Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Exocrine pancreatic function in chronic urticaria patients is normal

25 patients with chronic urticaria suspected to be of 'alimentary origin', were studied for a quantitative or qualitative deficiency of pancreatic enzyme secretion. All showed a normal fecal chymotrypsin excretion and 23/25 a normal bentiromide (PABA) and pancreolauryl test. In 2 females the urinary PABA and pancreolauryl tests were borderline pathological. This does not support the hypothesis that a pancreatic deficiency (of the kind which could be identified with the methods used) is associated with chronic urticaria in patients in whom improvement of urticaria occurs under a hydric or low antigenic diet.     

C3b receptors mediate the growth factor-induced proliferation of malignant B-chronic lymphocytic leukemia lymphocytes

We have investigated the function of C3b receptor (CR1) in the malignant lymphocytes of B-chronic lymphocytic leukemia (B-CLL) mimicking the physiological ligand C3b with the anti-CR1 monoclonal antibody CB04 covalently linked to Sepharose CL-4B (CB04-S). The binding of insolubilized CB04-S to CR1 gave a progression signal to B-CLL cells which became B cell growth factor (BCGF)-responsive. The cells of 13 of 14 cases treated with CB04-S showed an active time-dependent proliferation when BCGF was added to the culture. After 72 hr of exposure to BCGF, the growth fraction evaluated with the Ki67 monoclonal antibody was 23.4 +/- 8.9 and the proportion of cells in S phase assessed by the bromodeoxyuridine incorporation technique was 18.6 +/- 8.5%. The proper sequence of CB04-S followed by BCGF was also important since the proliferation was halved when the sequence was reversed or the two signals were delivered concomitantly. CB04-S and BCGF alone failed to induce any significant proliferation; the percentage of cycling cells was less than 1% overlapping that of control culture cells. On the contrary, the proliferation of normal tonsil B cells was triggered both by CB04-S and by BCGF used as single agents (bromodeoxyuridine+ cells 12.7 +/- 5.1% and 20.0 +/- 7.3, respectively). Together these data indicate that malignant B-CLL cells need a sequential two-step signal based upon CR1 binding in order to be activated in vitro. This is a major difference with normal tonsil B lymphocytes whose proliferation is triggered both by CB04-S and by BCGF used as single agents.     

Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP)

The gene for the most frequent from of X-linked retinitis pigmentosa (XLRP), RP3, has been assigned by genetic and physical mapping to a segment of less than 1000 kbp, which is flanked by the marker DXS1110 and the ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have screened the DNA of 30 unrelated patients with XLRP by employing a representative set of YAC-derived DNA fragments that were generated by restriction enzyme digestion and PCR amplification. In one of these patients, a 6.4 kbp microdeletion was detected which was not present in the DNA of 444 male controls. A cosmid contig spanning the deletion was constructed and used to isolate cDNAs from retina-specific libraries. Exons corresponding to these expressed sequences as well as other putative exons were identified by sequencing more than 30 kbp of the critical region. So far, no point mutations in these putative exon sequences have been identified.      

Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1

The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X- linked RP (XLRP), has been mapped previously to a chromosome interval of less than 1000 kbp between the DXS1110 marker and the OTC locus at Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization (YRH)', we have recently identified a small XLRP associated microdeletion in this interval, as well as several putative exons including the 3' end of a gene that was truncated by the deletion. cDNA library screening and sequencing of a cosmid centromeric to the deletion has now enabled us to identify numerous additional exons and to detect several point mutations in patients with XLRP. The predicted gene product shows homology to RCC1, the guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our findings suggest that we have cloned the long-sought RP3 gene, and that it may encode the GEF of a retina-specific GTP-binding protein.      

The role of pulmonary CO2 flow in the control of the phase i ventilatory response to exercise in humans

To gain an insight into the origin of the phase I ventilatory response to exercise (ph I) in humans, pulmonary ventilation WE) and end-tidal partial pressures of oxygen and carbon dioxide (P _ETO₂ and P _ETCO₂, respectively) were measured breath-by-breath in six male subjects during constant-intensity exercise on the cycle ergometer at 50, 100 and 150 W, with eupnoeic normocapnia (N) or hyperpnoeic hypocapnia (H) established prior to the exercise test. Cardiac output (Q₂) was also determined beat-by-beat by impedance cardiography on eight subjects during moderate exercise (50 W), and the C0₂ flow to the lungs (Q₂·C_vCO₂ where C_vCO₂ is concentration of CO₂ in mixed veneous blood) was estimated with a time resolution of one breathing cycle. In N, the initial abrupt increase of PE during ph I (V_E approximately 18 l · min^–1 above rest) was followed by a transient fall. When P _ETCO₂ started to increase (and P _ETO₂ decreased) V_E increased again (phase II ventilatory response, ph II). In H, during ph I V_E was similar to that of N. By contrast, during ph II V_E kept gradually decreasing and started to increase only when P _ETCO₂ had returned to approximately 40 mmHg (5.3 kPa). Thus, as a result of the prevailing initial conditions (N or H) a temporal shift of the time-course of V_E during ph II became apparent. No correlation was found between C0₂ flow to the lungs and V_E during ph I. These results are interpreted as suggesting that an increased C0₂ flow to the lungs does not constitute an important factor for the initial hyperventilatory response to exercise. They are rather compatible with a neural origin of ph I, and would support the neurohumoral theory of ventilatory control during exercise.     

Peripheral blood flows during colorectal distension in anaesthetised dogs

Distension of the descending colon elicits reflex cardiovascular responses, including increases in heart rate and arterial blood pressure. To study the relative contribution of vasoconstriction in individual vascular beds to this reflex response, experiments were performed on seven dogs anaesthetised with chloralose and instrumented with electromagnetic flowmeters around the superior mesenteric, the left renal and the left external iliac arteries. The colorectal portion of the intestine was distended at constant pressure (36.6 mm Hg, 4.9 kPa mean; range 25–50 mm Hg, 3.3–6.7 kPa) with warm Ringer solution for periods of 2 min. After a set of control distensions, the experiments were performed whilst the reflex rise in arterial pressure was prevented by removal of blood from the arterial tree. In control distensions arterial pressure increased by 11.3±1.5 mm Hg, 1.51±0.12 kPa (mean±SEM). In distensions at constant arterial pressure, peripheral blood flows were altered to different extents in the three territories studied: vascular resistance increased by 30.8±5.6% (P<0.01) in the mesenteric, by 4.1±1.5% (P<0.03) in the renal, and by 15.2±6.8% (NS) in the external iliac bed. We conclude that colorectal distension may reflect activation of a function-specific pathway of the sympathetic nervous system, which leads to much greater vasoconstriction in the splanchnic circulation than in renal or musculocutaneous circulations.     

Effects of acute hypoxia on ventilatory response at the onset of submaximal exercise

In order to investigate the effects of acute hypoxia and accompanying hypocapnia on the ventilatory response at the onset of dynamic exercise, four healthy adult men performed 50W rectangular loads on a cycle-ergometer in normoxic (FIO2 = 0.21) and hypoxic (FIO2 = 0.11) conditions. No statistically significant differences in the initial ventilatory responses to exercise (both delta VI and delta VE assessed on a breath-by-breath basis) were found between eucapnic normoxia (PETO2 approximately 95, PETCO2 approximately 42 Torr) and hypocapnic hypoxia (PETO2 approximately 45, PETCO2 approximately 35 Torr). The present findings support the contention that the neurogenic ventilatory drive at the onset of early exercise is independent from PO2 and PCO2.