PubMed Health⌕ Search

Biomedical subjects

M L Gonzalez

Publications and source records attributed to M L Gonzalez.

17 recordsLinked to original sources
PubMed2001

Relationship between complement activation and renal deposition of immune complexes made with IgG2a monoclonal antibodies.

Previous studies identified a single murine monoclonal IgG2a anti-dinitrophenyl antibody that, when combined with the antigen, formed immune complexes (IC) that were preferentially deposited in glomeruli. The present study examined the clearance and organ localization in Balb/c mice of expanded panels of radiolabeled IC containing murine monoclonal antibodies. The results identified a second IgG2a antibody that formed IC with a predilection for renal deposition. IC made with the two IgG2a antibodies that were preferentially deposited in the kidney were the least efficient binders of human C1q or homologous murine C3b and C4b within the IgG2a panel. These observations suggest a new model of IC-mediated renal disease initiation in which relatively weak complement activation leads to inefficient IC clearance by complement receptor-bearing circulating cells and consequent IC deposition in tissues susceptible to IC-mediated injury.

Animals↗
PubMed2000

Cocaine metabolism in human fetal and adult liver microsomes is related to cytochrome P450 3A expression.

Cocaine N-demethylation to norcocaine was studied in human liver microsomes of different ages. Norcocaine was formed at a considerable rate in fetal (45.4+/-18.2 nmol/mg x hour, n = 8) and adult specimens (82.0+/-46.6 nmol/mg x hour, n = 15), p = 0.04 (Mann-Whitney). Furthermore, the apparent Km values in fetal specimens (0.57 and 0.48 mM, n = 2) showed a higher affinity compared with those of adults (mean value 2.7 (1.8-4.25) mM, n = 4). Estimated enzyme metabolic clearance with respect to P450 total content was higher in fetal than in adult liver microsomes (2.22 ml/nmol P450 x hour, and 0.18 (0.14-0.23) ml/nmol P450 x hour, respectively). Several drugs, known to be CYP3A substrates, were used as potential inhibitors of cocaine metabolism. Midazolam, ergotamine and erythromycin showed strong inhibition (approx. 70 %) when used at concentrations of 500 microM (midazolam, erythromycin) or 200 microM (ergotamine). The metabolism of 1 mM cocaine correlated strongly with immunodetected CYP3A protein determined by Western blotting in both fetal (r = 0.89, p = 0.19) and adult specimens (r = 0.82, p < 0.01) . These findings further support CYP3A as a major catalyst of norcocaine formation in human liver microsomes. These results are important given the potential risk of toxicity to the foetus of maternal cocaine abuse during pregnancy. Although the high Km values found in adult livers reduce the importance of this enzyme pathway in cocaine detoxication, this pathway would emerge as significant in circumstances of CYP3A induction and/or drug interactions leading to potential liver toxicity in chronic cocaine abusers.

Adolescent↗
PubMed2000

Glomerular deposition of immune complexes made with IgG2a monoclonal antibodies.

The factors that determine whether immune complexes (IC) are cleared safely from the circulation or are deposited in vulnerable tissues such as glomeruli are not well defined. To better understand how IC are handled, the present study examined the fate in vivo of three model IC preparations with different immunochemical characteristics. Radiolabeled IC were constructed with murine IgG1, IgG2a, or IgG3 anti-DNP mAbs bound to DNP-BSA, designated IgG1 IC, IgG2a IC, and IgG3 IC, respectively. The IC were infused i.v. into BALB/c mice, and clearance and tissue localization of the three IC probes were compared. The results indicate that the major portion of each IC preparation was cleared from the circulation by the liver. However, compared with the other two probes, IgG2a IC were preferentially deposited in the kidney. Histologic examination revealed the presence of IgG2a IC in glomeruli. The enhanced renal uptake of IgG2a IC could not be attributed solely to such characteristics as IC size, Ag/Ab ratio, Ab charge, or affinity. However, the preferential renal deposition of IgG2a IC was abrogated by complement depletion. Thus, enhanced renal uptake in normal mice was complement dependent. These data suggest that interactions between IC and the complement system can influence the propensity of IC to deposit in tissues susceptible to IC-mediated injury.

Animals↗
PubMed1996

Simultaneous occurrence of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis.

UNLABELLED: To the best of our knowledge, 10 cases of Ankylosing Spondylitis (AS) and Diffuse Idiopathic Skeletal Hyperostosis (DISH) coexisting in the same patient have been reported. A new case was found in a female patient at Los Angeles Medical Center in 1993, which we report in this paper. We also review the literature (Medline 1970-1994) and analyze the features of the reported cases. In order to study the incidence of this association in our population we have reviewed 106 cases of AS for radiological features of DISH. We found only one case. CONCLUSION: this is a rare association with an incidence of 0.94% in our patients with AS. From the known cases, patients showing this association present clinically mild AS in which radiologic findings are the basis for the diagnosis. Finally we question the validity of excluding the diagnosis of DISH in patients with radiological features of sacroiliac ankylosis.

Adult↗
PubMed1994

Axon-glia interactions regulate ECM patterning in the postnatal rat olfactory bulb.

It has been suggested that an inhibitory ECM containing chondroitin-6-sulfate proteoglycan (C-6S-PG) and tenascin (TN), which appears homogeneously in the core of the OB following afferent fiber arrival, helps position ingrowing olfactory axons in the prospective glomerular layer (GL) (Gonzalez and Silver, 1992; Gonzalez et al., 1993). Later, a similar ECM associated with astrocytes envelopes axonal glomeruli in rings, suggesting that axons may control the precise ECM patterning. The question remains whether formation of the matrix ring pattern around each axonal glomerulus is an intrinsic property of the matrix-producing cells or a response to developing axons. To determine if the organization of glial associated matrix in the OB was dependent on the presence of axons, we studied the effect of unilateral injection of a neurotoxin into the olfactory epithelium of postnatal rats. Using olfactory marker protein (OMP), beta-tubulin (TUJ1) antibodies, and Nissl staining, we found that at 5 and 10 d following neurotoxin administration the number of glomeruli decreased by an average of 77.0% in the injected side. At the same time, we observed that the TN/C-6S-PG rings and periglomerular cells were present only around the remaining small number of glomeruli. Elsewhere, ECM expression and the periglomerular cell configuration were more disorganized in the GL. The pattern of glial fibrillary acidic protein (GFAP) did not change significantly. We found that OMP staining, beta-tubulin immunoreactivity, and periglomerular cells reformed in a glomerular-like pattern as the olfactory axons reformed by 20 d. As the glomeruli-shaped collection of axon terminals reappeared, TN/C-6S-PG immunoreactivity also reoccurred in rings around the new axon bundles. Again, at this later stage, the expression of GFAP was similar in both sides. In our previous study (Gonzalez et al., 1993), we suggested that the initial gross positioning of glomeruli may be controlled by the overall positioning of TN/C-6S-PG. In the present study, we suggest that the formation of TN/C-6S-PG in the precise ring pattern around glomeruli appears to be dependent upon the presence of bundled olfactory axons. Various mechanisms are discussed that may explain the dynamic change in ECM expression that occurs inside the glomerulus after the neurotoxin treatment.

Animals↗
PubMed1993

Energetics of intersubunit and intrasubunit interactions of Escherichia coli adenosine cyclic 3',5'-phosphate receptor protein.

Escherichia coli cAMP receptor protein (CRP) regulates the expression of a large number of catabolite-sensitive genes. The mechanism of CRP regulation most likely involves communication between subunits and domains. A specific message, such as the activation of CRP, may be manifested as a change in the interactions between these structural entities. Hence, the elucidation of the regulatory mechanism would require a quantitative evaluation of the energetics involved in these interactions. Thus, a study was initiated to define the conditions for reversible denaturation of CRP and to quantitatively assess the energetics involved in the intra- and intersubunit interactions in CRP. The denaturation of CRP was induced by guanidine hydrochloride. The equilibrium unfolding reaction of CRP was monitored by three spectroscopic techniques, namely, fluorescence intensity, fluorescence anisotropy, and circular dichroism. The spectroscopic data implied that CRP unfolds in a single cooperative transition. Sedimentation equilibrium data showed that CRP is dissociated into its monomeric state in high concentrations of denaturant. Unfolding of CRP is completely reversible, as indicated by fluorescence and circular dichroism measurements, and sedimentation data indicated that a dimeric structure of CRP was recovered. The functional and other structural properties of renatured and native CRP have also been examined. Quantitatively identical results were obtained. Results from additional studies as a function of protein concentration and from computer simulation demonstrated that the denaturation of CRP induced by guanidine hydrochloride proceeds according to the following pathway: (CRP2)Native<-->2(CRP)Native<-->2(CRP)Denatured. The delta G values for dissociation (delta Gd) and unfolding (delta G(u)) in the absence of guanidine hydrochloride were determined by linear extrapolation, yielding values of 12.0 +/- 0.6 and 7.2 +/- 0.1 kcal/mol, respectively. To examine the effect of the DNA binding domain on the stability of the cAMP binding domain, two proteolytically resistant cAMP binding cores were prepared from CRP in the presence of cAMP by subtilisin and chymotrypsin digestion, yielding S-CRP and CH-CRP, respectively. Results from an equilibrium denaturation study indicated that the denaturation of both CH-CRP and S-CRP is also completely reversible. Both S-CRP and CH-CRP exist as stable dimers with similar delta Gd values of 10.1 +/- 0.4 and 9.5 +/- 0.4 kcal/mol, respectively. Results from this study in conjunction with crystallographic data [McKay, D. B., Weber, I. T., & Stietz, T. A. (1982) J. Biol. Chem. 257, 9518-9524] indicate that the DNA binding domain and the C-helix are not the only structural elements that are responsible for subunit dimerization.(ABSTRACT TRUNCATED AT 400 WORDS)

Binding Sites↗
PubMed1993

A 7-year follow-up of newborns vaccinated against hepatitis B.

Of 79 children born to asymptomatic HBsAg chronic carrier mothers and vaccinated at birth against hepatitis B, a total of 71, 66 and 56 could be serologically assessed after 1, 5 and 7 years, respectively. Anti-HBs titres (geometric means) of responders decreased from 2475 to 143 IU l-1 between 1 and 5 years of age and dropped to 82 IU l-1 by 7 years. At this time, a booster dose given to 34 children who showed anti-HBs titres lower or slightly higher than 100 IU l-1 significantly increased titres from 34 to 2985 IU l-1 (p < 0.001). Children whose titres following perinatal vaccination reached 100 to 1000 IU l-1 or above 1000 IU l-1 maintained protective levels (> 10 IU l-1) for 3 and 5 years, respectively. As in adults, anti-HBs titres recorded after the initial vaccination indicate the time at which infants should receive booster vaccination.

Child↗
PubMed1991

Detection of clinically suspected deep vein thrombosis using light reflection rheography.

Venography is the current standard for the diagnosis of deep vein thrombosis (DVT). Noninvasive tests have differing sensitivity and specificity, are technically demanding, and may be subject to variability in interpretation. Light reflection rheography (LRR) is a noninvasive method utilizing light-emitting diodes and a sensor to measure light reflected from the skin surface. The intensity of reflected light establishes a graphic pattern that indirectly quantifies parameters of venous function by measuring changes in the microcirculation. Seventy-two patients who underwent contrast venography at our institution were also evaluated with LRR. Twenty-four patients were found to have DVT as demonstrated by venography. Of these, 23 also had DVT detected by LRR. No evidence of thrombus was seen in 45 patients studied by venography; in this group, 35 had normal venous emptying indicated by LRR. Using LRR, a sensitivity of 96% was achieved in the evaluation of clinically suspected DVT. This sensitivity is comparable with other noninvasive tests. In addition, LRR is easy to operate, portable, inexpensive, and not technically demanding. Further investigation is needed to confirm these data and further define the role of LRR in the evaluation of clinically suspected DVT.

Adult↗
PubMed1991

Physician referrals and the medical market place.

Factors determining the extent to which physicians obtain new patients through referrals are examined. A more thorough understanding of physician referral patterns can help to explain how competitive forces function in this market and how physician characteristics and credentials affect individual performance. Referral networks promote entry by young physicians into both primary and nonprimary care medical markets. Nevertheless, there are marked differences in referral patterns between primary care and nonprimary care providers. For instance, referrals are directly related to the degree of market competition and board-certification status among primary care physicians but not among nonprimary care specialists. Membership in a group practice is related to significantly more referral activity among nonprimary care physicians but not among primary care providers. No significant differences were found in referral patterns by physician sex. Although foreign medical graduates (FMGs) receive proportionately fewer referrals than do U.S. medical graduates, the differences are not large. While earlier research suggests that the returns to board certification are higher for female physicians, the present study finds little evidence that board certification is particularly helpful to either female physicians or to FMGs in terms of obtaining patients on referral.

Certification↗
PubMed1991

Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD.

Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C-PTH and MM-PTH serum levels by peritoneal losses of these fragments.

Humans↗
PubMedDate not supplied

The cost of medical professional liability.

The high cost of medical professional liability is a source of growing concern among policymakers, health care consumers, and the medical profession. While the concern is widespread, to date there has been little quantitative evidence on the overall economic impact of the problem. Utilizing data from the American Medical Association's Socioeconomic Monitoring System, the impact of medical professional liability (PL) on the cost of physicians' services has been estimated employing two different methods. Both estimates indicate that the costs of PL are substantial. In particular, the two methods yield estimates of the total cost of PL in 1984 of $13.7 and $12.1 billion, respectively--or approximately 15% of the total expenditures on physicians' services. Furthermore, increased costs associated with PL from 1983 to 1984 alone are estimated under the two methods to have accounted for 63% and 57%, respectively, of the increase in expenditures on physicians' services. These costs include PL insurance premiums, costs of practice changes made in response to increasing PL risk, and costs of incurring claims that are not covered by PL insurance.

American Medical Association↗