Regulation of erythropoietin production in a human hepatoblastoma cell line

Production of immuno and biologically active erythropoietin was documented to occur in the human hepatoblastoma cell line HepG-2. The expression of the erythropoietin gene was further verified by Northern blot analysis using a single stranded RNA probe. In vitro studies showed that erythropoietin production by these cells was not stimulated by hypoxia or cobalt chloride, but was related to the proliferative activity of the cells in culture. In addition it was found that the secretion of erythropoietin was almost completely abrogated by tunicamycin, an inhibitor of N-linked glycosylation. This effect of tunicamycin was also observed in a permanently transfected cell line that secretes erythropoietin in large quantities.     

An alternative extrinsic pathway of human blood coagulation

To study the interrelationships of the major human coagulation pathways, factor X activation in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin were added to plasma samples containing 3H-labeled factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin the rate of factor X activation in factor VIII or factor IX deficient plasma was only 10% of the activation rate seen for normal or factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, restored normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these experiments, it is inferred that normal activation of factor X in plasma due to dilute thromboplastin requires factors VII, IX and VIII. An alternative extrinsic pathway that involves factors VII, IX, and VIII may be a major physiologic extrinsic pathway, and this pathway may help to explain the clinical observations of bleeding diatheses in patients deficient in factors IX or VIII.     

Disturbed gastric and small bowel transit in severe idiopathic constipation

Many patients with severe idiopathic constipation complain of upper gastrointestinal symptoms, and these often persist after subtotal colectomy. To determine if there is a disturbance of upper gastrointestinal motility in this condition, we have studied gastric emptying for solids (¹¹¹In-containing pancake) and liquids (^99mTc-containing orange, juice) for a longer period after a meal (6 hr) than in previously reported gastric emptying studies. Small bowel transit for solids was also measured. All patients had emptied their colon the day before the study. Twelve women (mean age 36 years) with a bowel frequency of less than once per week, proven slow intestinal transit, and a normal diameter colon were studied. Twelve healthy controls (eight female and four male, mean age 33) were also studied. As a group the constipated patients demonstrated no statistically significant delay in emptying during the first 3 hr, although the emptying rate for three of 12 individuals fell outside the normal range. However, at 6 hr after ingestion of the meal, six of 10 patients had residual gastric contents greater than normal-up to 48% solid residue (median: 11% for patients and 0% for controls,P<0.01) and 40% of liquid (median 9% vs 0%P<0.01). Three of four patients with upper gastrointestinal symptoms 6 hr after the meal had gastric retention of solids markedly outside the normal range (48%, 32%, and 16%; normal<4%). Small bowel transit time was assessed as the time for the solid phase to pass from the duodenum to the cecum; the constipated patients demonstrated delayed transit (median: 75 vs 55 min,P<0.01). Effectiveness of small bowel transit was assessed by the proportion of solids in the cecum at the time the stomach had emptied 50% of the solid meal; this was reduced in the patients (median: 6 vs 18%,P<0.01). All patients with normal gastric emptying had normal small bowel transit, and all those with delayed gastric emptying had prolonged small bowel transit. Colonic transit of the radioisotope was slow in all patients (head of the radioisotope column, cecum to stool, median: 96 vs 31 hr,P<0.01). Many patients with severe idiopathic constipation have a disturbance of gastric and small bowel transit that may be related to symptoms and that have implications for treatment.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

Analysis of exercise-induced R wave amplitude changes in detection of coronary artery disease in asymptomatic men with left bundle branch block

The exercise electrocardiograms of 44 asymptomatic men with acquired left bundle branch block were analyzed for changes in R wave amplitude. Results were correlated with findings on selective coronary angiography. There were two subgroups: 7 men with significant angiographic coronary artery disease (Group I) and 37 with normal coronary angiograms (Group II). Exercise induced an increase in R wave amplitude in all seven men with coronary artery disease but in only 10 of the 37 men without significant coronary artery disease. This criterion thus had a sensitivity of 100 percent but a poor specificity of 73 percent, a predictive value of 41 percent and an accuracy rate of 77 percent for the diagnosis of coronary artery disease. The greater the increase in R wave amplitude the greater was the likelihood of some degree of left ventricular dysfunction as measured by wall motion abnormalities and elevated left ventricular end-diastolic pressure. The increase in R wave amplitude with exercise appears to be a sensitive test in identifying coronary artery disease in asymptomatic men with acquired left bundle branch block.     

The Premonitory Phase of Migraine – What Can We Learn From It?

This review aims to understand the prevalence of premonitory symptoms in migraine, postulate their mechanisms, and compare these with functional imaging studies. A thorough literature review was conducted using PubMed for prevalence studies of premonitory symptoms in migraine and functional imaging studies in the premonitory phase. The majority of studies have been retrospective reporting a prevalence of 7‐88% for premonitory symptoms in migraine. Only one study has investigated premonitory symptoms prospectively and used preselected patients with recognized premonitory symptoms. The majority of patients were able to predict correctly the onset of migraine headache. Only one functional imaging study has been conducted in the premonitory phase that showed activation of posterolateral hypothalamus, midbrain tegmental area and substantia nigra, periaqueductal gray, dorsal pons, and various cortical areas including occipital, temporal, and prefrontal cortex. Subgroup analysis of patients with photophobia more than without photophobia in the premonitory phase showed activation of the occipital cortex. Comparison of patients with nausea more than without nausea in the premonitory phase showed activation in upper dorsal medulla and periaqueductal gray. Premonitory symptoms are common in migraine, although the true prevalence cannot be stated with certainty in the absence of prospective studies in unselected patients. Hypothalamic involvement can explain many of the premonitory symptoms. Activation of the the brainstem structures and hypothalamus before pain suggests a pivotal role of these structures in the pathogenesis of migraine. Hypersensitivity to light and occurrence of nausea in migraine is associated with activation of central brain structures involved in these pathways, and this can occur in the absence of pain.     

A case report of transverse testicular ectopia with testicular microlithiasis

Transverse testicular ectopia is a rare congenital anomaly in which both testes migrate along the same inguinal canal toward the scrotum. This report describes the case of the rarest form of transverse testicular ectopia in a 23‐year‐old man with coexisting testicular microlithiasis in one of the two testes as diagnosed on sonography and confirmed on MRI. We are unaware of any previous published reports of this association. Although the etiology of both conditions is debatable, each is believed to be associated with an increased risk of testicular malignancy, and this poses a dilemma for the future management of this patient. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:520–523 2015     

Castleman's disease of the kidney: Sonographic findings

We report a case of rare Castleman's disease of the kidney that mimicked a renal neoplasm with emphasis on the imaging and histologic findings. A 47‐year‐old man presented with dyspeptic symptoms. Ultrasound revealed a vascular, heterogeneous mass in the left kidney. Multiphasic CT scan confirmed an enhancing lesion with enlarged left para‐aortic lymph nodes suspicious for nodal metastases. The provisional diagnosis was renal cell carcinoma. Percutaneous biopsy yielded a diagnosis of Castleman's disease of the hyaline‐vascular type. Despite advancement in imaging modalities, differentiation of hyaline‐vascular variant of Castleman's disease from hypervascular renal neoplasm remains difficult and the final diagnosis requires histopathological confirmation. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43 :438–442, 2015