The stability and fate of a spliced intron from vertebrate cells.

Introns constitute most of the length of typical pre-mRNAs in vertebrate cells. Thus, the turnover rate of introns may significantly influence the availability of ribonucleotides and splicing factors for further rounds of transcription and RNA splicing, respectively. Given the importance of intron turnover, it is surprising that there have been no reports on the half-life of introns from higher eukaryotic cells. Here, we determined the stability of IVS1Cbeta1, the first intron from the constant region of the mouse T-cell receptor-beta, (TCR-beta) gene. Using a tetracycline (tet)-regulated promoter, we demonstrate that spliced IVS1Cbeta1 and its pre-mRNA had half-lives of 6.0+/-1.4 min and 3.7+/-1.0 min, respectively. We also examined the half-lives of these transcripts by using actinomycin D (Act.D). Act.D significantly stabilized IVS1Cbeta1 and its pre-mRNA, suggesting that Act.D not only blocks transcription but exerts rapid and direct posttranscriptional effects in the nucleus. We observed that in vivo spliced IVS1Cbeta1 accumulated predominantly as lariat molecules that use a consensus branchpoint nucleotide. The accumulation of IVS1Cbeta1 as a lariat did not result from an intrinsic inability to be debranched, as it could be debranched in vitro, albeit somewhat less efficiently than an adenovirus intron. Subcellular-fractionation and sucrose-gradient analyses showed that most spliced IVS1Cbeta1 lariats cofractionated with pre-mRNA, but not always with mRNA in the nucleus. Some IVS1Cbeta1 also appeared to be selectively exported to the cytoplasm, whereas TCR-beta pre-mRNA remained in the nucleus. This study constitutes the first detailed analysis of the stability and fate of a spliced nuclear intron in vivo.

The role of T2-weighted gradient echo in MRI demonstration of spinal multiple myeloma.

Fifty patients with proven multiple myeloma (MM) underwent magnetic resonance (MR) examination of entire spine in sagittal view using T1-weighted image (T1), T2-weighted image (T2), and T2-weighted gradient echo (GE). In 18 patients, the myelomatous foci were hyperintensive in GE and T2 and hypointensive in T1. They corresponded with osteolytic lesions in computed tomography (CT) scan. In another 16 patients with MM, the hyperintensive vertebral foci demonstrated by GE, corresponded with unhomogenic pattern of the vertebral bone marrow in T1 and T2, and insignificant computed tomography (CT) scan. Needle biopsy confirmed histologically the diagnosis MM of involved vertebra in all of them. The vertebral bone marrow had lower signal intensity in GE, which ensured a good contrast between the myelomata and the uninvolved bone marrow. Practically GE enabled the radiologic diagnosis of the spine in 16 patients. It also can prevent a diagnostic pitfall when a fatty focus is suspicious for myeloma in T2 and its demonstration in T1 is poor. Fatty foci were demonstrated in a control group, which included 20 elderly patients who had no history of malignancy. The fatty foci had lower signal intensity in GE and different from the hyperintensive myelomata. Gadolinium diethylene triamine pentaocetic acid (Gd-DTPA) which was administered intravenously in three patients with spinal MM offered no advantage and obscured the lesions.

Acne conglobata and arthritis: report of a case and review of the literature.

The association of acne conglobata and arthritis is rare and has been reported in only single case reports in the literature. We describe a patient whose associated arthropathy appeared 21 years after the onset of the skin disease. The relevant literature is reviewed.

Mitral valve prolapse in psoriatic arthritis.

Twenty-five patients with psoriatic arthritis were studied by echocardiography in view of the known association of related seronegative arthropathies with aortic-valve lesions. The study group included 15 men and ten women with a mean age of 46.5 +/- 14.6 years. Twenty-two patients suffered from peripheral disease whereas three also had axial involvement. No aortic-valve lesions were found; however, mitral-valve prolapse (MVP) was detected in 14 patients (56%), nine men and five women. The mean age, mean duration of psoriasis, and mean duration of arthritis were similar in patients with and without MVP. HLA tissue typing, which was done in nine patients with MVP, revealed only one patient with HLA-B27. There was no predominance of any of the typical antigens found in psoriasis (HLA-B13, HLA-Cw6). In a control group of 32 psoriatic patients without arthritis, only two (6.4%) suffered from MVP.

Pleuro-pulmonary manifestations of systemic lupus erythematosus: clinical features of its subgroups. Prognostic and therapeutic implications.

Correct identification of the subsets of pulmonary lupus has an unquestioned importance in planning the proper therapeutic regimen in this extremely variegated disease. Asymptomatic pulmonary lupus needs no treatment; however, pulmonary involvement in lupus may be life threatening, in which case prompt and aggressive treatment is mandatory. The different aspects of pulmonary lupus are demonstrated through the clinical histories of patients who suffered from pleuro-pulmonary lupus. The following entities are presented: lupus pneumonitis, lymphocytic interstitial pneumonia, pulmonary hypertension, pulmonary hemorrhage, pulmonary embolism associated with circulating lupus anticoagulant, lupus pleuritis and weakness of the diaphragm.

Positive serological tests for infectious mononucleosis in a patient with Mediterranean spotted fever.

The Monospot test is an accurate and reliable test for infectious mononucleosis. False positive reactions have been seldom recorded. We report the conversion of the Monospot test from negative to positive during the course of Mediterranean spotted fever. Changes in the titre of the Paul-Bunnell test were observed also. The importance of measuring IgM antibodies as part of the routine investigation of infectious diseases is emphasised.

Anorexia nervosa, laxative abuse, hypopotassemia and distal renal tubular acidosis.

A case of anorexia nervosa in a 28-year-old woman with laxative abuse, hypopotassemia and severe metabolic acidosis, is described. The diagnosis of classical renal tubular acidosis, Type I, was confirmed by our inability to decrease urinary pH beyond 5.5 and to increase ammonia excretion during an ammonium chloride loading test. A bicarbonate loading test and normal plasma aldosterone with high renin activity excluded proximal renal tubular acidosis, hyporeninemic-hypoaldosteronemic renal tubular acidosis and Bartter's syndrome. The inability to increase ammonium excretion during severe metabolic acidosis following ammonium chloride loading did not favor the possibility of a transient physiological adaptation of ammoniagenesis at the tubular cell level, related to potassium depletion. Although mental disorder, laxative abuse, abstinence from food intake and severe potassium depletion intermingled in a vicious cycle, we assume that one of the following possibilities may explain the clinical presentation in our patient: either two separated and unrelated disorders, or laxative abuse as the cause of renal tubular acidification impairment.

Fever of undetermined origin as the presenting symptom of Behcet's disease: a favorable response to colchicine.

A 30-year-old man had fever of undetermined origin for 16 months, finally diagnosed as Behcet's disease. Colchicine gave good therapeutic results.

Guillain-Barré syndrome associated with acute cytomegalovirus mononucleosis syndrome.

A case of Guillain-Barré syndrome (GBS) in a young patient who suffered from an acute cytomegalovirus (CMV) infection is presented. The diagnosis was reached following the isolation of the virus from the urine and the demonstration of high titers of both IgM and IgG antibodies in the serum. In contrast to previous cases in which GBS was merely associated with positive serology for CMV, but with almost no clinical manifestations of CMV mononucleosis syndrome, our patient had a full blown picture of acute CMV mononucleosis, including peripheral lymphocytosis, splenomegaly, hepatic involvement and hemolysis. Severe transient hypocomplementemia was also noted.

Rheumatoid arthritis-like syndrome: a presenting symptom of malignancy. Report of 3 cases and review of the literature.

Recent onset arthritis might be an early manifestation of an occult malignancy. Three patients are described: one with carcinoma, primary site unknown; one with oat cell carcinoma of the bronchus; and one with breast cancer. The presenting symptom of their disease was polyarthritis. Two of the patients were seropositive and in two patients the arthritis regressed following the removal of the tumor. Awareness of paraneoplastic arthritis, especially if its appearance is explosive or in relatively old age, should caution the physician of the possibility of a potentially curable, but hidden neoplasm.

Familial palindromic rheumatism: a possible association with HLA.

Palindromic rheumatism is very rare in children. The familial occurrence of the disease has been only briefly reported previously. A family is described here in which the mother and her 3 children suffered from typical palindromic rheumatism, which ran a benign course. All 4 members were seronegative and the HLA types of the children were identical. The HLA genotype of the mother was HLA A2, Cw4, Bw41, Bw6, DR5, MT2/Aw32, CX, Bw44, Bw4, DR1, MT1. HLA DR5 has previously been found to be associated with juvenile rheumatoid arthritis, while DR1 in Jews is significantly associated with adult-onset rheumatoid arthritis. DR5 was shared by the mother and her 3 children. The presence of the antigen DR5 in this sibship suggests that palindromic rheumatism may be a variant of juvenile rheumatoid arthritis with a relatively late onset and a more benign course. Tissue typing of patients with palindromic rheumatism may give a clue to prognosis. The patients' youth and the familial involvement, with identical HLA characteristics, are the outstanding features of this family.

Hyposplenism in systemic lupus erythematosus.

Hyposplenism, which is suggested by a typical peripheral blood smear and by the absence of splenic activity in a 99m Tc sulphur colloid scan, has been recently found to be associated with various diseases. This condition increases the susceptibility of patients to certain bacterial infections principally by pneumococci, meningococci and Haemophilus influenzae. The association of SLE and hyposplenism has not often been reported before; thus we see fit to report another such case. The administration of polyvalent pneumococcal vaccine is recommended in this condition.

Finger clubbing associated with laxative abuse.

We have added two cases of finger clubbing in laxative-abusing patients to the four other cases recorded in the literature. Laxative abuse should be added to the already long list of diseases in which clubbing may appear. The pathophysiologic basis of clubbing is still obscure.

Transient post-partum hypothyroidism.

Transient hypothyroidism was observed in two young women a few months following childbirth. It is suggested that throughout their pregnancy they had already suffered from auto-immune thyroiditis, the symptoms of which were suppressed at that time, as found in many other auto-immune diseases. Being transient, post-partum hypothyroidism is an exception to the rule that treatment by thyroid hormone replacement should never be stopped in hypothyroidism. Post-partum hypothyroidism has to be considered in every suspected case of post-partum depression, because of the possible similarity in the clinical presentation.

Campylobacter enteritis associated with recurrent abortions in agammaglobulinemia.

Campylobacter enteritis and habitual abortions occurred in a 28-year-old patient suffering from agammaglobulinemia. Campylobacter jejuni has been recently recognized to be a common treatable cause of diarrhea in man. Since bacterial overgrowth of the small intestine is increased in hypo- or agammaglobulinemia, Campylobacter is expected to be found in those patients. As this patient's abortions might have been due to the same infection, Campylobacter should be considered in the differential diagnosis of habitual abortions, especially if associated with diarrheal disease. This treatable disease must be sought in every case of agammaglobulinemia and gastro-intestinal complaints, before complicated diagnostic procedures are performed or potentially toxic drugs are administered.

Recurrent transient ischemic attacks associated with thrombocytosis in rheumatoid arthritis.

Thrombocytosis may appear in rheumatoid arthritis, nevertheless, thromboembolic phenomena have rarely been recorded. This case describes a 71-year old patient suffering from long-standing seropositive and nodular rheumatoid arthritis with severe pulmonary involvement. During an exacerbation of her disease and following the appearance of thrombocytosis, several episodes of transient ischemic attacks occurred. The neurological manifestations were right facial nerve paralysis, paraesthesia of the right cheek and dysarthria. The patient was treated successfully by antiaggregants, anticoagulants and busulfan.