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G A Herrera

Publications and source records attributed to G A Herrera.

At least 19 recordsLinked to original sources

The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden.

Primary systemic amyloidosis (AL) is a protein conformation disorder in which monoclonal immunoglobulin light chains produced by clonal plasma cells are deposited as amyloid in the kidneys, heart, liver, or other organs. Why patients with AL present with amyloid disease that displays such organ tropism is unknown. This study tested the hypothesis that both the light-chain variable region (Ig V(L)) germ line genes used by AL clones and the plasma cell burden influenced AL organ tropism. To assess the renal tropism of some light chains, an in vitro renal mesangial cell model of amyloid formation was used. With reverse transcription-polymerase chain reaction, Ig V(L) genes were sequenced from 60 AL patients whose dominant involved organs were renal (52%), cardiac (25%), hepatic (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients with clones derived from the 6a V(lambdaVI) germ line gene were more likely to present with dominant renal involvement, whereas those with clones derived from the 1c, 2a2, and 3r V(lambda) genes were more likely to present with dominant cardiac and multisystem disease. Patients with V(kappa) clones were more likely to have dominant hepatic involvement and patients who met the Durie criteria for myeloma (38%, 23 of 60) were more likely to present with dominant cardiac involvement independent of germ line gene use. In the in vitro model, unlike all other AL light chains tested, lambdaVI light chains formed amyloid rapidly both with and without amyloid-enhancing factor. These data support the hypothesis that germ line gene use and plasma cell burden influence the organ tropism of AL. (Blood. 2001;98:714-720)

Adult↗

The contributions of electron microscopy to the understanding and diagnosis of plasma cell dyscrasia-related renal lesions.

Electron microscopy has been crucial in the definition of many renal diseases. Ultrastructural evaluation has been instrumental in the characterization of many of the morphological manifestations of plasma cell dyscrasia-related renal lesions. Although it is recognized that there is controversy in regards to what the term multiple myeloma specifically refers, for the purposes of this article, myeloma and plasma cell dyscrasia are used interchangeably without consideration to perhaps significant conceptual differences that may exist between the two. Although distal nephron obstructive nephropathy ("myeloma kidney") was rather accurately defined solely on the basis of light microscopic findings and the association of AL-amyloidosis with underlying myeloma was confirmed using histochemical stains, the more subtle and intricate expressions of plasma cell dyscrasia-associated pathology required the electron microscope for proper characterization. The fibrillary nature of amyloid was discerned ultrastructurally, and detecting its characteristic ultrastructural features remains paramount to make a definitive diagnosis of amyloidosis when evaluating difficult cases. Pristine light- and heavy-chain deposits were objectively confirmed as immunomorphological correlates were depicted by immunofluorescence and at the ultrastructural level, substantiating the findings. Tubular interstitial alterations in these disorders other than cast nephropathy were firmly documented when careful ultrastructural studies were conducted experimentally and using clinical material. Likewise, electron microscopy has also played an important role in assessing vascular pathology in these conditions, especially when changes are focal, segmental, subtle, or such that they are easily confused with other pathological entities by light microscopy. Had it not been for the electron microscope, a clear definition of the immunomorphological scope of plasma cell dyscrasia-associated lesions, as understood currently, would not have been possible. Immunoelectron microscopy has provided a welcome added dimension, allowing a thorough characterization by expanding merely morphological data and providing exquisite immunomorphological correlations. This review highlights the role that electron microscopy has played and continues playing in the characterization of plasma cell dyscrasias-related renal lesions.

Amyloidosis↗

The ultrastructural and immunohistochemical heterogeneity of CD-30-positive neoplasms: so-called anaplastic large cell Ki-1 lymphomas.

Anaplastic large cell lymphoma (ALCL), also referred to as Ki-1 lymphomas, was first recognized as an entity with characteristic light microscopic appearance in 1985. This tumor is composed of variably cohesive cells, often with large, markedly atypical, and multinucleated cellular forms. The recognition of ALCL resulted from the development of a monoclonal antibody in Kiel, Germany, named Ki-1, which was initially believed to be a putative marker for Reed-Sternberg cells. This antibody was later found to be specific against the epitope CD-30. Attempts to create strict criteria to preserve this neoplasm as a specific entity have undergone evolution. However, it is now clear that included in this group are a variety of pleomorphic neoplasms with CD-30 immunoreactivity. Some of these neoplasms are nonlymphoid and show marked heterogeneity in their immunohistochemical and ultrastructural profiles. This article aims to highlight the ultrastructural spectrum of neoplasms exhibiting CD-30 positivity that are within the spectrum of ALCL. It remains to be determined if there are subgroups of these CD-30-positive neoplasms that can be segregated on the basis of ultrastructural and immunohistochemical criteria with corresponding clinical correlates that may impact on their management, treatment, and prognosis. We review here the heterogeneity of CD-30-positive neoplasms (so-called anaplastic large cell Ki-1 lymphomas).

Abdominal Neoplasms↗

Variation in vaccination coverage among children of Hispanic ancestry.

BACKGROUND: Estimated vaccination coverage of Hispanic children is consistently lower than that of white non-Hispanic children. "Hispanic ethnicity" defines a highly heterogeneous group of the U.S. population; however, vaccination coverage by ancestry group has not been studied. This study explores differences in vaccination coverage among Hispanic children by ancestry group. METHODS: The National Immunization Survey (NIS) uses a random-digit-dial sample of telephone numbers in each state and in 28 urban areas. The NIS provides vaccination coverage information representative of all U.S. children aged 19 to 35 months. We pooled NIS data from 1996 through 1999 and selected Hispanic and white non-Hispanic children for analysis. We categorized Hispanic children into the following ancestry groups: Mexican, Central American, Puerto Rican, Cuban, South American, and Dominican. We used t tests to detect differences in coverage between children of Hispanic ancestry, by group, compared to white non-Hispanic children, by vaccine, and the vaccination series 4:3:1:3. RESULTS: Estimated vaccination coverage with 4:3:1:3 was 80.1% (95% CI, 79.6-80.6) among white non-Hispanic children. Estimated coverage was lower among Puerto Rican (75.8%; 95% CI, 72.1-79.5), Cuban (73.1%; 95% CI, 65.1-81.1), Mexican (71.7%; 95% CI, 69.9-73.5), and Central American (68.7%; 95% CI, 62.0-75.4) children, and was higher among South American (82.0%; 95% CI, 75.5-88.5) and Dominican (82.2%; 95% CI, 75.5-88.5) children; however, these differences were only statistically significant for Puerto Rican, Mexican, and Central American children. Among children living in poverty, estimated coverage with 4:3:1:3 was lower among Mexican (68.0%; 95% CI, 65.1-70.9), Central American (69.7%; 95% CI, 59.8-79.6), and South American (69.0%; 95% CI, 50.9-87.1) children than among white non-Hispanic children (73.4%; 95% CI, 71.6-75.2); however, this difference was significant only among Mexican children. Coverage was similar or somewhat higher among Puerto Rican (72.9%; 95% CI, 65.7-80.1) and Dominican (80.2%; 95% CI, 68.5-91.9) children than white non-Hispanic children living below poverty. CONCLUSIONS: Findings from the NIS strongly suggest that estimated vaccination coverage among children of Hispanic ancestry varies by group. Improved monitoring of vaccination coverage among Hispanics by community is necessary, and where undervaccination is identified, interventions should be matched to community needs.

Child, Preschool↗

Undervaccinated African-American preschoolers: a case of missed opportunities.

OBJECTIVE: To identify factors associated with undervaccination of African-American preschoolers, to describe the number of vaccination visits made by undervaccinated children and the number of visits needed to be series complete, and to describe the children who did not receive the single dose of measles-containing vaccine recommended for preschoolers. METHODS: We used the 1999 National Immunization Survey (NIS) to describe vaccination coverage for the 4:3:1:3 vaccine series (four doses of diphtheria and tetanus toxoids and pertussis vaccine, three doses of poliovirus vaccine, one dose of any measles-containing vaccine, and three doses of Haemophilus influenzae type b vaccine) among non-Hispanic, African-American preschoolers due to concerns that they may be at risk of undervaccination. Children who did not complete this basic vaccine series were classified for further analysis according to the number of doses they lacked (i.e., one dose missed, two or three doses missed, or four or more doses missed). Significant associations between demographic characteristics and vaccination status or degree of undervaccination were determined. RESULTS: Of the 26.2% of African-American preschoolers who did not complete the 4:3:1:3 vaccine series, 40.3% lacked one, 35.3% lacked two or three, and 25.0% lacked four or more doses of vaccine. Children who did not complete the 4:3:1:3 vaccine series were less likely to have married mothers, were less likely to have mothers aged > or = 35 years, or were less likely to be up to date at age 3 months than the children who completed the 4:3:1:3 vaccine series. Among the undervaccinated, 63.7% had a sufficient number of vaccination visits to have completed the basic series. However, most (78.7%) of the severely undervaccinated (children who lacked more than three doses of vaccine) had three or fewer vaccination visits. For 72.6% of the undervaccinated preschoolers, only one additional vaccination visit was needed to complete the 4:3:1:3 vaccine series; among these, 78.3% had an adequate number of vaccination visits to have completed the series. Overall, 9.9% of the African-American children aged 19 to 35 months (i.e., approximately 85,000 African-American children aged 19 to 35 months) were at risk for measles. Among the children who lacked more than three doses of vaccine, 68.1% were at risk. CONCLUSIONS: Our study suggests that the estimated coverage of 73.8% for the 4:3:1:3 vaccine series among African-American children aged 19 to 35 months was not a result of limited access to care. On the contrary, 90.5% of African-American children had enough vaccination visits to complete the series. To raise coverage and prevent potential outbreaks, providers should assess each child's vaccination status at every visit, and administer all needed vaccinations at that time. For the most severely undervaccinated children, this strategy may not be adequate, because they did not have the minimum number of vaccination visits required for series completion. For these children, other strategies are needed for increasing vaccination coverage.

Adult↗

Monoclonal light chain--mesangial cell interactions: early signaling events and subsequent pathologic effects.

Glomerulopathic monoclonal light chains (G-LC) interact with mesangial cells (MC), resulting in alterations of mesangial homeostasis. Early signaling events control mitogenic activities and cytokine production, which in turn participate in the subsequent pathologic events. Mesangial homeostasis is affected in two very different ways, depending on whether the G-LC is from a patient with light chain deposition disease (LCDD) or light chain-related amyloidosis (AL-Am). In contrast, tubulopathic (T)-LC chains from patients with myeloma cast nephropathy do not significantly interact with MC and result in no alterations in mesangial homeostasis. Therefore, understanding early events in the monoclonal LC-MC interactions is fundamental. MC in culture were exposed to LC obtained and purified from the urine of patients with plasma cell dyscrasias and biopsy-proven renal disease, including LCDD, AL-Am, and myeloma cast nephropathy. Incubation of MC with G-LC, but not T-LC, resulted in cytoskeletal and cell shape changes, activation of platelet-derived growth factor-beta (PDGF-beta) and its corresponding receptor, cytoplasmic to nuclear migration of c-fos and NF-kappa beta signals, and production of monocyte chemoattractant protein-1 (MCP-1), as well as increased expression of Ki-67, a proliferation marker. Although NF-kappa beta activation was directly related to MCP-1 production, c-fos activation regulated proliferative signals and cytoskeletal changes in MC. Amyloidogenic LC were avidly internalized by the MC, whereas LCDD-LC effector targets were located at the MC surface. These cellular events are likely initiated as a result of interactions of the G-LC with yet-uncharacterized MC surface receptors. Dissecting the events taking place when G-LC interact with MC may define potential important targets for selective therapeutic manipulation to ameliorate or prevent the glomerular injury that ensues.

Amyloidosis↗

Benign myoepithelioma of the lung: a case report and review of the literature.

This report describes a benign myoepithelioma of the lung that occurred in a 60-year-old woman. The patient had experienced hoarseness for 6 weeks, and a computed tomographic scan showed a nodule of approximately 2 cm in diameter at the peripheral portion of her right upper lung. Positron emission tomography showed no uptake of F-18 fluorodeoxyglucose in the nodule. Wedge biopsy of the lesion showed benign spindle cells arranged in a whorled pattern. The cells were positive for both cytokeratin and smooth muscle actin, which corresponded to the presence of tonofilaments and myofilaments that were identified ultrastructurally. The features of the present case of benign myoepithelioma that differ from features of previously reported benign and malignant cases of myoepithelioma in the lung are discussed in the report.

Actin Cytoskeleton↗

National, state, and urban area vaccination coverage levels among children aged 19-35 months--United States, 1998.

PROBLEM/CONDITION: High vaccination levels in the population are necessary to decrease disease transmission and prevent disease; therefore, an important component of the U.S. vaccination program is the assessment of vaccination coverage. Current goals are for > or = 90% coverage with recommended vaccines during the first 2 years of life. REPORTING PERIOD: January-December 1998. DESCRIPTION OF SYSTEMS: The National Immunization Survey (NIS) is an ongoing, random-digit-dialed telephone survey that gathers vaccination coverage data for children aged 19-35 months in all 50 states and 28 urban areas. Vaccination coverage rates derived from NIS data are adjusted statistically for households with multiple telephone lines, household nonresponse, the proportion of households without telephones, and vaccination provider nonresponse. The results were also adjusted to match the known total population of children in each survey area. RESULTS: On the basis of NIS data, national coverage was > or = 90% for three doses of poliovirus vaccine (Polio), three doses of Haemophilus influenzae type b vaccine (Hib), and one dose of measles-containing vaccine (MCV). Coverage was the highest ever reported for four doses of any diphtheria and tetanus toxoids and pertussis vaccine (DTP) (i.e., diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids [DT], or diphtheria and tetanus toxoids and acellular pertussis vaccine [DTaP]) (83.9%), three doses of hepatitis B vaccine (Hep B, 87.0%), and one dose of varicella vaccine (43.2%). The number of states achieving the > or = 90% goal was 47 for three doses of Hib, 40 for three doses of Polio, 40 for one dose of MCV, nine for three doses of Hep B, and seven for four doses of DTP. Proportionally fewer urban areas achieved the > or = 90% goal: 23 of 28 for three doses of Hib, 13 for three doses of Polio, 16 for one dose of MCV, five for three doses of Hep B, and one for four doses of DTP. No state or urban area has yet achieved the > or = 90% goal for varicella. INTERPRETATION: Findings from the 1998 NIS indicate that national vaccination coverage levels for routinely recommended childhood vaccines are at the highest levels ever reported. However, substantial variation in coverage remains at the state and urban area levels. PUBLIC HEALTH ACTIONS: The public health community and vaccination providers in areas with low coverage should intensify their efforts to implement recommended strategies for increasing vaccination coverage to ensure that children are equally well protected throughout the United States.

Child, Preschool↗

Renal manifestations of plasma cell dyscrasias: an appraisal from the patients' bedside to the research laboratory.

One of the most prominent features of plasma cell dyscrasias is the frequent occurrence of renal dysfunction. Renal insufficiency is a common finding with elevated serum creatinine in more than 50% of patients with multiple myeloma at the time of diagnosis. Renal failure is the second most common cause of death in myeloma surpassed only by infections. The reasons for renal failure are multifactorial and early accurate diagnosis of the renal alterations may significantly impact morbidity and survival. Renal failure may result from selective glomerular, tubular interstitial, or vascular pathology or from a combination of pathologic events. The disorders associated with plasma cell dyscrasias include those characterized by monoclonal light chain deposition, encompassing AL-amyloidosis, in addition to the less well-characterized entities, such as heavy chain deposition disease and heavy chain amyloidosis. Therefore, it is more accurate to refer to them as monoclonal immunoglobulin deposition diseases. Staining of renal biopsy specimens for kappa and lambda light chains using immunofluorescence techniques and more sophisticated advanced diagnostic techniques such as immunoelectron microscopy permit detailed characterization of the various renal pathologic manifestations. Renal biopsies can identify monoclonal immunoglobulin deposition, and nephrologists have an opportunity to detect an underlying plasma cell dyscrasia early in its clinical course before overt hematologic alterations become manifest and irreversible renal damage has occurred. The overall spectrum of clinical and pathologic manifestations of monoclonal immunoglobulin deposition renal diseases has expanded considerably in recent years. Recent developments in the research arena promise new therapeutic interventions aimed at avoiding or ameliorating renal damage and even promoting reversal of some of the pathologic alterations. Currently, the 5-year survival rate in myeloma is 29% in white patients and 30% in African-American patients, a rather modest improvement from 24% in the 1970s. Bone marrow ablation followed by transplantation is available as an alternative mode of therapy that may be extraordinarily helpful in a subset of patients with early myeloma.

Amyloidosis↗

Immunoelectron microscopy in the age of molecular pathology.

The introduction of molecular biology-based diagnostic procedures in pathology has created substantial expectations in regard to screening, characterization, monitoring, and detection of predisposition to a variety of diseases, most notably malignant neoplasms. It should be emphasized, however, that molecular studies are only one component of the diagnostic process and that more traditional methods are still required in the evaluation of tumors and management of patients. The data obtained from the molecular biology-based studies must be always interpreted in conjunction with the clinical history, immunomorphologic findings, and other pertinent ancillary data. Routine evaluation of tissues using traditional light microscopy remains the backbone of pathologic evaluation. The additive role of molecular diagnostics often depends on how accurate the initial evaluation has been. Ancillary techniques such as immunohistochemistry and electron microscopy remain essential in properly characterizing diseased tissues and in speciation of tumors. Ultrastructural immunolabeling capitalizes on combining these two techniques and providing exquisite immunomorphologic evaluation. The extra time and effort required are more than compensated by the degree of sophistication that can be achieved when this diagnostic technique is utilized and the added expense is rather reasonable. The value of molecular biology-based diagnostics is potentially questionable if the tissue samples are not initially accurately characterized. The question that molecular diagnostics may be trying to answer may be the wrong one or the answer obtained may be interpreted incorrectly if the context of the clinicopathologic situation has not been clearly defined using traditional diagnostic techniques.

Humans↗

Role of glutaraldehyde in calcification of porcine aortic valve fibroblasts.

Glutaraldehyde-treated porcine aortic valve xenografts frequently fail due to calcification. Calcification in the prostheses begins intracellularly. In a previous study, various types of cell injury to canine valvular fibroblasts, including glutaraldehyde treatment, led to calcification. An influx of extracellular Ca2+ into the phosphate-rich cytosol was theorized to be the mechanism of calcification. To test the Ca2+ influx theory, cytosolic Ca2+ and Pi concentrations were assessed in glutaraldehyde-treated porcine aortic valve fibroblasts, and their relationship to a subsequent calcification was studied. Glutaraldehyde caused an immediate and sustained massive cytosolic Ca2+ increase that was dose dependent and a several-fold increase in Pi. Calcification of cells followed within a week. The earliest calcification was observed in blebs formed on glutaraldehyde-treated cells. Live control cells or cells fixed with glutaraldehyde in Ca2+-free solution did not calcify under the same conditions. Concomitant increases in Ca2+ and Pi in glutaraldehyde-treated cells appear to underlie the mechanism of calcification, and the presence of extracellular Ca2+ during glutaraldehyde fixation promotes calcification.

Animals↗

STD testing policies and practices in U.S. city and county jails.

BACKGROUND AND OBJECTIVES: Studies have shown that sexually transmitted disease (STD) rates are high in the incarcerated population. However, little is known about STD testing policies or practices in jails. GOAL: To assess STD testing policies and practices in jails. STUDY DESIGN: The Division of STD Prevention developed and distributed an e-mail survey to 94 counties reporting more than 40 primary and secondary cases in 1996 or having cities with more than 200,000 persons. State and local STD program managers completed the assessment in collaboration with health departments and the main jail facilities in the selected counties. RESULTS: Most facilities (52-77%) had a policy for STD screening based only on symptoms or by arrestee request, and in these facilities, 0.2% to 6% of arrestees were tested. Facilities having a policy of offering routine testing tested only 3% to 45% of arrestees. Large facilities, facilities using public providers, and facilities routinely testing for syphilis using Stat RPR tested significantly more arrestees (P<0.05). Approximately half of the arrestees were released within 48 hours after intake, whereas 45% of facilities did not have STD testing results until after 48 hours. CONCLUSION: Most facilities had a policy for STD screening based only on symptoms or by arrestee request. Facilities having a policy of routine STD testing are not testing most of the arrestees. There is a small window (<48 hours) for STD testing and treatment before release. Smaller jails and facilities using private providers may need additional resources to increase STD testing levels. Correctional facilities should be considered an important setting for STD public health intervention where routine rapid STD screening and treatment on-site could be implemented.

Female↗

In vitro modulation of AL-amyloid formation by human mesangial cells exposed to amyloidogenic light chains.

We have shown in vitro AL-amyloid formation by human mesangial cells (HMCs). AL-amyloid formation may require lysosomal processing of the light chains (LCs) by HMCs for amyloidogenesis to occur. Chloroquine inhibits lysosomal activity. TGF-beta mediates extracellular matrix formation in many glomerulopathies. Thrombospondin (TSP) has been proposed as a mediator of cell proliferation and a marker of early fibrosis. We investigated amyloid formation by HMCs exposed to AL-LCs in the absence of amyloid enhancing factor (AEF). The effects of TGF-beta, TSP and chloroquine on in vitro amyloid formation were studied. HMCs were incubated with two AL-LCs, a light chain deposition disease (LCDD)-LC, or one of two tubulopathic LCs (T-LCs). Additional cells were treated with an AL-LC and chloroquine, TGF-beta, or TSP. Amyloid formation was evaluated microscopically using hematoxylin and eosin, Congo red and Thioflavin-T stains, as well as ultrastructurally. Amyloid was formed only when HMCs were incubated with AL-LCs. Addition of TSP significantly enhanced amyloid formation. In contrast, exogenous TGF-beta and chloroquine significantly attenuated amyloid formation. These findings show that some AL-LCs do not require AEF for amyloidogenesis to occur, and that chloroquine, TGF-beta and sTSP modulate in vitro AL-amyloidosis.

Amyloid↗

Increased acute-phase response and renal amyloidosis in aged CD2-fas-transgenic mice.

We previously demonstrated that increased Fas expression in T cells of aged CD2-fas transgenic (Fas-Tg) CD-1 mice results in an increased immune response and T cell apoptosis. Surprisingly, despite prevention of T cell immune senescence, the average life span of Fas-Tg mice is comparable with that of nontransgenic (non-Tg) mice. Histopathologic evaluation of tissue sections showed that nearly 50% of the aged (>18-mo-old) Fas-Tg mice developed renal amyloid A amyloidosis, whereas no amyloid deposition was observed in aged non-Tg mice. The amyloid A deposition was observed primarily in glomeruli by using immunohistochemical stains and electron microscopy. The full-length amino acid coding sequence of serum amyloid A2 cDNA in CD-1 mice was identical to that of amyloid A amyloidosis-susceptible BALB/c mice. Although there was no significant difference in steady-state serum amyloid A level in the serum of aged non-Tg and Fas-Tg mice, challenging mice with staphylococcal enterotoxin B resulted in significantly higher serum levels of serum amyloid A on day 2 and IL-6 on days 1 and 2 and a higher magnitude of weight loss on day 7 in aged Fas-Tg mice compared with young mice. These parameters, at the indicated time points, were equivalent between young and aged non-Tg mice. Taken together, our data suggest that prevention of T cell senescence in Fas-Tg mice may be a factor in induction of an excessive acute-phase response triggered by T cell activation. The Fas-Tg mice are a novel model for understanding the immunologic mechanisms leading to secondary amyloidosis.

Acute-Phase Reaction↗

Immunolocalization of acidic fibroblast growth factor and receptors in the tubulointerstitial compartment of chronically rejected human renal allografts.

Tubular damage and loss associated with interstitial inflammation and fibrosis may be the most important determinants in chronic renal allograft rejection. To elucidate potential pathophysiologic mechanisms associated with tubulointerstitial lesions, we examined the expression of a fibrogenic cytokine, acidic fibroblast growth factor (FGF-1) and its high-affinity receptors, in both relevant renal transplant controls (n=5) and tissue from patients (n=19) who underwent nephrectomy after graft loss, secondary to chronic rejection. In situ hybridization and immunohistochemical analyses demonstrated minimal expression of FGF-1 mRNA and protein in the tubulointerstitial compartment of the normal human kidney. In contrast, tubulointerstitial lesions in kidney allografts experiencing chronic rejection demonstrated the exaggerated appearance of both FGF-1 protein and mRNA in resident inflammatory and tubular epithelial cells. Patterns of staining were consistent throughout tubular compartments and did not appear to be localized to any particular region. The tubulointerstitium in kidneys with findings of chronic rejection also exhibited increased immunodetection of proliferating cell nuclear antigen in the tubular epithelium, inflammatory cell infiltrate, and neovascular structures. The enhanced appearance of FGF-1 and readily detectable fibroblast growth factor receptors suggests that this polypeptide mitogen may serve as an important mediator of growth and repair responses, associated with development of angiogenesis and tubulointerstitial lesions during chronic rejection of human renal allografts.

Biomarkers↗

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors.

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T-lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window-period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window-period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window-period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.

Biomarkers↗