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Biomedical subjects

H S Cooper

Publications and source records attributed to H S Cooper.

At least 37 records · Page 2Linked to original sources

Endoscopically removed malignant colorectal polyps: clinicopathologic correlations.

BACKGROUND/AIMS: Treatment options for patients with endoscopically removed malignant colorectal polyps are polypectomy alone vs. polypectomy followed by surgery. The aim of this study was to define histopathologic parameters that can be used for clinically relevant treatment decisions. METHODS: Five pathologists evaluated 140 polyps for the presence or absence of unfavorable histology. Unfavorable histology was tumor at or near (< or = 1.0 mm) the margin and/or grade III and/or lymphatic and/or venous invasion. Adverse outcome was recurrent and/or local cancer and/or lymph node metastasis. RESULTS: Adverse outcome was 19.7% (14 of 71), 8.6% (2 of 23), and 0% (0 of 46) when unfavorable histology was present, indefinite (lack of agreement), and absent, respectively (P < 0.0005, present vs. absent). Four patients with cancer > 1.0 mm from the margin had an adverse outcome (2 with lymphatic invasion and 2 indefinite for lymphatic invasion). Four patients with negative resections later developed distant metastases. Eight patients (6.3%) died of disease, and 2 of 69 without unfavorable histology (both indefinite for lymphatic invasion) had an adverse outcome. Interobserver strength of agreement was substantial to almost perfect for margin, grade, and venous invasion and fair to substantial for lymphatic invasion. CONCLUSIONS: This system is usable clinically. Patients with unfavorable histology are probably best managed by resection postpolypectomy, whereas in the absence of unfavorable histology, they probably can be treated by polypectomy only.

Colonic Polyps↗

Mycosis fungoides palmaris et plantaris.

BACKGROUND: Mycosis fungoides primarily localized to the palms and soles is rare and has been previously reported as cutaneous lymphoma in four patients or as Woringer-Kolopp disease in eight patients. OBSERVATIONS: Four patients were initially diagnosed and treated unsuccessfully for various palmoplantar dermatitides until histopathologic findings revealed mycosis fungoides. Each case exhibited a clonal rearrangement of T-cell receptor gamma genes and immunohistochemical studies consonant with mycosis fungoides. All patients had limited skin involvement without evidence of extracutaneous involvement. CONCLUSIONS: Mycosis fungoides palmaris et plantaris is an uncommon expression of mycosis fungoides that manifests primarily on the palms and soles and clinically may mimic various inflammatory palmoplantar dermatoses. A biopsy is recommended in the evaluation of recalcitrant palmoplantar dermatoses.

Diagnosis, Differential↗

Novel immunohistochemical localization of 28,000 molecular-weight (Mr) calcium binding protein (calbindin-D28k) in enterochromaffin cells of the human appendix and neuroendocrine tumors (carcinoids and small-cell carcinomas) of the midgut and foregut.

Calbindin-D28k is a highly conserved 28,000 (dalton) molecular-weight (Mr) calcium binding protein with broad tissue distribution, yet cell-type-specific expression predominantly in subpopulations of central and peripheral nervous system neurons, distal tubular cells of the kidney, and enteric neuroendocrine cells. A polyclonal antiserum against rat renal calbindin-D28k and a monoclonal antibody to calbindin-D28k purified from chicken intestine (clone CL-300) were used for immunohistochemical evaluation of formalin-fixed, paraffin-embedded tissues from multiple areas of the human small and large intestines and 93 primary neoplasms of the gastrointestinal tract (foregut, midgut, and hindgut derivatives) and the lung (foregut derivative). Calbindin-D28k immunostaining was obtained in a minority of enterochromaffin (neuroendocrine) cells, predominantly of the appendix and small intestine, as well as in autonomic neurons of the neural plexuses. Focal cytoplasmic Golgi-type staining was obtained with monoclonal antibody CL-300 in the appendiceal surface epithelium and dendritic macrophages confined to the appendiceal lymphoid follicles. Epithelial progenitor cells in enteric crypts and absorptive, goblet, and Paneth cells were calbindin-D28k negative, while no immunoreactivity was demonstrated in the mucosae of the colon and rectum. Calbindin-D28k staining was consistently detected in subpopulations of neuroendocrine phenotypes in midgut (appendiceal/ileal) and foregut (bronchial) carcinoids and small-cell carcinomas, but was absent in adenocarcinomas, squamous cell carcinomas, leiomyomas/leiomyosarcomas, schwannomas, and lymphomas. Our observations suggest that calbindin-D28k is a novel adjuvant neuroendocrine marker that is potentially useful in diagnostic tumor immunohistochemistry.

Adult↗

Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin.

The use of oral and intravenous cyclosporin represents a significant advance in the therapy of refractory inflammatory bowel diseases (IBD). However, oral administration of cyclosporin is fraught with improper delivery of cyclosporin to the colon for its topical action. Because of unpredictable metabolism by cytochrome P-450 IIIA, the targeted blood level for systemic effect is not reached at low doses. Furthermore, the doses that have been used for therapy of IBD have been shown to induce several adverse side effects. Thus, an alternate method of delivering cyclosporin to the colon is desirable. In this study, the effect of intracolonically administered cyclosporin was tested for its efficacy to heal mucosal erosions in dextran sulfate sodium (DSS)-induced colitis in mice. Both acute and chronic colitis was induced by feeding female Swiss-Webster mice with 5% DSS (30,000-40,000 mol wt) for five or seven days, respectively. Therapy was advocated prophylactically, prophylaxis plus therapy and therapeutically during the acute and chronic phase of the disease and therapeutically during the chronic phase of the disease. Intracolonic cyclosporin given prophylactically showed adverse effects by increasing the damage to the colonic mucosa. However, intracolonic cyclosporin given therapeutically in 2.5, 5, and 10 mg/kg after the induction of colitis resulted in dramatic responses in terms of reducing the disease activity and histologic scores, corroborated by complete histological resolution compared to oral cyclosporin given at identical doses. Intracolonic cyclosporin (5 mg/kg) was also very effective in reducing the chronic inflammation. The results of this study highlight the application of this animal model for therapeutic research. Furthermore, cyclosporin administered as an enema provides a new stratagem for the therapy of IBD because of its rapid onset of action at very low doses without the risk inherent in oral or systemic administration.

Acute Disease↗

Clinicopathologic study of dextran sulfate sodium experimental murine colitis.

BACKGROUND: We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis. EXPERIMENTAL DESIGN: Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS with animals sacrificed daily. Chronic colitis was induced by: (a) 7 days of oral DSS followed by 7 days of H2O (for 1, 2, and 3 cycles) and (b) 7 days of oral DSS followed by 14 and 21 days of H2O. In each experimental group, the entire colons were examined histologically and correlated with clinical symptoms. RESULTS: Acute clinical symptoms (diarrhea and/or grossly bloody stool) were associated with the presence of erosions and inflammation. More importantly, the earliest histologic changes which predated clinical colitis was loss of the basal one-third of the crypt (day 3), which progressed with time to loss of the entire crypt resulting in erosions on day 5. The earliest changes were very focal and not associated with inflammation. Inflammation was a secondary phenomena and only became significant after erosions appeared. Animals treated with only 7 days of DSS followed by 14 and 21 days of H2O developed a chronic colitis with the following histologic features: areas of activity (erosions and inflammation), inactivity, crypt distortion, florid epithelial proliferation and possible dysplasia. These changes were similar to animals given 3 cycles of DSS. The clinical disease activity index correlated significantly with pathologic changes in both the acute and chronic phases of the disease. CONCLUSIONS: The mechanism of DSS colitis is presently unknown. However, the finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena. This may be a good model to study how early mucosal changes lead to inflammation and the biology of the colonic enterocyte. Chronic colitis induced after only 7 days of DSS may serve as a useful model to study the effects of pharmacologic agents in human inflammatory disease and mechanisms of perpetuation of inflammation. Finally, we believe that this model has the potential to study the dysplasia cancer sequence in inflammatory disease.

Animals↗

Adenomyoepithelioma of the breast. A spectrum of biologic behavior.

Adenomyoepitheliomas of the breast have been considered to have limited metastatic potential; axillary node metastasis has been reported, but there has been no report of distant metastasis. We report six cases, including two malignant adenomyoepitheliomas, one of which metastasized to the lung and brain. Patient age ranged from 26 to 63 years (mean 46). Primary tumors were solitary and measured 0.9-3.5 cm (mean 1.7). Five of six tumors presented as palpable masses. Two patients treated by local resection have no evidence of disease at 5 and 18 months' follow-up. Two patients treated by local resection had recurrences, one at 48 the other at 60 months. The fifth patient had a spindle-cell type adenomyoepithelioma diagnosed as malignant because of high mitotic rate and cytologic atypicality of the myoepithelial component. This patient was treated by mastectomy and has no evidence of disease at 18 months. The sixth patient, initially treated by local excision, had six local recurrences over 52 months treated by reexcisions, mastectomies, and radiation. A lung metastasis was resected at 54 months and brain metastases were identified at 60 months with death occurring at 64 months. Both malignant adenomyoepitheliomas had high mitotic rates [11-14/10 high-power fields (HPF)] diffusely throughout the tumors and foci of cytologically malignant cells. The malignant adenomyoepithelioma that metastasized had an infiltrative growth pattern that increased with successive local recurrences. The four other tumors had only isolated areas of mitotic activity (maximum 1-9/10 HPF) and minimal cytologic atypia. Immunohistochemistry performed on five of six cases confirmed dual epithelial/myoepithelial cell populations in all tumors examined, including the metastasis. Electron microscopic examination of the malignant adenomyoepithelioma that metastasized also confirmed dual epithelial/myoepithelial cell populations in a local recurrence and the lung metastasis. We conclude that there is a spectrum of behavior for breast adenomyoepitheliomas with potential for local recurrence and, rarely, distant metastasis.

Adult↗

Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques.

In this study, double-labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens (BGA) that are differentiation antigens in the normal colon, and BGA that are sequential moieties in the same synthetic pathway. Paired-wise Sialylated-Le(a)/Le(y) and H-2/Le(y) was studied. The Sialylated-Le(a) and Le(y) are synthesized from type 1 and type 2 backbones, respectively. In the normal colon, the Le(y) and Sialylated-Le(a) are expressed by cells at the base and surface of the crypt, respectively, representing undifferentiated and differentiated enterocytes. The H-2 is considered oncofetal in nature, and is considered to be the immediate precursor in the synthesis of Le(y). In individual cancers. Sialylated-Lea and Le(y) were detected in different cancer cells within the same malignant glands, separately in different glands, and in different subcellular compartments of the same cell. Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of cancers expressing both these BGA. In 50% of the cancers, the H-2 and Le(y) also were expressed separately in different malignant glands within individual tumors. These findings indicate that, in colorectal cancers, differentiation antigens (Sialylated Le(a) and Le(y)) are expressed by different individual cells within the same malignant gland somewhat, recapitulating the normal colon crypt. Antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments. Precursor accumulation is common in cancers, and antigens in the same synthetic pathway are coexpressed in the same cell. The expression of H-2 and Le(y) in different glands (lack of coexpression) may be explained possibly by aberrant synthesis of Le(y) by an alternate pathway.

ABO Blood-Group System↗

G protein complement of SV40-transformed ciliary epithelial cells.

Guanine nucleotide-binding proteins (G proteins) are a family of receptor-coupled signal-transducing proteins that regulate a variety of second-messenger systems and ion channels. The complement of G proteins in SV40-transformed pigmented and nonpigmented ciliary epithelial cells was determined by Western blot analysis utilizing peptide and holoprotein derived antisera to known G protein alpha and beta subunits and cholera toxin catalyzed ADP-ribosylation. The complement of alpha subunits found in both SV40-transformed NPE and PE cells includes Gs alpha and all three members of the Gi alpha family. Neither cell type contains Go alpha or Gz alpha. Both cell lines contain beta 35 and beta 36. Future studies will examine the functional involvement of these G proteins in the regulation of aqueous humor stimulus-secretion coupling.

Amino Acid Sequence↗

Identification of cryptosporidium in paraffin-embedded tissue sections with the use of a monoclonal antibody.

Recently a monoclonal antibody has been developed against the oocyst form of Cryptosporidium species for use in detecting the organism in fecal material. The authors undertook this study to determine if this antibody could be used in identifying Cryptosporidium species in paraffin-embedded tissue sections. Three biopsies showing Cryptosporidiosis as diagnosed by characteristic appearance by light and electron microscopy were selected from the surgical pathology files at the authors' institution. Paraffin sections were examined with the use of both an indirect immunofluorescence and an avidin-biotin-peroxidase technique. In all the cases, prominent staining of oocysts was seen; however, intracellular trophozoites did not react with the antibody. The authors conclude that this antibody can be used to identify Cryptosporidium species oocysts in tissue sections and that the antibody appears to be specific for the oocyst form only.

Adult↗

Immunohistologic study of ulcerative colitis with monoclonal antibodies against tumor-associated and/or differentiation antigens.

We used monoclonal antibodies (MAbs) (19-9, 55-2, and 73-3) that detect tumor-associated or differentiation antigens, or both, to immunohistochemically study a well-defined group of patients with ulcerative colitis. Monoclonal antibody 19-9 detects the gastrointestinal cancer-associated antigen (sialylated Lewis A). Monoclonal antibody 55-2 detects the Lewis Y antigen and reacts with deep crypt cells in the normal colon. In the normal colon MAb 73-3 reacts with mature superficial columnar cells detecting the protein moiety of a 35,000-dalton glycoprotein. In cases of inactive or mildly active disease, MAbs 19-9, 55-2, and 73-3 had staining patterns similar to normal colon. In 72% and 44% of cases of severely active disease, MAb 19-9 and MAb 73-3, respectively, reacted with epithelial cells at all levels of the crypt, whereas MAb 55-2 reacted only with deep crypt cells. Monoclonal antibodies 19-9, 55-2, and 73-3 reacted with dysplastic epithelium in 70%, 10%, and 60% of cases, respectively. In severely active disease, proliferating epithelial cells "paradoxically" express markers of differentiated epithelium throughout the entire crypt. Similarly, colonic epithelial cells may have the ability to reversibly express tumor-associated antigens. Unfortunately, the MAbs used in this study cannot differentiate dysplasia from reactive epithelium.

Antibodies, Monoclonal↗

Immunohistochemical study of colorectal adenomas with monoclonal antibodies against blood group antigens (sialosyl-Le(a), Le(a), Le(b), Le(x), Le(y), A, B, and H).

We studied 40 colorectal adenomas with monoclonal antibodies against blood group antigens (sialosyl-Le(a), Le(a), Le(b), Le(x), Le(y), A, B, and H). Sialosyl-Le(a), Le(a), Le(x), and Le(y) are usually present in different compartments of the crypts of normal colorectum and can be considered markers of normal differentiation antigens (NDA). The former two antigens represent markers for differentiated colonic epithelium and the latter two, markers for "undifferentiated" crypt base epithelium. Le(b), A, B, and H are normally absent from the distal colon and rectum, but are expressed by fetal colon and carcinomas and are considered oncofetal tumor-associated antigens (OF-TAA). Individual adenomas could be characterized as to whether or not they expressed OF-TAA and NDA. Of the adenomas, 35% were OF-TAA+/NDA+, 40% were OF-TAA+/NDA-, 17.5% were OF-TAA-/NDA+, and 7.5% were OF-TAA-/NDA-. When NDA were present, they were expressed in the same compartment of the crypt as in the normal colon and rectum. In adenomas there was proliferation of the undifferentiated enterocyte marker Lex throughout the entire length of the crypt when compared with controls (p less than 0.01). Of the adenomas, 75% expressed OF-TAA, however, 35% of adenomas concomitantly expressed NDA in the same distribution as normal colon and rectum indicating that adenomas have features of both carcinoma and normal colorectum epithelium.

Adenocarcinoma↗

Gallbladder adenocarcinoma: the prognostic significance of histologic grade.

Gallbladder adenocarcinoma (GBA) postresection 5-year survival rates are less than 5%, but when histologically confined to the mucosa or submucosa, survival rates of 64% (5 years) and 44% (10 years) have been reported. Whether any other histologic features of GBA have prognostic significance is unknown. This investigation was conducted to determine if GBA histologic grade correlates with survival. Thirty patients with advanced stage GBA participating in Eastern Cooperative Oncology Group (ECOG) treatment protocol EST-2273 served as the study material. Using glandular tumor grade criteria recommended by others, a panel of 7 ECOG pathologists categorized the GBA as either predominantly low or high histologic grade. Each patient's GBA histologic section measured no less than 1.0 X 1.0 cm. Predominant grade was defined as being that grade present in greater than 75% of the histologic section. Patient survival times by grade were calculated from date of initiation of chemotherapy until date of death. The 13-week low grade GBA patient survival was significantly longer than the 7-week high grade GBA patient survival (p less than 0.01). Stratification of patients by either high or low predominant histologic grade is recommended in future GBA treatment studies.

Adenocarcinoma↗

Studies of neurofilaments that accumulate in proximal axons of rats intoxicated with beta,beta'-iminodipropionitrile (IDPN).

The paradigm of IDPN neuropathy was produced in rats in order to examine the neurofilaments (NFs) that accumulate in the proximal motor and sensory axons of intoxicated animals, and to compare the aggregated NFs with control NFs and with the depleted populations of NFs in the distal portions of the same experimental nerves. NFs were probed biochemically and histochemically, using a large and well-characterized library of monoclonal antibodies that included antibodies that are monospecific for each of the rat NF protein subunits (NF-H, NF-M, and NF-L) as well as antibodies that recognized differential phosphorylated states of rat NF-H and NF-M. All antibodies tested showed enhanced immunostaining of enlarged axons and of large spheroids in the spinal cord and dorsal root ganglia of experimental animals. Biochemical analyses of IDPN-treated animals revealed enrichment of NF-H, NF-M, and NF-L in homogenates of dorsal root ganglia and of proximal motor and sensory nerve roots as well as depletion of the three subunits in distal nerve roots and in sciatic nerves. Immunoblot revealed a uniform enrichment of NF-H, NF-M, and NF-L in NF aggregates as well as the same admixture of phosphorylated and dephosphorylated epitopes of NF-H and NF-M in experimental and in control tissues. The global increase of immunoreactivity in axonal swellings to antibodies that react with phosphorylated, nonphosphorylated, and phosphorylation-independent NF epitopes suggests that IDPN induces an accumulation of NFs in proximal axons without necessarily altering the state of NF phosphorylation.

Animals↗

Phosphorylation of neurofilament proteins and chromatolysis following transection of rat sciatic nerve.

States of phosphorylation of neurofilament proteins were examined in the perikarya of rat sensory and motor neurons between 3 and 28 d following either a distal transection [6-7 cm from the L4-L5 dorsal root ganglia (DRG)] or a proximal transection (1-2 cm from the L4-L5 DRG) of the sciatic nerve. Paraffin sections of the right (experimental) and left (control) L4 and L5 DRG from animals with unilateral transection of the right distal sciatic nerve were stained immunocytochemically with monoclonal antibodies to phosphorylation-dependent (NF-P), dephosphorylation-dependent (NF-dP), or phosphorylation-independent (NF-ind) epitopes on the largest (NF200), mid-sized (NF150), or smallest (NF68) neurofilament protein subunits. Increased immunoreactivity to NF-P on NF200 and NF150 was detected in experimental DRC at 10 d, peaking by 20 d, and declining to near control levels by 28 d. Conversely, immunoreactivity to NF-dP declined in experimental DRG beginning at 6 d, reaching a maximum decline at 10-16 d, and returning to near control levels by 28 d. Immunocytochemical changes were confirmed with biochemical studies on tissue homogenates that demonstrated an increase of immunoreactivity to NF-P and a decrease of reactivity to NF-dP in the experimental DRG. Changes in immunoreactivities to NF-P and NF-dP were observed only in the perikarya of large neurons and were closely associated with chromatolytic changes in these neurons. Marked enhancement of chromatolysis, as well as the immunoreactivities to NF-P and NF-dP, occurred following a proximal (left side) versus distal (right side) transection in the same animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hyperplastic polyps of the colon and rectum. An immunohistochemical study with monoclonal antibodies against blood groups antigens (sialosyl-Lea, Leb, Lex, Ley, A, B, H).

We studied 40 hyperplastic polyps (HP) immunohistochemically with monoclonal antibodies against 8 different blood group antigens (BGA) comparing their reactivity with normal control colon and colorectal adenocarcinomas. The 8 BGA studied were: Sialosyl-Lea, Lea, Leb, Lex, Ley, A,B, and H. sialosyl-Lea, Lea, Lex, and Ley can be though of as differentiation antigens. The former 2 BGA are expressed on mature (differentiated) epithelium while the latter 2 BGA are expressed by undifferentiated epithelium of the crypt base. A, B, H and Leb are not expressed in the normal distal colon, however, they are extensively expressed on distal colorectal cancers and adenomas and can be considered oncofetal BGA. HP expressed Lea, Lex, Ley in the same compartment of the crypt as normal colon and extensively expressed Sialosyl-Lea throughout the entire length of the crypt. This latter finding indicated maturation at a lower point in the crypt than in normals. All HP failed to express B and H BGA, while 6 of 40 expressed Leb and 5 of 40 HP expressed A BGA. Of the 6 HP expressing Leb BGA, 3 were from patients with synchronous or metachronous cancers and 2 from patients with mixed hyperplastic polyp-adenomas (HP/AD). Two of the HP expressing A BGA were from patients with HP/AD. The expression and distribution of these BGA in HP, especially the extensive expression of sialosyl-Lea correlates with the known cell kinetics of HP. While nonneoplastic in nature, HP may occasionally express true oncofetal BGA. Similarly, the HP component of HP/AD may also express true oncofetal BGA. These data suggest that the lesions classified morphologically as HP may be antigenically heterogenous.

ABO Blood-Group System↗