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A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse.

Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at our institute. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 mo after birth was established by crossing these diseased mice. Genetic studies on lymphadenopathy were conducted in F1, F2, and backcross populations from crosses between mutant CBA (CBA-m) and various inbred strains of mice. The results supported the control of lymphadenopathy by a single autosomal recessive gene. Since C3H/He-gld/gld (C3H-gld), MRL/MpJ-lpr/lpr (MRL-lpr), and C3H/HeJ-lpr/lpr (C3H-lpr) mice develop the same type of lymphoid hyperplasia, allelism of the mutant gene with gld or lpr was tested by investigating lymphadenopathy in F1 and backcross populations from crosses between CBA-m and C3H-gld, MRL-lpr, or C3H-lpr mice. The gene was confirmed to be allelic with lpr but not with gld. Interestingly, however, the mutant gene interacted with gld to induce less severe lymphadenopathy. Thus, the mutant gene was named lprcg, an lpr gene complementing gld in induction of lymphoproliferation. The genetic conclusion was supported by the same profile of surface markers of lymphoid cells with gld/gld, lpr/lpr, lprcg/lprcg, lprcg/lpr, and +/gld +/lprcg genotypes, as well as by massive lymph node hyperplasia and high titers of autoantibodies in the first four genotypes, but slight hyperplasia and insignificant autoantibody production in the last. The discovery of lprcg provided strong genetic evidence for the parallels between anomalous phenotypes of gld and lpr, and CBA/KlJms-lprcg/lprcg mice will contribute to elucidation of the mechanism of induction of the same abnormal differentiation and functions of lymphocytes by gld and lpr.

Alleles↗

Syndrome of the sea-blue histiocyte--the first case report in Japan and review of the literature--.

A case of the syndrome of sea-blue histiocyte is presented in a 53-year-old Japanese woman, which is the first recorded case in Japan. The patient had hepatosplenomegaly, bleeding manifestations, mild thrombocytopenia, fatty metamorphosis and cirrhosis of the liver, as well as abnormal serum lipid profiles. Her parents were consanguineous and her maternal grandmother with hepatomegaly died of hepatic failure. Histologically, peculiar histiocytes containing numerous, intracytoplasmic sea-blue stained granules on May-Giemsa stain were demonstrated in biopsy materials of the bone marrow, lymph node and liver. The sea-blue granules in these histiocytes proved to have histochemical staining characteristics of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic inclusions of heterogeneous nature, including electron-dense amorphous or variegatedly osmiophilic, frequently laminated materials. Enzyme cytochemically, localization of acid phosphatase activity was demonstrated in and around the intracytoplasmic inclusions. With regard to the pathogenesis of the sea-blue histiocytes in this case, it may be suggested that the existence of the abnormality in lipid metabolism plays an important role in intralysosomal ceroidogenesis in these histiocytes.

Acid Phosphatase↗

CT of the azygoesophageal recess in infants and children.

The contour of the azygoesophageal recess (AER) as seen with computed tomography (CT) is an important indicator of mediastinal disorders. Radiologists must recognize, however, that the AER contour varies with patient age. The configuration of the AER is dextroconvex in children younger than 6 years, nonconcave (ie, equally divided between convex and straight) in children aged 6-12 years, and concave (or adult-like) in adolescents and young adults (aged 12-20 years). The cause of this variation is not certain; however, chest wall configuration does not seem to be an important factor. Although a convex AER is normal and common in pediatric patients, this normal appearance must be distinguished from that of mediastinal abnormalities (eg, foregut malformation cysts, vascular anomalies, lymphadenopathy), which can also produce obvious or subtle convexity of the AER. An appreciation for the age-related variation in AER configuration helps in the interpretation of CT scans. Criteria such as attenuation, morphologic characteristics, cephalocaudal extent, and multicompartmental involvement may be helpful in the differential diagnosis, but, generally, mediastinal abnormalities that alter the AER are nonspecific in appearance.

Adolescent↗

Bronchoscopic aspects of renal cell carcinoma (RCC).

A symposium on RCC in July 1998 in Tübingen was where we to reviewed our patients with endobronchial metastatic RCC treated by bronchoscopy since 1981. 24 of 26 consecutive cases are the subject of the present study. Tumor history, X-ray findings, endobronchial appearance, treatment and the pathogenetic mechanisms of this special form of metastatic spread are demonstrated and discussed. In 5 patients > 10 years relapsed between nephrectomy and bronchoscopic tumor therapy. A thrombuslike tumor growth and bleeding were striking bronchoscopic features. In X-ray besides atelectasis, hilar or mediastinal masses were seen half of the patients, in 50% without parenchymal lung nodes, suggesting lymphogenic spread. In several patients bronchial recanalisation could be successfully repeated over long periods. Abnormal X-ray, haemoptysis or dyspnoa in patients with RCC demands bronchoscopy. In case of bronchial tumor obstruction bronchoscopic treatment offers excellent palliation.

Bronchoscopy↗

[NMR tomography of excised human lymph nodes].

The paper is concerned with the potentialities of the NMR-tomography technique (1H) for metastructure studying of the biopsied human lymph nodes both uninvolved and affected by tumor. Tomography was performed at 200 MHz using the Bruker CXP-200t mini-tomograph. Spin-echoes sequence and projection-reconstruction technique was employed. Spatial resolution was about 0.1 mm. Images of the uninvolved lymph nodes permitted one to detect the structure of the lymph nodes. NMR-imaging of unenlarged lymph nodes enabled one to localize the region of initial metastases. The reconstruction of various groups of spin-echo signals permitted a more precise detection of the regions differed in their spin-spin magnetic relaxation times T2 of protons in 1 mm slice. It may be assumed that the distinction in T2-relaxation rates of the normal and abnormal tissues displays an effective means to detect a pathological region using high-field tomography.

Adult↗

Prognostic factors predicting the outcome of sarcoidosis: an analysis of 818 patients.

A computerised, retrospective study of 818 patients with sarcoidosis was analysed to study the prognosis of each individual manifestation of the disease. The good prognosis of erythema nodosum, acute arthritis and bilateral hilar lymphadenopathy was confirmed, though 16 per cent of patients presenting with erythema nodosum pursued a chronic course. Cor pulmonale and nephrocalcinosis reflected the poorest prognosis while lupus pernio and sarcoidosis of the mucosa of the upper respiratory tract rarely resolved. Bone sarcoidosis also implied chronicity but in four of 31 patients there was no clinical evidence of disease activity two years after the initial diagnosis, although naturally the bone radiograph was still abnormal. Hepatomegaly carried a worse prognosis than splenomegaly, or indeed, than the finding of pulmonary mottling without hilar glands--a stage three chest radiograph.

Adult↗

[A case of Sjögren's syndrome accompanied by lymphadenopathy and IgG4 hypergammaglobulinemia].

A 78-year-old male patient suffered from slight dryness of his mouth and eyes, which was followed by swelling of the parotid and submandibular glands on both sides. Subsequently, he developed generalized lymphadenopathy accompanied by hypergammaglobulinemia IgG 7740 mg/dl, main subclass: IgG4, 5800 mg/dl. Histopathological examination of lymph nodes from his left neck showed follicular proliferation of plasma cells containing cytoplasmic kappa and lambda chains of IgG4, without destruction of the lymph node structure. His serum showed very low levels of complement: 0 U/ml of CH 50, 14 mg/ml of C3 and less than 11 mg/ml of C4. During treatment with prednisolone at 30 mg/day, the swelling of the salivary glands and lymph nodes reduced the IgG and IgG4 decreased and the complement increased. Finally, all lymph nodes, IgG and complement abnormalities were normalized. Anticomplementariness of IgG4 was demonstrated in this patient.

Aged↗

[Study of the expression of the epidermal growth factor-receptor in the laryngeal squamous cell carcinoma and the correlation with clinical pathology characteristics].

OBJECTIVE: The expression of the epidermal growth factor-receptor (EGF-R) in the laryngeal squamous cell carcinoma and the correlation with clinical characteristics of the tumor, difference of tissues. METHOD: Immunohistochemical detection. RESULTS: The EGF-R expression was evaluated in 36 laryngeal squamous cell carcinoma and 25 normal laryngeal tissues specimens. The EGF-R expression showed only in one specimen of normal laryngeal tissues, whereas twenty-four of thirty-six carcinomas showed positive staining reaction with the anti EGF-R antibodies. The EGF-R expression did not correlate with age, whereas it was higher in poorly differentiated tumors than in moderately and well differentiated tumors (P < 0.05) and it was higher in T3, 4 of TNM classification than in T1, 2 (P < 0.05). Four patients being the recurrence cancers after the operation had an enhanced expression of EGF-R. Six of seven patients with the metastatic cervicallymph-node involvement showed an enhanced expression of EGF-R. CONCLUSIONS: The uncontrolled cell growth and proliferation of the laryngeal squamous cell carcinomas may be related to the abnormal EGF-R expression. The enhanced expression of EGF-R can be identified as a poorly prognostic parameter.

Adult↗

Management of chronic testalgia by microsurgical testicular denervation.

OBJECTIVES: Chronic testicular pain (CTP) is defined as uni- or bilateral, intermittent or continuous testicular discomfort of at least 3 months duration that interferes with the patient's daily activities and prompts him to seek medical advice is a rather common urological manifestation of chronic pain syndrome. Diagnosis and treatment of CTP has been a difficult and often unrewarding clinical situation. Success rates of conservative and surgical measures including epididymectomy and orchiectomy rarely exceed 55-73% and 10-40%, respectively. We report our experience on microsurgical testicular denervation as therapeutic option in CTP. PATIENTS AND METHODS: Following an extensive preoperative work-up (urine/semen cultures, transrectal ultrasound, testicular sonography, pain and orthopedic consultation) not revealing any pathologic abnormalities and a positive response to spermatic cord block, 35 patients underwent microsurgical testicular denervation. In brief, spermatic cord was dissected, vas deferens, cremasteric muscle and testicular vessels were separated. After identification of the testicular artery by application of vasodilatating agents using magnifying loops or the operating microscope, all structures besides the testicular artery, vas deferens and 1-2 lymphatic vessels were coagulated and transsected using bipolar diathermy. RESULTS: After a mean follow-up of 31.5 months 34/35 (96%) patients are completely pain-free; no intra- or postoperative complications were encountered. No case of testicular atrophy or hydrocele formation was observed during postoperative follow-up. CONCLUSIONS: Microsurgical testicular denervation results in reliable and reproducible excellent therapeutic success rates of 96% and should be integrated in the management of CTP at an early stage. High success rates require adequate and meticulous diagnostic work-up of the patients by spermatic cord block using saline as placebo and different local anaesthetics as an initial therapeutic armentarium predicting postoperative outcome.

Adult↗

Malignant histiocytosis: a cytochemical and electron microscopic study of an unusual case.

A 25-year-old black female presented with lymphadenopathy, fever and anemia of two months duration. The diagnosis of malignant histiocytosis was made on the basis of histiocytic infiltrations in the sinuses of spleen, liver and lymph nodes and by the demonstration of erythrophagocytosis in bone marrow. Following splenectomy, the patient developed a leukemic phase with as many as 50 X 10(9) abnormal histiocytes/l and bone marrow necrosis. This patient was also atypical because of multiple granulomas in liver, spleen and lymph nodes. Cytochemical and immunofluorescent stains confirmed that the abnormal cells were derived from the monocyte-macrophage series. Electron microscopy was used to further characterize this abnormal cell population. The electron microscopic and cytochemical evidence confirms that the malignant cells in malignant histiocytosis are derived from monocytes.

Acid Phosphatase↗

Immunological and pathological consequences of mutations in both Fas and Fas ligand.

The lpr mutation in mice results in premature termination of transcription of the gene encoding the apoptosis-signaling receptor Fas. As a result, lpr mice develop severe lymphoproliferation and lupus-like autoantibodies. Growing evidence suggests that the lpr mutation is "leaky" and that low levels of Fas are expressed in lpr mice. To determine if Fas expressed in lpr mice is contributing to apoptosis we generated a novel strain of mice (B6/lprgld) which is homozygous for both the lpr mutation and the gld mutation which encodes nonfunctional Fas ligand (FasL) protein. If low levels of Fas in B6/lpr mice contribute to apoptosis and lessen the severity of disease, the B6/lprgld mice, which also lack functional FasL, would be expected to develop a more severe form of disease than B6/lpr mice. Our results revealed no significant increase in either lymphoproliferation or autoimmunity in B6/lprgld mice compared to B6/lpr or B6/gld mice. Additionally, no increase in surface expression of Fas was detected by flow cytometry on B6/lprgld lymphocytes compared to B6/lpr lymphocytes. However, histological examination of B6/lprgld liver revealed a marked increase in lymphocytic infiltration, compared to livers of B6/lpr and B6/gld mice. Our results suggest that, while low levels of Fas in lpr mice may not be contributing to amelioration of lymphoproliferation or autoimmunity, they may be partially protecting the liver from abnormalities which arise in the absence of Fas-mediated apoptosis.

Animals↗

Neuropeptides in pulmonary edema fluid of adult respiratory distress syndrome.

A role for peptidergic nerves in the adult respiratory distress syndrome (ARDS) was examined by radioimmunochemically quantifying neuropeptides in pulmonary edema (PE) fluids from seven patients with ARDS and six patients with PE from congestive heart failure (CHF). The PE fluid mean concentrations of substance P (SP) and gastrin-releasing peptide (GRP) were significantly higher in ARDS (0.59 +/- 0.29 SD and 0.10 +/- 0.03 nM, respectively, P < 0.001 for both) than in CHF (0.19 +/- 0.08 and 0.04 +/- 0.01), whereas no difference was detected between the mean levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the two forms of PE. Mean alveolar fluid concentration of SP was 8.7 nM (range 2.1-20.5 nM, N = 4) in sheep with acute lung injury from intravenous Pseudomonas aeruginosa, but was undetectable in sheep with balloon-induced high left atrial pressure simulating CHF (N = 2) or control sheep (N = 2). Pulmonary lymphatic clearance of SP, which reflected the rate of generation of SP in the lungs, attained a maximum of 25-95 pmol/h in sheep given P. aeruginosa intravenously, but was detected in only one of four control sheep at a lower level. Some pulmonary neuropeptides thus are released locally by acute lung injury and may contribute to endothelial and/or epithelial abnormalities underlying the altered capillary-alveolar permeability in ARDS.

Adult↗

Recurrent thyroid carcinoma: characteristics on MR images.

Magnetic resonance (MR) imaging was used in 32 patients, including eight with benign disease, after partial or total thyroidectomy to determine sensitivity and specificity of MR imaging in the detection of tumor recurrence, to compare signal intensities of scar versus recurrent tumor qualitatively and quantitatively, and to define the extent of recurrent tumor. Findings from surgery (n = 23), needle biopsy (n = 1), or clinical follow-up (n = 8) were used for verification. Of 24 patients with primary thyroid carcinoma, 15 had recurrence and nine had a normal postsurgical thyroid bed. Diagnosis from MR images was correct in 20 cases, but false positive in three and false negative in one. Local recurrence was characterized by low to medium intensity on short repetition time (TR)/short echo time (TE) images and medium to high intensity on long TR/long TE images. Scar in the normal postsurgical thyroid bed showed low intensity on both short and long TR/TE images. Local recurrence of thyroid carcinoma and lymph node metastasis produced positive contrast compared with muscle on short TR/short TE (31 + 19%) and long TR/long TE (85 + 30%) images; fibrosis produced negative contrast, particularly on long TR/long TE (-56, -80%) images. These results indicate the capability of MR imaging in the evaluation of recurrence of thyroid tumors and in the differentiation of abnormal tissue due to tumor recurrence from postoperative fibrosis by means of signal contrast relative to a reference tissue.

Adult↗

Ocular pathology in the elfin face syndrome (the Fanconi-Schlesinger type of idiopathic hypercalcaemia of infancy). Histochemical and ultrastructural study of a case.

The pathology, particularly the ocular pathology, is described in a 42-year-old mildly retarded man with a history of vomiting in infancy. He had an elfin-like face. He died having a pancreatic carcinoma. At autopsy, a supravalvular aortic stenosis and a hypoplastic aorta found clinically were confirmed. Stainings for calcium were positive in the aortic wall, the kidneys, the adrenals and the spleen. In the eyes, calcium was found in the corneal epithelium and endothelium, in corneal keratocytes and stroma, in conjunctival epithelium and in the sclera. Electron microscopy of the eyes revealed that calcium was deposited as hydroxyapatite intracellularly in aggregations of needle-like crystals and extracellularly as spherules morphologically different from the intracellular deposits. Although the serum values of calcium in this patient were normal during his adult life, the histopathological examination indicates an earlier period of raised serum calcium. We find it probable that he had idiopathic hypercalcaemia in infancy, thereby connecting this infantile condition with the elfin face and supravalvular aortic stenosis. In similar cases, the use of the above-mentioned technique is recommended for revealing abnormal calcium storage post-mortem and in vivo (by conjunctival biopsy) in order to substantiate the diagnosis of hypercalcaemia.

Adult↗

Sustained attention and executive functions in euthymic young people with bipolar disorder.

BACKGROUND: Persistent neuropsychological impairments have been reported in the euthymic phase of bipolar affective disorder. However, the findings have been confounded by multiple episodes, chronic illness and residual mood symptoms. AIMS: To assess sustained attention and executive functioning in euthymic young people with bipolar I disorder who had had no more than two affective episodes. METHOD: Thirty euthymic patients (with illness duration of less than 5 years and no more than two affective episodes) and 30 matched healthy individuals were assessed for sustained attention and executive functioning. RESULTS: The bipolar group (mean age 22.4 years, s.d.=2.52; duration of illness 20.87 months, s.d.=14.72), showed impairment on tasks of attention and executive functioning. Multivariate logistic regression analysis demonstrated that deficits in executive functioning differentiated cases from controls. There was no correlation between residual depressive symptoms and neuropsychological performance. CONCLUSIONS: Deficits in attention and executive functioning were present in young people who had experienced only a few episodes of bipolar disorder, suggesting that the deficits are possibly trait abnormalities. Whether these deficits worsen with progression of illness needs to be examined in longitudinal studies.

Adult↗

[Relationship between carcinoembryonic antigen and cyclooxygenase 2 expression and colorectal cancer].

BACKGROUND & OBJECTIVE: Some research showed that carcinoembryonic antigen(CEA) related to cell adhesion and cyclooxygenesis 2(COX2) may be related to colorectal carcinogenesis. This study was designed to investigate the expression of CEA and COX2 to evaluate their effects on the tumorigenesis and progression in the colorectal cancer. METHODS: The immunohistochemistry was used to determine the expression of CEA and COX2 in the 34 tissues of colorectal cancer,border of cancer, normal mucosa,and 19 metastatic lymph nodes. RESULTS: CEA expression level had a correlation with the differentiation of the tumor tissue (P< 0.05), but had no correlation with lymph node metastasis,Dukes' stage,the patients' age,sex,and the location of tumor (P >0.05). The level of COX2 increased in the majority of tumor tissues (31/34) and all of the lymph node metastases, but had no correlation with the tumor differentiation, stage,location,patients' age and sex(P >0.05). There was significant difference of expression of CEA and COX2 between tumor and nontumor tissues (P< 0.01). CONCLUSION: The abnormal expression of CEA and COX2 plays a role in the carcinogenesis and development of colorectal cancer.

Adult↗

Cytopathologic presentation of cerebral histiocytosis.

Histiocytoses involving the central nervous system are rare, and those in which the brain and meninges are the the only systems affected are rarer still. This paper presents such a case, in which cytologic study of cerebrospinal fluid during life showed large numbers of abnormal histiocytes and necropsy showed infiltration of brain and meninges by masses of similar cells, without other systems being involved. The cytologic features and differential diagnosis are discussed.

Adolescent↗