VpreB and lambda-like genes encode proteins that can associate to form a light-chain-like structure, the surrogate light chain (SLC). VpreB and lambda-like genes are selectively expressed in human progenitor B and precursor B (pre-B) cells. We analyzed the expression of VpreB and lambda-like genes in seven patients with common variable immunodeficiency (CVI). Gene expression was examined in the peripheral blood mononuclear cells (PBMCs) using the polymerase chain reaction. In four CVI patients, two of whom were brothers, the expression of the VpreB gene was detectable in the PBMCs. In the brothers with CVI, the expression of the VpreB gene was also examined in bone marrow cells, where it was found to be expressed in trace amounts. A number of the brothers' bone marrow cells were stained with mu and kappa antibodies using the avidin-biotin complex method. In lambda 5-gene-deleted mice, B cell development in the bone marrow is blocked at the pre-B stage, but the blockade is leaky. We suggest that expression of the SLC is weak in patients with CVI compared with their normal counterparts, and this may be one of the underlying mechanisms of CVI.

Adult↗

PubMed1995

[Castleman's lymphoma presenting marked bronchial obstruction and compression of the great vessels: a case report].

A 24-year-old Caucasian male from Chile developed mediastinal Castleman's lymphoma, hyaline-vascular type, occupying from upper pre-tracheal to sub-carinal region, severely compressing the trachea, left main bronchus, pulmonary artery, and pericardium. Bronchofiberscopy demonstrated complete obstruction of the left main bronchus and the severe telangiectasis of the mucosa. The patient complained of the stridor and shortness of breath. The left thoracotomy had been performed in Chile, but unsucceeded in extirpation because of the adherence and the hypervascularity of the tumor. After 24 Gy irradiation, we performed the right thoracotomy and succeeded in extirpation of the tumor. It was the key for success that we could approach from right side under left sided unilateral ventilation. Castleman's lymphoma is not a rare disease, but the manifestation due to the bronchial obstruction is uncommon. So we present this case and review the literatures.

Adult↗

PubMed1995

[Treatment of tuberculous tracheobronchial stenoses with expandable metallic stent (EMS)s placed during percutaneous cardiopulmonary support (PCPS)].

A 63-year-old woman was taken to a hospital by ambulance because of dyspnea. She was admitted in nearly complete cardiopulmonary arrest. CPR was started immediately, and the patient was mechanically ventilated via a tracheostomy tube. Abnormally high airway pressures 40-50 cmH2O were required during positive pressure ventilation. Saber-sheath like stenoses of the lower trachea 3 cm long and left main stem bronchus 2 cm long were found by bronchoscopy. It was difficult to pass a 3-mm-diameter bronchoscope through these stenoses. The right main stem bronchus was completely obstructed. A chest radiograph showed a completely collapsed right lung and a scarred upper lobe of the left lung, probably caused by previous tuberculosis. Weaning from the ventilator was attempted over three months. However, the patient could not breathe by herself because of airway obstruction. She was referred to our hospital for the placement of stents into the stenotic parts of the airways. A longitudinally connected Gianturcotype EMS, 15 mm in diameter and 50 mm long was placed in each area of stenosis under general anesthesia. During the placement of EMSs, PCPS was used for 113 minutes instead of mechanical ventilation of the lungs. Hemodynamics were stable during PCPS. A bypass flow of 2.0-2.8 l/min/m2 was used. Oxygen saturation of arterial blood taken from an earlobe was maintained at 100%. Blood taken from the left radial artery had a PaO2 of 269.4 mmHg and a PaCO2 of 40.2 mmHg. There were no complications after the procedure. One month later, the stenoses had become slightly dilated.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial Diseases↗

PubMed1995

Autoantibodies against glutamic acid decarboxylase 65 in Japanese patients with insulin-dependent diabetes mellitus (IDDM).

Glutamic acid decarboxylase (GAD) 65 antibodies were measured by a new quantitative immunoprecipitation followed by immunoblotting assay using Chinese hamster ovary cells to produce recombinant human islet GAD65 and were compared with islet cell antibodies (ICA), antibodies against 64,000-Mr islet cell proteins (64K antibodies) and antibodies against GAD purified from pig brain. This assay showed that sensitivity and specificity were 83.3% and 100%, respectively. GAD65 antibodies were assayed in 32 Japanese patients with insulin-dependent diabetes mellitus (IDDM), 25 patients with non-insulin-dependent diabetes mellitus (NIDDM and 25 healthy volunteers. GAD65 antibodies were found in 12 (80.0%) of 15 patients with newly-diagnosed IDDM and in 9 (52.9%) of 17 patients with long-term IDDM. GAD65 antibodies were detected in none of 25 patients with NIDDM or 25 healthy volunteers. The correlation between GAD65 antibodies and ICA, and 64K antibodies was observed to be significant (r = 0.60, P = 0.0003 and r = 0.47, P = 0.007, respectively). GAD65 antibodies and antibodies against GAD purified from pig brain correlated well (r = 0.70, P = 0.0001). The concordance between GAD65 antibodies and ICA, 64K antibodies, and antibodies against GAD purified from pig brain, including GAD65 and GAD67, were 87.5% (28/32), 75.0% (24/32) and 90.6% (29/32), respectively. We observed that a quantitative immunoprecipitation followed by immunoblotting assay had high sensitivity and specificity in detecting GAD65 antibodies, that the prevalence of GAD65 antibodies was as high as in Caucasians, and that GAD65 was also one of the major autoantigens in Japanese patients with IDDM.

Adult↗

PubMed1995

Characterization of receptors for endothelins in the guinea pig mesenteric vasculature.

In the present study we characterized the effects of and receptors for endothelins (ETs) in the guinea pig mesenteric arterial and venous vasculatures. Endothelin-1 (ET-1) (10-500 pmol) induced a dose-dependent increase of perfusion pressure of the arterial and venous beds. ET-2 (10-500 pmol) also induced a dose-dependent vasoconstriction on both sides of the mesenteric circulation but was less potent than ET-1. In contrast, ET-3 (10-1,000 pmol) and the selective ETB agonist IRL 1620 (1,000 pmol) were inactive. A nitric oxide (NO) synthase inhibitor, L-NAME (200 microM), markedly potentiated the vasoconstrictor response to ET-1 (100 pmol arterial side; 1,000 pmol venous side) on both sides of the mesenteric vasculature. In precontracted mesenteric vessels, ET-1 (0.1-5 pmol) and IRL-1620 (1,000 pmol) induced a small yet significant vasodilation only on the arterial side. Furthermore, BQ-123 (1 microM), an ETA receptor antagonist, significantly reduced the ET-1-induced venoconstriction and completely blocked the vasoconstriction on the arterial side. Hence, the arterial and venous mesenteric vessels of the guinea pig respond to ETs by activation of ETA receptors. Furthermore, the endothelium may act as a physiologic barrier to the constrictor effects of ETs by basally releasing NO.

Animals↗

PubMed1995

Hyperresponsiveness to ET-1 after treatment with a mixture of ETA and ETB receptor antagonists in the rabbit in vivo and in vitro.

We tested the reversibility of the response to endothelin-1 (ET-1) in the rabbit renal vasculature after termination of an infusion of either a selective ETA receptor antagonist, BQ-123, a selective ETB receptor antagonist, BQ-788, or a mixture of both antagonists. Previous studies from our laboratory have shown that, as in humans, vasoconstriction of the rabbit renal vasculature induced by ET-1 is mediated solely via the activation of ETA receptors. Therefore, a 15-min infusion of BQ-123 (1 microM) prevented the vasoconstrictor response to ET-1 (10 nM). Sixty minutes after the end of the infusion, the vasoconstrictor response to ET-1 was fully restored to control levels. Conversely, when the selective ETB receptor antagonist was administered, the vasoconstrictor response to ET-1 was markedly potentiated. After the infusion of the antagonist was ended there was no further potentiation of the response to ET-1. Co-infusion of supramaximal concentrations of BQ-123 (1 microM) and BQ-788 (10 nM) still reduced by about 90% the vasoconstrictor response to ET-1. However, after removal of the antagonists, the vasoconstriction to ET-1 was potentiated by more than 75% compared to control (n = 8; p < 0.05). Similarly, a mixture of both antagonists was less effective than BQ-123 alone in reducing the pressor effect of ET-1 in anesthetized rabbits. These results show that blockade of ETB receptors produces marked potentiation in the vasoconstrictor responses to ET-1. Furthermore, a rebound hyperresponsiveness is found after treatment with a mixture of BQ-123 and BQ-788. These results suggest that the systemic and renal vasculatures would respond to ET-1 with enhanced vasoconstriction after treatment with mixed ETA/ETB receptor antagonists owing to the slow reversibility of the antagonism of the ETB receptor-mediated release of nitric oxide.

Animals↗

PubMed1995

[Phe22]-big endothelin-1[19-37]: a new and potent inhibitor of the endothelin-converting enzyme.

To develop a new family of endothelin-converting enzyme (ECE) inhibitors, we assessed the inhibitory properties of an N- and C-terminal-truncated analogue of big endothelin (ET)-1[1-38], [Phe22]-big-ET-1 [19-37], on the renal vasoconstrictor properties of big ET-1 and ET-1. We had previously shown that a 60-min infusion of phosphoramidon (100 microM) potently inhibits big-ET-1 but not ET-1-induced vasoconstriction in the rabbit perfused kidney. A 1-min preinfusion of the analogue (100 microM) was sufficient to markedly blunt the vasoconstrictor actions of big ET-1 (250 pmol) (control 19.3 +/- 1.0 mm Hg; in presence of [Phe22]-big ET-1[19-37] 4.8 +/- 1.6 mm Hg; n = 6, p < 0.001). A 10- and 60-min preinfusion of the substrate analogue at concentrations of 50 and 5 microM, respectively, reduced the response of big ET-1 to 9.3 +/- 2.3 mm Hg and 3.6 +/- 1.8 mm Hg (n = 3, p < 0.01 compared to control). [Phe22]-big ET-1[19-37] was inactive against ET-1-induced vasoconstriction (10 pmol) and was devoided of intrinsic vasoactivity. All experiments were performed on kidneys pretreated with SQ-28603 (1 microM), a neutral endopeptidase inhibitor. Our results suggest that [Phe22]-big ET-1[19-37] may be a useful lead molecule for the development of more selective and enzyme-resistant inhibitors of the membrane-bound ECE.

Animals↗