Expression of tenascin by vascular smooth muscle cells. Alterations in hypertensive rats and stimulation by angiotensin II.

The extracellular matrix glycoprotein tenascin is associated with remodeling events in many embryonic and pathologic tissues. The expression of tenascin has been investigated by immunohistochemistry in blood vessels of Wistar-Kyoto (normotensive) and spontaneously hypertensive rats. Weak tenascin staining was present throughout the tunica media of large and small arteries from normotensive animals; strong staining was only detectable at branching sites. In arteries from hypertensive animals, foci of strong tenascin staining were scattered throughout the tunica media. The expression of tenascin mRNA and protein by rat aortic smooth muscle cells cultured in serum-free medium was induced by the vasoconstrictor peptide angiotensin II. Transforming growth factor-beta and platelet-derived growth factor also stimulated tenascin mRNA expression. Vascular smooth muscle cells attached specifically to a substratum of tenascin, but remained rounded. Thus, increased focal tenascin expression by vascular smooth muscle cells is associated with hypertension, and may mediate angiotensin II-induced changes in vascular structure in hypertension.     

Leucocyte Migration Test and Hypersensitivity to Glafenin

The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin.     

The homogeneous photopolymerization of methyl methacrylate by colloidal cadmium sulfide

A completely new method of initiating the homogeneous radical polymerization of methyl methacrylate in bulk or in solution via the photogeneration of an electron hole pair in colloidal cadmium sulfide is presented. A polymerization mechanism involving an excited cadmium sulfide particle in both the initiation and termination steps is proposed. In the initiation a methyl methacrylate molecule is oxidized by a positive hole photogenerated in a CdS particle, which results in a novel chain-end structure of the poly(methyl methacrylate) (PMMA). Degradative chain transfer to reduced excited cadmium sulfide particles is responsible for chain termination. Thus, for the first time, a detailed polymerization mechanism in which all states of the polymerization, i.e., initiation, propagation, chain transfer and termination, is presented for the polymerization of vinyl monomers initiated by semiconductors. Thermogravimetry (TG) showed that the newly synthesized PMMA has greatly enhanced thermal stability when compared to normal radically prepared PMMA. In fact, the thermal stability approaches that of anionically prepared PMMA but is experimentally much easier to prepare. This technique enables the homogeneous embedding of CdS particles in a polymer matrix.     

How well does the CSF inform upon pathology in the brain in Creutzfeldt-Jakob and Alzheimer's diseases?

Analysis of lumbar cerebrospinal fluid (CSF) plays a major role in the investigation of central nervous system disease, but how well do the changes in the CSF reflect pathology within the brain and spinal cord parenchyma? Both Creutzfeldt-Jakob (CJD) and Alzheimer's disease (AD) are characterized by the deposition of insoluble beta-pleated sheet peptides [prion protein (PrP) and beta-amyloid (Abeta), respectively] in the extracellular spaces of grey matter in the brain, but there is discordance in both diseases between the peptide levels in the brain and in the CSF. Experimental studies using tracers have shown that interstitial fluid (ISF) drains through very narrow intercellular spaces within grey matter into bulk flow perivascular channels that surround penetrating arteries. ISF then flows to the surface of the brain and joins CSF to drain to cervical lymph nodes. Such drainage of ISF and CSF to regional lymph nodes in the rat plays a significant role in B-cell and T-cell immune reactions within the brain. In man, the pia mater separates the periarterial ISF drainage pathways from the CSF in the subarachnoid space. The almost complete lack of insoluble protease-resistant PrP entering the CSF from the brain in patients with CJD, reported by Wong et al. in this issue of the Journal of Pathology, illustrates the limitations of ISF drainage pathways for the elimination of insoluble peptides from brain tissue. Insoluble Abeta accumulates in the extracellular spaces as plaques in AD and in periarterial ISF drainage pathways as cerebral amyloid angiopathy. Soluble Abeta appears to become entrapped by the insoluble Abeta in the ISF drainage pathways; thus, as the level of soluble Abeta in the brain rises in AD, the level in the CSF falls. Thus, the changes in the CSF do not accurately reflect the accumulation of the abnormal peptides in the brain parenchyma in either CJD or AD. In both diseases, facilitation of ISF drainage and elimination of PrP and Abeta peptides from the extracellular spaces of the brain may lead to practical therapeutic strategies for these devastating disorders.     

Uptake and esterification of arachidonic acid by trophozoites of Giardia lamblia

Although trophozoites of Giardia lamblia have not been demonstrated to possess the capacity for synthesis of phospholipids, these protozoan parasites would be exposed to fatty acids within the human small intestine. We have evaluated the metabolic incorporation of arachidonic and palmitic acids by Giardia trophozoites. Trophozoites (2.25 X 10(6)) were incubated with 12 nM [3H]fatty acid for up to 60 min. Uptake of [3H]arachidonate by trophozoites was rapid, increasing from 37% at 1 min to 65% at 10 min. Uptake of palmitate was rapid but less extensive. In contrast to palmitate, almost all of the trophozoite-associated [3H]arachidonate was esterified into phospholipids and neutral lipids. By 1 and 60 min 37% and 82% of [3H]arachidonate, respectively, were incorporated into phospholipids, including phosphatidylinositol and phosphatidylcholine. Peak incorporation of [3H]arachidonate into phosphatidylcholine (30 mmol [3H]fatty acid (mol phospholipid)-1) occurred at 60 min; whereas incorporation into the pool of phosphatidylinositol, which accounted for only 4% of trophozoite phospholipid, was maximal at 10 min (190 mmol [3H]fatty acid (mol phospholipid)-1) and declined significantly thereafter as arachidonic acid was released from phosphatidylinositol. Therefore, Giardia trophozoites not only utilize exogenous fatty acids in the formation of glycerolipids but also preferentially incorporate arachidonic acid into a metabolically active pool of phosphatidylinositol.     

Intrathecal IgM response in disseminated cerebrospinal metastasis from malignant melanoma

Summary Neurological complications are a major cause of morbidity and mortality in patients with disseminated malignant melanoma. We have studied and correlated clinical and cerebrospinal fluid (CSF) findings in 20 patients with central nervous system metastases from malignant melanoma including 8 patients with metastatic meningeal melanomatosis (MMM) and 12 patients with solid cerebral metastases (SCM). The putative CSF tumor markers, fibronectin and ₂-microglobulin, were elevated significantly in MMM but not in SCM patients. A prominent increase in the IgM index, which reflects intrathecal B-cell stimulation, and a rise of IgG index, interleukin-6, and tumor necrosis factor- in MMM patients provide preliminary evidence for a local intrathecal immune response triggered by melanoma cell invasion of the subarachnoid space.     

Proliferative vitreoretinopathy — is it anything more than wound healing at the wrong place?

Proliferative vitreoretinopathy (PVR) is a reactive process of the ocular tissue after perforating trauma, retinal detachment, and surgical manipulations. Although several studies, most of them experimental, have focused on the detection of specific etiologic factors in the development of PVR, there is compelling evidence that PVR is nothing more than a physiologic tissue repair process with undesirable consequences for the retina. Important features of PVR involving the role of platelets, mononuclear phagocytes, and fibroblasts parallel the chain of events observed in tissue repair elsewhere in the body. Numerous experimental models for PVR, originally designed to find specific stimuli for the generation of intraocular traction membrane formation, have shown that the process of PVR is the common pathway of the eye's reaction to vitreoretinal trauma of any kind. Accordingly, vitreoretinal surgeons could learn a lot from the work of other disciplines, e.g. surgery and dermatology, on wound healing, and the factors known to modify wound healing elsewhere in the body should be taken into consideration. The well-established impairment of tissue repair processes caused by medical treatment with corticosteroids and cytotoxic agents suggests a combined medical approach to PVR as an adjunct to surgical treatment, using refined methods of application and dosage. Steroids and cytotoxic drugs will influence the course of PVR by suppressing macrophage recruitment and the initial inflammatory reaction as well as the proliferative phase of wound healing with traction retinal detachment, respectively.     

Sex hormone receptor status of the dental pulp and lesions of pulpal origin

OBJECTIVE: The purpose of this study was to determine whether the dental pulp and lesions of pulpal origin (eg, pulp polyps, periapical granulomas, and periapical cysts) exhibit receptors for the sex steroid hormones estrogen, progesterone, and androgen. STUDY DESIGN: Staining for the receptors of the hormones estrogen, progesterone, and androgen was accomplished through use of available immunohistochemical detection techniques. Pulpal tissues were obtained from freshly extracted human third molars; the other tissues were obtained from the Oral and Maxillofacial Pathology Laboratory archives. Ten samples of each tissue were processed and immunostained for these specific receptors. RESULTS: Staining for estrogen and androgen receptors was essentially negative for all cell populations examined. However, positive progesterone receptor staining of varying degrees was noted in 8 of 10 pulpal specimens. Primarily, pulpal fibroblasts and odontoblasts exhibited positive immunoreactivity. CONCLUSIONS: The results of this study suggest that although the dental pulp may be a potential target tissue for progesterone, evidence is lacking with respect to the other sex steroid hormones.