Biomedical subjects

C K Ma

Publications and source records attributed to C K Ma.

At least 19 recordsLinked to original sources

PubMed1995

Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection.

BACKGROUND & AIMS: Multiple tests are available for determining Helicobacter pylori infection. Our aim was to compare the sensitivity, specificity, and negative and positive predictive value of the most widely available tests for diagnosis of H. pylori. METHODS: A total of 268 patients (mean age, 53.7 +/- 15.8 years; 142 male and 126 female; 125 white and 143 nonwhite) was tested for H. pylori infection by [13C]urea breath test (UBT), measurement of serum immunoglobulin (Ig) G and IgA antibody levels, and antral biopsy specimens for CLO test, histology, and Warthin-Starry stain. No patient received specific treatment for H. pylori before testing. The infection status for each patient was established by a concordance of test results. RESULTS: Warthin-Starry staining had the best sensitivity and specificity, although CLO test, UBT, and IgG levels were not statistically different in determining the correct diagnosis. The absence of chronic antral inflammation was the best method to exclude infection. Stratification of results by clinical characteristics showed that UBT and chronic inflammation were the best predictors of H. pylori status in patients older than 60 years of age. IgA was a better predictor in white patients. CONCLUSIONS: The noninvasive UBT and IgG serology test are as accurate in predicting H. pylori status in untreated patients as the invasive tests of CLO and Warthin-Starry.

Adult↗

PubMed1994

Control of translation by mRNA secondary structure: the importance of the kinetics of structure formation.

RNA secondary structure is important in a wide variety of biological processes, but relatively little is known about the pathways and kinetics of RNA folding. When the IS10 transposase (tnp) gene is transcribed from a promoter outside the element, little increase in tnp expression is observed. This protection from outside transcription (pot) occurs at the translational level, presumably resulting from mRNA secondary structure proposed to sequester the tnp ribosome-binding site. Here, we confirm the pot RNA structure and show that it blocks 30S ribosomal subunit binding in vitro. Point mutations that abolish protection in vivo map to the pot structure. Surprisingly, these pot mutations do not severely alter the pot secondary structure or increase 30S subunit binding in vitro, except in one case. Using an oligonucleotide hybridization assay, we show that most of the pot mutations slow the kinetics of pot structure formation, with little or no effect on the inhibitory function of the final structure. Moreover, a suppressor mutation reverses this effect. We propose a pathway for pot mRNA folding that is consistent with the mutations and implicates the formation of important kinetic intermediates. The significance of these observations for the RNA folding problem in general is discussed.

Base Sequence↗

PubMed1994

Decrease in ornithine decarboxylase activity after eradication of Helicobacter pylori.

OBJECTIVE: Our aim was to determine whether gastric mucosal ODC activity is altered after successful eradication of HP. Recent reports have suggested that Helicobacter pylori (HP) infection of the stomach is associated with the development of gastric cancer. Gastrointestinal cancers usually do not arise de novo; a series of mucosal changes leading to neoplastic transformation and degrees of dysplasia are believed to precede the development of cancer. These conditions are associated with increased cellular proliferation. Ornithine decarboxylase (ODC) activity is induced by factors that stimulate cellular proliferation, and has been shown to be elevated in gastrointestinal neoplasia, including gastric cancer. METHODS: Gastric antral and body biopsies were obtained from 17 HP-positive patients at endoscopy, for ODC activity and histology (including Warthin Starry stain) before and 4-6 wk after successful triple therapy. RESULTS: Patients included 12 males and five females, with a mean age of 55 yr (27-73 yr). Mean ODC activity (in pmol CO2/mg protein/h) was significantly decreased after eradication of HP, compared with pretreatment levels in antral (147 +/- 26 vs. 80 +/- 15) and body mucosa (76 +/- 21 vs. 20 +/- 5) (p < 0.05). CONCLUSION: Successful eradication of HP decreases mucosal proliferative activity, as reflected by decreased ODC activity. We speculate that by decreasing mucosal proliferative activity, HP eradication may help decrease the subsequent risk of gastric cancer.

Adult↗

PubMed1993

Ulcer risk factors: interactions between Helicobacter pylori infection, nonsteroidal use, and age.

PURPOSE: To evaluate the influence of Helicobacter pylori, nonsteroidal anti-inflammatory drug (NSAID) use, tobacco and alcohol use, age, gender, ethnic group, and the indication for endoscopy on the frequency of gastric and duodenal ulcers in patients referred for upper endoscopy. PATIENTS AND METHODS: One thousand eighty-eight consecutive patients without prior antrectomy or active bleeding at endoscopy who were able to provide a history were interviewed prior to endoscopy, and antral biopsies were performed for H. pylori at endoscopy. Variables were tested for univariate association with duodenal or gastric ulcer and those variables with p < 0.25 were included in the logistic regression model building. RESULTS: One hundred seven patients had duodenal ulcer, 97 had gastric ulcers, and 5 had both. Significant risk factors in the final model for duodenal ulcer were H. pylori, history of previous ulcer, male gender, bleeding, and pain at presentation (p < 0.001), whereas alcohol was associated with a decreased risk (p = 0.026). H. pylori presence (p = 0.011), aspirin use (p = 0.009), and bleeding (p = 0.012) were associated with gastric ulcer in the final model; esophageal symptoms were associated with decreased risk of gastric ulcer (p = 0.003). NSAID use was associated with gastric ulcers only in those over 55 (p < 0.05), especially whites, and in nonwhites without prior ulcer. There was no interaction between H. pylori and NSAIDs. CONCLUSIONS: H. pylori was associated with an increased risk of duodenal and gastric ulcers. Aspirin increases the risk for gastric ulcer in patients of all ages, whereas nonaspirin, nonsteroidal use increases the risk for gastric ulcers to varying degrees in patients over age 55, depending on race and history of ulcer.

Adult↗

PubMed1993

Myenteric plexus destruction alters morphology of rat intestine.

BACKGROUND: It has been shown previously that myenteric plexus destruction by benzalkonium chloride (BAC) increased villus height, crypt depth, and muscle thickness, suggesting that these neurons influence intestinal morphology. A nonspecific trophic effect of BAC, intraluminal stasis, and inflammation resulting from the chemical treatment could also be causes for these changes. Our goals were to (1) show that the morphological sequelae of BAC treatment are caused by myenteric plexus removal and not the factors listed above, and (2) determine whether segmental myenteric plexus removal alters morphology elsewhere in the small intestine. METHODS: Six groups of rats were studied: control, chemical denervation (3 mmol/L BAC), surgical denervation, intraluminal stasis produced by partial obstruction, chemical inflammation (5% acetic acid), and surgical inflammation (serosa removal only). Tissue for histological study was taken from the treated segment, 15-20 cm proximal to the treated segment, and 5-10 cm distal to the treated segment 28 days after treatment. RESULTS: Chemical and surgical denervation reduced the number of myenteric neurons by 94% and 98%, respectively. Denervation had a direct effect on morphology; it increased villus height, crypt depth, and muscle thickness in the treated and proximal segments, but only muscle thickness was increased in the distal segment. The other treatments had minimal morphological sequelae. CONCLUSIONS: Segmental myenteric plexus removal alters the mucosa in the treated and proximal segments but influences muscle thickness throughout the intestine.

Acetates↗

PubMed1993

Ki-67 and proliferating cell nuclear antigen tumor proliferative indices in DNA diploid colorectal adenocarcinomas. Correlation with histopathologic characteristics and cell cycle analysis with two-color DNA flow cytometry.

The prognostic significance of tumor proliferative activity (TPA) in colorectal adenocarcinomas (CA) determined by proliferating cell nuclear antigen (PCNA) and Ki-67 staining is not well defined. Previous investigations of TPA using Ki-67 immunohistologic studies and flow cytometric (FCM) analysis have found no correlation with conventional histopathologic parameters. To better define the relationship of these various TPA measurements in CA, the authors selected 46 tumors with diploid DNA content previously analyzed by two-color DNA FCM analysis of fresh specimens to more effectively assess actual S-phase fractions (SPFs) from cytokeratin-gated DNA histograms for comparison with the following: (1) immunohistologic Ki-67 and PCNA tumor proliferation indices (TPIs); and (2) conventional histopathologic observations of prognostic import. These data show no significant correlation coefficient between Ki-67 or PCNA TPIs and SPFs derived from FCM analysis; however, the DNA diploid tumor subset categorized as having a greater than median SPF value had a significantly higher mean Ki-67 but not PCNA proliferation index. There was no correlation of any measure of proliferation with any of the eight histopathologic features of known prognostic significance.

Adenocarcinoma↗

PubMed1993

Prognostic value of proliferating cell nuclear antigen index in gastric stromal tumors. Correlation with mitotic count and clinical outcome.

Morphologic studies of gastric stromal tumors (GSTs) indicate that mitotic counts (MCs) and tumor size are major discriminants predictive of biologic behavior. The authors evaluated the tumor proliferation of GSTs with anti-proliferating cell nuclear antigen (PCNA; DAKO clone PC10, DAKO Corporation, Carpinteria, CA) for correlation with MCs, histologic cell type, and clinical outcome. Fifty-eight tumors ranging from 1.5 to 45 cm in size were selected for clinicopathologic assessment. Mitotic activity was counted per 50 high-power fields (MC). For this study, combined parameters of MC and tumor size were used to categorize tumors into three groups: (1) benign: MC less than 5, tumor smaller than 5 cm; (2) borderline: MC less than 5, tumor larger than 5 cm; and (3) malignant: MC greater than 5, tumor any size. The PCNA tumor proliferation index (TPI) was assessed from evaluation of 200 tumor cells per case and expressed as the percentage of cells with positive results. Clinical follow-up was available in 45 cases. None of the 19 benign or 16 borderline tumors recurred or metastasized, whereas 7 of 10 malignant tumors metastasized and 1 of 10 recurred. The mean PCNA TPI values among benign (11.2%), borderline (16%), and malignant (34.5%) tumors were significantly different (P = 0.0002, Kruskal-Wallis test). When the pathologic tumor categories were compared, the mean TPI of benign tumors was significantly different from that of borderline tumors (P = 0.0306, Kruskal-Wallis), and the TPI of borderline tumors was different from that of the malignant tumors (P = 0.0060, Kruskal-Wallis test). The Spearman rank correlation showed a significant relationship between the MC and PCNA TPI (P = 0.0003, r = 0.4543). Logistic regression analysis showed that the TPI, independent of MC and size, contributed significantly (P = 0.00295) to the prediction of outcome. In the malignant group, the mean TPI for malignant tumors with metastases (43.6%) was significantly different (P = 0.0411, Kruskal-Wallis test) from that of malignant tumors without metastases (including the case with probable recurrence) (11.83%). No correlation was found when PCNA TPIs for epithelioid GCTs were compared with those of spindle cell GSTs.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Neoplasm↗

PubMed1993

Comparative immunohistochemical study of primary and metastatic carcinomas of the liver.

Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.

Adenocarcinoma↗

PubMed1993

Signet ring variant of lobular carcinoma of the breast: a clinicopathologic and immunohistochemical study.

Signet ring carcinoma of the breast often metastasizes to gastrointestinal tract and female genital tract. We report clinicopathologic features of 10 breast carcinomas with signet ring features, five of which had unusual metastatic patterns. The primary breast tumor in all these cases was lobular carcinoma. Although signet ring cells were prominent in metastatic sites, the primary tumor lacked signet ring cells in two cases. A linitis plastica-like presentation and presence of signet ring cells in gastric metastases raised a strong possibility of primary gastric carcinoma in three cases. The monoclonal antibody to gross cystic disease fluid protein (GCDFP-15) was positive in signet ring cell-rich areas in the primary breast tumor (8/10) and/or in the metastases in all cases. For comparison we studied GCDFP-15 immunoreactivity in 10 infiltrating lobular and 10 infiltrating ductal breast carcinomas with no obvious signet ring cells, and in 14 signet ring carcinomas from other sites (10 gastric, 2 prostatic, 2 colonic). The gastric, colonic, and one prostatic signet ring carcinoma were nonreactive. One prostatic signet ring carcinoma exhibited focal but unequivocal positivity with GCDFP-15. The cases of this report reinforce the concept that signet ring carcinoma of the breast is usually a variant of lobular carcinoma and not a distinct entity. Signet ring cell predominance in metastases, even in the absence of signet ring cells in the primary tumor, attest to the morpho-functional heterogeneity of lobular carcinoma. GCDFP-15 is a sensitive marker for signet ring breast carcinoma and a very useful adjunct tool in the diagnosis of metastatic signet ring carcinoma of mammary origin.

Adult↗

PubMed1993

Immunohistologic characterization of gastrointestinal stromal tumors: a study of 82 cases compared with 11 cases of leiomyomas.

The histogenesis of stromal tumors of the gastrointestinal tract (GIST) is still controversial. Recent immunohistologic and ultrastructural studies have been inconsistent and suggest various cells of origin. In view of these uncertainties, we studied the immuno-profiles of 82 cases of GISTs and 11 cases of stromal tumors that we classified as leiomyomas based on histology. The 82 cases of GIST were subclassified as spindle or epithelioid type stromal tumors based on the predominant pattern and further divided into benign (< 5 cm in size and < 5 mitosis/50 HPF), malignant (> 5 mitosis/50 HPF), and borderline lesions (> 5 cm and < 5 mitosis/50 HPF). A panel of antibodies was used to characterize differentiation toward myogenic cells [pan-muscle actin (HHF-35), alpha-smooth muscle actin (SMA) and desmin], Schwann cells (S-100 protein), enteric glial [(glial fibrillary acidic protein (GFAP)], and nerve cells (neurofilaments). All leiomyomas were strongly positive for the three muscle markers. Of the 82 GISTs, only four cases (5%) were positive for desmin. However, 63% (52 cases) were positive with anti-pan-muscle actins and 39% (32 cases) were positive with anti-SMA. Compared with gastric tumors, the positivity rates were much higher for small bowel tumors. Seventy-nine cases (96%) were positive for vimentin, only five cases and two cases were focally and weakly reactive for S-100 protein and GFAP respectively, and none stained for neurofilaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

PubMed1992

Immunohistochemical characterization of atypical fibroxanthoma and dermatofibrosarcoma protuberans.

Atypical fibroxanthoma (AFX) and dermatofibrosarcoma protuberans (DFSP) have generated undue interest regarding their histogenesis, biological behavior, and differentiation from other forms of spindle cell tumors of the skin, including spindle cell squamous carcinomas and desmoplastic melanomas. To identify characteristic immunophenotypes, 12 AFXs and 15 DFSPs were examined with a panel of antibodies against cytokeratin; vimentin; desmin; proteolytic enzymes (alpha-1-antitrypsin and alpha-1-antichymotrypsin); melanoma-associated antigens defined by HMB-45, HMB-50, and NKI/C3; muscle-specific actin (HHF-35); and S-100 protein. The staining patterns of these two tumors were nearly identical. All cases tested negative for cytokeratin, desmin, and S-100 protein and strongly positive for vimentin. Six (50%) AFXs and 12 (80%) DFSPs tested focally positive for muscle-specific actin. None of the cases were reactive with melanoma antibodies HMB-45 and HMB-50; NKI/C3 strongly stained 26 of 27 tumors. Compared to HMB-45 and HMB-50, NKI/C3 cross-reacted with nonmelanocytic neoplasms. Two AFXs stained for alpha-1-antitrypsin and alpha-1-antichymotrypsin. This study confirms (1) the immunophenotypic similarity of AFX and DFSP, (2) the presence of myofibroblastic differentiation in both tumors, as reflected by HHF-35 staining, and (3) that AFX and DFSP are easily distinguished from spindle cell squamous carcinoma and desmoplastic melanoma by the absence of cytokeratin, HMB-45, and HMB-50 staining.

Adult↗

PubMed1992

Increased density of Helicobacter pylori on antral biopsy is associated with severity of acute and chronic inflammation and likelihood of duodenal ulceration.

An increased risk of ulcers and severity of inflammation with increased degree of Helicobacter pylori (HP) infection (biological gradient) would support the hypothesis that HP causes ulcers. A blinded pathologist evaluated antral biopsies obtained at endoscopy in 903 patients. The level of HP infection was assessed on Warthin Starry stain, and the severity of acute and chronic inflammation on hematoxylin and eosin graded from 0 to 3. The presence of duodenal ulcers was associated with increasing HP density (grade 0, 6%; grade 1, 16%; grade 2, 19%; and grade 3, 27%) (p less than 0.0001, Wilcoxon rank sum test). Only a weak association between HP and gastric ulcers was detected (p = 0.06, Wilcoxon rank sum test), and this association diminished after adjusting for other risk factors. An increased acute and chronic inflammatory response correlated with increasing HP concentration (p less than 0.0001, Cochran-Mantel-Haenszel correlation statistic. The presence of this biologic gradient supports the hypothesis that HP is pathogenic in duodenal ulcers and in acute and chronic gastritis.

Acute Disease↗

PubMed1991

Helicobacter pylori-negative duodenal ulcer.

UNLABELLED: PURPOSE PATIENTS AND METHODS: Helicobacter pylori (HP) is present in more than 90% of duodenal ulcers (DUs). To investigate the pathophysiology in those patients with DU who are HP-negative compared with those who are HP-positive, we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease. At esophagogastroduodenoscopy, antral biopsy specimens were obtained for urease test, culture, and Warthin Starry staining for HP in all patients with DU who did not have active bleeding. RESULTS: Compared with HP-positive patients who had DU, HP-negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers. HP-positive patients with DU had more severe antral inflammation than HP-negative patients. Whites were more likely to be HP-negative than blacks. HP-negative patients with DU most commonly presented with bleeding, whereas HP-positive patients with DU presented with pain. CONCLUSIONS: Our findings suggest a different mechanism for DUs in patients who are HP-positive versus those who are HP-negative, and this difference might have a bearing on treatment. The absence of HP should lead to a more thorough search for nonsteroidal anti-inflammatory drug/aspirin use, Zollinger-Ellison syndrome, and other potential causes of DUs.

Aspirin↗

PubMed1991

Collagenous colitis: report of nine cases and review of the literature.

Collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by a distinctive band of collagen deposited below the colonic epithelium and an inflammatory cell infiltrate of the lamina propria. Since 1976, more than 100 cases have been described. We report an additional nine cases occurring in five women and four men ranging in age from 18 to 80 years. Diarrhea was present before diagnosis for 2 to 4 months in four cases and for 1 to 25 years in another four cases. One patient did not have diarrhea. Results of radiologic and stool studies were normal in all cases. All patients had flexible sigmoidoscopy or colonoscopy. Microscopic examination of biopsy material was interpreted as characteristic of collagenous colitis. Two cases resolved with psyllium mucilloid therapy alone. Of the five patients treated with azulfidine, three had marked improvement, one had partial response, and one had no change.

Adolescent↗

PubMed1990

Diversion colitis: a clinicopathologic study of 21 cases.

Inflammation occurring in a defunctionalized portion of bowel, following either ileostomy or colostomy, has long been recognized by endoscopists. However, little has been written about this entity, particularly the histopathologic changes. Glotzer et al in 1981 described 10 cases, and coined the term "diversion colitis". We studied 21 patients without previous history of inflammatory bowel disease who, for reasons including perforated diverticulitis, carcinoma, or trauma, had loop colostomies or Hartmann's procedure performed. Many of these patients became symptomatic with complaints related to the defunctionalized bowel, including rectal discomfort, pain, discharge, and bleeding. Nineteen patients had endoscopic examinations, which revealed a variety of findings including mucous plugs, friability, petechia, erythema, ulcers, exudate, and nodules or polyps. All except one case had tissue from the excluded portions of bowel available for pathologic examination. Most displayed nonspecific changes with mild-to-moderate lymphoplasmacytic infiltrates in the lamina propria, mild architectural alterations of the crypts, and slight decrease in crypt numbers. Ulceration, cryptitis, and crypt abscesses simulating ulcerative colitis were uncommon findings and were observed almost exclusively in more severe cases. Granulomas were observed in two cases, raising the possibility of Crohn's disease.

Adult↗

PubMed1990

Hemangiomas with localized nodular proliferation of the liver. A suggestion on the pathogenesis of focal nodular hyperplasia.

Multiple cavernous hemangiomas circumscribed by focal regenerative nodules of hepatocytes were incidental findings at the autopsy of two elderly men. Neither patient was on steroids or had venous thrombosis. The lesions were not typical for other nodular proliferations of the liver, such as focal nodular hyperplasia, nodular regenerative hyperplasia, or liver cell adenoma, and they have not been previously reported. We also explore the roles of vascular malformation, oral contraceptives, and thrombosis in the pathogenesis of localized nodular proliferation of the liver.

Aged↗

PubMed1990

Peritoneal mesothelioma: an unusual cause of esophageal achalasia.

Secondary esophageal achalasia due to malignancy is a rare condition; only 53 such cases have been reported to date. Sixty-two percent of the cases were due to gastric adenocarcinoma. Mesothelioma of the peritoneum is an uncommon neoplasm. The usual presenting symptoms are abdominal pain, abdominal mass, or abdominal distention. The patient we are reporting had peritoneal mesothelioma which presented with dysphagia and weight loss, in addition to the radiological and manometric picture of achalasia. Secondary achalasia was suspected clinically, and was confirmed by computed tomography and laparotomy. The diagnosis of peritoneal mesothelioma was made only by histopathological examination. We are not aware of any other report documenting the association of peritoneal mesothelioma and achalasia.

Aged↗

PubMed1990

Flow cytometric DNA and clinicopathologic analysis of Dukes' A&B colonic adenocarcinomas: a retrospective study.

We retrospectively evaluated DNA content flow cytometrically in a series of 124 colonic adenocarcinomas selected for uniformity of stage (A and B), anatomical location (right or transverse colon), and treatment (surgical only) in order to precisely define the significance of ploidy. Aneuploid populations were detected in 43% overall and more commonly with advancing stage (31% Stage A versus 45% Stage B), although this trend did not reach statistical significance (P = 0.16). Overall, as well as stage corrected, 5-yr patient survival was higher for patients with diploid range tumors, but not significantly (71% diploid range versus 60% aneuploid, P = 0.19). Dukes' stage, in contrast, was strongly predictive for 5-yr survival (89% Stage A versus 61% Stage B, P less than or equal to 0.005). Abnormal DNA content was significantly associated with increased patient age (P = 0.02) and presence of angiolymphatic invasion (P = 0.013) but not tumor grade (P = greater than or equal to 0.10). We conclude that flow cytometrically determined abnormal DNA content is weakly related to pathologic features of biologic aggressiveness in colonic adenocarcinoma and is less predictive of patient outcome than conventional Duke's stage.

Adenocarcinoma↗