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H C Maguire

Publications and source records attributed to H C Maguire.

At least 19 recordsLinked to original sources
PubMed1992

Expression of c-erbB-2 in in situ and in adjacent invasive ductal adenocarcinomas of the female breast.

Several lines of evidence have demonstrated that expression of the c-erbB-2 gene product contributes to the malignant phenotype. We and others have determined that c-erbB-2 is substantially expressed in most ductal in situ carcinomas of the comedo type, but not in other patterns of ductal carcinoma in situ or in atypical ductal hyperplasia of the breast. In the present investigation, by immunohistochemistry we inquired whether invasive ductal adenocarcinomas retained the c-erbB-2 expression status of the in situ carcinomas from which they derived. Of twelve specimens containing both cribriform/micropapillary in situ and derivative invasive adenocarcinomas in the same section, all tumor cells were negative for c-erbB-2 expression. In thirteen in situ carcinomas of the comedo type, with identifiable invasive components, ten had definite c-erbB-2 expression, and in every case there was comparable c-erbB-2 protein staining of in situ and invasive components; in three of these ten cases the staining in the in situ component tended to be more intense. These findings imply that a significant proportion of invasive mammary adenocarcinomas expressing c-erbB-2 protein is derived from ductal in situ carcinomas of the comedo type.

Breast Neoplasms↗
PubMed1991

The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy.

Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.

Animals↗
PubMed1991

Immunization with haptenized, autologous tumor cells induces inflammation of human melanoma metastases.

Twenty-four patients with metastatic melanoma were treated with a novel form of active immunotherapy, autologous tumor cell vaccine conjugated to the hapten, dinitrophenyl. This approach is based on the idea, well established in animal systems, that presentation of tumor antigens in the context of a strongly immunogenic hapten augments the development of immunity to those antigens. After being sensitized to dinitrophenyl, patients were given injections of dinitrophenyl-vaccine every 28 days following pretreatment with low dose cyclophosphamide. The vaccine induced a striking inflammatory response in superficial metastases in 14 of 24 patients, consisting of erythema, swelling, warmth, and tenderness over tumor masses. Immunohistochemistry and flow cytometric analysis of biopsy specimens showed marked infiltration with lymphocytes, the majority of which were CD8+, HLA-DR+ T-cells. These observations suggest that a T-cell-mediated immune response against melanoma-associated antigens was facilitated by the "helper" effect of the anti-hapten response.

Antibodies, Monoclonal↗
PubMed1991

A large outbreak of food poisoning of unknown aetiology associated with Stilton cheese.

Between November 1988 and January 1989, a total of 155 people in 36 reported outbreaks suffered gastrointestinal symptoms associated with eating Stilton cheese, produced from unpasteurized cow's milk in the English midlands. Symptoms were suggestive of a staphylococcal illness but extensive laboratory testing of cheeses implicated in several of the outbreaks failed to detect any pathogen, toxin or chemical. Control measures were implemented, and included a voluntary withdrawal of the implicated Stilton cheese from sale on 23 January 1989 and a subsequent decision to use pasteurized milk in production of the cheese.

Abdominal Pain↗
PubMed1991

Expression of c-erbB-2 in human pancreatic adenocarcinomas.

The c-erbB-2 (neu) gene encodes a transmembrane phosphoglycoprotein (p185erbB-2) which resembles a growth factor receptor-like molecule closely related to the epidermal growth factor receptor. Overexpression of c-erbB-2 induces cell transformation in vitro. Poorer survival rates and elevated recurrence rates following treatment have been shown in patients whose breast adenocarcinomas demonstrate increased c-erbB-2 expression. Using immunoprecipitation and immunoperoxidase staining, we surveyed human cell lines for p185erbB-2. Cell lines from most tumor types (e.g. lymphomas, neuroblastomas, melanomas) demonstrated negligible p185erB-2; however, 3 of 6 pancreatic cell lines overexpressed c-erbB-2. Southern blot analysis revealed that c-erbB-2 was amplified in two of these cell lines and was both rearranged and amplified in one of them. Based on these findings, we examined tissue sections from archival specimens of primary human pancreatic adenocarcinomas. A substantial proportion of specimens had increased p185erbB-2, as judged by increased immunostaining of the tumor cells. In such pancreatic tumors p185erbB-2 may contribute to the malignant phenotype and could provide a target for immunodiagnostic or immunotherapeutic strategies.

Adenocarcinoma↗
PubMed1990

The role of autologous tumor cells in preventing lymphokine-activated killer cell induction in vitro.

Peripheral blood lymphocytes (PBL), when cultured in vitro in the presence of autologous irradiated tumor and interleukin-2 (IL-2), become more restricted in the spectrum of their cytotoxicity. The cells continue to exhibit cytotoxicity for autologous tumor cells and major histocompatibility complex (MHC)-concordant allogeneic tumor cells of similar histologic type but not for the natural killer target cell line, K562. Furthermore, the addition of autologous tumor at different time points after the initiation with IL-2 alone of conventional lymphokine-activated killer cell cultures modifies both the specificity and the degree of cytotoxicity of these lymphocytes for tumor targets. By varying the culture conditions it may be possible to generate killer cells that will exhibit similarly enhanced and more restricted antitumor effects in vivo.

Antibodies, Monoclonal↗
PubMed1990

Relapse of infant botulism.

We report on 3 infants who had relapse of infant botulism after apparent resolution of clinical symptoms. This group represented 5% of the infants with confirmed infant botulism who were treated at our institution since 1976. The exact cause for these relapses was unclear, but three potential mechanisms are examined. There were no historical, clinical, or electrophysiological predictors of relapse. Although at the time of writing recovery from relapse appeared complete, close follow-up of patients recovering from a bout of infant botulism is necessary.

Botulism↗
PubMed1990

Analysis of c-erbB-2 protein expression in conjunction with DNA content using multiparameter flow cytometry.

Breast cancer is a leading cause of cancer death among women. Factors useful for determining the prognosis of breast cancer include axillary lymph node involvement, tumor size, hormonal receptor status, nuclear grade, and relative DNA content. The c-erbB-2 protooncogene is amplified in 10-40% of primary breast tumors, as well as in breast cancer cell lines; where it is amplified there is increased expression of its product. We have investigated the DNA content and c-erbB-1 protein expression in tumor cell lines and in breast cancer patient specimens by multiparameter flow cytometry. The study was enabled by the discovery that both cellular integrity and c-erbB-2 antigen reactivity were preserved in cells and tissues following fixation in 70% ethanol. We demonstrate that flow cytometric analysis of c-erbB-2 expression in populations of ethanol-fixed tumor cells is a reliable and sensitive quantitative method that correlates well with previously documented semiquantitative techniques. This is a feasible method for analyzing archived clinical samples, and further allows correlations between c-erbB-2 levels and other cellular parameters. Additionally, this method detects abnormal populations not identified by DNA content analysis alone. Further studies utilizing this approach are necessary to evaluate the prognostic value of this oncoprotein in human breast cancer.

Adenocarcinoma↗
PubMed1990

Neu (c-erbB-2), a tumor marker in carcinoma of the female breast.

The c-erbB-2 oncogene encodes a transmembrane phosphoglycoprotein. This molecule appears to be a growth factor receptor in the family of tyrosine kinase growth factor receptors; however, its ligand has not yet been identified. Amplification and/or overexpression of c-erbB-2 in breast adenocarcinomas occurs frequently and its occurrence implies a more advanced malignancy. This functional tumor marker is readily identified by appropriate DNA and antibody probes. The large external domain of the c-erbB-2 gene product is a promising target for immunodiagnostic and immunotherapeutic modalities.

Adenocarcinoma↗
PubMed1990

Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients.

We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 x 10(6) autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guérin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84+ months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P less than .001; day 0 v day 161, P less than .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P less than .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value.

Adult↗
PubMed1990

Immunohistochemical evaluation of c-erbB-2 oncogene expression in ductal carcinoma in situ and atypical ductal hyperplasia of the breast.

Cases of ductal carcinoma in situ (DCIS) and atypical ductal hyperplasia (ADH) of the breast were examined for expression of the protein product of the c-erbB-2 (neu, HER-2) oncogene using two different polyclonal antibodies via an avidin-biotin immunoperoxidase method on formalin- or Bouin'-fixed, paraffin-embedded tissue. Fifty-five percent (18/33) of DCIS and 10% (2/21) of ADH were positive. Significant c-erbB-2 expression in DCIS was generally divided on histologic grounds: ten of ten comedocarcinomas showed strong membrane staining, while only one of 14 small cell DCIS cases (micropapillary or cribiform patterns) showed immunostaining (which was weak and basilar in this single case). DCIS cases of mixed histology were strongly positive in areas of comedocarcinoma. In two of three cases of associated Paget's disease strong membrane staining was seen. The two c-erbB-2-positive ADH cases showed weak basilar staining akin to the small cell DCIS cases. Five cases of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) associated with DCIS or ADH were negative for c-erbB-2 expression. We conclude that comedocarcinoma in situ and Paget's disease frequently express the c-erbB-2 protein and are both histologically and biochemically distinct from ADH and small cell patterns of DCIS. We advocate precise subclassification of DCIS on histopathologic reports, particularly in view of reports that overexpression of the c-erbB-2 oncogene in infiltrating breast carcinomas may be associated with a poor prognosis.

Breast↗
PubMed1989

Cell-mediated immune responses to vaccine peptides derived from the circumsporozoite protein of Plasmodium falciparum.

T cell epitopes residing within vaccine candidate peptides have been identified by delayed-type hypersensitivity (DTH) responses in mice. The recombinant sporozoite vaccine candidate, R32tet32, contains at least two T epitopes, one located within the repeat region and another in the tet tail. When C57BL/6 (H-2b) and BALB/c (H-2d) mice were sensitized intradermally with R32tet32 or the truncated protein R32LR emulsified in CFA and challenged 5 days later with R32tet32, only H-2b mice recognized a T epitope located within the major repeat sequence (NANP) and encoded by four or less repeats. H-2d mice responded solely to the T epitope located on the tet tail. Ear swelling was maximal at 48 h and revealed a histologic pattern characteristic of DTH. CD4+ T cell lines derived from immunized animals demonstrated the ability to mediate local DTH, proliferate, and secrete lymphokines in response to stimulation with Ag. High dose i.v. administration of R32tet32 in C57BL/6 and BALB/c mice before intradermal sensitization with R32tet32 revealed that DTH responses were suppressed only in BALB/c mice. Further experiments localized the suppressive determinant to the tet tail. Collectively, these data indicate that DTH may prove to be a useful method to characterize the biologic activity of T epitopes, furthermore they suggest that candidate vaccine peptides should be tested for suppressive activity before inclusion in a vaccine.

Animals↗
PubMed1989

Distribution of neu (c-erbB-2) protein in human skin.

The neu (c-erbB-2) gene encodes a transmembrane protein with tyrosine kinase activity that appears to be a growth factor receptor. Antibody was generated by immunization of rabbits with a synthetic polypeptide that was based on an internal sequence at the carboxy terminus of the molecule. This antibody was used to survey the expression of neu in human skin by immunohistochemistry. Significant protein was found in the squamous cell layer of the surface epidermis, in squamous cell carcinomas, in the external root sheath of hair follicles, and in eccrine gland secretory cells; it was poorly expressed in the basal cell layer and in a basal cell carcinomas. Increased neu expression appears to be associated with the differentiation of keratinocytes.

Antibody Specificity↗
PubMed1989

Local murine recombinant gamma interferon enhances the acquisition of allergic contact dermatitis in the mouse.

Using the model of allergic contact dermatitis in mice, we have demonstrated that local administration of recombinant (r) murine gamma interferon (gamma-rIFN) to the sensitization site substantially enhances the acquisition of delayed-type hypersensitivity. Single doses of gamma-rIFN from 500 to 2,000 U immunopotentiate successfully, with a suggestion of a better response at the higher doses. The immunoadjuvant effect is lost when the injections of gamma-rIFN are at a site distant from the sensitization site. Kinetic studies imply that gamma-rIFN is most effective when given at the time of sensitization, but significant immunopotentiation can be seen when gamma-rIFN is given several days before or after sensitization.

Adjuvants, Immunologic↗