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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 469 records · Page 26Linked to original sources
PubMed1989

Murine osteoblasts release bone-resorbing factors of high and low molecular weights: stimulation by mechanical deformation.

Murine calvarial osteoblasts in monolayer culture were found to constitutively produce bone-resorbing factors; mechanical deformation significantly increased the synthesis and/or release of these factors. In short-term cultures (2 h) the resorptive activity was largely dialysable, indicating a relative molecular mass (Mr) less than 2000. Intermittent mechanical deformation stimulated the synthesis of these low Mr factors irrespective of serum conditions. Continuous deformation, however, was without effect. When the culture period was extended to 24 h, bone resorptive activity was stimulated by both intermittent and continuous deformation in the presence of 10% serum. This activity was dialysable. Over this same period in cultures with 2% serum, intermittent deformation also produced a non-dialysable bone-resorbing factor. We also cultured osteoblasts for 72 h in serum-free conditions and deformed the cells intermittently. Fractionation of the medium by high pressure liquid chromatography (HPLC) resolved three peaks of bone resorptive activity: peak I (Mr 50-60,000); peak II (Mr 5-20,000); and peak III (Mr less than 1000). Only peaks II and III were stimulated by mechanical deformation. These bone-resorbing factors remain as yet poorly characterized, but none of the activity in the HPLC fractions was attributable to interleukin-1 or prostaglandin E2.

Animals↗
PubMed1989

Interleukin 1-like activity in cystic lesions of the jaw.

Odontogenic cyst capsules were cultured in vitro and the culture media analysed for bone-resorption and interleukin 1-like activity. Five cysts synthesised a non-dialysable bone resorbing factor with significant interleukin 1-like activity. One specimen thought to be a cyst with little interleukin 1 activity proved to be antral lining. The results indicate that interleukin 1 may play an important role in cyst expansion by its direct effects on fibroblast proliferation and bone resorption and by stimulating prostaglandin synthesis in stromal fibroblasts of the cyst capsule.

Adult↗
PubMed1989

DNA content in high and intermediate grade non-Hodgkin's lymphoma-prognostic significance and clinicopathological correlations.

Flow cytometric (FCM) estimation of DNA content has been performed on tumour tissue from 197 patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) to investigate the clinicopathological correlations and prognostic significance of DNA ploidy and proliferative activity. Fifty-one per cent of tumours were diploid; the remaining non-diploid tumours were near diploid (14%), aneuploid (28%) and tetraploid (7%). In 81 tumours multiple analyses were performed from different regions of the tumour, ploidy discrepancy was seen within the same tumour in 13/81 tumours (16%), and intra-tumour variation in proliferative index (PI) in 72 tumours was estimated at +/- 5%. Ploidy status did not correlate with histological subtype (Kiel or Rappaport), Ann Arbor stage or the site of disease at presentation. There was no significant difference in response rate, relapse-free survival (RFS) or overall survival rate between the different ploidy categories. Tumour proliferative index (PI) varied markedly between patients (range 2-51%, median 14%). A significant association was observed between PI and histological subtype in the Kiel classification (P = 0.001). The median PI for the lymphoblastic lymphomas was 20% compared with 10% for the centrocytic tumours. An elevated PI was significantly associated with a reduced rate (P = 0.023), with 71% of patients with a low PI (less than 20%) achieving complete remission (CR) compared with 49% patients with a high PI (greater than 20%). Despite this correlation with CR, PI was not significantly associated with overall survival. When the DNA data was combined with over 20 other potential prognostic factors in multivariate analysis, ploidy and proliferative activity did not prove to be of independent prognostic significance for response, RFS or overall survival. In 20 patients additional biopsy material was available from the site of subsequent relapse. In these cases, although the histology at relapse remained unchanged, ploidy status altered in 13/20 patients, and there was a significant rise in tumour PI at relapse compared with the initial pre treatment biopsy (P = 0.017). We conclude that in high and intermediate grade NHL, DNA ploidy as assessed using conventional FCM analysis is not significantly associated with clinical outcome. However, proliferative activity does correlate with histological subtype and response to therapy, and this parameter warrants further evaluation in future studies.

Adolescent↗
PubMed1989

Prognostic factors in high and intermediate grade non-Hodgkin's lymphoma.

An analysis of prognostic factors has been performed on 260 patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) treated over an 11-year period between 1975 and 1986. The overall 5-year survival rate was 50% with a median follow-up of 72 months. Over 20 clinical, radiological and laboratory parameters have been studied, including variables reported to be important indicators of prognosis in previous series, and these variables have been subjected to univariate and multivariate analysis. Attainment of complete remission (CR) was the most important predictor of overall survival, low serum lactate dehydrogenase (LDH), limited stage disease and a high serum albumin were also independently associated with prolonged survival in multivariate analysis. After removing remission status from the model, Ann Arbor clinical stage became the most significant pre-treatment prognostic indicator. Sixty-five per cent of patients achieved CR, and a discriminant analysis showed that failure to attain CR was associated with advanced stage disease, constitutional symptoms, increasing patient age, a low serum albumin and the presence of bulk disease. Advanced clinical stage and an elevated serum LDH predicted independently for a poor relapse-free survival, and reduced overall survival following CR. There was no significant correlation between histological subtype in the Kiel classification and prognosis. This study confirms the prognostic significance of remission status and Ann Arbor clinical stage, and illustrates additional factors including serum levels of albumin and LDH, which serve to enhance the pre-treatment prognostic evaluation of patients with unfavourable histology NHL.

Adolescent↗
PubMed1989

Luteinizing hormone in women is secreted in superimposed pulse patterns.

1. The pulsatile nature of luteinizing hormone (LH) secretion has recognized physiological and clinical importance, but because of the difficulties with statistical analysis of serial data the precise nature of this pulsed signal is poorly understood. Several groups have noted small-amplitude, high-frequency pulses superimposed on large slower pulses, but, using conventional methods of analysis, it is not possible to distinguish these from assay variation or to characterize them. 2. In an alternative approach we have applied the methods of time series analysis which identify the harmonic patterns within data. Twenty-four healthy women in the early follicular phase of the cycle had blood samples taken at intervals of 1, 5 or 10 min for up to 6 h. 3. We found that LH secretion consists of superimposed harmonics of varying amplitude which occur in frequency bands of about (a) 1-3 h and (b) 2-3 min. Investigations excluded a reproducible pulsatility in our LH assay, implying that the small fast pulses are physiological events. 4. We conclude that LH release is highly complex and that the methods of time series analysis permit identification and characterization of the multiple pulses.

Adult↗
PubMed1989

High-grade non-Hodgkin's lymphoma complicating polypoid nodular lymphoid hyperplasia and multiple lymphomatous polyposis of the intestine.

Three patients with multiple lymphoid polyps of the small intestine--two with nodular lymphoid hyperplasia and one with multiple lymphomatous polyposis--developed high-grade B-cell lymphomas. A literature search has revealed only 10 previous cases of nodular lymphoid hyperplasia complicated by lymphoma and none of an association between multiple lymphomatous polyposis and high-grade lymphoma.

Adult↗
PubMed1989

Signet ring cell lymphoma of T cell type.

A rare variant of non-Hodgkin's lymphoma, signet ring lymphoma of T cell phenotype (only the fourth to be reported) in a 75 year old man was studied by light microscopy, immunohistochemistry, electron microscopy and gene rearrangement studies. Ultrastructurally, a wider spectrum of cell size and nuclear shape was observed in this case than in the previously recorded cases. The morphology of the signet ring vacuoles was identical to that found in the commoner B cell signet ring lymphoma of clear vacuole type, and it is suggested that the vacuoles derive from multivesicular bodies. The four cases reported so far have all presented with skin disease, and the limited evidence available suggests that the prognosis may be good.

Aged↗
PubMed1989

Development and validation of in vitro induction assays for toxic halogenated aromatic mixtures: a review.

Halogenated aromatic industrial compounds, typified by the polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) have been identified as residues in almost every component of the global ecosystem. Risk assessment of the complex mixtures of halogenated aromatics found in environmental samples is complicated by analytical problems and the lack of toxicological information on individual compounds and mixtures. Research in our laboratory has focused on the development and vadidation of the in vitro aryl hydrocarbon hydroxylase (AHH) induction assay in rat hepatoma H-4-II E cells in culture for quantitating individual toxic halogenated aryl hydrocarbons and their mixtures. For several PCB, PCDD, PCDF congeners, their mixed bromo/chloro analogs and reconstituted mixtures there was an excellent linear correlation between their -log ED50 values for AHH induction in rat hepatoma cells and their -log ED50 values for in vivo hepatic microsomal AHH induction, inhibition of body weight gain and thymic atrophy in the rat. It has also been shown for selected compounds that there was a good correlation between their in vitro AHH induction potencies and their effects in guinea pigs (AHH induction, inhibition of body weight gain) and mice (immunotoxicity). This assay system has been utilized to quantitative the "2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents" present in extracts from diverse sources including fly ash from a municipal incinerator and pyrolyzed brominated flame retardants which contain a complex mixture of halogenated dibenzo-p-dioxins and dibenzofurans.

Animals↗
PubMed1989

A comparative study of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease.

A clinical comparison of the nodular and diffuse variants of lymphocyte-predominant Hodgkin's disease (HD-LP) has shown them to be similar in all respects, including survival and relapse-free survival (RFS). In addition, they appear similar to mixed cellularity (MC) and nodular sclerosing Hodgkin's disease (HD-NS) with regard to clinical course. Thus, the reported phenotypic differences between nodular lymphocyte predominant Hodgkin's disease (HD-LP[N]) and other forms of the disease do not appear to be reflected in clinical behavior.

Adult↗
PubMed1989

Vacuum-stiffened beanbag for cranial remodeling procedures in modified prone position. Technical note.

In surgical correction of multiple-suture synostosis, placing the patient in the modified prone position permits access to the calvarium from the supraorbital ridge to the occipital bone below the transverse sinus. The modified prone position thereby enables surgeons to perform cranial remodeling procedures at one stage under direct vision, contributing to improved surgical results. However, no satisfactory head-frame for this position has been available. The authors report the successful use of a vinyl bag filled with styrofoam beads to achieve the modified prone position in young children. This widely available, economical device provides a safe, reliable means of positioning the child's head for cranial remodeling procedures.

Child, Preschool↗
PubMed1989

The ultrastructure of epithelioid sarcoma.

We have described clinical, histological immunohistochemical and ultrastructural features of four typical examples of epithelioid sarcoma. Smooth-muscle-type focal densities amid fine actin-like filaments in typical epithelioid cells often containing prominent rER have been observed, as well as a structure in the form of a densely granular cytoplasmic body. These features are suggestive of myofibroblastic differentiation. A tumour with light microscopy features typical of epithelioid sarcoma but of spindle-cell appearance is also described. Ultrastructurally this consists of myofibroblasts and it is suggested that this may be an unusual variant in which myofibroblastic differentiation is a major feature.

Adult↗
PubMed1989

Partial antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated induction of aryl hydrocarbon hydroxylase by 6-methyl-1,3,8-trichlorodibenzofuran: mechanistic studies.

6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) binds with moderate affinity to the aryl hydrocarbon (Ah) receptor protein (4.9 x 10(-8) M) but is a weak Ah receptor agonist. Cotreatment of male Long Evans rats with MCDF (50 mumol/kg) and a dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) that causes a near-maximal induction of hepatic microsomal aryl hydrocarbon hydroxylase and ethoxyresorufin O-deethylase activities resulted in a significant inhibition of these activities for up to 96 hr. Comparable results were obtained with MCDF (10(-7) M) and TCDD (10(-8) M) in rat hepatoma H-4-II E cells in culture over 36 hr. TCDD treatment of rats resulted in an initial decrease of hepatic cytosolic Ah receptor within 6 hr and this was followed by a subsequent 138% increase in cytosolic receptor levels 72 hr after treatment. Although MCDF (50 mumol/kg) did not significantly alter rat hepatic cytosolic Ah receptor levels in animals cotreated with TCDD plus MCDF, the latter compound significantly inhibited TCDD-mediated replenishment of the cytosolic Ah receptor. In contrast, treatment of rat hepatoma H-4-II E cells with TCDD (10(-8) M) resulted in the rapid (within 1 hr) depletion of cytosolic Ah receptor, which remained undetectable for up to 36 hr; cotreatment of the cells with MCDF (10(-7) M) and TCDD (10(-8) M) resulted in cytosolic Ah receptor levels that were similar to those observed after treatment with TCDD alone. The effects of MCDF on the uptake and persistence of nuclear [3H]TCDD-Ah receptor complex levels were also determined in rat liver and rat hepatoma H-4-II E cells in culture. MCDF did not significantly decrease levels of occupied nuclear Ah receptor complexes in the rat or rat hepatoma cells. Moreover, using the sucrose density gradient assay procedure, the sedimentation coefficients of the cytosolic and nuclear TCDD-Ah receptor complexes in the presence or absence of MCDF were comparable. The results of these and other related studies with 6-substituted-1,3,8-trichlorodibenzofurans suggest that MCDF may act as a partial TCDD antagonist by competing with TCDD for nuclear binding sites.

Animals↗
PubMed1989

Induction of tumor-infiltrating lymphocytes in human malignant melanoma metastases by immunization to melanoma antigen vaccine.

We report a statistically significant increase in tumor-infiltrating lymphocytes in subcutaneous melanoma metastases removed from patients immunized with a melanoma vaccine. Dense cellular infiltrates were seen in 10 of 11 nodules from vaccine-immunized patients, compared with 9 of 22 nodules from non-immunized patients (p = 0.02). Furthermore, these dense lymphocytic collections more frequently infiltrated the body of tumor nodules from immunized patients, whereas in non-immunized patients, lymphocytes were more often present only in the dermal tissue at the periphery of the nodule. Thus, allogeneic melanoma vaccines may augment immune responses to a patient's own tumor.

Antigens, Neoplasm↗
PubMed1989

Arterial bullet embolism.

We report a case of an arterial bullet embolus and compare it with other cases found in the literature. A 27-year-old white male sustained a .22 caliber gunshot wound that penetrated the abdominal aorta and traveled within the arterial system to occlude the left superficial femoral artery. The case was typical in that projectiles that embolize within the vascular system originate as a low kinetic energy missile injury of the trunk. Atypically, the patient developed ischemic changes from the embolus immediately. After direct aorta repair and immediate transverse arteriotomy bullet removal, the patient recovered fully.

Adult↗