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J A Hayman

Publications and source records attributed to J A Hayman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Detection of Mycobacterium ulcerans in environmental samples during an outbreak of ulcerative disease.

Mycobacterium ulcerans is an environmental bacterium which causes chronic skin ulcers. Despite significant epidemiological evidence to suggest that water is the source of infection, the organism has never been identified in the environment. Environmental water samples were collected from a small town in which an outbreak of 29 cases had occurred in a 3-year period. These were examined by mycobacterial culture and PCR amplification. Similar to previous studies, M. ulcerans was not cultured from the water samples. However, five samples were positive for M. ulcerans by PCR. These samples were collected from a swamp and a golf course irrigation system within the outbreak area. This is the first time that M. ulcerans has been demonstrated to be present in the environment and supports the postulated epidemiology of disease due to this organism.

DNA, Bacterial↗
PubMed1997

Patient preferences concerning the trade-off between the risks and benefits of routine radiation therapy after conservative surgery for early-stage breast cancer.

PURPOSE: To assess patients' preferences regarding the trade-off between risks and benefits of radiation therapy after conservative surgery for early-stage breast cancer. PATIENTS AND METHODS: Utilities (measures of preference) of 97 early-stage breast cancer patients treated with conservative surgery and radiation therapy and 20 medical oncology nurses were assessed for five health states using standard gambles. RESULTS: Patients had the highest mean utility for treatment with conservative surgery and radiation therapy without a local recurrence (0.92), intermediate utilities for treatment with conservative surgery alone followed either by no local recurrence or by a local recurrence salvaged by conservative surgery and radiation therapy (0.88 and 0.87, respectively), and the lowest utilities for treatment with or without radiation therapy followed by a local recurrence salvaged by mastectomy and reconstructive surgery (0.82 and 0.81, respectively). All differences between health states' utilities were significant (P < .0001), except between the two intermediate and two lowest rated health states. None of the clinical or sociodemographic factors examined explained more than 5% of the variability in the patients' utilities or their differences. Nurses' utilities were similar to those of the patients. CONCLUSIONS: These results strongly suggest that fear of a local recurrence and an actual local recurrence leading to mastectomy have such a negative impact on quality of life that patients are willing to accept the risks and inconvenience of radiation therapy to avoid them. There is also considerable interpatient variability that was not explained by the clinical or sociodemographic factors examined.

Adult↗
PubMed1996

Underexpression of the 43 kDa inositol polyphosphate 5-phosphatase is associated with cellular transformation.

The 43 kDa inositol polyphosphate 5-phosphatase (5-phosphatase) hydrolyses the second messenger molecules inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. We have underexpressed the 43 kDa 5-phosphatase by stably transfecting normal rat kidney cells with the cDNA encoding the enzyme, cloned in the antisense orientation into the tetracycline-inducible expression vector pUHD10-3. Antisense-transfected cells demonstrated a 45% reduction in Ins(1,4,5)P3 5-phosphatase activity in the total cell homogenate upon withdrawal of tetracycline, and an approximately 80% reduction in the detergent-soluble membrane fraction of the cell, as compared with antisense-transfected cells in the presence of tetracycline. Unstimulated antisense-transfected cells showed a concomitant 2-fold increase in Ins(1,4,5)P3 and 4-fold increase in Ins(1,3,4,5)P4 levels. The basal intracellular calcium concentration of antisense-transfected cells (170 +/- 25 nM) was increased 1.9-fold, compared with cells transfected with vector alone (90 +/- 25 nM). Cells underexpressing the 43 kDa 5-phosphatase demonstrated a transformed phenotype. Antisense-transfected cells grew at a 1.7-fold faster rate, reached confluence at higher density and demonstrated increased [3H]thymidine incorporation compared with cells transfected with vector alone. Furthermore, antisense-transfected cells formed colonies in soft agar and tumours in nude mice. These studies support the contention that a decrease in Ins(1,4,5)P3 5-phosphatase activity is associated with cellular transformation.

3T3 Cells↗
PubMed1996

Proteinase inhibitor 6 cannot be secreted, which suggests it is a new type of cellular serpin.

We have recently described a new serine proteinase inhibitor, proteinase inhibitor 6 (PI-6). This serpin has features that suggest it may function intracellularly, but its close resemblance to ovalbumin serpins like plasminogen activator inhibitor 2 (PAI-2) raises the possibility that it is secreted to regulate an extracellular proteinase. To determine whether PI-6 is secreted, we have examined its cellular distribution by immunohistochemistry and have attempted to induce its release from platelets and from cultured cells. We find that PI-6 is present in endothelial and epithelial cells, but it is apparently cytoplasmic and it is not released from cells in response to phorbol ester, dibutyryl cAMP or tumor necrosis factor alpha treatment. It is also not released from activated platelets. The addition of a conventional signal peptide to the amino terminus of PI-6 directed its translocation into the endoplasmic reticulum (ER), resulting in glycosylation but not secretion of the molecule. By contrast, the addition of the same signal peptide to PAI-2 markedly enhanced its translocation and secretion. Glycosylated PI-6 was sequestered in the ER and was incapable of interacting with thrombin. The failure of PI-6 to move along the secretory pathway, and the loss of inhibitory function of ER-localized PI-6, demonstrates that unlike PAI-2, PI-6 is not naturally secreted. Taken together, these results suggest that PI-6 has evolved to fulfil an intracellular role and that it represents a new type of cellular serpin.

Amino Acid Sequence↗
PubMed1996

The emergence of Mycobacterium ulcerans infection near Melbourne.

OBJECTIVE: To document the emergence of new foci of Mycobacterium ulcerans infection (Bairnsdale ulcer) in Victoria. METHODS: From data kept by one of us (JAH) and records from the Mycobacterium Reference Laboratory, Fairfield Hospital, we reviewed cases of M. ulcerans infection in Victoria between 1980 and 1995, and identified those apparently acquired outside the east Gippsland endemic region. A case was defined as a person with a lesion suggestive of M. ulcerans infection, from which the organism had been cultured or, in the absence of culture information, from which a histological specimen characteristic of M. ulcerans infection had been obtained. RESULTS: We identified 45 people who appeared to have acquired their infections in Victoria but outside the east Gippsland region. A new focus appeared on the northern shores of Western Port, near Melbourne, in 1982, and there was a dramatic increase in cases between 1991 and 1994 associated with foci on Phillip Island, and in the Frankston-Langwarrin area of outer suburban Melbourne. Single cases came from Crib Point, Narre Warren and Bendigo. CONCLUSIONS: There have been at least three new foci of M. ulcerans infection within 80 km of Melbourne since 1982. Victorian clinicians should consider the possibility of Bairnsdale ulcer when dealing with unusual skin lesions.

Adolescent↗
PubMed1996

Altered thrombomodulin staining in blistering dermatoses.

The immunocytochemical distribution of thrombomodulin (TM) was examined in sections of skin from patients with blistering dermatoses occurring in the presence and absence of acantholysis. Skin sections were stained using polyclonal and monoclonal anti-human TM antibodies and were correlated with the staining pattern that resulted when using the monoclonal antibody 32-2B, which recognises the chief desmosomal adhesion molecule desmoglein I (DG I). Our study demonstrates a loss of TM staining in acantholytic dermatoses, occurring only in the region of actual disruption of the intercellular bridging between keratinocytes in the stratum spinosum. The thrombomodulin antigen expression paralleled the DG I expression. The strong correlation between the DG I and TM immunostaining pattern in both normal skin and acantholytic dermatoses supports the concept that TM has a role in mediating adhesion processes between keratinocytes.

Acantholysis↗
PubMed1996

Malignant pulmonary lymphoid disease: case reports illustrating anatomical pattern of disease as a prognostic marker.

Although a well documented phenomenon in Hodgkin's disease, malignant pulmonary lymphoid disease in other lymphoproliferative diseases, such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), is less frequently described. We present 3 patients, 2 with NHL and one with CLL, all demonstrating pulmonary malignant lymphoid involvement. We briefly review the probable mechanism underlying the development of this disease process and identify anatomical distribution of malignant pulmonary lymphoid disease as a prognostic marker in this condition.

Aged↗
PubMed1996

Pseudoepitheliomatous hyperplasia in Mycobacterium ulcerans infection.

Pseudoepitheliomatous hyperplasia of the epidermis occurring with Mycobacterium ulcerans skin infection may result in localization of the infected area with discharge of necrotic material, followed by healing leaving a depressed scar. The process represents more than simple re-epithelization of an ulcerated skin surface; it is a mechanism which produces active extrusion of necrotic material containing viable mycobacteria and should be seen as part of a protective physiological response to the infection.

Adult↗
PubMed1996

Adenocarcinoma in situ of the uterine cervix progressing to invasive adenocarcinoma.

This report documents a case of adenocarcinoma in situ (AIS) of the cervix progressing to invasive adenocarcinoma. The patient, who was 32-years-old at the time of diagnosis of AIS, was followed with negative smears for 7 years after conization when a smear showed malignant glandular cells. A repeat conization demonstrated well differentiated papillary adenocarcinoma. The patient remains well 8 years after radical hysterectomy and lymph node dissection. The clinicopathological features of this case and a brief review of the literature are presented.

Adenocarcinoma↗
PubMed1995

Immunohistochemical localization of thrombomodulin in normal human skin and skin tumours.

Thrombomodulin (TM) expression has been investigated in sections of normal human skin, in cultured normal human keratinocytes, and in a variety of skin tumours. TM was present in squamous epithelial cells in the spinous layer of normal epidermis and in the outer root sheath of hair follicles, but was absent in the cells of the basal layer. It appeared to be predominantly localized to the cell membrane and the intercellular bridges in these areas. Cultured normal human keratinocytes demonstrated functionally active constitutive TM expression on their cell surface. Immunoperoxidase staining of skin tumours using anti-human TM antibodies demonstrated a typical cell membrane positivity in tumours with squamous or hair follicle differentiation. Basal cell carcinomas showed TM expression only in areas where incomplete squamoid metaplasia occurred. Sweat gland tumours and lesions of the melanogenic system failed to express TM. The localization of TM by immunostaining in various benign and malignant skin tumours typically correlated with their normal skin element of origin. The physiological significance of TM expression in the epidermis is currently undefined.

Basal Cell Carcinoma↗
PubMed1993

Parathyroid hormone related protein in breast cancers of widely varying prognosis.

Parathyroid hormone related protein (PTHrP) is a novel calcium regulating hormone that may have a significant role in the pathophysiology of breast cancer. We have previously demonstrated a relationship between immunohistochemically detectable PTHrP in primary breast tumours and the subsequent development of bone metastases and hypercalcaemia. The aim of this study was to compare the PTHrP status in the primary tumours from three groups of patients with widely varying prognosis. (1) The favourable outcome group; all patients had a favourable prognosis and minimum 3 years disease free follow up (n = 30). (2) The unfavourable outcome group; all patients presented with localized breast cancer but developed distant disease within 3 years (n = 26). (3) The unfavourable presentation group; all had distant disease at first presentation (n = 26). No differences in PTHrP status of the primary tumour amongst the three patient groups were found (66%, 65% and 61% positive respectively). The development of bone with liver metastases and hypercalcaemia was associated with increased positive PTHrP status of the primary tumor.

Bone Neoplasms↗
PubMed1992

Myb expression is higher in malignant human colonic carcinoma and premalignant adenomatous polyps than in normal mucosa.

Expression of the protooncogene c-Myb protein was assessed in normal mucosa and in tumor samples resected from six patients. We found that the tumor samples always expressed higher levels of full length Myb protein than the normal tissue. This contrasts with the situation in c-myb-associated hemopoietic malignancies of the mouse and chicken, in which Myb proteins are generally amino or carboxyl truncated. Tissues from five patients with colonic adenomatous polyps were also examined and found to express levels of Myb that were, in general, intermediate between those found in normal tissues and tumors. Of particular interest is that the more dysplastic polyps displayed higher Myb levels. In one patient with carcinoma and multiple colonic polyps, some polyps had intermediate levels of Myb, whereas one polyp with carcinoma in situ expressed tumor-like levels of Myb. To directly test the hypothesis that Myb expression may be important in determining the rate of colonic cell proliferation, we examined three colonic carcinoma cell lines and one polyp cell line. We found that the cell lines with the most rapid doubling times exhibited the highest Myb levels. In addition, we show that antisense myb oligonucleotides retard the proliferation of one of these colonic cell lines which expresses the highest level of Myb.

Base Sequence↗
PubMed1991

Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites.

Parathyroid hormone-related protein (PTHrP) has recently been identified in 60% of a series of primary breast cancers. The detection of a bone-resorbing factor in tumors with a propensity to metastasize to bone prompted study of PTHrP in breast cancer metastasis. PTHrP was localized by immunohistology in 12 of 13 (92%) breast cancer metastases in bone and in 3 of 18 (17%) metastases in non-bone sites. The statistical difference was highly significant (P less than 0.0001). Production of PTHrP as a bone-resorbing agent may contribute to the ability of breast cancers to grow as bone metastases.

Bone Neoplasms↗