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Biomedical subjects

M J Homer

Publications and source records attributed to M J Homer.

At least 19 recordsLinked to original sources
PubMed2001

Innate resistance to Babesia infection is influenced by genetic background and gender.

Infection of severe combined immunodeficient mice with Babesia sp. strain WA1 was studied to assess the contributions of innate and adaptive immunity in resistance to acute babesiosis. The scid mutation showed little effect in genetically susceptible C3H mice and did not decrease the inherent resistance of C57BL/6 mice to the infection, suggesting that innate immunity plays a central role in determining the course of Babesia infection in these strains. In contrast, the scid mutation dramatically impaired resistance in moderately susceptible BALB/c mice, suggesting that acquired immunity may play an important secondary role. In comparison to their female counterparts, male mice of different genetic backgrounds showed increased resistance to the infection, indicating that the gender of the host may influence protection against babesiosis.

Animals↗
PubMed2000

Babesiosis.

Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by hematotropic parasites of the genus Babesia. Babesial parasites (and those of the closely related genus Theileria) are some of the most ubiquitous and widespread blood parasites in the world, second only to the trypanosomes, and consequently have considerable worldwide economic, medical, and veterinary impact. The parasites are intraerythrocytic and are commonly called piroplasms due to the pear-shaped forms found within infected red blood cells. The piroplasms are transmitted by ixodid ticks and are capable of infecting a wide variety of vertebrate hosts which are competent in maintaining the transmission cycle. Studies involving animal hosts other than humans have contributed significantly to our understanding of the disease process, including possible pathogenic mechanisms of the parasite and immunological responses of the host. To date, there are several species of Babesia that can infect humans, Babesia microti being the most prevalent. Infections with Babesia species generally follow regional distributions; cases in the United States are caused primarily by B. microti, whereas cases in Europe are usually caused by Babesia divergens. The spectrum of disease manifestation is broad, ranging from a silent infection to a fulminant, malaria-like disease, resulting in severe hemolysis and occasionally in death. Recent advances have resulted in the development of several diagnostic tests which have increased the level of sensitivity in detection, thereby facilitating diagnosis, expediting appropriate patient management, and resulting in a more accurate epidemiological description.

Animals↗
PubMed2000

A polymorphic multigene family encoding an immunodominant protein from Babesia microti.

Human babesiosis in the United States is caused predominantly by Babesia microti, a tick-transmitted blood parasite. Improved testing methods for the detection of infection with this parasite are needed, since asymptomatic B. microti infection represents a potential threat to the blood supply in areas where B. microti is endemic. We performed immunoscreening of an expression library of genomic DNA from a human isolate of B. microti (strain MN1). Among 17 unique immunoreactive clones, we identified 9 which represent a related family of genes with little sequence homology to other known sequences but with an architecture resembling that of several surface proteins of Plasmodium. Within this family, a tandem array of a degenerate six-amino-acid repeat (SEAGGP, SEAGWP, SGTGWP, SGTVGP) was found in various lengths between relatively well conserved segments at the N and C termini. In order to examine within-clone variation, we developed a PCR protocol for direct recovery of a specific bmn1-6 homologue directly from 30 human blood isolates, 4 corresponding hamster isolates, and 5 geographically corresponding Peromyscus leucopus (white-footed mouse) isolates. Isolates from the hamsters had the same sequences as those found in the corresponding human blood, suggesting that genetic variation of bmn1-6 does not occur during passage. However, clones from different patients were often substantially different from each other with regard to the number and location of the degenerate repeats within the bmn1-6 homologue. Moreover, we found that strains that were closely related geographically were also closely related at the sequence level; nine patients, all from Nantucket Island, Mass., harbored clones that were indistinguishable from each other but that were distinct from those found in other northeastern or upper midwestern strains. We conclude that considerable genetic and antigenic diversity exists among isolates of B. microti from the United States and that geographic clustering of subtypes may exist. The nature of the bmn1-6 gene family suggests a mechanism of antigenic variation in B. microti that may occur by recombination, differential expression, or a combination of both mechanisms.

Amino Acid Sequence↗
PubMed2000

Metallic fragments on mammography after intraoperative deployment of radiopaque clips.

OBJECTIVE: Our objective was to report the occurrence and determine the frequency of metallic fragments in the breast after placement of surgical clips that are used to delineate the margins of the biopsy cavity. CONCLUSION: Metallic fragments are commonly present in patients who have surgical clips placed during breast biopsy for both benign and malignant disease. Awareness of this phenomenon may prevent the misidentification of these fragments as microcalcifications and thus avert unnecessary concern or biopsy.

Aged↗
PubMed1999

Detection of enzootic babesiosis in baboons (Papio cynocephalus) and phylogenetic evidence supporting synonymy of the genera Entopolypoides and Babesia.

Blood smear evaluation of two baboons (Papio cynocephalus) experiencing acute hemolytic crises following experimental stem cell transplantation revealed numerous intraerythrocytic organisms typical of the genus Babesia. Both animals had received whole-blood transfusions from two baboon donors, one of which was subsequently found to display rare trophozoites of Entopolypoides macaci. An investigation was then undertaken to determine the prevalence of hematozoa in baboons held in our primate colony and to determine the relationship, if any, between the involved species. Analysis of thick and thin blood films from 65 healthy baboons (23 originating from our breeding facility, 26 originating from an out-of-state breeding facility, and 16 imported from Africa) for hematozoa revealed rare E. macaci parasites in 31%, with respective prevalences of 39, 35, and 12%. Phylogenetic analysis of nuclear small-subunit rRNA gene sequences amplified from peripheral blood of a baboon chronically infected with E. macaci demonstrated this parasite to be most closely related to Babesia microti (97.9% sequence similarity); sera from infected animals did not react in indirect fluorescent-antibody tests with Babesia microti antigen, however, suggesting that they represent different species. These results support an emerging view that the genus Entopolypoides Mayer 1933 is synonymous with that of the genus Babesia Starcovici 1893 and that the morphological variation noted among intracellular forms is a function of alteration in host immune status. The presence of an underrecognized, but highly enzootic, Babesia sp. in baboons may result in substantial, unanticipated impact on research programs. The similarity of this parasite to the known human pathogen B. microti may also pose risks to humans undergoing xenotransplantation, mandating effective screening of donor animals.

Animals↗
PubMed1997

Management of microcalcifications that develop at the lumpectomy site after breast-conserving therapy.

PURPOSE: To design a decision tree according to time from irradiation and site, morphology, and number of microcalcifications for the rational treatment of patients with microcalcifications at the lumpectomy site after breast-conserving therapy (BCT), to minimize performance of biopsy. MATERIALS AND METHODS: From a database of 504 women selected to receive BCT, those developing probably benign microcalcifications within 3 years of BCT received close follow-up with mammography. Patients developing fewer than four probably benign microcalcifications more than 3 years after treatment were offered mammography or biopsy. If microcalcifications appeared malignant or patients developed four or more microcalcifications after 3 years, biopsy was performed. RESULTS: Twenty-eight patients (29 breasts [5.7%]) developed microcalcifications confined to the lumpectomy site. Fifteen patients (15 breasts) developed microcalcifications within 3 years of BCT and were followed up with mammography. Thirteen patients (14 breasts) developed microcalcifications confined to the lumpectomy site after more than 3 years. Among the latter group, microcalcifications appeared malignant in four breasts, and biopsy specimens revealed three recurrences. The remaining 10 breasts were followed up with mammography. No patient undergoing mammographic follow-up without biopsy has had clinical evidence of local failure throughout the follow-up period. CONCLUSION: Follow-up mammography is an option when benign-appearing microcalcifications develop at the lumpectomy site depending on time of appearance and number; it is the primary recommendation when these microcalcifications develop within 3 years after treatment.

Adult↗
PubMed1996

Age-related differences in patients with nonpalpable breast carcinomas.

BACKGROUND: The survival benefit of screening mammography may be influenced by the age of the screened population. The current series examines the influence of age on the clinical, histopathologic, and prognostic features of nonpalpable breast carcinoma. METHODS: Needle localization and biopsy of suspicious mammographic lesions identified 173 breast carcinomas that were occult by physical examination. The mammographic appearance, the tumor histology and size, as well as axillary lymph node and estrogen receptor status of these carcinomas were reviewed. RESULTS: Mammographic findings of a mass or density (without calcifications) were most common (46%) and the majority of tumors were invasive ductal carcinoma (70%). The median age of the patients was 59 years. Tumor histology and mammographic findings varied by age: women with ductal carcinoma in situ (DCIS) had a median age of 50 years, whereas patients with invasive ductal carcinoma without associated intraductal tumor had a median age of 65 years. Both younger age (P = 0.001) and microcalcifications (P = 0.0001) were strongly correlated with DCIS. The mean greatest tumor dimension was 1.34 cm. Axillary metastases were found in 21%, 15%, and 50% of invasive tumors with sizes of < 1 cm, < 2 cm, and > 2 cm, respectively, and were uninfluenced by age. Estrogen receptor analysis of invasive tumors was > 10 fmol/mg in 47% and 84% of women aged < 50 years and > 50 years, respectively. CONCLUSIONS: Mammographically detected lesions in younger women are typified by a higher incidence of DCIS or tumors with an intraductal component. Nonpalpable invasive carcinomas in women < or = 50 years and > 50 years appear to be biologically similar by virtue of axillary lymph node status, although estrogen receptor positive tumors are more common in older patients. These age-related differences may partially account for age-related variations in the survival impact of mammographic screening programs.

Adult↗
PubMed1996

Perturbation of nifT expression in Klebsiella pneumoniae has limited effect on nitrogen fixation.

In the nitrogenase system of Klebsiella pneumoniae, nifT is located between nifDK, the structural genes for dinitrogenase, and nifY, whose product is involved in nitrogenase maturation. It is, therefore, a reasonable hypothesis that the NifT protein might also have a role in the maturation of nitrogenase. However, the phenotypic characterization of nifT and nifT-overexpressing strains for effects on the regulation, maturation, and activity of nitrogenase identified no properties that were distinct from those of the wild type. We conclude that the K. pneumoniae NifT protein is not essential for nitrogen fixation under the conditions examined.

Bacterial Proteins↗
PubMed1995

Characterization of the gamma protein and its involvement in the metallocluster assembly and maturation of dinitrogenase from Azotobacter vinelandii.

Dinitrogenase, the enzyme capable of catalyzing the reduction of N2, is a heterotetramer (alpha 2 beta 2) and contains the iron-molybdenum cofactor (FeMo-co) at the active site of the enzyme. Mutant strains unable to synthesize FeMo-co accumulate an apo form of dinitrogenase, which is enzymatically inactive but can be activated in vitro by the addition of purified FeMo-co. Apodinitrogenase from certain mutant strains of Azotobacter vinelandii has a subunit composition of alpha 2 beta 2 gamma 2. The gamma subunit has been implicated as necessary for the efficient activation of apodinitrogenase in vitro. Characterization of gamma protein in crude extracts and partially pure fractions has suggested that it is a chaperone-insertase required by apodinitrogenase for the insertion of FeMo-co. These are three major forms of gamma protein detectable by Western analysis of native gels. An apodinitrogenase-associated form is found in extracts of nifB or nifNE strains and dissociates from the apocomplex upon addition of purified FeMo-co. A second form of gamma protein is unassociated with other proteins and exists as a homodimer. Both of these forms of gamma protein can be converted to a third form by the addition of purified FeMo-co. This conversion requires the addition of active FeMo-co and correlates with the incorporation of iron into gamma protein. Crude extracts that contain this form of gamma protein are capable of donating FeMo-co to apodinitrogenase, thereby activating the apodinitrogenase. These data support a model in which gamma protein is able to interact with both FeMo-co and apodinitrogenase, facilitate FeMo-co insertion into apodinitrogenase, and then dissociate from the activated dinitrogenase complex.

Azotobacter vinelandii↗
PubMed1994

Dermal calcifications in fixed orientation: the tattoo sign.

Calcifications located in the dermis of the breast may appear indistinguishable from intramammary calcifications. The authors present a sign, called the tattoo sign, that can help radiologists identify dermal calcifications. When mammograms are compared, calcifications that maintain a fixed relationship to each other suggest a dermal location. This can be verified with standard techniques. Understanding the tattoo sign may help prevent unnecessary needle localization and biopsy procedures.

Breast Neoplasms↗
PubMed1994

The efficacy of specimen radiography in evaluating the surgical margins of impalpable breast carcinoma.

OBJECTIVE: The purpose of this study was to determine if the presence or absence of tumor at the surgical margin in cases of impalpable breast carcinoma could be predicted accurately with specimen radiography. MATERIALS AND METHODS: We obtained single-view radiographs of 119 consecutive surgical biopsy specimens of impalpable invasive or in situ ductal carcinoma. Radiographic lesions were classified as a mass with moderately well defined margins, a mass with poorly defined margins, or microcalcifications without an associated mass. The radiographic appearance of the impalpable cancer, the margin as judged from the specimen radiograph, the tumor's histologic appearance, and the histologic appearance of the tumor margin were then correlated. RESULTS: Specimen radiographs showed tumor at the surgical margin in 63 cases; 62 of these were confirmed histologically (positive predictive value, 98%). Specimen radiographs showed tumor-free surgical margins in 56 cases; 18 of these were confirmed histologically (negative predictive value, 32%). These results were independent of the radiographic appearance of the lesion or the tumor's histologic appearance. CONCLUSION: Decisions based on findings on specimen radiographs were valid only if the radiographs showed tumor at the margin of the specimen.

Biopsy↗
PubMed1994

Safety, accuracy, and diagnostic yield of needle localization biopsy of the breast performed using local anesthesia.

BACKGROUND: In changing our technique to performing needle localization breast biopsies (NLBB) using local anesthesia in an outpatient setting, we investigated whether or not our complication rates with local anesthesia were acceptable when compared with complications from a cohort of biopsies of the breast performed for palpable masses. We were also interested in determining whether or not our rate of missed biopsies was within acceptable ranges. STUDY DESIGN: Complications occurring in 283 patients who underwent 301 NLBB using local anesthesia between 1983 and 1991 were compared with complications occurring after excision of 249 palpable masses of the breast excised using local anesthesia during this period. RESULTS: Complications associated with NLBB were missed lesions, six (1.99 percent) of 301; hematoma, 12 (3.99 percent) of 301; abscess, three (0.99 percent) of 301; seroma, one (0.33 percent) of 301, and wound separation, two (0.66 percent) of 301, for a total of 24 complications (7.96 percent). These rates were not statistically different from the rates of complication after biopsies of palpable lesions using local anesthesia (p < 0.49). The 301 NLBB revealed 87 carcinomas (28.9 percent); 50 invasive and 37 in situ. Of the nonpalpable carcinomas, 43 percent were in situ. Only 11 percent carcinomas, 43 percent were in situ. Only 11 percent of the palpable lesions were in situ (p < 0.001). Forty-four patients with nonpalpable invasive carcinoma had a 25 percent rate of positive axillary lymph nodes. CONCLUSIONS: Needle localization breast biopsies can be performed using local anesthesia exclusively with less than a 2 percent chance of missed lesions and complication rates similar to those associated with biopsies of palpable lesions. The biology of these lesions varies. Although there is a high rate of in situ carcinoma, there is a significant rate of node positivity in the patients with nonpalpable invasive carcinoma.

Adolescent↗