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Biomedical subjects

T A Godwin

Publications and source records attributed to T A Godwin.

12 recordsLinked to original sources

Loss of colonic HLA antigens in familial adenomatous polyposis.

The loss of HLA antigens by neoplastic cells is considered important for tumor growth and metastasis, since it may allow tumors to escape immune surveillance. We studied the expression of HLA class I and II antigens in the colons of 10 patients with familial adenomatous polyposis (FAP), a condition which leads inevitably to colorectal cancer. Expression of HLA class antigens was studied by immunohistochemistry in (a) adenomas from patients with FAP, (b) histologically normal mucosa distant from the adenomas, and (c) histologically normal colonic mucosa from normal subjects. The expression of HLA class I and II antigens was decreased in histologically normal mucosa from FAP patients compared to normal controls. Adenomas showed a similar but quantitatively more pronounced reduction (or loss) of HLA antigen expression. The reduction of HLA expression in adenomas was comparable to that observed in sporadic colon carcinomas. This generalized suppression of HLA gene expression in the colon of FAP patients, which precedes the onset of overt histological manifestations of neoplasia, may be an important early event in colon carcinogenesis.

Adenomatous Polyposis Coli

Extensive diffuse pulmonary ossification.

Diffuse lung injury can either heal normally or progress to fibrosis. Calcification in the setting of fibrosis is common. The appearance of mature woven bone is not. We report a patient with extensive diffuse pulmonary ossification and discuss some of the theories relating to the development of this phenomenon.

Adult

Infrared spectroscopy of exfoliated human cervical cells: evidence of extensive structural changes during carcinogenesis.

Infrared spectra were obtained from exfoliated cervical cells from 156 females, of whom 136 were normal, 12 had cervical cancer, and 8 had dysplasia. The spectra of the normal women, essentially identical, differed from those obtained from patients with either cancer or dysplasia. In malignant samples we noted (i) significant changes in the intensity of the glycogen bands at 1025 cm-1 and 1047 cm-1, the bands at 1082 cm-1 and 1244 cm-1, the C--O stretching band at 1155 cm-1, and the band at 1303 cm-1, (ii) significant shifts of the peaks normally appearing at 1082 cm-1, 1155 cm-1, and 1244 cm-1, and (iii) an additional band at 970 cm-1. Further study of several of these bands, including the pressure dependence of their frequencies, revealed that in the malignant cervical tissue there were extensive changes in the degree of hydrogen bonding of phosphodiester groups of nucleic acids and C--OH groups of proteins, as well as changes in the degree of disorder of methylene chains of lipids. The IR spectra of samples with dysplasia demonstrated the same changes with cancer samples, except that the changes were of lesser magnitude and the phosphodiester peak normally appearing at 1082 cm-1 did not shift. These spectroscopic changes appear to progress in tandem with the morphological changes that lead normal cervical epithelium to cancer through the premalignant stage of dysplasia. The diagnostic potential of IR spectroscopy is discussed.

Cervix Uteri

Ploidy in invasive colorectal cancer. Implications for metastatic disease.

A retrospective study was performed to determine the ploidy of superficial (above muscularis propria) and deep (below muscularis propria) biopsy specimens from the primary colorectal cancer of 88 patients with Dukes Stage C2 and D colorectal tumors. The ploidy of lymph node and liver metastases was compared with that of the superficial and deep specimen from the corresponding primary tumor. Among the tumors studied, 78% exhibited nondiploid stemlines. In 19% of the tumors, the ploidy of the superficial biopsy differed from that of the deep biopsy. Among these discordant tumors, all of the deep biopsy specimens corresponded in ploidy to the liver metastases, whereas most of the superficial specimens were similar in ploidy to the lymph node metastases. Our observations suggest that measurement of a single site may not be sufficient to detect nondiploid stemlines within a tumor. They also suggest that measurement of deeper parts of invasive tumors may be more reflective of the phenotype of distant metastases than measurement of superficial specimens.

Colorectal Neoplasms

Cryptosporidiosis in the acquired immunodeficiency syndrome: a study of 15 autopsy cases.

The pathologic changes associated with human cryptosporidiosis have not been well characterized. In this report, 15 cases of cryptosporidiosis in acquired immunodeficiency syndrome patients are described. Organisms were found in autopsy tissue specimens in 13 cases, and only in antemortem stool samples in two. Gastrointestinal/hepatobiliary distribution of organisms was as follows: small intestine (13 cases), extrahepatic bile ducts (eight), intrahepatic bile ducts (seven), large intestine (six), pancreas (five), stomach (three), and esophagus (one). At all sites, infection was usually associated with nonspecific reactive epithelial changes, architectural abnormalities such as villous flattening in the small intestine, and interstitial edema with mixed inflammatory cell infiltrates. Presence of organisms and associated mucosal injury were patchy and of variable severity in the intestine. In the biliary tract, injury was commonly diffuse and severe. Pancreatic duct injury was generally mild and often limited to hyperplastic squamous metaplasia. In late-stage acquired immunodeficiency syndrome patients with cryptosporidiosis, widespread infection in the gastrointestinal and biliary systems by this coccidian was more common and severe than previously suggested. Although the mechanisms have yet to be determined, infection usually is accompanied by pathologic changes that may be causally related to pathophysiologic abnormalities, such as diarrhea and malabsorption, and may account for other clinical manifestations of pancreatitis, cholangitis, and obstructive cholestasis.

Acquired Immunodeficiency Syndrome

Immunohistochemistry and gene rearrangement studies in the diagnosis of malignant lymphomas: a comparison of 152 cases.

One hundred fifty-two cases (155 specimens) of lymphoproliferative disorders were studied by immunohistochemistry and gene rearrangement analysis. Ninety-five of 96 B-cell lymphomas (99%) showed genotypic B-cell monoclonality. Of these, five cases had rearranged T-cell receptor (TCR) beta chain gene in addition to immunoglobulin heavy chain (IgH) and kappa light chain (Ig-K), one case had rearranged IgH and TCR-gamma chain but not Ig-K or TCR-beta, and two cases had only Ig-K rearrangement. One exceptional case in the B-cell lymphoma group had unrearranged, germline genotypes. In contrast, only 10 of 19 (53%) phenotypic T-cell lymphomas had rearranged TCR-beta, eight with concurrent TCR-gamma rearrangement. Of the remaining nine cases, six had germline configuration, two had rearranged Ig-K only, and one had both IgH and Ig-K rearrangement. This last case was reclassified as T-cell predominant, B-cell lymphoma. Thirteen of 16 cases of Hodgkin's disease had germline configuration; three cases had rearranged IgH and Ig-K, of which two were lymphocyte predominant with light chain monoclonality and one was a recurrence. Among 21 reactive lesions, 17 had germline configuration and four had rearranged IgH and Ig-K genes. Of these four cases, two were orbital lesions, one was a partially involved lymph node, and one developed a nodular lymphoma 9 months later. Our results indicate that almost all B-cell lymphomas have IgH and/or Ig-K rearrangement. In contrast, peripheral T-cell lymphomas have greater genotypic heterogeneity, and germline patterns for TCR genes are not uncommon. Reactive lesions and Hodgkin's disease tend to retain germline configuration, and any exception is often associated with an unusual clinical setting and/or histology. Genotypic analysis is thus most indicated in B-cell lymphomas with equivocal immunohistochemistry findings, T-cell lymphomas, and atypical cases of Hodgkin's disease and reactive lesions.

Antigens, Differentiation

Mycobacteremia in acquired immune deficiency syndrome. Rapid diagnosis based on inclusions in the peripheral blood smear.

In 16 cases of human immunodeficiency virus-associated Mycobacterium avium-intracellulare complex (MAC) infection, 7 were diagnosed after finding intracytoplasmic negatively staining linear inclusions within histiocytes using Romanowsky-stained bone marrow aspirate smears. Four patients had inclusions within monocytes and neutrophils in the peripheral blood smear. The authors believe these cases represent the first reported examples of MAC inclusions observed within leukocytes in Wright's-stained peripheral blood smears. Inclusions usually were found in the setting of prominent toxic changes in leukocytes such as large Dohle bodies, marked granulation, and vacuolation. These inclusions are characteristic of mycobacteria and can be confirmed by acid fast stains and mycobacteriologic culture. The authors present the clinical and laboratory setting in which identification of inclusions in peripheral blood smears may be a rapid, minimally invasive, and cost-effective method of diagnosing mycobacterial infection.

Acquired Immunodeficiency Syndrome

Cryptosporidiosis of the biliary tract in AIDS.

Cryptosporidiosis of the biliary system was studied retrospectively in 13 patients with acquired immunodeficiency syndrome (AIDS). The diagnosis was made by means of histologic examination (n = 9) or imaging studies and the presence of intestinal cryptosporidiosis (n = 4). Imaging studies were done in 10 patients. Ultrasound (US) and computed tomography (CT) showed dilatation of the biliary ducts, some with wall thickening, thickening of the gallbladder wall and pericholecystic fluid. Cholangiograms showed attenuation and pruning of the intrahepatic bile ducts, some with beading and dilatation of the common bile duct. Three patients had papillary stenosis. Numerous Cryptosporidium organisms were found in three resected gallbladders and in the biliary ducts of seven patients in whom autopsy was performed, accompanied by an exuberant inflammatory response. Correlation of the radiologic and pathologic findings establishes a direct etiologic role of Cryptosporidium as one of the major infectious agents in cholangitis associated with AIDS.

Acquired Immunodeficiency Syndrome

Fatal embolization of intestinal contents through a duodenocaval fistula.

Embolization of intestinal contents to the lung is an exceedingly rare event, which to our knowledge, has never been reported as a cause of death. Equally rare is duodenocaval fistula resulting from a penetrating duodenal peptic ulcer. We present the case of a 51-year-old man whose duodenal ulcer led to a fistulous tract with the inferior vena cava and subsequently to progressive pulmonary embolization of intestinal contents, ultimately resulting in death from respiratory failure.

Duodenal Diseases

Occlusive vasculopathy in systemic lupus erythematosus. Association with anticardiolipin antibody.

Patients with systemic lupus erythematosus and with antiphospholipid antibody are subject to sudden occlusion of multiple blood vessels. We describe two patients with systemic lupus erythematosus with acute, catastrophic, widespread non-inflammatory visceral vascular occlusions associated with high-titer antiphospholipid antibody. The histopathologic features clearly distinguished these patients from classic systemic lupus erythematosus vasculitis. We further suggest that, based on a probable pathogenesis related to the presence of antiphospholipid antibody, and based on the non-inflammatory vascular occlusion, steroids and other immunosuppressive medications are of limited value. Plasmapheresis along with anticoagulant therapy should be considered.

Adult

Abnormal DNA ploidy and proliferative patterns in superficial colonic epithelium adjacent to colorectal cancer.

Superficial colonic cells were taken from normal-appearing mucosa at 2, 5, and 10 cm proximal and distal to colorectal cancer margins in 37 patients. The DNA ploidy and proliferative pattern of each sample were determined using flow cytometry. In 11 patients, histology of mucosal sections from the same sites also was analyzed. We found a higher frequency of aneuploidy than previously reported in mucosa up to 10 cm from a colorectal cancer; 62% (23/37) of the primary cancers were aneuploid, and of these, 48% (11/23) were associated with adjacent aneuploid mucosa. The mucosa adjacent to the 14 diploid cancers had only diploid characteristics. The proliferative activity (as reflected by synthetic (S) phase fraction) of aneuploid cancers (21.1 +/- 2.0% SEM) and aneuploid mucosa as far as 10 cm away (21.2 +/- 2.1% SEM) was higher than in normal controls (10.2 +/- 0.7% SEM) (P less than 0.0005). Parallel cytology excluded shed cancer cells as an explanation for these findings. Histology showed diffuse, generally mild and reactive, mucosal abnormalities in eight of 11 patients. Ploidy did not correlate with histologic abnormalities. The findings of aneuploidy and high S-phase fraction in uninvolved superficial mucosa provide evidence for a field defect in mucosa adjacent to colorectal cancer and support the concept that the large bowel mucosa behaves as a unit in carcinogenesis.

Adult

Value of necropsy in acquired immunodeficiency syndrome.

Necropsy findings in 101 adult patients with the acquired immunodeficiency syndrome (AIDS) from two metropolitan hospitals were compared retrospectively with the antemortem clinical diagnoses. 94% of the patients were male and 68% were homosexual or bisexual. 75 (74%) patients had AIDS-related diseases at necropsy that were not suspected clinically. The commonest of the unsuspected AIDS-related diseases were cytomegalovirus infection (49% of all cases), systemic fungal infection (20%), systemic Kaposi's sarcoma (14%), Mycobacterium avium intracellulare infection (11%), and systemic herpes infection (9%). Cryptococcal infection and cytomegalovirus retinitis were always diagnosed antemortem; and Pneumocystis carinii pneumonia went undiagnosed in only 5 of 58 (9%) patients who had proven infection either clinically or at necropsy. 8 patients who died with fungal pneumonia had undergone bronchoscopy; however, in only 1 patient was it diagnosed antemortem. Tuberculosis was undiagnosed in 4 patients. 4 cases of central nervous system lymphoma diagnosed only at necropsy had been treated empirically for toxoplasmosis. Bacterial pneumonias contributed considerably to mortality in 30% of the patients.

Acquired Immunodeficiency Syndrome