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Biomedical subjects

M Hertz

Publications and source records attributed to M Hertz.

At least 19 recordsLinked to original sources

V(D)J recombinase induction in splenic B lymphocytes is inhibited by antigen-receptor signalling.

In lymphocytes, DNA recombinations that generate the antigen-receptor genes can sometimes be reinduced in receptor-bearing cells in a process called receptor editing, which modifies the specificity of the receptor for antigen. In immature B lymphocytes, B-cell antigen receptor (BCR) signalling stimulates immune tolerance by receptor editing. More mature splenic B cells can also be induced to undergo V(D)J recombination, which generates diversity in the immune system, either by immunization with foreign proteins or by stimulation in vitro with interleukin-4 and lipopolysaccharides. Here we show that immune tolerance is unlikely to induce V(D)J recombination in mature B cells, because BCR ligation actively inhibits V(D)J recombination induced by interleukin-4 and lipopolysaccharide. Furthermore, immunization of immunoglobulin transgenic mice with ligands of varying avidities for the BCR showed that low-avidity antigen could induce strong V(D)J recombination, whereas non-binding or high-avidity ligands could not. These data suggest that V(D)J recombination induced during the immune response modifies the antigen receptors of B cells with weak, but not strong, reactivity to antigen, potentially rescuing cells with improved receptor affinity and promoting their contribution to the immune response. Thus BCR signalling regulates V(D)J recombination in both tolerance and immunity, but in strikingly different ways.

Animals

Intussusception in adults: CT diagnosis.

PURPOSE: Intussusception in adults is nowadays usually diagnosed on computed tomography (CT), as CT is often the first modality for the investigation of prolonged abdominal pain from which these patients suffer. We wish to present the CT, clinical and pathological findings of 16 adult patients with intussusception seen over a 5-year period. MATERIALS AND METHODS: The abdominal scans of 16 patients with intussusception were reviewed. Special attention was directed to the location of the mass, its shape and fat content, possible underlying pathology and dilatation of the bowel proximally. The findings were correlated with clinical and pathological data. RESULTS: Eight men and eight women, aged 34-81 years, were studied. The most frequent indication for CT was prolonged abdominal pain. CT findings included an inhomogeneous soft tissue mass, target or sausage-shaped, depending on the angle of the CT beam vs. the intussusception, with a fatty component in 14 of the 16. Intussusception was enteroenteric (six), ileocolic (three), or colocolic (seven). Complete small bowel obstruction was present only in one case and some bowel dilatation in three. The underlying pathology could be diagnosed on CT in only two cases of lipoma. Nine patients had an underlying malignant process, eight of them unsuspected. Of the other five, two had coeliac disease, two were classified as idiopathic and one had a necrotic polyp of undetermined pathology. CONCLUSION: Intussusception on CT presented a characteristic mass lesion containing fat stripes in almost all patients. Obstruction was rarely seen. Malignant lesions were the most common cause and therefore early diagnosis and prompt intervention are essential.

Abdominal Pain

Promoting adherence to an electronic home spirometry research program after lung transplantation.

Adherence with any long-term treatment or research protocol is a challenge; this has been found to be the case with lung transplant recipients participating in an electronic home spirometry research program. Because the purpose of the current study is to develop a system for detecting early infection and rejection in lung transplant recipients, regular transmission of data by subjects to the research data center is imperative to the success of the study. Various adherence-promoting strategies have been developed by the research team to increase subject adherence with the program. An increased adherence rate has been reported after implementation of these various strategies, yet work remains to promote continually regular participation in the program by all subjects. It remains a challenge for the research team to devise creative and effective strategies for increasing adherence to regular spirometer use to provide data to develop a computerized system for detecting early infection and rejection of transplanted lung tissue.

Algorithms

Receptor editing and commitment in B lymphocytes.

B cells that fail to pass a developmental checkpoint, either as immature or mature B cells, can be rescued by creating a new B cell antigen receptor through nested secondary immunoglobulin gene rearrangements, a process termed receptor editing. Tolerance-mediated receptor editing occurs in self-reactive immature bone marrow B cells, while peripheral receptor editing probably occurs in low-affinity B cells competing for antigen and for survival signals within the germinal center response.

Animals

BCR ligation induces receptor editing in IgM+IgD- bone marrow B cells in vitro.

The ability of BCR cross-linking to stimulate receptor editing was analyzed in vitro using bone marrow B cells from immunoglobulin (Ig) transgenic (Tg) and non-Tg mice. In cultured Ig-Tg cells, BCR ligation induced receptor editing as measured by up-regulation of RAG gene expression, light chain gene DNA rearrangements, and expression of lambda-light chain protein in cells that previously expressed kappa. In the culture conditions used, BCR ligation induced light chain rearrangements in most immature IgM+IgD- bone marrow B cells in the absence of significant cell death or cell growth. Receptor editing in non-Tg B cells was also documented in cultures treated with anti-immunoglobulin. These results provide direct evidence for the ability of BCR ligation to stimulate immunoglobulin light chain gene rearrangements in immature B cells.

Animals

Coronary artery bypass after single lung transplant: a case report.

Chronic obstructive pulmonary disease (COPD) is the most common indication for adult single lung transplantation. These patients commonly have one or more risk factors for coronary artery disease. Traditionally previous lung transplantation has been considered a contraindication to coronary artery bypass grafting (CABG). This report describes a case of CABG 3 yr after single lung transplantation and briefly discusses the risks of cardiac surgery in lung transplant patients.

Contraindications

The impact of fetal screening on indications for cystourethrography in infants.

To evaluate cystourethrography in the era of fetal screening, we evaluated retrospectively the clinical and imaging findings of all children up to the age of 1 year who underwent a cystourethrogram in a 5-year period (1987-1992). There were 292 children, 64 neonates (< 1 month, 51 boys, 13 girls) and 228 infants (1 month-1 year, 111 boys, 117 girls). Hydronephrosis detected prenatally and confirmed after birth by US was the indication for cystourethrography in 88 children (72 boys, 16 girls). This 4.5 to 1, male to female ratio is very unusual compared to children with urinary tract infection, the great majority of whom are girls. The findings based on imaging studies in these 88 children with hydronephrosis included 31 with vesicoureteral reflux (VUR) (in 4 this was secondary), 23 with obstruction at the ureteropelvic junction (UPJ), 13 with multicystic dysplastic kidney, 2 with obstruction at the ureterovesical junction, 1 with ectopic ureterocele and 1 with posterior urethral valves, both the latter without reflux. Eleven children had normal postnatal studies and six children were lost to follow-up. Urinary tract infection (UTI) was the indication in 163 children (62 boys, 101 girls). Forty-one children were examined for other causes. Although most cases of hydronephrosis were detected on fetal screening, UTI was still the most common indication for cystourethrography and some significant abnormalities were found in these symptomatic children.

Female

Hematuria and voiding disorders in children caused by congenital urethral polyps. Principles of diagnosis and management.

Congenital urethral polyps may cause hematuria, various degrees of outflow obstruction and display a variety of, mostly nonspecific micturition abnormalities in young boys and infants, and should be considered and investigated when recurrent or persistent hematuria and voiding disturbances are encountered. Voiding cystography is the best available diagnostic method to detect urethral polyps. Following diagnosis, prompt complete resection of polyp is indicated. Resolution of signs and symptoms and excellent prognosis are the rule in most of the reported cases. In view of the rarity of this significant pathological condition, we present our experience with 6 children who suffered from urethral polyps and outline the principles of diagnostic evaluation and management of the child with urethral polyp.

Child, Preschool

A new in situ hybridization technique for spliced RNA species documents the bone marrow origin of pulmonary macrophages in chronic myelogenous leukemia.

Tissue macrophages derive from monocytes of bone marrow origin. Because monocytes from patients with chronic myelogenous leukemia (CML) contain the Philadelphia chromosome (Ph), it seemed probable that tissue macrophages in CML would originate from the malignant clone. Using powerful molecular techniques, we studied pulmonary alveolar macrophages (PAM) from two patients with CML. PAM from Patient 1, a patient in chronic phase studied before bone marrow transplantation (BMT), contained the Ph by Southern blot analysis. Patient 2, an accelerated phase patient, was studied after post-BMT relapse. PAM from this patient not only contained the Ph, but also expressed the BCR/ABL message documented by a new splice junction in situ hybridization technique. This new technique allows detection of BCR/ABL mRNA and determination of splice useage in individual cells. These data confirm the continued replenishing of PAM from peripheral blood monocytes in non-BMT settings and represent the first direct evidence that tissue macrophages are derived from the malignant clone in patients with CML.

Adult

The B cell antigen receptor complex: association of Ig-alpha and Ig-beta with distinct cytoplasmic effectors.

The B cell antigen receptor complex is a hetero-oligomeric structure composed of antigen binding, membrane immunoglobulin, and transducer-transporter substructures. The transducer-transporter substructure is composed of disulfide-linked dimers of immunoglobulin (Ig)-alpha and Ig-beta/gamma subunits that are products of the mb-1(alpha) and B29 (beta/gamma) genes. Although the receptor complex associates with Src family kinases that are activated after receptor ligation, the site of interaction of these and other cytoplasmic effector molecules with receptor subunits is unknown. The cytoplasmic tails of Ig-alpha and Ig-beta chains were found to associate with distinct sets of effector molecules. The Ig-alpha chain cytoplasmic domain bound to the Src family kinases Lyn and Fyn, phosphatidylinositol-3 kinase (PI-3 kinase), and an unidentified 38-kilodalton phosphoprotein; the cytoplasmic tail of Ig-beta bound PI-3 kinase and unidentified 40- and 42-kilodalton phosphoproteins. Binding activity was found to occur within a 26-amino acid sequence of Ig-alpha and Ig-beta that contains a motif [(Asp or Glu)-(any amino acid)7-(Asp or Glu)-Tyr-(any amino acid)3-Leu-(any amino acid)7-Tyr-(any amino acid)2-(Leu or Ile)] previously implicated in signal transduction via other receptors including the Fc epsilon receptor I and the T cell antigen receptor. These findings indicate that the subunits act independently to activate distinct second messenger pathways.

Amino Acid Sequence

Ectopic ureterocele in adults with a comparison of the anomaly in children.

Ectopic ureteroceles, while not uncommon in children, have been reported only rarely in adults. We present five adults with ectopic ureteroceles with emphasis on the varied clinical and radiographic manifestations. These findings were compared with those in 32 children with ectopic ureterocele. It was found that the clinical presentation differed in adults and children, but the radiological findings were similar. The diagnosis was in some cases delayed for many years. The anomaly could not be detected by imaging means in two of five adults and eight of 32 children, and was found only at surgery.

Adult

Diverticula of the male urethra: a review of 61 cases.

Sixty-one cases of diverticulum of the male urethra were reviewed. This group included 10 patients with congenital and 51 with acquired diverticula. The etiology of the acquired variety, the radiological findings, and the frequency of appearance in both congenital and acquired diverticula of the urethra during a 30-year period are described.

Adolescent

CT of the urinary tract after abdominoperineal resection for rectal carcinoma.

Computed tomography (CT) after abdominoperineal (AP) resection for rectal carcinoma is a routine procedure for the detection of recurrent tumor and distal metastases. We reviewed sequential CT scans after AP resection in 52 patients in order to see whether the urinary tract as a neighboring organ is involved in recurrent malignancy. Bladder displacement in itself was not associated with hydronephrosis. Such hydronephrosis developed, however, in 14 patients--13 with a presacral mass, and one with retroperitoneal lymphadenopathy. In 23 of the 52 patients a presacral mass appeared, either fibrosis, infection, or recurrence. Severe hydronephrosis was found only with malignancy. We suggest that marked hydronephrosis associated with a presacral mass after AP resection is an indirect sign of malignancy.

Adult

Low loop cutaneous ureterostomy and subsequent reconstruction: 20 years of experience.

Between 1970 and 1990 we constructed low loop cutaneous ureterostomies in 50 patients with grossly dilated collecting systems. Patient age ranged from 6 days to 3 years. The indication for all urinary diversions was an anomaly of the lower urinary tract associated with marked ureteral dilatation considered to require decompression because of either urinary tract infections or renal functional impairment. Clinical and radiological followup was maintained between establishment of the cutaneous ureterostomy and complete reconstruction, and revealed marked improvement indistinguishable from that obtained by high diversions. Undiversion was performed after 3 to 69 months, usually simultaneously with definitive correction of the underlying anomaly. The main advantage of our presented technique is the opportunity to resect the distal ureteral limb and to perform simple ureteroneocystostomy using the proximal limb. Besides its technical simplicity, this technique obviates possible complications that may be attributed to ureteral anastomosis and compromised blood supply, thus, it is well recommended.

Child, Preschool

Differentiation of class I- and class II-directed donor-specific alloreactivity in bronchoalveolar lavage lymphocytes from lung transplant recipients.

Previous studies have demonstrated that donor antigen-specific primed-lymphocyte-test (PLT) reactivity of bronchoalveolar lavage lymphocytes is strongly associated with acute pulmonary rejection and with obliterative bronchiolitis (OB); however, a systematic analysis of PLT reactivity as being class I-or II-directed has not been performed. To assess reactivity directed against individual class I or II antigens, we tested a total of 67 BAL-derived lymphocyte samples from 26 recipients for alloreactivity in the PLT, using a pool of allogeneic cells and selected homozygous typing cells (HTCs) representing the HLA class I and II antigens expressed by the recipient and donor cells. The results obtained by PLT were correlated with the clinical status of the recipient with regard to rejection, infection, and OB. In 9 of 10 cases where transbronchial biopsy results were consistent with rejection, donor antigen-specific allogeneic PLT reactivity was observed and, more specifically, could be determined to be directed toward donor class II antigen in 8 of these cases. For 3 of 4 recipients tested chronologically, positive donor antigen-specific PLT reactivity was observed at the time of and 2-3 1/2 months prior to the diagnosis of rejection by transbronchial biopsy. During periods of acute infection, donor antigen-specific PLT reactivity was not observed; instead, non-specific PLT reactivity of BAL-derived cells (i.e., reactivity that did not correlate with any defined HLA antigens) was observed as well as reactivity associated with the self-antigens expressed by the recipients' cells. The PLT reactivity of BAL-derived cells from a recipient diagnosed with OB correlated specifically with one of the disparate donor class I antigens (HLA-B44). In 23 cases, BAL cells were propagated in the presence of autologous cells and rIL-2, thereby allowing for sufficient numbers of cells to test with a panel of 29 HTCs and to analyze for cell surface phenotype. The cultured BAL cells from 4 recipients undergoing a rejection episode demonstrated a predominant CD4+ phenotype consistent with the class II-directed reactivity observed in PLT. However, these results did not demonstrate a phenotype distinctive from the 7 BAL results obtained from 4 quiescent recipients. In marked contrast, the cultured BAL cells obtained from 4 recipients diagnosed with OB demonstrated a predominant CD8+ phenotype, with 60-92% of the cultured cells being CD8+. These results are consistent with the class I-directed reactivity observed in PLT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent