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J A Hightower

Publications and source records attributed to J A Hightower.

15 recordsLinked to original sources
PubMed1994

Intramembranous bone matrix is osteoinductive.

All known bone-derived osteoinductive factors have been isolated from endochondral (EC) bones and all initiate bone induction via EC ossification. However, to date no attempt has been made to isolate comparable factors from bones which form initially and completely via intramembranous (IM) ossification. The purpose of this work was to isolate osteoinductive proteins from IM bones. To accomplish this, we extracted proteins from bovine frontal bone matrix (intramembranous origin) using methods previously described for endochondral (EC) bone matrix (i.e., femur). Bone powder (< 1 mm) was decalcified and proteins extracted with 4 M guanidine hydrochloride. Ultrafiltration was used to isolate and concentrate a 10-100 kilodalton (kDa) fraction, upon which heparin-Sepharose (HS) affinity chromatography was performed. HS-binding (HS-B) and non-binding proteins (HS-NB) were lyophilized with bovine type I collagen (Vitrogen) to form pellets which were implanted subcutaneously in rats. Radiology as well as brightfield, fluorescent, and polarizing microscopy were used to assess the formation of ectopic bone at the site of pellet implantation. In this report we demonstrate that a heparin-Sepharose binding, osteoinductive factor can be extracted and partially purified from bovine intramembranous bone matrix. This factor has a different sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) banding pattern than a comparable osteoinductive/chondroinductive factor isolated from EC bone.

Animals↗
PubMed1991

The matrix of endochondral bone differs from the matrix of intramembranous bone.

Osseous tissue develops via two distinctly different processes: endochondral (EC) ossification and intramembranous (IM) ossification. The present study tests the hypothesis that each type of osseous tissue contains unique inducing factors for the promotion of cartilage and bone development. Previous work suggests that subcutaneous implants of demineralized EC and IM bone matrices both induce endochondral ossification. Thus, it concludes that the bone growth promotion properties of the respective matrices are very similar. As it was unclear to us why EC and IM bone powders should possess identical osteoinductive properties, we attempted to reproduce these results. We implanted EC (femoral) demineralized bone matrix (DBM), IM (frontal) DBM, or a mixture of the two into the ventral thoracic subcutaneous tissue of 12 to 15-week-old male Sprague Dawley rats. Morphological and radiolabeling techniques in this study demonstrated that implants of EC bone matrix induce bone formation via EC ossification in contrast to implants of IM bone matrix which do not induce EC ossification. Our findings suggest that the matrix of EC bone differs qualitatively from the matrix of IM bone due to their respective abilities to induce cartilage and/or bone formation. These observations differ from those previously reported possibly because our IM DBM preparations were not contaminated with tissues of endochondral origin. In current clinical practice, EC DBM allografts are often used to induce new bone formation in defects involving both IM and EC bone. We conclude that there may be clinical settings in which it would be more appropriate to replace bone originally formed via IM ossification with IM DBM rather than EC DBM.

Animals↗
PubMed1989

Systemic injection of group A streptococcal peptidoglycan-polysaccharide complexes elicits persistent neutrophilia and monocytosis associated with polyarthritis in rats.

The perpetuation of inflammatory changes within joints elicited by persisting, poorly biodegradable group A streptococcal cell walls (peptidoglycan-polysaccharide complexes [PG-PS]) is well documented. Chronic changes in the bloodstream induced by PG-PS have not been described previously. We demonstrated that leukocytosis occurs within 3 days after intraperitoneal injection of PG-PS and remains elevated 20 weeks later. Chronic neutrophilia, monocytosis, and lymphocytosis were observed in all experiments. Chronic changes in platelet, erythrocyte, and reticulocyte counts were not seen. The newly documented leukocytosis, lasting for months after PG-PS administration, provided a circulating pool of leukocytes that may participate in chronic inflammatory events in the joint. Although the central role of the macrophage in PG-PS-mediated inflammation has been emphasized (F. G. Dalldorf, W. J. Cromartie, S. K. Anderle, R. L. Clark, and J. H. Schwab, Am. J. Pathol. 100:383-402, 1980), the polymorphonuclear cell may be involved in periods of exacerbation of streptococcal cell wall-mediated polyarthritis. This was supported by our observations that neutrophilia and monocytosis correlate well with the degree of chronic joint inflammation.

Animals↗
PubMed1987

Effects of acute graft-vs-host disease on the liver of the brown Norway rat.

In this study we examined the effects of acute graft-vs-host disease (aGVHD) on the Brown Norway (BN) rat liver. When clinical signs of the disease appeared, rats were inoculated with fluorescent latex beads and 30 min later nonparenchymal cells were isolated from the liver. The cells were then analyzed via flow cytometry, histochemistry, and electron microscopy. Flow cytometry demonstrated that 58% of the cells from the 80 ml/min elutriation fraction (normally rich in Kupffer cells) of the non-GVHD liver had high fluorescence intensity compared to 8% in rats with aGVHD. Determination of the cellular composition of the various fractions with electron microscopy confirmed flow cytometry observations in that only 9% of the 80 ml/min elutriation fraction of GVHD livers had peroxidase-positive rough ER and the morphological appearance of macrophages as compared to 60% in the non-GVHD liver. The low percentage of fluorescent-positive Kupffer cells in the 80 ml/min elutriation fraction of the GVHD liver is attributed to a massive lymphocytic invasion of the liver and not necessarily to a defect in the mononuclear phagocyte system.

Acute Disease↗
PubMed1987

An ultrastructural examination of murine alveolar macrophages following intranasal administration of propionibacterium acnes.

Light and electron microscopic analysis of murine lungs or isolated pulmonary cells was performed three days after intranasal administration of the bacterial immunostimulant, Propionibacterium acnes (P. acnes). Our observations indicated that pulmonary alveolar and airway macrophages (PAMs) were the only cells with P. acnes bacilli in their cytoplasm. Bacilli were not observed in pulmonary interstitial macrophages, granulocytes, lymphocytes or pulmonary parenchymal cells such as type I and type II pneumocytes. Because of the morphological heterogeneity of PAMs observed in control and experimental animals, it was not possible from these studies to be certain about the relative abundance or complexity of lysosomes, endoplasmic reticulum, Golgi and other organelles in the two groups. However, we noted that it was not uncommon to observe in the same PAM, profiles of P. acnes and a well developed Golgi complex and endoplasmic reticulum. These P. acnes--associated morphological alterations occurred at a time when functional activities (e.g., phagocytosis, cytostasis) of PAMs were enhanced.

Animals↗
PubMed1985

Phagocytic activity of alveolar macrophages in patients with bronchogenic carcinoma.

Human bronchoalveolar cells were obtained by lavage during diagnostic fiberoptic bronchoscopy of 21 patients suspected of having lung malignancies. Of these patients 11 were diagnosed as having primary lung cancer (Group I) and included individuals with squamous cell carcinoma, adenocarcinoma, undifferentiated large and oat cell carcinoma at varying locations and TNM stages, 4 patients demonstrated nonprimary metastatic carcinoma (Group II), and 6 patients did not reveal detectable tumors by bronchoscopy or follow-up (Group III) and were included as study controls. We examined the ability of pulmonary alveolar macrophages (PAMs) lavaged from patients in each of the three study groups to phagocytose opsonized sheep red blood cells. Phagocytic activity varied among patients in the same and different study groups; however, no significant differences were observed in the phagocytic or tumoristatic activities of PAMs recovered from tumor-bearing and nontumor-bearing lung regions of the same patient. Moreover, lavage fluids collected from tumor-bearing regions did not suppress the phagocytic activity of PAMs collected from control lungs nor lung regions contralateral to the tumor-bearing lung. The data do not support the view that bronchial neoplasms or their secreted products suppress phagocytic functions of alveolar macrophages.

Adult↗
PubMed1983

Enhancement of natural resistance to influenza virus in lipopolysaccharide-responsive and -nonresponsive mice by Propionibacterium acnes.

Lipopolysaccharide-responsive C3H/HeN mice were rendered resistant to a mouse-adapted strain of influenza (Aichi, H(3)N(2)) virus when Propionibacterium acnes was given either intranasally or intraperitoneally several days before virus infection. The time of P. acnes treatment was important since no protection was demonstrated when this agent was given either on the same day as or several days after virus challenge. In contrast, lipopolysaccharide-nonresponsive C3H/HeJ mice were not protected when P. acnes was administered intranasally at any time before infection; however, protection was demonstrated when P. acnes was given by the intraperitoneal route. Depending on the route of inoculation, P. acnes induced several distinctive immunological responses in the lungs of both C3H/HeN and C3H/HeJ mice. Intranasal inoculation was more effective in activating pulmonary macrophages in C3H/HeN than in C3H/HeJ mice. In contrast, intraperitoneal inoculation activated pulmonary natural killer cells in both mouse lines but did not activate pulmonary macrophages.

Adjuvants, Immunologic↗
PubMed1976

A light and electron microscopic investigation of the hepatic parenchyma of the adult newt, Notophthalmus viridescens.

This light and electron microscopic study demonstrates that the liver of the adult newt, Notophthalmus viridescens, consists of a mass of hepatocytes interrupted by blood sinusoids which allow blood to percolate through the parenchyma. The plates separating adjacent sinusoids are usually two or more cells thick and the bile canaliculi lie between 2-6 neighboring cells. Fine structural characteristics of hepatocytes include abundant lipid and glycogen inclusions. Melanophores with developing melanosomes are situated throughout the hepatic parenchyma.

Animals↗
PubMed1975

A light and electron microscopic study of myelopoietic cells in the perihepatic subcapsular region of the liver in the adult aquatic newt, Notophthalmus viridescens.

The liver of the newt, Notophthalmus viridescens, consists of several incompletely separated lobes of parenchymal tissue each of which is covered by a perihepatic subcapsular region (SSR) of the myeloid tissue. This tissue contains neutrophils and eosinophils in various stages of differentiation. As neutrophils developfrom myeloblasts to late neutrophilic myelocytes, two types of granules appear. The primary granules (type of granules formed first) are more electron dense and smaller than the secondary granules (type of granules formed later). The primary granules first appear at the stage designated early neutrophilic myelocyte, and the secondary granules appear at the stage of the maturing neutrophilic myelocyte. The eosinophils present are characterized by much larger granules than those observed in neutrophils. Cells in the PSR which superficially resemble small lymphocytes are primitive stem cells that give rise to neutrophils and eosinophils. The liver PSR is invested by a visceral peritoneum of simple squamous mesothelial cells some of which are ciliated.

Animals↗
PubMed1975

DNA synthesis in the thymus of the adult newt Notophthalmus viridescens.

Lymphocytic activity was examined in thymuses of adult newts by studying the number, location, morphology and fate of cells within thymuses which had been processed for autoradiography 15 min, 2 and 4 h, and 2, 4, and 10 days subsequent to the injection of tritiated thymidine. Results of this study indicate (1) that the adult thymus is a highly proliferative organ, (2) that large and medium-sized lymphocytes present in the peripheral parenchyma give rise to smaller lymphocytes which move centrally and emigrate from the thymus, and (3) that many thymocytes leave the thymus within 2-4 days after they have been produced. The significance of these findings is discussed.

Animals↗