Non-anatomical reconstruction of lateral ulnar collateral ligament of the elbow after tumor resection.

We present the case of an 80-year-old man with a tumor recurrence on his right arm 6 years after initial treatment. The lateral aspect of the elbow joint, involving overlaying skin, muscles, tendons, joint capsule, lateral collateral ligament complex, the lateral 1/3 of the capitellum, and lateral epicondyle of humerus were excised in the tumor resection. Intraoperative assessment revealed multidirectional instability of the elbow, and joint stabilization was needed. Because the lateral epicondyle was resected, graft placement in an anatomical position was impossible to carry out. Therefore, non-anatomical reconstruction of lateral ulnar collateral ligament with palmaris longus tendon graft was performed. The skin was reconstructed using an antegrade pedicled radial forearm flap. For wrist extension reconstruction, the pronator quadratus tendon was transferred to the extensor carpi radialis brevis tendon. One year after the operation, elbow range of motion was 5-130°. The patient remains symptom free. The Mayo elbow performance score is good. The Musculoskeletal Tumor Society rating score is excellent. To our knowledge, this is the first report of an elbow lateral ulnar collateral ligament reconstruction after tumor resection.

Comparison of acute non-haemolytic transfusion reactions in female and male patients receiving female or male blood components.

To study the relationship between antibodies detected in patients' and/or donors' sera and the clinical features of acute non-haemolytic transfusion reactions (ANHTRs), and to determine any gender-related difference. ANHTRs range from urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are implicated in some of the ANHTRs. A higher antibody positivity is expected for females than for males. A comparative study of ANHTRs for antibody positivity and their clinical features between females and males for both patients and donors is helpful for characterizing ANHTRs including TRALI more clearly, but such studies are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45 hospitals between October 2000 and July 2005 were analysed. The patients and 196 donors of suspect blood products were screened for antibodies to HLA Class I, HLA Class II, granulocytes, and platelets. The patients were also screened for anti-plasma protein antibodies. The types and severity of ANHTR did not differ significantly between female and male patients. The frequency of the anti-HLA antibodies, but not that of the non-HLA antibodies, was significantly higher in females. Non-HLA antibodies were significantly associated with severe reactions in females. All the TRALI cases had predisposing risk factors for acute lung injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti-HLA antibodies were detected more frequently in females than males, no significant association of ANHTRs including TRALI with gender, not only for patients, but also for donors, could be shown in this study.

Effectiveness of washed platelet concentrate and red cell transfusions for a patient with anhaptoglobinemia with antihaptoglobin antibody.

A 71-year-old Japanese male with myelodysplastic syndrome progressing to overt leukaemia and hepatocellular carcinoma developed dyspnea and urticaria immediately after infusion of platelet concentrate (PC). He exhibited an identical reaction following blood transfusion. Serum haptoglobin was undetectable. The patient was determined to be homozygous for Hp(del) by polymerase chain reaction (PCR). Antibody to haptoglobin was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. No antibodies against human leucocyte antigen (HLA) or platelet-specific antigens were detected. Washed PC and washed red blood cells were effective in preventing the transfusion-related anaphylactoid reactions.

Nucleotide sequence of a new Fc gamma receptor IIIB allele that codes for a neutrophil antigen.

A new allele of the human neutrophil antigen (HNA) system (tentatively called NA2M) was discovered and its nucleotide sequence was determined. NA2M differs in a single nucleotide (193G-->A) from FCGR3B*2(NA2), resulting in an amino acid change (54Glu-->Lys). The frequency of the NA2M gene in the Japanese population was estimated to be 0.008. Granulocytes of individuals possessing NA2M reacted with HNA-1b(NA2)-specific monoclonal antibody (TAG2) in the GIFT assay.

Simple PCR detection of haptoglobin gene deletion in anhaptoglobinemic patients with antihaptoglobin antibody that causes anaphylactic transfusion reactions.

Two anhaptoglobinemic patients showing anaphylactic transfusion reactions by antihaptoglobin antibody were found. Southern blot analysis indicated that 2 patients were homozygous for the deleted allele of the haptoglobin gene (Hp(del)) as reported previously. We have identified the junction region of the deletion from genomic DNA of 1 patient using cassette-mediated polymerase chain reaction (PCR). Then, the deleted region from the 5' breakpoint to the promoter region of the Hp was amplified from genomic DNA of a control individual using PCR. DNA sequence analysis of these regions indicated that the 5' breakpoint of the Hp(del) allele was located 5. 2 kilobase (kb) upstream of exon 1 of the Hp and the 3' breakpoint was positioned between 52 and 53 base pair (bp) upstream of exon 5 of the haptoglobin-related gene. There was no significant homology between the DNA sequences flanking the 5' and 3' breakpoints, except for a 2-bp (TG) identity. To examine the gene frequency, we have developed a simple PCR method to detect the gene deletion. We found 8, 16, and 17 Hp(del) alleles in 157 Koreans, 523 Japanese, and in 284 Chinese, respectively, but did not find the Hp(del) in 101 Africans or in 100 European-Africans. The incidence of individuals homozygous for the Hp(del) allele was therefore expected to be 1/4000 in Japanese, 1/1500 in Koreans, and 1/1000 in Chinese. This incidence is higher than that of IgA deficiency in Japanese. More attention should be paid on haptoglobin deficiency and antihaptoglobin antibody as the cause of transfusion-related anaphylactic reactions in Asian populations. (Blood. 2000;95:1138-1143)

Intussusception due to vanishing colon cancer with metastasis of the regional lymph nodes: report of a case.

We present herein a case report of vanishing colon cancer with intussusception. A 70-year-old man with hematochezia was admitted to our hospital. Preoperative images showed ileus due to a colonic tumor. At operation, normograde intussusception without any tumor was recognized at the sigmoid colon. Interestingly, the regional lymph nodes were found to be invaded by tubular adenocarcinoma cells, thus suggesting that the colon cancer existed before the necrosis of the wall took place.

[Detection of anti-IgA alloantibody in a case of non-hemolytic transfusion reaction].

A 59-year-old man with myelodysplastic syndrome exhibited unticaria, dyspnea, fever, and hypotension immediately after the start of platelet concentrate (PC) transfusion on the 15th day of hospitalization. On the 17th and 21st day of hospitalization, the patient exhibited severe unticaria resembling that of erythroderma after the start of PC transfusion. Anti-IgA IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA) on the 28th day of hospitalization. Anti-IgA (purified from pooled human plasma) was detected by Western blotting. The patient's IgA level was normal. No antibodies against HLA or platelet-specific antigens were detected in serum. The patient had no reaction to administration of washed PC. These findings suggest that anti-IgA antibody might have been responsible for the nonhemolytic transfusion reaction in this patient.

[A case report of selective IgA deficiency in rheumatoid arthritis and anti-IgA antibody induced anaphylactic transfusion].

We described a case of rheumatoid arthritis (RA) with selective IgA deficiency. A 69 year-old female with RA was admitted because of gall bladder cancer, and also had selective IgA deficiency which serum IgA level was less than 5.0 mg/dl, and IgA 1 and IgA 2 subclasses were not detected. Prior to the operation, she was given red cell compatible blood transfusion because of severe anemia. After 30 min of transfusion, she developed chill, nausea, vomiting and hypotension. These anaphylactic reactions might be induced by the presence of anti-IgA antibody, since the level of this antibody titers in her serum was elevated, assessed by the methods of ELISA and Western blotting. Although a case of RA associated with selective IgA deficiency, and also with elevated serum anti-IgA antibody level is extremely uncommon, attention should be paid to the presence of anti-IgA antibody in patients with selective IgA deficiency to avoid any unexpected anaphylactic reactions.

Molecular cloning and characterization of human keratan sulfate Gal-6-sulfotransferase.

We have previously cloned chondroitin 6-sulfotransferase (C6ST) cDNA from chick embryo chondrocytes. C6ST catalyzes sulfation of chondroitin, keratan sulfate, and sialyl N-acetyllactosamine oligosaccharides. In this study, we report the cloning and characterization of a novel sulfotransferase that catalyzes sulfation of keratan sulfate. This new sulfotransferase cDNA clone was obtained from a human fetal brain library by cross-hybridization with chick C6ST cDNA. The cDNA clone obtained contains a single open reading frame that predicts a type II transmembrane protein composed of 411 amino acid residues. When the cDNA was introduced into a eukaryotic expression vector and transfected in COS-7 cells, keratan sulfate sulfotransferase activity was overexpressed, but C6ST activity was not increased over that of the control. Structural analysis of 35S-labeled glycosaminoglycan, which was formed from keratan sulfate by the reaction with 35S-labeled 3'-phosphoadenosine 5'-phosphosulfate and the recombinant sulfotransferase, showed that keratan sulfate was sulfated at position 6 of Gal residues. On the basis of the acceptor substrate specificity, we propose keratan sulfate Gal-6-sulfotransferase (KSGal6ST) for the name of the newly cloned sulfotransferase. KSGal6ST was assigned to chromosome 11p11. 1-11.2 by fluorescence in situ hybridization. Among various human adult tissues, a 2.8-kilobase message of KSGal6ST was expressed mainly in the brain. When poly(A)+ RNAs from the chick embryo cornea and brain were probed with the human KSGal6ST cDNA in Northern hybridization, a clear band with about 2.8 kilobases was detected. These observations suggest that KSGal6ST may participate in the biosynthesis of keratan sulfate in the brain and cornea.

Serum levels of cytokines in patients with colorectal cancer: possible involvement of interleukin-6 and interleukin-8 in hematogenous metastasis.

Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured preoperatively in 24 patients with colorectal cancer. IL-1 beta was not elevated, IL-6 and IL-8 were markedly elevated, and GM-CSF was slightly elevated. TNF-alpha was not detected in most patients. Serum IL-6 levels correlated closely with serum IL-8 levels and with serum carbohydrate antigen (CA) 19-9 levels. Serum IL-6 levels were significantly higher in patients whose tumors exceeding 5.0 cm in diameter or spreading circumferentially. Serum IL-8 levels showed significant differences according to histological type, being lower in well differentiated adenocarcinoma compared to other types. Serum levels of IL-6 and IL-8 were significantly higher in patients with liver metastasis than in those without liver metastasis and serum levels of both these cytokines were also significantly higher in patients with lung metastasis than in those without lung metastasis. These results suggest that IL-6 and IL-8 may play an important role in the hematogenous metastasis of colorectal cancer.

The clinicopathologic features of serum CA 19-9-positive colorectal cancers.

The preoperative serum levels of carbohydrate antigen 19-9 (CA 19-9) were determined in 206 patients with colorectal cancer, 52 (25.2%) of whom were found to be positive. All of these patients had advanced cancers and significantly higher incidences of tumor invasion through the muscularis propria (91.3%) and lymph node involvement (54.5%). The incidences of liver metastasis and Dukes' stage D in the CA 19-9-positive group were 38.5% and 42.9%, respectively, significantly higher than those in the CA 19-9-negative group of 6.5% and 14.8%, respectively. Moreover, the incidence of liver metastasis in the CA 19-9-positive group patients with Dukes' stage D cancer was 95.2% (20/21); CA 19-9 showing higher specificity (81.7%) and a more positive predictive value (38.5%) for liver metastasis than the carcinoembryonic antigen (CEA). When a cutoff value of 160 U/ml was used, the specificity and positive predictive value reached 97.7% and 81.0%, respectively. An analysis of response operating characteristic (ROC) curves for liver metastasis revealed that CA 19-9 was more useful than CEA. The long-term survival of the CA 19-9-positive group patients was significantly worse than that of the CA 19-9-negative group patients (P < 0.0001), with no 1.25-year survivors in the former group when the cutoff value of 160 U/ml was used. These results suggest that serum CA 19-9 as a useful preoperative indicator of liver metastasis and prognosis in colorectal cancer.

Study of c-erbB-2 protein and epidermal growth factor receptor expression and DNA ploidy pattern in colorectal carcinoma.

Correlation of c-erbB-2 protein (n = 44), epidermal growth factor receptor (EGFR) (n = 41) expression, and DNA ploidy pattern (n = 42) with clinical outcomes of human colorectal cancers was studied. Using monoclonal antibodies against c-erbB-2 protein and EGFR, an immunohistochemical study of the expression of c-erbB-2 protein and EGFR in frozen tissue sections from the lesion was performed. There was no significant correlation between the expression of c-erbB-2 protein and clinicopathological findings such as, tumor size, histological type, depth of invasion, lymph node metastasis, lymphatic vessel invasion, or venous invasion. However, the incidence of c-erbB-2 protein expression in Dukes D was significantly higher (9/10, 90%) than that in Dukes A to C (16/34, 47.1%). Similar tendency was also observed in the expression of EGFR. Aneuploid case was observed in 12 of observed 25 (48%) cases without lymph node metastasis, while it was observed in 16 of 17 cases (94.1%) with lymph node metastasis and there was significant association between DNA ploidy pattern and lymph node metastasis (P < 0.01) and most of the cases (17/20, 85%) were aneuploidy in Dukes C and D. The results above suggest that the expression of c-erbB-2 protein or EGFR was associated with distant metastasis, while on the other hand DNA ploidy pattern was correlated with lymph node metastasis.

[Immunohistochemical study of the coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 protein in colorectal cancer].

The coexpression of EGFR and c-erbB-2 protein was examined immunohistochemically in a total of 62 freshly frozen specimens of colorectal cancer, and correlations between the coexpression of both receptors and their clinicopathological variables were analyzed. Positive staining of both receptors was found in 21 cases, and it was related to the degree of lymphatic or vascular invasion of cancer cell, the synchronous metastasis to liver or lung, and the most advanced stage (Dukes' D). Moreover, the incidence of the distant metastasis including metachronous metastasis to other organs such as liver, lung or peritoneum were significantly higher in the positive cases of both receptors. These results suggest that the coexpression of EGFR and c-erbB-2 protein may be related to the distant metastasis of colorectal cancer.

[Immunohistochemical study of the c-erbB-2 protein in human gastric carcinoma].

One hundred and thirty cases of gastric carcinoma were immunohistochemically examined in regard to the expression of c-erbB-2 protein. C-erbB-2 protein was expressed in 36 cases. Number of cases in the differentiated type was 31 out of 78 cases, whereas that of the undifferentiated type was 5 out of 52 cases. And there were 2 positive cases among 26 cases of early type, whereas there were 34 positive cases of advanced type. In 60 cases of differentiated and advanced type carcinomas, the positive staining related significantly with tumor size, infiltrative growth pattern and peritoneal dissemination. The 5 year survival rate after curative resection was analyzed among the patients with differentiated type carcinoma. The rate of 39 negative cases was 78.0%, whereas it was 46.4% in 20 positive cases. These results indicate that the expression of c-erbB-2 protein in gastric carcinoma may be related to the degree of differentiation and the stage of progression, and further, it seems well correlated with the biological behavior of the differentiated but advanced carcinoma as shown by the positive tendency in larger size, deeper infiltration and shorter 5 year survival.

Involvement of central cholinergic mechanism in RU-24969-induced behavioral deficits.

The present study was undertaken to investigate the role of cholinergic mechanisms in the behavioral effects of RU-24969, a compound with serotonin1B (5-HT1B) receptor agonist properties. RU-24969 caused an increase in locomotion (2-5 mg/kg IP) and an impairment of spontaneous alternation (SA) behavior in a T-maze (0.5-2.0 mg/kg IP) in mice, effects that were also induced by the cholinergic hypofunction with scopolamine treatment (0.5-5.0 mg/kg IP), an acetylcholine (ACh) receptor antagonist. The impairment of the SA behavior by RU-24969 was enhanced by scopolamine. Both the hyperlocomotion and the SA impairment by RU-24969 were markedly reduced by propranolol (20 mg/kg IP) which has 5-HT1A/5-HT1B receptor antagonist properties, as well as by physostigmine (0.05-0.2 mg/kg IP), an ACh esterase inhibitor, and oxotremorine (0.005-0.01 mg/kg IP), an ACh receptor agonist. Moreover, these behavioral deficits of RU-24969 were diminished in mice pretreated intracerebroventricularly with AF64A (30 nmol/body), a presynaptic cholinergic neurotoxin, whereas scopolamine induced the deficits even in animals with the same treatment. These results suggest that the serotonergic behavioral deficits observed after RU-24969 treatment may be caused by an inhibition of ACh release through its action on the presynaptic receptor (particularly RU-24969-sensitive sites) localized on the cholinergic terminals.