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Biomedical subjects

D T Rowlands

Publications and source records attributed to D T Rowlands.

At least 19 recordsLinked to original sources

Argyrophilic nucleolar organizer regions in breast carcinoma. Correlation with DNA flow cytometry, histopathology, and lymph node status.

Argyrophilic nucleolar organizer regions (AgNOR) have been correlated with proliferative activity of neoplasms. Increased AgNOR may reflect increased proliferative activity of cells or ploidy. To explore this hypothesis, 41 breast carcinomas were processed for AgNOR silver staining and DNA flow cytometry. AgNOR counts were expressed as mean AgNOR/nucleus and percentage of tumor cells with more than five AgNOR/nucleus. The first count was designated mean AgNOR or mAgNOR, and the second count was designated AgNOR proliferative index or pAgNOR. Using Mantel-Haensel statistical analysis, carcinomas that exhibited mAgNOR of 2.4 or more had a high likelihood of aneuploidy (P less than 0.0001), an S-phase fraction of more than 5.8% (P less than 0.003), or a diameter greater than 2 cm (P less than 0.007). In addition, tumors with pAgNOR of 8% or more showed a statistically significant correlation with aneuploidy (P less than 0.004), tumor grade (P less than 0.04), and a more significant one with high S-phase fraction (P less than 0.0001). No significant correlation was obtained between pAgNOR and tumor size or lymph node status. These data indicate that AgNOR quantitation reflects changes in DNA ploidy and cell proliferation. They also suggest that the mean AgNOR counts correlate best with the DNA mass or ploidy and that the frequency of cells with higher AgNOR count best reflects proliferative activity or S-phase fraction.

Aneuploidy

Argyrophilic nucleolar organizer regions in Wilms' tumors and related lesions: a histologic and chromosomal correlation.

The argyrophilic nucleolar organizer regions (AgNORs) have been extensively investigated in different neoplasms, and their increased number has been frequently linked to aggressive tumor behavior. To evaluate this association, 22 specimens from 21 patients with Wilms' tumors and related lesions were stained by the AgNOR silver-staining technique in formalin-fixed, paraffin-embedded tissue. The aim of the study was to assess the significance of AgNOR count independently or in relation to histology in predicting the behavior of these neoplasms. Eleven nonneoplastic pediatric kidneys were used as controls. The controls had a range of 1.55 to 2.26 AgNOR/nucleus with a mean +/- SD of 1.91 +/- 0.22. The tumors showed a range of 1.25 to 2.86 AgNOR/nucleus with a mean +/- SD of 2.10 +/- 0.38 with obvious overlap between tumors and controls. The two unfavorable histology Wilms' tumors and the malignant rhabdoid tumor showed no increase in the number of AgNOR (1.66, 2.04, and 2.05, respectively). We further quantitated the nucleolar organizer regions (NOR) in metaphase spreads of three of the neoplasms, compared those with the patients' peripheral blood, and showed no difference in NOR numbers except for an occasional decrease in G-group NORs in the tumor cells. Tumors that had metaphase NOR counts of 6 to 9/nucleus had a mean interphase AgNOR count of less than 2.5. These results suggest that quantitative analysis of AgNORs in Wilms' tumors and related lesions is not a reliable predictor of aggressive tumor behavior. The discrepancy between metaphase and interphase NOR counts indicates that AgNOR counts are merely the reflection of the spatial arrangement of NOR-bearing chromosomes.

Child

Studies of the modified venous allograft.

Segments of rat inferior vena cava were modified by proteolytic digestion and dialdehyde starch tanning in an attempt to alter their antigenic nature and increase their tensile strength. These tissues were found to retain their ability to sensitize allogeneic recipients in both the intradermal and intra-aortic positions in all 50 experimental animals. Furthermore, these grafts had a very high aneurysm formation (100%), and aneurysm rupture (54%) rate even in isogeneic recipients, suggesting that the modification procedure so damages the structural integrity of venous tissue that its use in clinical situations may have disastrous consequences. Histologic evidence of intimal thickening, elastic disruption, and often severe acute and chronic inflammation supported the gross evidence of mechanical and immunologic damage and suggests that a mild brief course of immunosuppression may be indicated in clinical trials in situation in which autogenous saphenous vein in unavailable. Although the use of prosthetic mesh support for the graft may help to avoid structural changes, the introduction of synthetic materials may offset the theoretical advantages of the venous tissue.

Aldehydes

Levamisole: anthelmintic activity in calves following dermal application.

A series of seven experiments designed to evaluate the anthelmintic efficacy of levamisole (1-tetramisole) by dermal application is described. This work involved use of 181 artificially infested calves. The drug was formulated at a concentration of 10% m/v levamisole base in a solvent system promoting dermal absorption and was applied to both sides of the spine in the lumber region at a dose rate of 10 mg levamisole base per kg livemass. A consistent performance was achieved in these investigations, the results from all of which were based upon necropsy findings. Efficacy of treatment was assessed against the third and fourth larval stages and fifth stage larvae/adult worms of six nematode species; the respective efficacies obtained were Haemonchus placei 72,0%; 99,3%; and 100%: Ostertagia ostertagi 85,5%; 38,1% and 74,5%: Cooperia spp. 98,9%; 99,9% and 100%: Bunostomum phlebotomum 83,0%; 100% and 98,5%: Oesophagostomum radiatum 47,4%; 94,9% and 99,6% and Dictyocaulus viviparus 79,5%; 94,1%; 90.9% (fifth stage larvae) and 93,8% (adult worms). The anthelmintic efficacy of levamisole in these experiments is of the same order as that achieved by orthodox methods of administration at dose rates between 7,5 and 10,0 mg levamisole HC1 per kg livemass. These findings add a new dimension to the use of levamisole and to anthelmintic therapy in general.

Administration, Topical

Tubulointerstitial nephritis and glomerulonephritis in Brown-Norway rats immunized with heterologous glomerular basement membrane.

Tubulointerstitial nephritis and glomerulonephritis were produced in Brown-Norway rats (BN) by a single immunization with 2 mg of lyophilized bovine glomerular basement membrane. Tubulointerstitial nephritis was evident before glomerulonephritis. Antibody first bound to tubular basement membranes (TBM), and then the renal cortex was infiltrated with inflammatory cells. The TBM was split, and many renal tubules, especially proximal tubules, were destroyed. Approximately 14 days after the beginning of the tubular phase, antibody was observed to be bound to glomerular basement membranes (GBM) in linear fashion. There was epithelial and mesangial cell proliferation, splitting and reduplication of GBM, crescent formation, and glomerular scarring and atrophy.

Animals

Humoral immune responses in Rana catesbiana frogs and tadpoles.

Rana catesbiana adult frogs and tadpoles were immunized with the bacteriophage F2, 0X-174, and T4 and the haptens 2,4 dinitrophenyl (DNP) and fluorescein (FTC). The haptens were conjugated with bovine serum albumin (BSA), bovine gamma globulin (BGG), or horsehoe crab hemocyanin (Hycn). Sera were obtained from immunized animals at invervals up to six months after immunization. The antibody activities were measured by bacteriophage neutralization techniques. Sucrose density gradients were used to separate the antibody classes. Both adults and tadpoles responded to each of the antigens tested. High molecular weight antibodies were predominant in both groups of animals. Low molecular weight antibody activity was not found in adults until nine weeks post immunization but, thereafter, this fraction increased throughout the immune response. Low molecular weight antibodies could also be identified in serum of tadpoles, but only under certain conditions.

Animals

Antibodies to T cells in sarcoidosis.

Antibodies to a proportion of T lymphocytes were detected in the sera of 9 of 15 patients with sarcoidosis. Patients were studied within one year of tissue diagnosis, none were taking steroids, and all had hilar adenopathy with pulmonary infiltrates (Stage II). Antibodies were identified by three assays using a panel of T cells purified (greater than or equal to 90%) from the peripheral blood of healthy donors by the nylon column technique. Nine of fifteen sarcoid inhibited the capacity of normal T cells to adhere to sheep red blood cells (E rosettes) with an average reduction of 33% (range 21-46%) from control values. Antibodies to T cells were also identified using the indirect immunofluorescent method; 7 of 15 sera contained antibodies (IgM and IgG) to a portion of T cells (mean 36%, range 24-52%). Four of these sera were also cytotoxic to a fraction (18-31%) of T cells when incubated (15 degrees, 90 min) in the presence of rabbit complement. The antibodies to T cells identified in the sera of sarcoid patients may account for some of the immunological abnormalities found in this disease.

Animals

Lymphocyte subpopulations in sarcoidosis: correlation with disease aetivity and duration.

We studied lymphocytes from the peripheral blood of 29 sarcoid patients to relate T- and B-cell populations with disease activity and duration. In patients with acute (less than 1 year) and chronic (greater than or equal to 9 years) active disease, the absolute lymphocyte count was reduced; the absolute number of T cells was reduced; and the proliferative response of lymphocytes to phytohemagglutinin was depressed compared with control subjects. Ten of 21 patients with active disease had 5% to 32% atypical lymphocytes. The proportion of cells bearing surface immunoglobulin (Ig) was increased in patients with active disease, but the absolute number of cells bearing surface Ig did not differ significantly from controls. However, studies using overnight in-vitro culture indicated that a large fraction of these cells bound exogenous Ig. The number of cells indentified by complement receptors was significantly reduced in patients with active disease. In contrast, patients who had complete reasolution of their disease showed no significant differences from controls in either T- or B-cell populations or in the proliferative response of their lymphocytes to phytohemagglutinin.

Acute Disease

The antigenicity of venous allografts.

Segments of rat inferior vena cava modified by proteolytic digestion and dialdehyde starch tanning were found to retain their ability to sensitize allogeneic recipients both in the intradermal and intra-aortic positions. Furthermore, these grafts had a very high aneurysm formation (100%) and aneurysm rupture rate (63%), even when used as isografts, suggesting that the modification procedure so damages the structural integrity of the grafts that use in clinical situations may have disastrous consequences. Clinical trials must be undertaken with great caution and a mild, brief course of immunosuppression may be indicated when modified venous allografts are contemplated in potential organ transplant recipients. Furthermore, prosthetic mesh may be required for support whenever modified allogeneic veins are used for arterial substitutes. In the absence of autologous tissue, the bovine xenograft is probably the material of choice for reconstruction or bypass of small vessels.

Animals