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Biomedical subjects

A F Hood

Publications and source records attributed to A F Hood.

At least 19 recordsLinked to original sources
PubMed2001

Calciphylaxis is associated with hyperphosphatemia and increased osteopontin expression by vascular smooth muscle cells.

Calciphylaxis or calcific uremic arteriolopathy (CUA) is a fatal disease in dialysis patients due to calcification of cutaneous blood vessels. The pathogenesis has been attributed to elevated parathyroid hormone (PTH). However, recent studies evaluating vascular calcification in nondialysis patients have found that the smooth muscle cells play an active role, including production of the bone matrix protein osteopontin. To examine the involvement of various clinical parameters and smooth muscle cells of CUA, we performed a case-control analysis comparing 10 CUA patients with our current dialysis patients. Available histologic sections were immunostained for osteopontin, markers of smooth muscle cells, endothelial cells, and macrophages. Compared with our current dialysis population, patients with CUA were more likely to be obese, white, and female (P < 0.02). Comparison of laboratory values found CUA patients with lower serum albumin, greater serum phosphorus, and greater calcium X phosphorus product (P < 0.01). In contrast, there was no difference in the concentration of PTH or calcium between the 2 groups. Immunostaining of calcified blood vessels showed that all calcified vessels stained positive for osteopontin, whereas all the noncalcifed vessels showed no osteopontin localization. Staining for smooth muscle alpha-actin decreased in the medial layer with calcification, with cells appearing to be sloughed off, leading to near occlusion of the vessel lumen. Our case-control study demonstrates that hyperphosphatemia and an elevated calcium X phosphorus product is associated with CUA. Histologic examination suggests that the calcification is associated with increased expression of osteopontin by smooth muscle cells.

Adult↗
PubMed2001

DsrA-deficient mutant of Haemophilus ducreyi is impaired in its ability to infect human volunteers.

Haemophilus ducreyi produces an outer membrane protein called DsrA, which is required for serum resistance. An isogenic dsrA mutant, FX517, was constructed previously in H. ducreyi 35000. Compared to its parent, FX517 cannot survive in normal human serum. When complemented in trans with a plasmid containing dsrA, FX517 is converted to a serum-resistant phenotype (C. Elkins, K. J. Morrow, Jr., and B. Olsen, Infect. Immun. 68:1608-1619, 2000). To test whether dsrA was transcribed in vivo, we successfully amplified transcripts in five biopsies obtained from four experimentally infected human subjects. To test whether DsrA was required for virulence, six volunteers were experimentally infected with 35000 and FX517 and observed for papule and pustule formation. Each subject was inoculated with two doses (70 to 80 CFU) of live 35000 and 1 dose of heat-killed bacteria on one arm and with three doses (ranging from 35 to 800 CFU) of live FX517 on the other arm. Papules developed at similar rates at sites inoculated with the mutant or parent. However, mutant papule surface areas were significantly smaller than parent papules. The pustule formation rate was 58% (95% confidence interval [CI] of 28 to 85%) at 12 parent sites, and 0% (95% CI of 0 to 15%) at 18 mutant sites (P = 0.0004). Although biosafety regulations precluded our testing the complemented mutant in humans, these results suggest that expression of DsrA facilitates the ability of H. ducreyi to progress to the pustular stage of disease.

Adult↗
PubMed2001

Expression of cytolethal distending toxin and hemolysin is not required for pustule formation by Haemophilus ducreyi in human volunteers.

Haemophilus ducreyi makes cytolethal distending toxin (CDT) and hemolysin. In a previous human challenge trial, an isogenic hemolysin-deficient mutant caused pustules with a rate similar to that of its parent. To test whether CDT was required for pustule formation, six human subjects were inoculated with a CDT mutant and parent at multiple sites. The pustule formation rates were similar at both parent and mutant sites. A CDT and hemolysin double mutant was constructed and tested in five additional subjects. The pustule formation rates were similar for the parent and double mutant. These results indicate that neither the expression of CDT, nor that of hemolysin, nor both are required for pustule formation by H. ducreyi in humans.

Adult↗
PubMed2001

Haemophilus ducreyi lipooligosaccharide mutant defective in expression of beta-1,4-glucosyltransferase is virulent in humans.

The lipooligosaccharide (LOS) of Haemophilus ducreyi contains a major glycoform that is immunochemically identical to paragloboside, a glycosphingolipid precursor of major human blood group antigens. We recently identified the gene responsible for the glucosyltransferase activity and constructed an isogenic mutant (35000glu-) deficient in this activity. 35000glu- makes an LOS that consists only of the heptose trisaccharide core and 2-keto-deoxyoctulosonic acid (KDO). For this study, the mutant was reconstructed in the 35000HP (human passaged [HP]) background. Five human subjects were inoculated with 35000HP and 35000HPglu- in a dose-response trial. The pustule formation rates were 40% (95% confidence interval [CI], 13.7 to 72.6%) at 10 sites for 35000HP and 46.7% (95% CI, 24.8 to 69.9%) at 15 sites for 35000HPglu-. The histopathology and recovery rates of H. ducreyi from surface cultures and biopsies obtained from mutant and parent sites were similar. These results indicate that the expression of glycoforms with sugar moieties extending beyond the heptose trisaccharide core is not required for pustule formation by H. ducreyi in humans.

Adult↗
PubMed2000

Epithelioid sarcoma arising on the nose of a child: a case report and review of the literature.

A 4-year-old boy presented with a 6-month history of a red papule on the nasal septum. Physical examination was otherwise unremarkable. A biopsy specimen showed an epithelioid sarcoma characterized by nodular collections of epithelioid tumor cells with central, tumor cell necrosis. By immunohistochemistry the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and CD34, but negative for S-100, CD31, factor VIII-related antigen, CD68, actin, desmin and myoglobin. Epithelioid sarcoma is an uncommon tumor of uncertain histogenesis that typically arises in the extremities of young adults. Both the age of our patient and the location of his tumor are unusual, emphasizing the spectrum of presentations that may occur with epithelioid sarcoma. Epithelioid sarcoma should be considered in the differential diagnosis of granulomatous diseases and epithelioid tumors of children, even in unusual locations.

Antigens, CD34↗
PubMed2000

An isogenic hemoglobin receptor-deficient mutant of Haemophilus ducreyi is attenuated in the human model of experimental infection.

Haemophilus ducreyi expresses a conserved hemoglobin-binding outer-membrane protein (HgbA). To test the role of HgbA in pathogenesis, we infected 9 adults with isolate 35000 and its isogenic hgbA-inactivated mutant (FX504) on their upper arms in a double-blinded, escalating dose-response study. Papules developed at similar rates at sites inoculated with the mutant or parent. The pustule-formation rate was 55% (95% confidence interval [CI], 30. 8%-78.5%) at parent sites and 0 (95% CI, 0-10.5%) at mutant sites (P<.0001). The recovery rate of H. ducreyi from surface cultures was 16% (n=142) from parent sites and 0 (n=213) from mutant sites (P<. 0001). H. ducreyi was recovered at biopsy from 6 of 7 parent sites and from 0 of 3 mutant sites. The results indicate that hemoglobin may be a critical source of heme or iron for the establishment of H. ducreyi infection in humans.

Adult↗
PubMed2000

A pilus-deficient mutant of Haemophilus ducreyi is virulent in the human model of experimental infection.

Haemophilus ducreyi expresses fine tangled pili, which are composed predominantly of a major subunit (FtpA). Confocal microscopy showed that an FtpA-specific monoclonal antibody bound to bacteria in biopsy samples obtained from infected human volunteers. To test the role of pili in pathogenesis, an isogenic mutant (35000HP-SMS1) was constructed by insertionally inactivating ftpA. 35000HP-SMS1 did not express FtpA and was nonpiliated but was otherwise identical to its parent, 35000HP. Seven healthy adults were challenged on the upper arm with the isogenic isolates in a double-blinded, escalating dose-response study. Sites inoculated with the mutant produced papules and pustules at rates similar to the rates observed at sites inoculated with the parent. The recovery rate of H. ducreyi from cultures and the histopathology of biopsy samples obtained from pustules inoculated with 35000HP or 35000HP-SMS1 were similar. Although pili are expressed in vivo, FtpA is not required for pustule formation in the human challenge model.

Adult↗
PubMed2000

Expression of peptidoglycan-associated lipoprotein is required for virulence in the human model of Haemophilus ducreyi infection.

Haemophilus ducreyi expresses a peptidoglycan-associated lipoprotein (PAL) that exhibits extensive homology to Haemophilus influenzae protein 6. We constructed an isogenic PAL mutant (35000HP-SMS4) by the use of a suicide vector that contains lacZ as a counterselectable marker. H. ducreyi 35000HP-SMS4 and its parent, 35000HP, had similar growth rates in broth and similar lipooligosaccharide profiles. 35000HP-SMS4 formed smaller, more transparent colonies than 35000HP and, unlike its parent, was hypersensitive to antibiotics. Complementation of the mutant in trans restored the parental phenotypes. To test whether expression of PAL is required for virulence, nine human volunteers were experimentally infected. Each subject was inoculated with two doses (41 to 89 CFU) of live 35000HP and one dose of heat-killed bacteria on one arm and with three doses (ranging from 28 to 800 CFU) of live 35000HP-SMS4 on the other arm. Papules developed at similar rates at sites inoculated with the mutant or parent but were significantly smaller at mutant-inoculated sites than at parent-inoculated sites. The pustule formation rate was 72% (95% confidence interval [CI], 46.5 to 90.3%) at 18 parent sites and 11% (95% CI, 2.4 to 29.2%) at 27 mutant sites (P < 0.0001). The rates of recovery of H. ducreyi from surface cultures were 8% (n = 130; 95% CI, 4.3 to 14.6%) for parent-inoculated sites and 0% (n = 120; 95% CI, 0.0 to 2.5%) for mutant-inoculated sites (P < 0.001). H. ducreyi was recovered from six of seven biopsied parent-inoculated sites and from one of three biopsied mutant-inoculated sites. Confocal microscopy confirmed that the bacteria present in a mutant inoculation site pustule lacked a PAL-specific epitope. Although biosafety regulations precluded our testing the complemented mutant in humans, these results suggest that expression of PAL facilitates the ability of H. ducreyi to progress to the pustular stage of disease.

Adult↗
PubMed2000

Evaluation of an isogenic major outer membrane protein-deficient mutant in the human model of Haemophilus ducreyi infection.

Haemophilus ducreyi expresses 2 OmpA homologs, designated MOMP and OmpA2, whose genes are arranged in tandem on the chromosome. Northern blot analysis indicated that momp and ompA2 are transcribed independently. Sequences of the momp open reading frame (ORF) lacking the transcriptional start site were amplified by PCR, and an Omega-Km2 cassette was ligated into the ORF. A plasmid containing this construction was electroporated into H. ducreyi 35000HP, and an isogenic MOMP-deficient mutant (35000HP-SMS2) was generated by allele exchange. In Southern blotting, 35000HP-SMS2 contained one copy of the Omega-Km2 cassette in momp. 35000HP and 35000HP-SMS2 had similar outer membrane protein (OMP) and lipooligosaccharide profiles and growth rates except for up-regulation of a putative porin protein in the mutant. Five subjects were inoculated with three doses of live 35000HP-SMS2 on one arm and two doses of live 35000HP and one dose of a heat-killed control on the other arm in a double-blind escalating dose-response trial. Pustules developed at 7 of 10 sites inoculated with 35000HP and at 6 of 15 sites inoculated with 35000HP-SMS2 (P = 0.14). 35000HP and 35000HP-SMS2 were recovered at similar rates from daily surface cultures and semiquantitative cultures. The data suggest that expression of MOMP is not required for pustule formation by H. ducreyi in the human model of infection.

Adult↗
PubMed2000

Lobular capillary hemangiomas: An epidemiologic report, with emphasis on cutaneous lesions.

BACKGROUND: Lobular capillary hemangiomas (pyogenic granulomas) occur on both mucosal and cutaneous surfaces. There are conflicting data regarding the increased prevalence of lobular capillary hemangiomas in female versus male subjects. Some studies have noted a female predominance of lobular capillary hemangiomas, but other studies do not reveal such a disparity. Because of an increased prevalence during pregnancy, oral tumors are also known as "granuloma gravidarum" or "pregnancy tumors." A hormonal influence for these mucosal lesions has been postulated. There are, however, no studies that address a possible relationship between hormones and cutaneous lesions. OBJECTIVE: This study presents the epidemiology of lobular capillary hemangiomas, with an emphasis on cutaneous lesions. METHODS: We reviewed 63,759 dermatopathology reports from a regional, private dermatopathology laboratory and found 325 cases of lobular capillary hemangiomas over a 1-year period. RESULTS: In our study of lobular capillary hemangiomas, cutaneous lesions accounted for 86%, with mucosal lesions representing only 12% of cases. Seven cases were excluded (one was intravascular, two were subcutaneous, and in 4 the location was not specified). Overall, male patients outnumbered female patients. The peak incidence for cutaneous lobular capillary hemangiomas was found in the second decade of life. The most common cutaneous sites were the trunk, upper extremities, and head. Mucosal lesions were primarily seen on the lips, gingiva, and tongue, and these affected females more than males by a ratio of 2:1, most commonly in the fourth decade of life. CONCLUSION: Cutaneous lobular capillary hemangiomas were equally prevalent in male and female patients. This would refute a female hormonal influence in the induction of cutaneous lobular capillary hemangiomas. Our data may suggest a hormonal influence on mucosal lesions because mucosal lobular capillary hemangiomas were twice as common in female patients. However, the small number of lesions in our study precludes us from making such a conclusion.

Adolescent↗
PubMed1999

Proliferative verrucous leukoplakia with cutaneous involvement.

Proliferative verrucous leukoplakia (PVL) is a distinct variant of oral leukoplakia characterized by a high rate of malignant transformation. Histologic features are variable and range from epithelial dysplasia to verrucous squamous cell carcinoma. To our knowledge, there have been no previous reports of cutaneous PVL. We present an interesting case of PVL involving the skin.

Aged↗
PubMed1999

The diagnostic yield in submitting nevi for histologic examination.

BACKGROUND: Dermatologists have expertise in the clinical diagnosis of benign melanocytic nevi. However, there are no data to confirm the accuracy of diagnosis. Differences in the diagnostic accuracy between dermatologists and nondermatologists with regard to cutaneous tumors has been infrequently studied. OBJECTIVE: We examined the rate of malignant tumors occurring in lesions submitted for routine microscopic examination that were clinically diagnosed as benign melanocytic nevi. METHODS: We conducted a study at a regional, non-hospital-based dermatopathology laboratory using specimens submitted by physicians of various specialties who were practicing in a 5-state Midwest region of the United States. The preoperative and postoperative diagnoses were examined on the basis of information provided by the clinician and of the subsequent histopathologic diagnosis. A total of 7734 cutaneous pathology reports were reviewed. Specimens submitted with a preoperative clinical diagnosis of mole or nevus, with or without a modifier, were examined and compared with postoperative microscopic diagnoses. RESULTS: Of 1946 specimens clinically diagnosed and submitted as benign nevi, 45 (2.3%) were histologically diagnosed as malignant tumors. This included 12 melanomas, 30 basal cell carcinomas, and 3 squamous cell carcinomas. For specimens submitted by dermatologists, the rate of malignant tumors increased when clinical information suggested findings beyond the classic benign clinical presentation with the addition of modifiers such as irritated or atypical, or if a malignancy was considered in the differential diagnosis (trend for increasing clinical suspicion: P = .00002). Fewer dermatologists than nondermatologists mistook a malignant tumor for a benign nevus (1.3% vs 3.8%, P = .003). CONCLUSION: Our data document that 2.3% of clinically diagnosed benign nevi were microscopically diagnosed as malignant tumors. Whether this malignancy rate in clinically diagnosed, benign, melanocytic nevi is above or below the threshold to establish a policy for submission for histopathologic examination remains to be determined as a collective societal and medical professional responsibility.

Biopsy↗
PubMed1999

Experimental infection of human volunteers with Haemophilus ducreyi does not confer protection against subsequent challenge.

Two groups of human volunteers were inoculated with 2 doses of live Haemophilus ducreyi 35000HP. The reinfection group consisted of 7 subjects who previously had participated in experimental infection with 35000HP to the pustular stage of disease. The control group consisted of 7 naive subjects. Papules developed at 92.8% (95% confidence interval [CI], 66.1%-99.8%) of sites inoculated with live bacteria, in the reinfection group, and at 85.7% (95% CI, 57.2%-98. 2%) of sites in the control group. Sixty-nine percent (95% CI, 36. 8%-90.9%) of papules evolved into pustules in the reinfection group, compared with 41% (95% CI, 15.2%-72.3%) in the control group. The recovery rates of H. ducreyi from surface cultures and the histopathology of biopsies obtained from both groups were similar. Thus, experimental infection to the pustular stage of disease does not provide protective immunity against subsequent challenge.

Adult↗