Macrophage-colony-stimulating factor regulates expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 by murine bone marrow macrophages.

We observed that when monocyte/macrophage precursors derived from murine bone marrow were treated with macrophage-colony-stimulating factor (M-CSF), there was a dose-dependent increase in both the number of adherent cells and the degree to which the cells were highly spread. Attachment was supported by fibronectin, but not by vitronectin or laminin, suggesting that the integrins alpha 4 beta 1 and/or alpha 5 beta 1 might mediate this event. Binding to fibronectin was blocked partially by antibodies to either integrin, and inhibition was almost complete when the antibodies were used in combination. By a combination of surface labeling with 125I and metabolic labeling with [35S]methionine and [35S]cysteine, we demonstrated that M-CSF treatment led to increased synthesis and surface expression of the two beta 1 integrins. Since attachment to fibronectin and/or stromal cells plays an important role in the maturation of other hematopoietic lineages, we propose that the action of M-CSF in the differentiation of immature monocytes/macrophages includes stimulated expression of the integrins alpha 4 beta 1 and alpha 5 beta 1, leading to interactions with components of the marrow microenvironment necessary for cell maturation.     

Molecular Genetic Analysis of the ABO Blood Group System: 2. cis-AB Alleles

We have determined the nucleotide sequence of the coding region in the last two coding exons of ABO genes from two cis -AB individuals (genotype cis -AB/O) with no consanguinity. In this region, cis -AB alleles from these 2 individuals were identical to one another while different from the A¹ allele by two nucleotide substitutions. Both of these nucleotide substitutions result in amino acid substitutions. The first substitution is identical to the one previously found in the A² allele. The other substitution is found at the fourth position of the four amino acid substitutions which discriminate A¹ and B transferases.     

Pancreatic tissue damage by transcatheter arterial embolization for hepatoma

We analyzed the serial changes in serum pancreatic enzyme activities by transcatheter arterial embolization (TAE) in 20 hepatoma patients with liver cirrhosis in an attempt to evaluate the incidence of the pancreatic tissue damage by TAE. Serum amylase activities increased in two (10%) cases, elastase 1 levels in six (30%) cases, and trypsin and pancreatic secretory trypsin inhibitor (PSTI) levels in each of five (25%) cases. Consequently, TAE resulted in the elevation of at least more than one serum pancreatic enzyme in eitht (40%) of 20 cases, although none had clinical symptoms related to pancreatitis When the adverse effect on the pancreatic tissue was compared among 6 cases of the superselective TAE and 14 cases of the nonsuperselective TAE, which were perfomed from the segmental and the nonsegmental hepatic arteries, respectively, the elevation of serum pancreatic enzymes was caused only by nonsuperselective TAE, not by superselective TAE. The volumes of Spongel and lipiodol used or the injected doses of the anticancer agent mitomycin C were not different between the two groups. These results indicate that TAE for the treatment of hepatoma frequently causes pancreatic tissue damage, and the position of the inserted catheter tip is very important to avoid the pancreatic tissue damage by TAE.     

Usefulness of dobutamine stress echocardiography in a patient with aortic valve stenosis and left ventricular dysfunction: a case report

A 76-year-old man with previous antero-septal myocardial infarction and aorto-coronary bypass surgery developed exertional dyspnea. Echocardiography revealed diffuse left ventricular hypokinesis and aortic stenosis with a mean pressure gradient of 29 mmHg. Coronary angiography showed no significant lesions in the bypass grafts and total occlusions of the proximal left anterior descending artery and mid circumflex artery. Dobutamine stress echocardiography was performed to evaluate the severity of aortic stenosis and left ventricular functional reversibility. Administration of dobutamine increased the mean pressure gradients to 48 mmHg and increased the stroke volume by 28% without change in aortic valve area of about 0.5 cm2. We considered that our patient had severe aortic stenosis with contractile reserve. After aortic valve replacement, he improved with better left ventricular function.     

吡喹酮与甲苯达唑药盐治疗福建棘隙吸虫病的疗效比较

目的：探讨用吡喹酮与甲苯达唑药盐治疗福建棘隙吸虫病的效果。方法：对１０９例粪检福建棘隙吸虫卵阳性者随机分为４组，分别用吡喹酮（Ａ）５ｍｇ／ｋｇ；（Ｂ）２．５ｍｇ／ｋｇ顿服与甲苯达唑（Ｃ）总剂量８００ｍｇ，８０ｍｇ／ｄ，连服１０ｄ；（Ｄ）总剂量４００ｍｇ，４０ｍｇ／ｄ，连服１０ｄ（药盐）治疗，于治后１ｗｋ和４ｗｋ复查，以虫卵阴转率和减少率为评价疗效。结果：４ｗｋ后上述４组阴转率依次为１００％、９２．３％、８５．２％和７１．４％；虫卵减少率为８４．８％—１００％，Ａ、Ｂ组疗效显著优于Ｄ组。结论：吡喹酮（２．５—５ｍｇ／ｋｇ）疗效高，疗程短，服药简便，为治疗本病的首选药物；甲苯达唑疗效尚可，在伴有肠道线虫感染时可用５００ｍｇ治疗。     

T-cell receptor alpha-chain gene is split in a human T-cell leukemia cell line with a t(11;14)(p15;q11).

Chromosomal rearrangements in malignant T-cell disease frequently involve the chromosome bands containing the T-cell receptor genes. The RPMI 8402 cell line, which was established from the leukemia cells of a patient with T-cell acute lymphoblastic leukemia, is characterized by a translocation involving chromosome 14 (band q11) and chromosome 11 (band p15) [t(11;14)(p15;q11)]. By using in situ chromosomal hybridization and Southern blot analysis to examine RPMI 8402 cells, we determined that the break at 14q11 occurs within the variable region sequences of the T-cell receptor alpha-chain gene (TCRA); the break at 11p15 occurs between the HRAS1 gene and the genes for insulin and the insulin-like growth factor 2. These results suggest that the TCRA sequences activate a cellular gene located at 11p15 in malignant T-cell disorders.     

Improvement in Castleman's disease by humanized anti-interleukin-6 receptor antibody therapy

Castleman's disease, an atypical lymphoproliferative disorder, can be classified into 2 types: hyaline-vascular and plasma cell types according to the histologic features of the affected lymph nodes. The plasma cell type is frequently associated with systemic manifestations and is often refractory to systemic therapy including corticosteroids and chemotherapy, particularly in multicentric form. Dysregulated overproduction of interleukin-6 (IL-6) from affected lymph nodes is thought to be responsible for the systemic manifestations of this disease. Therefore, interference with IL-6 signal transduction may constitute a new therapeutic strategy for this disease. We used humanized anti-IL-6 receptor antibody (rhPM-1) to treat 7 patients with multicentric plasma cell or mixed type Castleman's disease. All patients had systemic manifestations including secondary amyloidosis in 3. With the approval of our institution's ethics committee and the consent of the patients, they were treated with 50 to 100 mg rhPM-1 either once or twice weekly. Immediately after administration of rhPM-1, fever and fatigue disappeared, and anemia as well as serum levels of C-reactive protein (CRP), fibrinogen, and albumin started to improve. After 3 months of treatment, hypergammaglobulinemia and lymphadenopathy were remarkably alleviated, as were renal function abnormalities in patients with amyloidosis. Treatment was well tolerated with only transient leukopenia. Histopathologic examination revealed reduced follicular hyperplasia and vascularity after rhPM-1 treatment. The pathophysiologic significance of IL-6 in Castleman's disease was thus confirmed, and blockade of the IL-6 signal by rhPM-1 is thought to have potential as a new therapy based on the pathophysiologic mechanism of multicentric Castleman's disease. (Blood. 2000;95:56-61)     

VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions

VEGF-B primarily provides neuroprotection and improves survival in CNS-derived neurons. However, its actions on the peripheral nervous system have been less characterized. We examined whether VEGF-B mediates peripheral nerve repair. We found that VEGF-B induced extensive neurite growth and branching in trigeminal ganglia neurons in a manner that required selective activation of transmembrane receptors and was distinct from VEGF-A–induced neuronal growth. VEGF-B–induced neurite elongation required PI3K and Notch signaling. In vivo, VEGF-B is required for normal nerve regeneration: mice lacking VEGF-B showed impaired nerve repair with concomitant impaired trophic function. VEGF-B treatment increased nerve regeneration, sensation recovery, and trophic functions of injured corneal peripheral nerves in VEGF-B–deficient and wild-type animals, without affecting uninjured nerves. These selective effects of VEGF-B on injured nerves and its lack of angiogenic activity makes VEGF-B a suitable therapeutic target to treat nerve injury.Nerves can be damaged either through trauma or disease. Nerves from the peripheral nervous system (PNS) have significantly greater capacity to regenerate and reinnervate their original targets after injury, compared with nerves from the CNS. The successful regeneration of PNS neurons requires a number of intrinsic and extrinsic factors, as well as a permissive microenvironment for axonal regrowth (1). Among the numerous growth factors able to induce nerve regeneration, the family of VEGFs has been implicated as a potent mediator of developmental neurogenesis and adult nerve regeneration (2–4). VEGF-A is a well-characterized and potent angiogenic factor but is also a strong inducer of nerve growth. Several studies have demonstrated that both VEGF-A and -B are expressed during peripheral nerve injury (2, 5). In the setting of injury, VEGF-B plays a role in cell survival, nerve protection, and growth (5, 6). The survival effect of VEGF-B on brain cortical neurons, retinal neurons, and motor neurons in the spinal cord is indicative of its pleiotropic role (5). VEGF-B treatment reduced stroke volume in a middle cerebral artery ligation model and increased survival of retinal ganglion cells in an optic nerve crush injury model (7), and VEGF-B knockout mice suffered severe strokes and exacerbated retinal ganglion cell death in both injury models (7–9). VEGF-B has also been used with promising results in Parkinson’s disease (10) and amyotrophic lateral sclerosis models (11).Given the ability of VEGF-B to regulate both vascular endothelial cells (angiogenesis) as well as axonal growth and survival after injury, it is unclear whether VEGF-B exerts its effects on nerve regeneration through the increase in blood supply or through direct effects on nerve tissue. Indeed, specific studies on its role on peripheral neurons independent of its vascular role are lacking. We have previously reported that VEGF-A can stimulate trigeminal neuronal cell growth and enhance cornea nerve regeneration, resulting in anatomical and functional recovery of peripheral injured nerves independently of its angiogenic effects (12). Here we studied the neuro-regenerative potential of VEGF-B in an avascular model of peripheral nerve injury in mice and the signaling elements involved in the induction of nerve growth. Our results demonstrated tha (i) peripheral nerve regeneration is impaired in mice lacking VEGF-B, (ii) VEGF-B can restore the anatomic and function innervation of target tissues by induction of nerve growth and nerve regeneration, (iii) the effects of VEGF-B are specific for injured nerves and are independent of any vascular effect, and (iv) the effects of VEGF-B on nerve regeneration are distinct from those observed for VEGF-A.