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Biomedical subjects

J J Jacobs

Publications and source records attributed to J J Jacobs.

At least 109 records · Page 6Linked to original sources
PubMed1993

Histology of porous-coated acetabular components. 25 cementless cups retrieved after arthroplasty.

25 hemispherical acetabular components retrieved from patients who had a total hip arthroplasty (THA) were studied histologically. All of the components had titanium fiber metal porous coatings and were implanted with adjuvant screw fixation, 18 in primary THA and 7 in revision THA. None of the cups had been removed because of infection or failure of fixation. The components had been in place an average of 30 (1-140) weeks. 18 cups had bone ingrowth into the porous coating. Up to one third of the available void space within the porous coating was occupied by bone, while the maximal proportion of the area of the bone-implant interface with bone ingrowth was over 80 percent. Bone ingrowth was more often observed at the dome and in the vicinity of sites of screw fixation than elsewhere. Peripherally, bone ingrowth was less consistent, and in isolated areas fibrocartilage and mineralized fibrocartilage were occasionally observed. The longer-term cases had more bone ingrowth than the shorter-term cases. Apparent metallic debris was observed within histiocytes adjacent to screw holes, and the amount of this material increased with duration of implantation.

Acetabulum↗
PubMed1993

Mechanisms of bone loss associated with total hip replacement.

The pathogenesis of bone loss after total hip arthroplasty is discussed. Two separate processes are considered: adaptive bone remodeling ("stress-shielding") and osteolysis. Clinical and experimental studies that provide the basis for current and future strategies to minimize the occurrence and severity of these phenomena are summarized.

Adaptation, Physiological↗
PubMed1992

Antiproliferative and depigmenting effects of the histamine (H2) agonist dimaprit and its derivatives on human melanoma cells.

Human melanoma cells were treated in culture with the histamine (H2) agonist S-(3-(N-N-dimethylamino)propyl)isothiourea (dimaprit), a partial agonist, S-(2-(N,N-dimethylamino)ethyl)-isothiourea (nordimaprit), and two analogues of nordimaprit, S-(2-(N,N-diethylamino)ethyl)isothiourea (DENOR) and S-(2-(N,N-diisopropylamino)ethyl)isothiourea (DINOR), to investigate the effects on toxicity and tyrosinase activity. Cell survival studies showed highest toxicity in the constitutively pigmented human melanoma cell line MM418, DINOR being the most effective agent. Toxicity was not blocked by the H2 antagonist cimetidine. Dimaprit and its derivatives decreased tyrosinase activity in the amelanotic human melanoma cell line MM96E and inhibited expression of a melanosomal antigen. Loss of tyrosinase activity could be prevented by cimetidine and ranitidine, an H2 antagonist. Although the tyrosinase activity in MM418 cells was much more resistant to inhibition by these agents compared with that in MM96E cells, prolonged growth in the presence of non-toxic levels of DINOR caused a decrease in tyrosinase activity and subsequent depigmentation. Ultrastructural examination of the depigmented cells showed a decrease in the number of melanized melanosomes and the appearance of premelanosomes. These results indicate that bulky substituents on the tertiary amine group in nordimaprit significantly enhance potency for depigmentation and cell killing but only the former effect is mediated by the H2 receptor.

Cell Division↗
PubMed1992

Physiological modeling of disposition of potential tumor-imaging radiopharmaceuticals in tumor-bearing mice.

Radiopharmaceuticals have great potential in the early detection of human tumors. Three potential 99mTc-labeled platinum compounds based on cisplatin have been synthesized and tested in tumored mice. This report presents the analysis of the disposition data obtained after a single intravenous injection with an empirical, physiologically based pharmacokinetic model. The radioactivity of each radiopharmaceutical after administration was measured in blood, urine, and 15 tissues, including tumor. Parameters included in the model were tissue volumes (experimentally determined), tissue blood flows (determined from literature values), tissue:blood extraction ratios (determined by nonlinear least-squares regression with MULTI-FORTE), and clearance terms (also determined by nonlinear least-squares regression). Data were weighted by the reciprocal of the square of the observed values. Good fits to the experimental data were obtained. As expected, the compound producing the best tumor:blood profile (3) also had the highest tumor extraction ratio (6.2 versus 2.0 and 1.3 for 1 and 2, respectively). Total body clearance values for the radioactivity associated with the three compounds 1-3 were calculated to be 0.09, 0.04, and 0.016 mL/min, respectively. Analysis of data with such an empirical, physiologically based model may assist future development of suitable tumor-imaging agents.

Animals↗
PubMed1992

Local response to biomaterials: bone loss in cementless femoral stems.

While cementless, porous-coated prosthetic components have shown a high percentage of satisfactory clinical results in short and intermediate term follow-up, there are biologic problems associated with implantation of cementless devices that may predispose to clinical failure at longer term follow-up. Central to the issue of long-term performance is the problem of bone loss secondary either to adaptive bone remodeling processes or to the phenomenon of focal osteolysis. The stiffness of the femoral stem and the relative biologic inertness of the materials used are two properties of critical importance. In the future, continuing developments in the areas of prosthetic design, enhancement of fixation, biocompatibility, and biomaterials research will seek to address and resolve these problems.

Animals↗
PubMed1991

Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy.

Serum concentration and urinary excretion of titanium, aluminum, and vanadium were measured for patients who had a well functioning cementless primary total hip replacement of one of two different designs, for patients who had a loose total hip replacement that was to be revised, and for control subjects who had no implant. Serum concentrations of titanium were elevated approximately twofold in the patients who had a loose implant, compared with the values for the control subjects. No major differences in terms of urine concentration of titanium, serum concentration of aluminum, or urine concentration of aluminum were observed among any of the groups that were studied. Concentrations of vanadium were uniformly low in all groups.

Adult↗
PubMed1990

The effect of porous coating processing on the corrosion behavior of cast Co-Cr-Mo surgical implant alloys.

The manufacture of porous coated cobalt-based surgical implant alloys requires sintering--a high temperature process above the incipient melting temperature of this alloy system. The metallurgical changes produced by the high temperature sinter cycle consist of dissolution of interdendritic carbides, massive precipitation of lamellar carbide eutectic phases at grain boundaries, localized porosity from incipient melting that is not completely eliminated by subsequent hot isostatic pressing, and grain growth in fine-grained materials. These microstructural changes, which are known to affect the mechanical properties, do not affect the static in vitro localized and generalized corrosion behavior of the bulk material as determined by anodic polarization measurements in a buffered saline environment and direct examination by scanning electron and optical microscopy. Additionally, cast Co-Cr-Mo surgical implant alloys are found to be immune to crevice corrosion (in the absence of mechanical fretting) in the saline environment studied. The hysteretic component of the anodic polarization curve is not due to crevice corrosion; rather, as suggested by the electrochemical tests and Auger spectroscopy, the hysteresis is due to redox reactions in the chromium-rich surface layer.

Bone and Bones↗
PubMed1990

Genotoxicity and cell cycle effects of platinum-based imaging agents in cisplatin-resistant human tumour cells.

A series of cis-dichloroplatinum(II) 2,3-diaminopropionamide complexes synthesised as potential imaging agents was tested for activity against a human ovarian tumour cell line (CI-80-13S) with high natural resistance to cisplatin and carboplatin as compared with other human cells. The most potent compound, the dimethyl ester of dichloro-[4-(methyleneiminodiacetic acid)phenyl (2',3'-diamino-propionamide)]platinum(II) (complex III), exhibited toxicity towards CI-80-13S cells similar to that observed in other cell lines, an effect that was not shown by the ligand alone or by cis-dichloroplatinum(II) 2,3-diaminopropionamide. However, complex III ester reproduced the genotoxic effects of cisplatin as judged by differential inactivation of two strains of adenovirus and by inhibition of cellular DNA and RNA synthesis; no major differences in these properties were observed between CI-80-13S and cisplatin-sensitive cells. Substantial inhibition of DNA and RNA synthesis was found within 2 h of treatment, much earlier than the effect of cisplatin. Complex III ester, which was 30- to 100-fold less potent than cisplatin, inhibited cell cycle progression in a similar way to equitoxic cisplatin, with cells accumulating in G2 at a dose of low toxicity and being arrested in all stages at higher levels. The latter in combination with colcemid caused extensive fragmentation of CI-80-13S cells. These results suggest that the mechanism of toxicity of such complexes involves factors, in addition to DNA damage, which rapidly inhibit nucleic acid synthesis and overcome natural resistance to cisplatin in the CI-80-13S cell line.

Adenoviridae↗
PubMed1990

Biological evaluation of 99mTc labelled cis-platinum containing benzyliminodiacetic acids as potential tumour imaging agents.

The synthesis of three new potential tumour-imaging radiopharmaceuticals in which a cis-platin derivative is attached to benzyl iminodiacetic acid, a ligand capable of forming a stable complex with 99mTc, has previously been reported by us [Awaluddin et al. Appl. Radiat. Isot. 38, 671-674 (1987)]. We have now carried out extensive biodistribution studies on these compounds as well as on two fragments of their structures which do not contain platinum. The results suggest that the presence of platinum is not essential for the tumour-localizing properties of the radiopharmaceuticals.

Animals↗
PubMed1989

Extracranial skeletal metastasis from a pinealoblastoma. A case report and review of the literature.

Osseous metastases from primary central nervous system (CNS) tumors are rare. The CNS tumors that most frequently metastasize to bone are the glioblastoma multiforme and the medulloblastoma. In this report, a 22-year-old woman sought treatment for a lytic lesion in her right proximal femur 18 months after a craniotomy to remove a pinealoblastoma, a rare primitive neuroectodermal tumor of the pineal gland. An extensive evaluation demonstrated no other primary tumors. A biopsy of the femoral lesion revealed that it was morphologically identical to the pinealoblastoma, and special immunohistochemical stains were performed that verified neuronal differentiation. This may be the first report of a pinealoblastoma associated with an extracranial skeletal metastasis.

Adult↗
PubMed1987

Synthesis and characterization of potential tumor scintigraphic agents.

Potential tumor imaging radiopharmaceutical agents have been prepared by attaching a cisplatin derivative to a ligand capable of forming a stable complex with 99mTc. Three new organometallic compounds, with iminodiacetic acid as the 99mTc chelating group and 2,3-diaminopropionamide as the platinum complexing group, have been prepared and characterized. Preliminary biodistribution studies in tumor bearing mice support the utility of this approach.

Animals↗
PubMed1984

Metal ion release from titanium-based prosthetic segmental replacements of long bones in baboons: a long-term study.

Forty-five baboons that had received titanium-based fiber metal composite segmental bone replacements were studied along with 13 controls without implants. Thirty-eight baboons with implants were sacrificed, and titanium, aluminum, and vanadium levels were assayed in homogenized lung, kidney, spleen, liver, adjacent muscle, and regional lymph nodes. In seven living baboons with implants, blood and urine samples were obtained for trace metal analysis as well as for biochemical and hematological profiles. In the 38 sacrificed baboons with implants, increased titanium levels were noted in the lungs, spleen, adjacent muscle (quadriceps, soleus, and triceps), and regional lymph nodes (inguinal, axillary, and popliteal) in comparison to those of six sacrificed controls without implants. In addition, vanadium was significantly elevated in the lungs of some animals, while aluminum increases were noted in adjacent muscle (quadriceps, soleus, and triceps), lung, and regional lymph nodes (inguinal, axillary, and popliteal). In the seven living baboons with implants, a sixfold increase (p less than 0.0005) in the urine titanium level was noted in comparison to that of seven living controls without implants. Additionally, elevated aluminum levels were found in the serum (p less than 0.0005) of the group with implants. Biochemical and hematological studies did not indicate statistically significant differences in serum electrolytes, in liver and renal function tests, or in complete blood counts between the seven living baboons with implants and their controls.

Aluminum↗
PubMed1982

Cyclo (His-Pro): mapping hypothalamic sites for its hypothermic action.

Hypothalamic loci of Sprague-Dawley rats were individually injected with cyclo (His-Pro) to determine the sites where that metabolite of thyrotropin-releasing hormone acts to produce hypothermia. There was almost always a positive hypothermic response in the preoptic-anterior hypothalamic area (POA/AHA); injection into the posterior or middle hypothalamic areas or into the hippocampus caused no significant decrease in core temperature. The fact that only injection into the POA/AHA evoked hypothermia suggests that this area is a major hypothalamic site of action of cyclo (His-Pro) in modulating thermoregulation in the rat.

Animals↗
PubMed1981

A model of the inguinal canal.

Medical students often find it difficult ot conceptualize and learn the anatomy of the inguinal region and canal. A model of the inguinal canal, appropriate for lecture and laboratory presentations, has been used for many years by one of the authors (J.J.J.), and based on student and staff feedback, is judged a successful visual learning aid. This paper outlines a step-by-step procedure for constructing the model out of plexiglass and colored, felt-tipped marking pens.

Humans↗
PubMed1981

The mutagenic action of aliphatic epoxides.

The mutagenic action of 45 epoxides was investigates in Luria and Delbrück's fluctuation test with Klebsiella pneumoniae as test organism. In this test, 36 of the 45 epoxides appeared to be mutagenic. The mutagenicity of 1,2-epoxides decreased with increasing length of the carbon chain. The mutagenic activity of compounds with a non-terminal epoxide group appeared to be less than that of substances with a terminal one. Generally 1,2-epoxide compounds with electronegative groups were more mutagenic than 1,2-epoxypropane. Of the diepoxides, 1,2,3,4-diepoxybutane appeared to be more mutagenic than 1,2,7,8-diepoxyoctane, while the ring compounds 1,2,5,6-diepoxycyclooctane was hardly mutagenic. The ring compound 4-vinylcyclohexenedioxide, used in electron microscopy that the antibiotic fosfomycin is among the more potent mutagenic substances investigated in this study.

Epoxy Compounds↗