed a selective loss of AGTH-secreting cells over immunohistochemical study. Electron microscope could easily visualize somatotroph, mammotroph, thyrotroph, FSH- and LH-gonadtroph, but corticotroph was difficult to be discerned. Adrenocortical cells demonstrated atrophy and degeneration, for which the zona fasciculata and zona reticularis were narrowed. The zona glomerulosa was slightly enlarged In width.     

Giant inflammatory polyposis of the descending colon associated with a Crohn's disease-like colitis

A case of giant inflammatory polyposis associated with a localized inflammatory bowel disease of the descending colon in a 49-year-old man is presented. Lower abdominal distension rapidly appeared without any previous history of gastrointestinal disease. Two months later, he underwent a left hemicolectomy. Postoperative recovery was complete and he remains in good health more than 2 years later. The resected colon showed a giant and bizarre polyposis measuring up to 12 cm in length and 2 cm in height and covering the entire circumference of the colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregularly shaped ulcers, which sometimes extended into muscularis propria. Although longitudinal ulcers or scars, stricture, and a cobble-stone appearance were not observed, transmural inflammation and deep fissures were found in the interpolypoid area. From these findings, this case seems to be more similar to Crohn's disease than other inflammatory bowel diseases.     

Nucleotide sequence of dengue type 3 virus genomic RNA encoding viral structural proteins

Complementary DNAs to the 5 proximal region of the dengue virus type 3 RNA were cloned into bacterial plasmids and the nucleotide sequence of 3,000 bases from the 5 terminus of the genome were determined by DNA and RNA sequencing methods using dideoxy chain-termination reactions. Comparison of the nucleotide sequence thus obtained with those of other flavivirus genomes revealed significant homology existing in nucleotide sequence of the flavivirus genomes. When we compared amino acid sequence deduced from the nucleotide sequence with those of other flaviviruses, this genome region was found to include sequences encoding three viral structural proteins C, M, and E and a part of the viral nonstructural protein NS1 in this order in addition to the 5-noncoding sequence. The characteristics and functions of these proteins were discussed based on the deduced amino acid sequences and their hydrophobic profiles. The genetic relationship of flaviviruses was also discussed based on the genetic variation observed in their genomes.     

An autopsy case of hepatic sarcomatoid tumor: Immunohistochemical comparison with a sarcomatous component of hepatocellular carcinoma

A case of primary hepatic tumor exclusively composed of malignant cells with sarcomatous features is described and compared immunohistochemically with two cases of hepatocellular carcinoma (HCC) with a sarcomatous component. More than 30% of HCC cells were positively stained with anti-cytokeratin (CAM5.2), anti-albumin, anti-fibrinogen and anti-α₁-antitrypsin antibodies, and some with anti-epithelial membrane antigen. The present sarcomatoid tumor and the sarcomatous component with HCC showed similar immuno-histochemistry; many tumor cells were strongly immuno-reactive for vimentin and some positive for cytokeratin, albumin, fibrinogen and u,-antitrypsin. Other immunohistochemical markers, indicating specific differentiations to lineage of macrophages, muscle cells, glial cells, endothelial cells and so forth, were not detected in sarcomatous tumor cells of all cases. These findings suggest that the present sarcomatoid tumor would belong to an anaplastic sarcomatous variant of HCC.     

Deposition of complement protein C3b on mixed self-assembled monolayers carrying surface hydroxyl and methyl groups studied by surface plasmon resonance

Since complement activation is recognized as a common response of the host defense system when an artificial medical device is applied to a patient, great effort has been devoted to studies on the interaction of the complement system with artificial materials. However, some uncertainties remain, partially because of the lack of well characterized surfaces and suitable analytic methods for study of the surface phenomena that occur on artificial materials under physiologic conditions. In this study, we employed self-assembled monolayers (SAMs) and the surface plasmon resonance (SPR) technique to study interactions of the serum complement with well characterized surfaces. Self-assembled monolayers carrying various concentrations of hydroxyl groups were prepared using 11-mercapto-1-undecanol (C11-OH) and one of n-nonanethiol, n-dodecanethiol, and n-hexadecanethiol. The amount of NHS deposition on the SAMs increased with increasing C11-OH content of the SAMs, and the amount of anti-C3b antibody immobilization formed on the NHS deposition layers increased with increasing C11-OH content of the SAMs. These results clearly demonstrate that a large amount of C3b, produced through the activation of the complement system, binds covalently to and is adsorbed by hydroxyl-group-rich surfaces. The combination of SAMs and the SPR technique is suitable for studying the interaction of the complement system with solid surfaces, and the results should give basic information needed for a rational design of biocompatible surfaces on synthetic materials.     

Sustained interleukin-6 signalling leads to the development of lymphoid organ-like structures in the lung

A variety of pathological changes are seen in lymphoproliferative disorders of the lung but the histogenesis of these abnormalities is not yet fully understood. We previously showed that adenovirus vector-mediated transient expression of both the human interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes, but not the IL-6 gene alone, in the rat lung induced lymphocytic alveolitis. In the present study, we explored the lung pathology of human IL-6 and IL-6R double transgenic mice to elucidate the effects of prolonged IL-6 signalling on the lung. The transgenic animals developed mononuclear cell accumulation in peribronchovascular regions, but little infiltration into alveolar spaces. Immunohistochemical analysis revealed that the cellular accumulations contained not only mixtures of inflammatory cells but also lymphoid tissue-like structures. As the expression of CXCL13/BLC, the indispensable chemokine for lymphoid organogenesis, was recognized in the B cell follicles of the pulmonary lesions, we speculate that this chemokine plays an inductive role in the development of the lymphoid tissue-like structures. These structures were distinguished from bronchus-associated lymphoid tissues (BALTs) by their location and by the lack of lymphoepithelium, which is a characteristic of BALT. These findings imply that IL-6 signalling may play a role in the pathogenesis of lymphoproliferative disorders of the lung.     

Mevalonic acidemia: First case of Japan

Summary Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation, postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level was found by GC/MS.