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Biomedical subjects

M B Cohen

Publications and source records attributed to M B Cohen.

At least 19 recordsLinked to original sources
PubMed1992

A host-inducible cytochrome P-450 from a host-specific caterpillar: molecular cloning and evolution.

Cytochrome P-450 monooxygenases (P-450s) play a critical role in the detoxification of natural and synthetic toxins in a wide range of organisms. We have isolated and sequenced cDNA clones encoding a P-450, CYP6B1, from larvae of Papilio polyxenes (Lepidoptera: Papilionidae), the black swallowtail butterfly. This P-450, cloned from a herbivorous insect, is highly inducible by xanthotoxin, a secondary metabolite abundant in the host plants of this specialized herbivore. On Northern blots, mRNAs crossreactive with CYP6B1 were detected in three Papilio species that, like the black swallowtail, have high levels of xanthotoxin-metabolic P-450 activity and encounter xanthotoxin or related compounds in their host plants; in contrast, no crossreactive mRNAs were detectable in three papilinid species that never encounter xanthotoxin in their host plants and lack detectable xanthotoxin-metabolic activity. These results provide evidence that new P-450s can arise as herbivores colonize different host plants and support the hypothesis that interactions between herbivores and their toxin-producing host plants have contributed to the diversification of the P-450 superfamily.

Amino Acid Sequence↗
PubMed1992

A gradient in expression of the Escherichia coli heat-stable enterotoxin receptor exists along the villus-to-crypt axis of rat small intestine.

Binding of Escherichia coli heat-stable enterotoxin to its receptor is critical to the initiation of toxin-induced secretion and diarrheal disease; it is also likely, however, that this receptor binds an endogenous ligand. In order to characterize the expression of the heat-stable enterotoxin receptor in the small intestine, we isolated epithelial cells from villus tip to crypt in rat jejunum and ileum. Binding of radiolabeled toxin was maximal in the villus preparations and gradually decreased along the villus-to-crypt axis, paralleling the decline of sucrase activity. Northern blots of total RNA identified a single heat stable enterotoxin receptor transcript (3.8 kb), predominantly in the villus cell fractions. In situ hybridization demonstrated clear signal in the villus cells with no apparent signal in the crypt cells, lamina propria or muscularis. Expression of this receptor was greatest after enterocytes leave the proliferative cycle and enter villi. This pattern of gene and protein expression may reflect a role of this receptor in binding endogenous ligands which in turn may regulate intestinal ion flux along the villus-to-crypt axis.

Animals↗
PubMed1992

Origin of all three coronary arteries from separate ostia in the right sinus of Valsalva: a rarely reported coronary artery anomaly.

Anomalous origin of the circumflex and left anterior descending coronary arteries from separate ostia in the right sinus of Valsalva is a rarely reported phenomenon. Few clinical details concerning patients with this anomaly are available in the literature. Angiographic and clinical data in an adult patient with this finding are reported here.

Cardiac Catheterization↗
PubMed1992

Complications of percutaneous liver biopsy in children.

To determine the frequency and nature of complications after liver biopsy and whether risk factors could be identified to predict these complications, the medical records of all patients (age, 1 week to 28 years) who underwent a percutaneous liver biopsy at Children's Hospital over a 6-year period (1981-1986) were reviewed. Data were collected from 469 (97%) of 483 eligible charts. Twenty-one patients (4.5%) experienced major complications including bile leak (n = 3, 0.6%), prolonged drainage of ascitic fluid (n = 1, 0.2%), pneumothorax (n = 1, 0.2%), bleeding requiring transfusion (n = 13, 2.8%), and death (n = 3, 0.6%). A subgroup of patients (n = 37) with cancer or bone marrow transplantation was found to be at a nearly fivefold greater risk for transfusion than patients with other diagnoses (P = 0.02). All three deaths in previously stable patients occurred in this same high-risk group of patients with cancer or bone marrow transplantation (P less than 0.001). Two deaths resulted from disseminated intravascular coagulation and one from bleeding. Diagnosis, age, number of percutaneous passes, and prebiopsy coagulation studies were not predictive of subsequent complications. It is concluded that bleeding that requires transfusion is the most common liver biopsy complication and that it occurs more frequently in children than previously reported. Children with cancer or those who have undergone bone marrow transplantation are at a greater risk for bleeding and death following percutaneous liver biopsy.

Abdominal Pain↗
PubMed1992

Escherichia coli enterotoxin (STa) binds to receptors, stimulates guanyl cyclase, and impairs absorption in rat colon.

To determine the contribution of the colon in Escherichia coli heat-stable enterotoxin-mediated diarrheal disease, toxin binding, guanyl cyclase activation, and toxin-induced water flux in the rat colon and ileum were compared. Scatchard analysis suggested a single class of heat-stable enterotoxin receptors with an affinity constant of binding of 10(9) L/mol in both colonocytes and ileocytes; however, the number of toxin receptors per cell was 3.5-fold greater in coloncytes than ileocytes (8.32 +/- 1.33 x 10(5) vs. 2.33 +/- 0.28 x 10(5) receptors per cell; P = 0.02). Heat-stable enterotoxin stimulated guanyl cyclase activation in an identical dose-dependent manner in proximal colonic and ileal membranes, with similar sensitivity and maximum response. Heat-stable enterotoxin also inhibited net water flux to a similar degree in both colon and ileum (-47.8 vs. -48.4 microL.cm-1.h-1, respectively) at a dose of 8 nmol/L. At this dose in the colon, because of a higher baseline of absorption, absorption continued, but at a diminished level. At this dose in the ileum, heat-stable enterotoxin induced net secretion. These data are consistent with the concept that heat-stable enterotoxin-induced diarrheal disease results from a decreased absorptive capacity in the colon in the face of increased small intestinal fluid secretion.

Analysis of Variance↗
PubMed1992

Jejunal toxin inactivation regulates susceptibility of the immature rat to STa.

The immature rat jejunum demonstrates an increased response, sensitivity, and susceptibility to heat-stable enterotoxin. In the present study, the hypothesis that this increased secretory response results from diminished jejunal toxin inactivation and persistence of biologically active toxin was tested. A modification of toxin injected into ligated jejunal loops was observed in both adult and immature rats. However, in the immature jejunum there was also persistence of biologically active toxin and continued toxin-induced secretion. In contrast, in the adult jejunum there was inactivation of toxin and cessation of secretion. Incubation of toxin with luminal fluid, pancreatic fluid, or jejunal brush border membranes resulted in toxin alteration. However, a completely inactive toxin species was generated only after incubation with jejunal organ culture slices. It is concluded that (a) incomplete toxin inactivation in the immature rat jejunum contributes to prolonged intestinal secretion and that (b) the inactivation process is multifactorial, but it is likely that final toxin inactivation requires the participation of the enterocyte. These findings may help explain the increased responsiveness of the immature intestine to heat-stable enterotoxin.

Animals↗
PubMed1992

Lymphoid pneumonitis in 50 adult patients infected with the human immunodeficiency virus: lymphocytic interstitial pneumonitis versus nonspecific interstitial pneumonitis.

Lymphocytic interstitial pneumonitis (LIP) and nonspecific interstitial pneumonitis (NIP) are pulmonary complications of human immunodeficiency virus (HIV) infection that occur in the absence of a detectable opportunistic infection or neoplasm. We reviewed lung biopsy specimens from 50 adult HIV-infected patients, of whom four had LIP and 46 had NIP. The majority (47 of 50) of specimens from patients with NIP showed mild chronic interstitial pneumonitis (CIP/NIP), with three showing features of diffuse alveolar damage, organizing phase. In contrast to CIP/NIP, the five specimens from four patients with LIP demonstrated more extensive lymphocytic interstitial infiltrates that extended into the alveolar septal interstitium. The majority of the interstitial lymphocytes in both NIP and LIP were of T-cell origin and stained for UCHL-1. The etiologies of NIP and LIP remain unknown. Since the common opportunistic infections were excluded by routine methods, we sought, with special techniques, to investigate whether HIV, Epstein-Barr virus (EBV), or cytomegalovirus (CMV) could be identified in lung biopsy specimens from these patients. By in situ hybridization, we found one LIP specimen with expression of large amounts of HIV RNA primarily within macrophages in germinal centers; in the remaining specimens, occasional cells expressing HIV RNA were found (two LIP and four NIP). Neither CMV nor EBV was found by in situ hybridization in seven specimens; in these same specimens EBV was detected using the polymerase chain reaction in only one case of NIP, similar to results in control specimens. These results, together with the knowledge that lymphocytic pulmonary lesions may be caused by lentiviruses in humans and animals, suggest that HIV plays a significant role in the pathogenesis of both NIP and LIP in adult HIV-infected patients; in contrast, our data do not demonstrate a direct role for either EBV or CMV.

Adult↗
PubMed1992

Simple cysts of testis.

Three cases of benign intraparenchymal cysts of the testis are described. A nine-month-old infant and a forty-two-year-old man were seen with painless testicular enlargement and underwent orchiectomy and cyst excision, respectively. The third patient, a sixty-eight-year-old man, was asymptomatic with the cyst discovered following orchiectomy for prostatic carcinoma. In each case the cyst was multilocular and lined with a simple cuboidal epithelium. In 1 case special and immunohistochemical stains were performed. Review of the literature in conjunction with the cysts' staining characteristics are strongly supportive of its derivation from ectopic epithelium.

Adult↗
PubMed1992

Detection and staging of prostatic carcinoma after transurethral resection or open enucleation of the prostate: accuracy of magnetic resonance imaging.

A total of 17 patients who had undergone transurethral (16) or open (1) enucleation of the prostate for presumed benign prostatic hyperplasia had prostatic adenocarcinoma: 10 on the basis of examination of the resected specimen (stage A) and 7 upon rectal examination performed 2 to 120 months after prostatectomy for benign prostatic hyperplasia (stage B). In all patients magnetic resonance imaging (MRI) of the prostate was performed before radical retropubic prostatectomy. Preoperative imaging was compared to pathological findings with respect to the presence, location and stage of singular or multiple prostatic carcinomas. Carcinomas were categorized according to the location within the prostate: whether on the right or left side, and whether in the peripheral zone (anterior, anterolateral or posterior) or the transition zone. The sensitivity of tumor detection for cancers originating in the peripheral zone was 81%. However, the sensitivity of detection decreased to 0% for tumors confined to the transition zone. Tumor staging was not compromised by previous prostatic enucleation or transurethral resection. MRI correctly identifies carcinomas originating in the peripheral zone but cannot detect those confined to the transition zone.

Adenocarcinoma↗
PubMed1992

SPECT brain imaging in Alzheimer's disease during treatment with oral tetrahydroaminoacridine and lecithin.

Quantitative SPECT brain imaging was performed in five normal subjects and in six ambulatory patients with Alzheimer's disease before the initiation of treatment with tetrahydroaminoacridine (THA) and lecithin. Imaging data were acquired with a single-head SPECT camera and a high-resolution collimator after the intravenous injection of 5 mCi of (p,5n) I-123 IMP. Uptake per pixel in 28 regions of interest in the transverse projection of each study was normalized to uptake per pixel in the cerebellum. Perfusion in the patients with Alzheimer's disease was decreased compared with that of the subjects. Perfusion was decreased greater than 2 SD below the mean in the posterior parietal cortex of 5/6 patients, in the temporal cortex of 3/6 patients, and in the frontal cortex of 2/6 patients with Alzheimer's disease. SPECT imaging was repeated in the six patients after initial titration to peak therapy with oral THA (75 to 200mg per day). The same abnormalities were again seen in the same patients. No dramatic clinical or behavioral change in cerebral perfusion was observed from initial treatment of Alzheimer's disease with THA and lecithin.

Administration, Oral↗
PubMed1992

Novel sites for expression of an Escherichia coli heat-stable enterotoxin receptor in the developing rat.

Escherichia coli heat-stable enterotoxin (STa) mediates diarrheal disease by binding to and activating an intestinal transmembrane receptor, guanylate cyclase C (GC-C). To test the hypotheses that there was 1) increased perinatal expression of GC-C in rat intestine and 2) GC-C expression and STa binding in extraintestinal tissues of immature rat, we prepared whole cell membranes and total RNA from jejunum, ileum, colon, liver, kidney, heart, lung, brain, testis, and placenta of rats ranging in age from 12 days gestation to adult. Northern analysis demonstrated the presence of a unique 3.8-kb mRNA transcript at all ages in the jejunum, ileum, colon, and, to a lesser degree, in the testis. GC-C was also detected by Northern analysis in liver (from gestational age 18 days through 14 days postnatal) and in placenta. Steady-state mRNA encoding GC-C was not detected by Northern analysis in the other organs examined. GC-C-specific mRNA expression was greatest in the perinatal period in the jejunum, ileum, and liver. Specific binding of 125I-labeled STa was found in each of the tissue membranes in which GC-C mRNA was present; binding was not present in those tissues that had no detectable GC-C mRNA. The existence of GC-C in extraintestinal organs in the rat, and the development changes in GC-C expression support our hypothesis that GC-C, apart from its role as an STa receptor in mediating diarrheal disease, also serves as a receptor for an endogenous ligand.

Animals↗
PubMed1992

The jejunal secretory response to Escherichia coli heat-stable enterotoxin is prolonged in malnourished rats.

Undernutrition in human infants is associated with more prolonged episodes of diarrheal disease. Therefore, we tested the hypothesis that malnutrition prolongs the duration of Escherichia coli heat-stable enterotoxin-induced rat jejunal secretion. At weaning, rats were separated into two groups: malnourished rats were fed 50% of the previous day's intake of the fully fed control group. After approximately 2 wk of pair feeding, when malnourished rats weighed less than or equal to 60% of the full fed control group, we measured the secretory response to heat-stable enterotoxin in ligated jejunal loops. Toxin-induced secretion was equal in both groups until 30 min incubation time, after which net secretion continued to increase in the malnourished group but decreased in the fully fed group. Jejunal brush border membranes prepared from malnourished and fully fed rats demonstrated similar heat-stable enterotoxin receptor density, avidity of binding and guanyl cyclase activation. In both groups, radiolabeled toxin injected into in situ jejunal loops was converted into an altered radioligand unable to bind to brush border membranes. However, in malnourished rats, there was both increased appearance of two additional radioligands that still retained their ability to bind to brush border membranes and persistence of biologically active unlabeled toxin as measured in the suckling mouse bioassay. Our studies demonstrate that reduced or delayed inactivation of heat-stable enterotoxin, with continued presence of active toxin species, may contribute to prolonged secretion in the jejunum of malnourished rats.

Animals↗
PubMed1992

Signet-ring cell carcinoma of the prostate.

We report an intriguing case of signet-ring cell carcinoma of the prostate, ie, a rare histopathologic pattern of prostatic carcinoma. We present the results of histologic, immunohistologic, and electron microscopic examinations in our case, and we compare the findings with those of cases that have been previously reported. Although the histopathologic findings in the rare cases of signet-ring cell carcinoma of the prostate thus far reported have varied greatly, the following conclusions can be made: (1) signet-ring cell carcinoma of the prostate is a high-grade carcinoma; (2) a prostatic primary should be considered in cases of metastatic signet-ring cell carcinoma, especially when results of gastrointestinal studies are unelucidating; and (3) staining for mucin, lipid, prostate-specific antigen, prostate-specific acid phosphatase, and carcinoembryonic antigen is variable.

Adenocarcinoma, Mucinous↗
PubMed1992

Hemorrhagic colitis associated with Escherichia coli O157:H7.

E. coli O157:H7, the predominant serotype of EHEC, is a cause of both outbreaks and sporadic cases of hemorrhagic colitis. In sporadic cases, and especially in outbreaks, there is an association with the consumption of improperly cooked ground beef. Both young children and geriatric patients have an increased attack rate for EHEC infection as well as an increased incidence of the two sequelae of intestinal infection with EHEC, hemolyticuremic syndrome, and thrombotic thrombocytopenic purpura. The hallmark of hemorrhagic colitis due to EHEC is the development of bloody diarrhea several days after the onset of nonbloody diarrhea and abdominal pain. Fever is usually absent or low-grade. The pathogenesis of EHEC infection is probably related to at least two bacterial virulence factors: adherence of bacteria to intestinal mucosa and production of one or more cytotoxins. These cytotoxins are closely related to Shiga toxin and therefore are often referred to as Shiga-like toxins. Treatment for hemorrhagic colitis is supportive care; most illnesses are self-limited. At present, there is no evidence that antimicrobial therapy shortens the course of illness or prevents the development of sequelae.

Canada↗