PubMed Health⌕ Search

Biomedical subjects

B M Heatfield

Publications and source records attributed to B M Heatfield.

At least 19 recordsLinked to original sources
PubMed1993

Causes and costs of injuries in multiple trauma patients requiring extrication from motor vehicle crashes.

Prospective and contemporaneous medical and economic cost studies of 144 victims of motor vehicle crashes admitted to a regional level I trauma center with multiple injuries (ISS > or = 16) revealed 122 non-ejected patients, of whom 102 required extrication (EXTRIC) from the vehicle for physical or medical reasons and 20 who did not (N group). There were no differences in age (EXTRIC, 34 +/- 17 years; N, 41 +/- 24 years), type of crash (Frontal: 57% EXTRIC, 60% N; Lateral: 32% EXTRIC, 35% N) restraint use (35% EXTRIC, 35% N), or mortality (29% EXTRIC, 30% N). However, the estimated maximum speed before the crash was higher in EXTRIC patients (50 +/- 16 mph vs. 46 +/- 18 mph N, p < 0.04), as was the change in velocity (delta V) on impact (EXTRIC 30 +/- 15 mph; N, 24 +/- 8 mph, p < 0.01). Brain injuries (51% EXTRIC vs. 35% N) and lower extremity injuries were more numerous in EXTRIC patients (59% vs. 20% N, p < 0.003) and the number of splenic, lower extremity, and pelvic injuries associated with shock was greater in EXTRIC patients, p < 0.02; as were postinjury complications. As a result, operating room costs from orthopedic and plastic surgery increased professional charges in the EXTRIC group versus the N group ($20,000, EXTRIC; $17,000, N) and critical care costs ($13,000, EXTRIC; $4,000, N) with total costs of $72,000 and $77,000, respectively. The lower extremity injuries in EXTRIC patients were primarily a result of body part contacts with intrusions (CIs) of the car occupant compartment structures [73% with vs. 24% without (p < 0.0001)]. In lateral MVCs, brain injuries were also more commonly associated with CIs of the side window frame or A pillar (72% CI vs. 25% no CI; p < 0.035); but as a whole in MVCs in which extrication was necessary, lower extremity injuries from instrument panel or toepan CIs appeared more frequent than those resulting from contacts only (p < 0.0001). In EXTRIC patients, 69% of those in shock had CI injuries, and 80% of the deaths in the EXTRIC group were associated with CI injury. These data suggest that measures designed to prevent CIs by strengthening car passenger compartment structures may reduce the incidence of severe brain and lower extremity injuries and may reduce the need for extrication after MVCs.

Accidents, Traffic↗
PubMed1990

Correlation of cytokeratin patterns with histopathology during neoplastic progression in the rat urinary bladder.

The discrimination of atypical (premalignant) cells from invasive neoplastic cells in primary bladder lesions is a major diagnostic problem in cytopathology and surgical pathology. We have used an animal model of urinary bladder carcinogenesis to determine the specific changes which occur in the expression of certain cytokeratins (CK) during the progression of lesions from regenerative hyperplasia and carcinoma in situ to transitional cell carcinomas. At sequential time points following exposure of the rat bladder epithelium to N-methyl-N-nitrosourea in vivo, immunohistochemical staining of CKs was evaluated in ethanol-fixed samples from the induced urothelial lesions using commercially available anti-CK mouse monoclonal antibodies. Specific changes were found in the expression of CKs 13, 18, and 19 during the neoplastic progression of induced urothelial lesions in the rat. These changes included the reciprocal loss of expression of CK 19 and the reappearance of CK 18 as malignant tumors developed. Invasive cells also did not express CK 13. Our results, based on the rat model, are similar to those reported by others on CK expression in human bladder tumors. Because these changes in CK expression occurred at specific points in the progression of urothelial lesions, the antibodies utilized in this study may be helpful in predicting the invasive potential of cells present in cytopathological specimens and tissue biopsies from human urothelial lesions.

Animals↗
PubMed1987

Isolation and primary culture of urothelial cells from normal human bladder.

Trypsinization (WT) was employed to disaggregate urothelial cells from normal human urinary bladder mucosa for the preparation of primary cultures. Urinary bladders of two male adults both 25 years old were obtained autopsy 1-2 h after death. The mucosa was incubated in HBSS containing 0.25% trypsin at 37 degrees C. Mean cell yield, viability, and attachment were 14.6 X 10(7), 76%, and 42.5% after WT. In histologic sections of treated mucosa, most of the urothelium was removed by WT. Following plating and attachment, cells obtained by WT formed a monolayer of flattened epithelial-like cells. When stained with polyclonal antikeratin antibody using the indirect immunoperoxidase technique, all of the cells were immunoreactive indicating an epithelial origin. In conclusion, based on morphology and immunocytochemistry, WT removed virtually all of the urothelial cells from the mucosa and no contamination by mesenchymal cells resulted from this procedure. Thus, WT is an appropriate technique for the isolation of urothelial cells and initiation of primary cultures of normal human urothelial cells for subsequent study.

Adult↗
PubMed1987

Histomorphometry and cell kinetics of normal human bladder mucosa in vitro.

In this study, we have quantified the morphologic and kinetic parameters of explant cultured normal adult human urinary bladder mucosa. Quantitative parameters studied were urothelial height, cell density, labelling index and mitotic index. For these studies, urinary bladders from seven adults with no previous history of urologic disease were obtained at autopsy. Mucosal explants were maintained in rocking culture on Gelfoam rafts for up to 33 days using supplemented CMRL 1066 medium. Prior to sampling, cultures were treated with tritiated thymidine and colchicine to investigate tissue kinetics. Data was based on histologic autoradiograms. During culture, urothelial cells retained normal polarity. During the first week of culture, urothelial height increased and cell density decreased. DNA synthesis and mitotic activity occurred primarily among basal cells. DNA synthesis was first noted on day 2 of culture; mitotic activity began after 3 days of culture. Morphologically, human urothelium was well maintained; DNA synthesis and mitotic activity was variable but continued throughout culture.

Adolescent↗
PubMed1987

Immunohistochemistry of the cytoskeleton of human prostatic epithelium. Evidence for disturbed organization in neoplasia.

An indirect immunoperoxidase technique was used to evaluate keratin, actin, tubulin, and calmodulin immunoreactivity in histologic sections of normal, hyperplastic, and neoplastic human prostate. Polyclonal as well as monoclonal keratin antibodies produced equivalent and intense staining of normal epithelium. The immunoreactivity of normal prostate with keratin antibodies was more pronounced than with antibodies to the other components of the cytoskeleton. Variation in staining for components of the cytoskeleton was minimal. The same findings applied to hyperplastic prostate. The immunoreactivity of prostate tumors with antibodies to these cytoskeletal proteins differed markedly from normal prostate. Prostatic carcinomas showed reduced keratin immunoreactivity with a panepithelial antibody, but unaltered or enhanced immunoreactivity with tubulin, actin, and calmodulin antibodies. Many tumors were unreactive with a monoclonal keratin antibody that was strongly reactive with tissues that contained cytokeratin 18 (45-kd) and which intensely stained normal and hyperplastic prostate. In addition, prostate carcinomas often yielded heterogeneous patterns of staining with actin, tubulin, and calmodulin antibodies in contrast to normal and hyperplastic prostate, which showed uniform staining. The results suggest that a disturbance in the organization of the cytoskeleton may accompany neoplastic transformation of human prostate.

Actins↗
PubMed1984

Immunocytochemical evaluation of human prostatic carcinomas for carcinoembryonic antigen, nonspecific cross-reacting antigen, beta-chorionic gonadotrophin, and prostate-specific antigen.

The unlabeled antibody peroxidase-antiperoxidase technique was used to examine human malignant prostatic tissue (primary tumors) for the presence of prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), nonspecific cross-reacting antigen (NCA), and beta-chorionic gonadotrophin (HCG). The results were compared to those obtained with normal and hyperplastic prostate tissue (BPH). All specimens of neoplastic, hyperplastic, and normal prostate tissue showed immunostaining reactions for PSA. Immunostaining for PSA was relatively uniform among samples of normal and BPH tissue, but variations with respect to intensity of PSA immunostaining were noted among prostate tumors as well as between the neoplastic cells of individual tumors. Some areas of normal or hyperplastic prostatic epithelium within tumors showed stronger staining reactions for PSA than the tumor cells themselves. Using an antiserum which was able to detect both NCA and CEA, it was found that 16 of 38 tumors (42%) had positive immunostaining reactions. Of these, 15 were subsequently shown to contain only NCA immunoreactivity, and 1 tumor had both NCA and CEA immunoreactivity. NCA, but not CEA, immunoreactivity was identified in hyperplastic prostate tissue within tumor specimens and in BPH specimens. Neither antigen was detected in normal prostatic epithelium. Three of 38 tumors (8%) were found to contain neoplastic cells with HCG immunoreactivity. HCG immunoreactivity was not identified in BPH or normal prostatic tissue. Therefore, HCG and CEA immunoreactivity appear to be tumor-associated antigens in prostate cancer which are expressed with a low incidence. The results of the study identified prostate tumors with different patterns of immunocytochemical markers: 22 of 38 tumors (58%) contained only PSA immunoreactivity; 13 of 38 tumors (34%) contained PSA and NCA immunoreactivity; 2 of 38 tumors (5%) were positive for PSA, NCA, and HCG immunoreactivity; and 1 of 38 tumors (3%) contained PSA, NCA, HCG, and CEA immunoreactivity. Apart from PSA, which was present in all tumors, the markers studied here appeared to be more frequently expressed in well-differentiated tumors than in less-differentiated tumors. Our results suggest the possibility of subclassifying prostate tumors by means of immunocytochemistry.

Antigens↗
PubMed1982

Studies on carcinogenesis of human prostate. II. Long-term explant culture of normal prostate and benign prostatic hyperplasia: light microscopy.

Light microscopic and histochemical changes in normal human prostate and benign prostatic hyperplasia (BPH) during long-term explant culture were characterized. Normal human prostate obtained at immediate autopsy of young adults or BPH obtained at the time of surgery were maintained in explant culture as long as 24 weeks. Morphologic alterations in glandular epithelium and stroma in response to culture conditions were assessed by light microscopy and histochemistry of mucosubstances. The histologic and histochemical responses of normal prostate and BPH to in vitro conditions were essentially identical. Within 1 week, secretory epithelial cells became necrotic and sloughed into acinar lumina. Remaining epithelial cells proliferated, repopulated acinar structures, and migrated onto explant surfaces forming a new well-differentiated epithelium characterized by synthesis and secretion of neutral and acidic mucosubstances. During subsequent periods in vitro, synthesis and secretion of mucosubstances gradually diminished whereas the stroma and deep glandular structures became necrotic. Our observations suggest that cells comprising the new epithelium in cultured explants of normal human prostate and BPH are derived from prostatic basal cells.

Adolescent↗
PubMed1982

Studies on carcinogenesis of human prostate. III. Long-term explant culture of normal prostate and benign prostatic hyperplasia: transmission and scanning electron microscopy.

Ultrastructural changes in normal human prostate and benign prostatic hyperplasia (BPH) during long-term explant culture were compared. Explants of normal prostate obtained at immediate autopsy of young adults of BPH obtained at the time of surgery were maintained as long as 24 weeks in vitro. Ultrastructural changes occurring in epithelial cells during culture were monitored by transmission and scanning electron microscopy. Essentially identical results were found for normal prostate and BPH. During the first week of culture, secretory epithelial cells degenerated and sloughed into the acinar lumen, resulting in an accumulation of necrotic debris. During this period, however, epithelial cells with ultrastructural characteristics of basal cells remained viable, repopulated glandular structures, migrated from glands and ducts, and epithelialized adjacent cut surfaces, eventually covering the explant. On explant surfaces, these basal cells initially were squamous-like, but they later became typically cuboidal, polygonal, or sometimes columnar and formed an epithelium, two cells or more thick. Epithelium with similar features lined acini within explants. Epithelial cells at the surface or within explants were distinguished by the presence of microvilli, junctional complexes, multiple Golgi complexes, well-developed rough endoplasmic reticulum, polyribosomes, nuclei with prominent nucleoli, orthodox mitochondria, scattered tonofilaments, and a basal lamina. Some epithelial cells extended from the lumen to the basal lamina; others were oriented along the basal lamina and did not extend to the lumen. By 1--2 weeks in vitro, these epithelial cells began synthesis of mucus-like material. At later intervals of culture, microvilli were shortened and mucosubstances were reduced. During culture, the stroma became progressively hypocellular and necrotic. In summary, explant-cultured epithelial cells of normal human prostate or BPH were similar ultrastructurally and were found to originate from basal cells, which alone survive culture conditions.

Adolescent↗
PubMed1982

N-Methyl-N-nitrosourea and saccharin: effects on epithelium of normal human urinary bladder in vitro.

The effects of N-methyl-N-nitrosourea (MNU) and saccharin on the histology of normal human bladder "urothelium" (i.e., the epithelium of the urinary bladder) were studied in long-term explant cultures. In MNU-treated cultures, a dose response was observed. Single doses of 1-100 micrograms MNU/ml induced atypical focal hyperplasia, which reverted to a single or a double cell layer as seen in controls. Exophytic, papillary-like hyperplastic structures were noted after a single dose of 10 or 100 micrograms MNU/ml. In contrast to single doses, multiple doses (given every 2 wk) of MNU at 5 or 10 micrograms/ml resulted in striking focal proliferation of dysplastic spindle cells in as little as 6 weeks (three doses of MNU). At 0.5% saccharin, urothelium on explant surfaces resembled that of controls, except in one instance in which mild focal hyperplasia persisted. In the presence of saccharin, hyperplasia induced by a single dose of MNU persisted. Following three multiple doses of MNU in the presence of saccharin, spindle cell hyperplasia was induced similar to that seen with multiple doses of MNU alone, although nuclei appeared more pleomorphic and hyperchromatic in the presence of saccharin.

Cocarcinogenesis↗
PubMed1981

Aryl hydrocarbon hydroxylase in human prostate.

Aryl hydrocarbon hydroxylase (AHH) was present in explant cultures of human prostate obtained from surgery of benign prostatic hyperplasia and was inducible by benz[a]anthracene (BA). The induction of AHH ranged from 14- to 150-fold when compared with control values and 10-fold variation of AHH inducibility among individuals was observed. Epithelial cells grown from human prostate tissue also contained measurable AHH activity and AHH was inducible by BA and 7,12-dimethylbenz[a]anthracene (DMBA). Inducibility of AHH by BA ranged from 2- to 63-fold. The inducibility of AHH by DMBA was always less than that by BA. In cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), there were no changes in AHH activity. These findings support the view that the human prostate is susceptible to environmental polycyclic hydrocarbon carcinogens and that environmental and occupational factors might contribute to the etiology of human prostatic carcinoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Adenocarcinoma of the kidney. III. Histogenesis of renal adenocarcinomas induced in rats by N-(4'-fluoro-4-biphenylyl)acetamide.

The histogenesis of renal adenocarcinoma induced in F344 rats by the carcinogen N-(4'-fluoro-4-biphenylyl)acetamide (FBPA) was described in order to clarify the site of origin of this neoplasm within the nephron. FBPA was added to the diet up to 48 weeks, and the animals were killed at intervals from 4 to 52 weeks after initiation of the carcinogenic diet. As seen by light microscopy, tumors appeared to arise from the pars recta of the proximal tubule in a series of stages progressing from focal hyperplasia with dysplasia to development of small, then large, neoplastic nodules composed of moderately basophilic, closely packed tumor cells arranged in individual aggregates or lobules surrounded by basement membrane-like material. Karyomegaly, cystic lesions, foam cell lesions, interstitial fibrosis, and casts also accompanied tumorigenesis in this animal model.

Adenocarcinoma↗
PubMed1980

Adenocarcinoma of the kidney. IV. Electron microscopic study of the development of renal adenocarcinomas induced in rats by N-(4'-fluoro-4-biphenylyl)acetamide.

Ultrastructural features of various stages in the histogenesis of renal adenocarcinoma induced in F344 rats by the carcinogen N-(4'-fluoro-4-biphenylyl)acetamide (FBPA) are described. FBPA was added to the diet up to 48 weeks; animals were killed at intervals from 4 to 52 weeks. Characterized were foci of cellular alterations followed by foci of proliferation with dysplasia leading to solid and cystic lesions, carcinoma in situ, and finally, carcinoma. Other lesions included foam cell nodules. Alterations also were noted in distal tubules. By electron microscopy, subtle changes in some proximal tubule cells of the pars recta were noted by 4 weeks (foci of cellular alteration). By 12 weeks there was evidence of dedifferentiation and reduction of cell polarity, thickening of basal lamina, alterations in endoplasmic reticulum and mitochondria, and increases in residual bodies. Nuclei of these cells possessed large nucleoli. From 24 to 36 weeks foci of proliferation were seen and consisted of tumor cells arranged in solid and cystic configurations. In solid lesions (less than 3 mm), in addition to the above alterations, cells showed a microvillus brush border in unusual locations, small and irregular mitochondria, multiple Golgi complexes and basal lamina, and loss of cell polarity. From 36 to 52 weeks carcinoma in situ consisted of cells similar to tumor cells described above. In addition, intracellular canaliculi were present. Areas of tumor cell degeneration and necrosis also were seen. Cells of larger carcinomas (greater than 3 mm), also observed at this interval, were identical to those of carcinoma in situ. Calcification of necrotic debris was noted.

Adenocarcinoma↗
PubMed1980

Cell surface changes in preneoplastic and neoplastic epithelium.

Reviewed are studies on alterations of the plasma membrane of neoplastic epithelial cells. Changes in the plasma membrane are probably of unique importance in the major clinical manifestations of cancer. Discussed are sequences in cell membrane changes in vivo and in vitro in both human tumors and chemical-induced animal models of carcinogenesis. Emphasis is placed on alterations in specializations of the plasma membrane, including cell junctions, antigenic and enzyme markers, intramembranous components, ion regulation, and the cytoskeleton. In general, the plasma membrane of neoplastic cells is less specialized than the cell of origin. In mammalian bladder, pleomorphis microvilli may occur concomitant with neoplastic transformation. Cell junctions in tumor cells may be reduced in number of functional characteristics compared to normal cells, which may affect cell-cell communication. Such alterations may be related to tumor cell invasion and metastasis. Normal membrane antigens may be lost or new ones gained in neoplasia. Thus, ABO blood group antigens may be lost in the case of human bronchus and bladder, while carcinoembryonic antigen occurs de novo in tumors of the colon and lung. Similarly, several marker enzymes may be reduced in activity, or appear de novo. Alterations in the number and pattern of distribution of intramembranous particles have been observed in bladder tumors, possibly related to changes in membrane function. Shifts in ion ratios (Na+/K+/Ca++) within neoplastic cells may result in abnormalities in cell shape, cell movement, and cell-cell communication. Many of these changes may reflect defects in function of the Golgi apparatus, which synthesizes components of the plasma membrane. Alterations in one or more components of the cytoskeleton may adversely affect cell shape, mobility of membrane proteins, cell-cell adhesion, etc., and play a major role in malignant cell behavior.

Animals↗