[Mid- and long-term results of surgical treatment of brachiocephalic Takayasu arteritis].

Objective: To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis. Methods: This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates. Results: All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%. Conclusion: For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient's condition,and the mid-and long-term outcomes are satisfactory.

Expansion and de novo occurrence of Y chromosome microdeletions occurring via natural vertical transmission in northeastern China.

OBJECTIVE: To determine characteristics of classical and partial deletions of the Y chromosome azoospermia factor (AZF) region transmitted from father to son by natural fertilization. METHODS: Patients from northeastern China with primary male infertility (n = 10) and their fathers were investigated. Healthy fertile men and women were recruited as positive and negative controls, respectively. The Y chromosome microdeletions were detected by polymerase chain reaction. Serum concentrations of reproductive hormones were determined by electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay. RESULTS: Expansions of microdeletions were observed in seven father­son pairs; de novo microdeletions were found in the remaining three father­son pairs. The Y chromosome microdeletions were larger in sons than in their fathers. Patients with infertility had significantly higher levels of follicle stimulating hormone and lower levels of inhibin B than fertile men. CONCLUSIONS: The Y chromosome microdeletions were transmitted from father to son via natural transmission. These microdeletions may expand during transmission or arise de novo, possibly resulting in reduced fertility.

Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis.

The pathophysiology of human chronic pancreatitis is not well understood and difficult to follow on a molecular basis. Therefore, we used a rat model [Wistar-Bonn/Kobori (WBN/Kob)] that exhibits spontaneous chronic inflammation and fibrosis in the pancreas. Using microarrays we compared gene expression patterns in the pancreas during development of inflammation and fibrosis of WBN/Kob rats with age-matched healthy Wistar rats. The extracellular matrix protein SPARC (secreted protein, acidic, and rich in cysteines) and other transcripts of inflammatory genes were quantified by real-time PCR, and some were localized by immunohistochemistry. When pancreatic inflammation becomes obvious at the age of 16 wk, several hundred genes are increased between 3- and 50-fold in WBN/Kob rats compared with healthy Wistar rats. Proteins produced by acinar cells and characteristic for inflammation, e.g., pancreatitis-associated protein, are highly upregulated. Other proteins, derived from infiltrating inflammatory cells and from activated stellate cells (fibrosis) such as collagens and fibronectins are also significantly upregulated. SPARC was localized to acinar cells where it increased in the vicinity of inflammatory foci. However, acinar expression of SPARC was lost during destruction of acinar cells. In human pancreatic specimens with chronic pancreatitis, SPARC exhibited a similar expression profile. During chronic inflammation and fibrosis in the WBN/Kob rat, inflammatory genes, growth factors, and structural genes exhibit a high increase of expression. A temporal profile including pre- and postinflammatory phases indicates a concurrent activation of inflammatory and fibrotic changes. Inflammation dependent expression of SPARC appears to be lost during acinar-to-duct metaplasia both in rat and human pancreas.

Arachnoiditis ossificans.

Arachnoiditis ossificans is a rare type of chronic arachnoiditis characterised by the presence of calcification or ossification of the spinal arachnoid. There are a few reports of this condition in Japanese and western populations but no case has been reported in a Chinese population before. We describe a 35-year-old woman with typical findings of arachnoiditis ossificans. A brief review of the literature is also presented.

Spinal infection caused by Mycobacterium avium complex in a patient with no acquired immune deficiency syndrome: a case report.

Spinal infection caused by Mycobacterium avium complex (MAC) is rarely seen in people who do not have acquired immune deficiency syndrome. We report such a case in a 60-year-old man who underwent anterior spinal fusion after treatment with antibiotics had failed. The presentation of MAC spinal infection is different from that seen in MAC lung infection, with more than half presenting with urgent or semi-urgent neurological deficits. Younger patients who are not immunocompromised can also be infected. It should be considered as a differential diagnosis in patients with tuberculosis of the spine. The use of antibiotics should be based on the cultured organism's sensitivity results. Indications for surgery are progressive bony destruction, abscess formation, and neurological compression.

Spontaneous spinal epidural haematoma in a 15-month-old boy presenting with a wry neck: a case report.

A 15-month-old boy presented with a 2-day history of a wry neck (bent to the left side) with no definite trauma. He had bilateral upper limb weakness and was afebrile, conscious, and stable. There was no spontaneous movement in both upper limbs. Magnetic resonance imaging of the cervical and thoracic spine demonstrated an extensive spontaneous spinal epidural haematoma from C3 to T8. 23 hours after admission, the patient underwent an emergency right-sided C3 to T8 hemi-laminectomy and haematoma evacuation. The patent's strength gradually recovered and he attained full power 3 weeks after operation. Spontaneous spinal epidural haematoma is a rare disease in children. A high index of suspicion is essential for its effective management as the interval to operation is the most important prognostic factor.

Subchondral insufficiency fracture of the femoral head.

Subchondral insufficiency fracture of the femoral head is a recently recognised entity. There are a few cases reported in Japanese and Caucasian patients but none in the Hong Kong population. The condition typically occurs in elderly females with osteoporosis. Acute hip pain is the usual presentation. The patient may have concomitant insufficiency fractures elsewhere. Magnetic resonance imaging is usually required to make the diagnosis. The prognosis of the condition is unknown. Reported complications include rapid collapse of the femoral head and coxopathy. Joint replacement should be considered if conservative management fails.

A selective COX-2 inhibitor suppresses chronic pancreatitis in an animal model (WBN/Kob rats): significant reduction of macrophage infiltration and fibrosis.

INTRODUCTION: Therapeutic strategies to treat chronic pancreatitis (CP) are very limited. Other chronic inflammatory diseases can be successfully suppressed by selective cyclooxygenase 2 (COX-2) inhibitors. As COX-2 is elevated in CP, we attempted to inhibit COX-2 activity in an animal model of CP (WBN/Kob rat). We then analysed the effect of COX-2 inhibition on macrophages, important mediators of chronic inflammation. METHODS: Male WBN/Kob rats were continuously fed the COX-2 inhibitor rofecoxib, starting at the age of seven weeks. Animals were sacrificed 2, 5, 9, 17, 29, 41, and 47 weeks later. In some animals, treatment was discontinued after 17 weeks, and animals were observed for another 24 weeks. RESULTS: Compared with the spontaneous development of inflammatory injury and fibrosis in WBN/Kob control rats, animals treated with rofecoxib exhibited a significant reduction and delay (p<0.0001) in inflammation. Collagen and transforming growth factor beta synthesis were significantly reduced. Similarly, prostaglandin E(2) levels were markedly lower, indicating strong inhibition of COX-2 activity (p<0.003). If treatment was discontinued at 24 weeks of age, all parameters of inflammation strongly increased comparable with that in untreated rats. The correlation of initial infiltration with subsequent fibrosis led us to determine the effect of rofecoxib on macrophage migration. In chemotaxis experiments, macrophages became insensitive to the chemoattractant fMLP in the presence of rofecoxib. CONCLUSION: In the WBN/Kob rat, chronic inflammatory changes and subsequent fibrosis can be inhibited by rofecoxib. Initial events include infiltration of macrophages. Cell culture experiments indicate that migration of macrophages is COX-2 dependent.

Fusion rate of anterior cervical plating after corpectomy.

PURPOSE: To evaluate the neurological recovery and fusion rate of patients with myelopathy who were treated with anterior corpectomy and anterior cervical plating. METHODS: The results of 17 cervical myelopathy patients who underwent decompression and anterior cervical plating were retrospectively reviewed at a mean follow-up of 2 years. RESULTS: By Kurokawa score, 82.4% of patients showed excellent-to-good results. The fusion rates of 2-level and 3-level anterior cervical corpectomy, and of anterior plate fixation were 100%. There were no implant- or graft-related complications. Transient dysphagia in 9 (52.9%) patients resolved after a mean of 3 months (range, 1-9 months). CONCLUSION: The use of anterior cervical plating after anterior corpectomy and fusion with autologous bone graft greatly enhances arthrodesis. The improved fusion rate and low complication rate associated with anterior cervical plating may justify its use in the treatment of cervical spondylotic myelopathy.

The management of superior dislocation of the patella with interlocking osteophytes--an update on a rare problem.

The superior dislocation of the patella with interlocking osteophytes is a rare condition. A review of the English literature revealed only 12 reported cases. The purpose of reviewing these case reports is to highlight the unusual presentation and the injury mechanism in 2 of our patients, and to present our treatment algorithm. Closed reduction with manipulation of the patella, with or without anaesthesia, was performed without difficulty. We recommend an intermediate step of trying a regional nerve block before proceeding to general anaesthesia. Our patients had full range-of-motion after reduction and they were symptom-free after 3 years of follow-up. There were no recurrent dislocations in our patients.

Microbial contamination of femoral head allografts.

OBJECTIVE: To study the incidence of microbial contamination at the bone bank of the United Christian Hospital. DESIGN. Retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 151 patients (33 men and 118 women) who underwent hip arthroplasty surgery and from whom femoral head allografts were retrieved between January 1994 and March 2000; and 81 patients in whom allografts were implanted. MAIN OUTCOME MEASURES: Bone biopsies were taken from the femoral head and used to detect any microbial contamination that might have occurred during removal and after storage. The rates of infection among recipients and donors were also assessed. RESULTS: Of the 151 allografts, 94 non-contaminated allografts were implanted by the end of the study. Fourteen (9.3%) heads showed positive culture results after retrieval and were discarded. Four (4.3%) of the 94 stored allografts that were implanted tested positive for microbial growth, but the recipients of these allografts did not develop any clinical infection. Three (3.2%) had wound infections after implantation of the stored allografts although the grafts had previously been tested negative for any microbial contamination. CONCLUSION: Our centre has a low allograft contamination rate. The wound infection rate among recipients was also low. The culture of a bone biopsy sample is a reliable method to detect contamination of bone grafts. However, the contamination rate among stored allografts should prompt orthopaedics departments to review allograft handling procedures, so as to minimise the chance of contamination.

CD44-mediated cyclooxygenase-2 expression and thromboxane A2 production in RAW 264.7 macrophages.

OBJECTIVE AND DESIGN: CD44 is the major cell surface receptor for hyaluronan (HA) on macrophages. Stimulation of macrophages via the HA-CD44 pathway leads to the enhanced expression of inflammatory gene products, including cytokines, chemokines, and adhesion molecules. We have examined whether activation of CD44 by crosslinking is capable of activating the cyclooxygenase (COX) and prostaglandin (PG)/thromboxane (TX) pathway in cultured macrophages. MATERIALS AND METHODS: CD44 was crosslinked on RAW 264.7 mouse macrophages using specific rat anti-mouse CD44 monoclonal antibodies and anti-rat IgG. Total RNA was extracted and subjected to RT-PCR analysis for genes of the PG/TX synthetic pathway. Supernatants were analyzed for PGE2 and TXB2 using specific ELISAs. RESULTS: Transcripts for COX-1, COX-2, TX synthase (TXS), and PGE2 synthase (PGES) were all constitutively expressed in the mouse macrophage cell line RAW 264.7. Crosslinking of CD44 markedly enhanced COX-2 and weakly increased TXS mRNA, whereas COX-1 and PGES mRNA did not change significantly in these cells. Crosslinking of CD44 selectively increased the production of TXB2 but not PGE2. CONCLUSIONS: These findings suggest that the activation of the CD44 pathway plays a unique role in PG synthesis. Activation of this pathway results in enhanced TXA2 but not PGE2 production. This leads to an imbalance of the TXA2/PGE2 profile which favors a proinflammatory and vasoconstrictory response.

Hyaluronan-induced cyclooxygenase-2 expression promotes thromboxane A2 production by renal cells.

BACKGROUND: Matrix degradation products such as fragmented hyaluronan (HA) display important proinflammatory effects on renal tubular epithelial cells (TECs) and macrophages (MPhis). We hypothesized that HA could up-regulate cyclooxygenase type 2 (COX-2) in these cells and that the subsequent production of thromboxane A2 (TXA2) could play a role in inflammatory renal lesions. METHODS: We used an in vitro approach to examine the expression of COX-1 and COX-2 and the production of TXA2 in response to fragments of HA. COX-2 mRNA, protein, and the resulting TXA2 production were measured in CD44-positive, HA-responsive cells lines of TECs and MPhi. COX-2 mRNA was also measured in vivo in MRL-Faslpr mice and in mice with anti-glomerular basement membrane (anti-GBM) nephritis. RESULTS: In TECs and MPhis, HA increased the steady-state COX-2 mRNA and protein levels markedly, whereas COX-1 mRNA levels did not change. The HA-induced response was comparable to lipopolysaccharide stimulation. In comparison with MPhi, the response was much weaker in TECs. Likewise, the production of TXA2 in response to HA was markedly increased in MPhi, but less in TECs. In TECs and in MPhi, the HA-stimulated TXA2 synthesis was inhibited with the COX-2-selective inhibitors SC58125 (12.5 micromol/L) or celecoxib (0.25 to 5.00 micromol/L). COX-2 mRNA levels were increased in nephritic mice with MRL-Faslpr lupus nephritis and in mice with anti-GBM disease. CONCLUSIONS: HA is a proinflammatory factor that stimulates COX-2 expression and subsequent TXA2 production. Since HA accumulates markedly in renal injury, we speculate that this matrix molecule could therefore play a significant role in thromboxane-mediated immune events in the kidney.

Cytotoxic effect through fas/APO-1 expression due to vitamin K in human glioma cells.

Congeners of vitamin K have been found to inhibit growth in various rodent and human tumor cells, but the mechanisms of the inhibitory action are still not well understood. To investigate the modes of actions of vitamin K, we used several vitamin K analogs and examined their cytotoxic effect for human glioma cell lines RBR17T and U251. The analogs included vitamin K1 (VK1), vitamin K2 (VK2), vitamin K3 (VK3), and geranylgeraniol (GGO) which form an unsaturated side chain of VK2. Cell viability was estimated by MTT assay. DNA fragmentation was demonstrated by gel electrophoresis and flow cytometry. In order to study the mechanism of apoptosis, we measured the changes of intracellular reactive oxygen intermediates (ROI) and Fas/APO-1 expression by flow cytometry. The results showed: (1) VK2, VK3, and GGO inhibited cell growth; (2) VK3 had a more potent cytotoxic effect than VK2, and VK3 enhanced the cytotoxic effect of antitumor agents (ACNU and IFN-beta) in RBR17T cells; (3) VK2, VK3, and GGO induce apoptosis: (4) VK3 increased the expression of Fas/APO-1 although VK2 and GGO did not increase its expression in glioma cells; (5) VK3 increased the production of intracellular ROI. Catalase and reduced glutathione (GSH) inhibited production of intracellular ROI and antagonized inhibition of cell-growth induced by VK3, but failed to antagonize that of VK2 and GGO. We hypothesize that VK3 induces apoptosis by promoting the generation of intracellular ROI and Fas/APO-1 expression. On the other hand, VK2 and GGO induce apoptosis but most likely by some other unknown pathway.

Antigen-specific immunoglobulin-A prevents increased airway responsiveness and lung eosinophilia after airway challenge in sensitized mice.

Aeroallergens such as Amb a I from short ragweed are important in the development of allergic airway disease. We tested the ability of a human monoclonal immunoglobulin-A (IgA) antibody specific for Amb a I (A-IgA) to modulate airway responsiveness and lung eosinophilia after airway challenge with nebulized Amb a I or ragweed extract in mice sensitized to Amb a I or ragweed extract, respectively. A-IgA or nonspecific IgA (C-IgA) were given intranasally up to 8 h before each challenge. Allergen challenge resulted in increases in airway responsiveness, in numbers of lung eosinophils, and in Amb a I-specific IgE levels. These were prevented by pretreatment with A-IgA but not with C-IgA. Decreases in IFN-gamma and increases in IL-4 and IL-5 production following challenge with Amb a I were also reduced by A-IgA treatment. In contrast, increases in total IgE and total IgG and in numbers of lung neutrophils after challenge were not significantly affected by A-IgA, which additionally induced increased levels of Amb a I-specific IgG2a antibodies. In mice sensitized and challenged with ovalbumin (OVA), A-IgA did not affect airway responsiveness, lung eosinophilia, cytokine production, or immunoglobulin levels. These data indicate that allergen-specific IgA can prevent airway hyperresponsiveness and reduce eosinophil influx into the lungs following allergen challenge via the airways in sensitized mice, and these effects are allergen-specific. Neutralization of allergen may contribute to the effects of IgA, but the induction of allergen-specific IgG2a in A-IgA-treated mice suggests an immunomodulatory action for A-IgA.

Human IgA monoclonal antibodies specific for a major ragweed pollen antigen.

Human hybridoma cell lines secreting IgG specific for the major allergen in the pollen of short ragweed, Amb a I, were established from patients who had been receiving antigen injections for immunotherapy. Recombinant Ig genes were then constructed by cloning the heavy and light chain variable region genes of the human hybridoma cell line and joining them to the human alpha or kappa constant region genes in mammalian expression vectors. Amb a I-specific IgA was expressed in two mouse myeloma cell lines, NS0 and Sp2/0. In both systems, transfected alpha and kappa chains were assembled into IgA monomers or into dimers covalently linked by the endogenous murine J chains. We propose that recombinant IgA monoclonal antibodies specific for airborne allergens may be applied to the mucosal surface of the nasal linings or of the lower airway of sensitized individuals to inhibit the entry of allergenic molecules across the mucosal epithelium and, therefore, to prevent the development of allergic responses.

Construction and characterization of chimeric and humanized forms of a broadly neutralizing monoclonal antibody to HIV-1.

Murine monoclonal antibody (MAb) G3-519 has been shown to recognize a conserved neutralizing epitope in the fourth constant (C4) region of the external glycoprotein gp120 of HIV-1. Inasmuch as this antibody effectively neutralized the infectivity of diverse HIV-1 isolates, it has been selected to be developed for passive immunization against HIV-1 infection in humans. In order to minimize the problem of immunogenicity of murine antibodies and to confer additional accessory immune functions, we have constructed mouse/human chimeric and humanized forms of the antibody. The chimeric antibody was constructed by cloning the murine variable regions and replacing the mouse constant regions with those from human Ig gamma 1,kappa. The humanized antibody was constructed using the human KAS variable region framework sequences as template. Engineering was guided by a three dimensional model of the murine variable region. The murine, chimeric and humanized forms of the antibody exhibited similar reactivity with the peptidic antigen in ELISA, and comparably neutralized the infectivity of HIV-1 in vitro. Taken together, our results show that the chimeric and humanized forms of G3-519 essentially retain the binding activity of the mouse parental antibody. Clinical development is planned to assess the prophylactic and therapeutic usefulness of these reshaped antibodies in humans.

Can anti-IgE be used to treat allergy?

A summary of the properties of CGP 51901 is shown in Table 3. On the basis of its binding to IgE and IgE-secreting cells and its activity in vitro and in vivo, CGP 51901 is expected to be able to decrease serum IgE by direct clearance of IgE and by reduction of the numbers and productivity of IgE-secreting cells. The end result of reduction of IgE in the circulation and on mast cells is expected to be the attenuation of IgE-mediated reactions and the improvement in allergy symptoms. The effective serum concentration of CGP 51901 is expected to be in the range 1-10 micrograms/ml. Because CGP 51901 is an antibody specific for IgE, it is expected to be highly selective in its activity. Because IgE does not appear to be essential and because CGP 51901 has been rigorously tested to confirm its non-anaphylactic nature, this treatment is not expected to have any adverse effects. Therefore, CGP 51901 is expected to be safe and to have a good probability of being effective when it is tested in human clinical trials.

A new isoform of human membrane-bound IgE.

The epsilon-chain of membrane-bound IgE on the surface of B lymphocytes is known to contain a membrane-anchoring peptide segment that is encoded by two membrane exons, me.1 and me.2. In analyzing pertinent segments in mRNA from human IgE-expressing B cells by using PCR methods and Northern blotting analyses, we have identified three species of mRNA of epsilon-chain with variations in the splicing of the membrane exons. The conventional species (m/s) contains the predicted me.1 and me.2; species m/1 harbors 156 extra nucleotides 5' of me.1 with unaltered reading frame; species s/t lacks me.1 and hence the segment encoding the hydrophobic transmembrane stretch and contains a shifted me.2 reading frame. Rabbit antibodies, which were prepared by immunization using a peptide of 36 amino acid residues representing an encoded segment unique to mRNA species m/l, could specifically bind to human IgE-expressing B cell lines and react with an epsilon-chain on Western immunoblots. These results indicate that there exists a previously unidentified isoform of human membrane-bound IgE.

Transfectomas expressing both secreted and membrane-bound forms of chimeric IgE with anti-viral specificity.

Because of the lack of a cell line expressing on surface and secreting human IgE of known Ag specificity, the construction of a transfectoma line possessing such properties would be useful for studying the roles of surface IgE and the effects of anti-IgE antibodies on IgE-producing B cells. Toward this goal, the human genomic DNA segment encompassing the two exons encoding the membrane anchor peptide of epsilon-chain and their flanking regions was sequenced. Hybrid epsilon and kappa genomic DNA comprising the C regions of human epsilon- and kappa-chains and the H and L chain V regions of the murine mAb BAT123, which reacts with the gp120 envelope protein of HIV-1, were constructed. Mammalian expression vectors containing these fusion genes were used to transfect murine myeloma Sp2/0 cells, and transfectants stably expressing on surface and secreting into culture medium chimeric IgE were obtained. The chimeric IgE showed identical Ag-binding properties as the murine mAb BAT123. Acting in concert with the specific peptide Ag polyvalently coupled to a protein carrier, the chimeric antibody could induce histamine release from human blood basophils. These results demonstrate the potential utility of the transfectoma cells and the chimeric IgE in studying the roles of membrane-bound IgE and effects of anti-IgE antibodies on IgE-producing B cells.