Maffucci’s syndrome associated with spindle cell hemangioendothelioma

 The case of a 49-year-old man with Maffucci’s syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented. The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal enchondromatosis.     

In vitro andin vivo characterizations of established human follicular carcinoma cell line derived from thyroid cancer: A novel model for well-differentiated thyroid malignant tumor

A continuous cell line, named SMC R86 F1, was established from a surgically resected primary thyroid lesion. The cell grew as an adhering monolayer with a doubling time of about 25 hours in modified Eagle's medium supplemented with fetal bovine serum. When the cells were transplanted into athymic nude mice, tumors developed at the site of inoculation. The cells not only showed epithelial origin upon light and electron microscopic examination but also possessed a biosynthetic marker human thyroglobulin (hTg). In order to examine the iodide trapping ability of the xenografts, radioiodine at doses of 3.7 MBq was injected into the peritoneum of 131I treated nude mice bearing xenografts at about 4 weeks after the cell inoculation. Judging from the results of scintigraphic, autoradiographic and biodistribution studies, viable tissue of the xenografts in the treated mice had the ability to trap radioiodine. Histological sections of the xenografts resected from the treated mice consisted of follicle-like and trabecular growing structures, and immunohistochemically the cytoplasm of the tissues was hTg positive. The cells possessed the ability to trap radioactive iodine in vitro under the control of TSH. In addition, the expression of iodinated 19S Tg in the cell cytoplasms in the monolayer cultures was revealed by immunoblotting and autoradiographic assays. These observations provide strong evidence that the SMC R86 F1 cell line possesses well-differentiated properties of the malignant thyroid follicular epithelial cells.     

Intense and prolonged Tl-201 accumulation in a slow growing bronchioloalveolar carcinoma

Thallium-201 SPECT was performed to evaluate a pulmonary lesion in a 73-year-old male which had been considered to be an inflammatory lesion for two years. The lesion has slowly increased in size on x-CT. Tl-201 was intensely taken up and retained in the lesion, suggesting a malignant lesion. Histological examination revealed that the lesion was bronchioloalveolar carcinoma. This case suggested that Tl-201 uptake of pulmonary carcinoma would not be necessarily related to cell growth rate.     

Immunology: Diversity of the blocking effects of antisperm antibodies on fertilization in human and mouse

The blocking effects of complement-dependent sperm immobilizingantibodies in the sera of infertile women and monoclonal antispermantibodies against humans and mice on fertilization were investigated.The hemizona assay (HZA) and sperm penetration assay (SPA) wereused to study the inhibitory effects of sera from 22 infertilepatients positive for sperm immobilizing antibodies. Use ofthese tests allowed us to differentiate whether the antibodyblocked sperm—zona pellucida tight binding and/or spermpenetration into the ooplasm. The zona pellucida penetrationassay (ZPA) was also used to study the effects of four monoclonalantibodies (mAbs) on human sperm penetration into the zona pellucida.Seven mAbs against murine spermatozoa were tested for theirinhibitory effects on in-vitro fertilization (IVF) and HZA inmice. Of 22 patient sera with sperm immobilizing antibodies,21 (95.5%) inhibited HZA attachment and penetration, whereasthis did not occur in any of 13 patient sera without these antibodies.However, 19 of 22 (86.4%) patient sera with sperm immobilizingantibodies and eight of 13 (61.5%) patient sera without theseantibodies inhibited the SPA. Two (2C6, 1G12) of four mAbs againsthuman spermatozoa showed strong inhibitory effects in all theassays (HZA, ZPA and SPA). One mAb (3B10) did not inhibit HZAbut blocked ZPA and SPA. Another mAb (H6-3C4) seemed to haveno inhibitory effects on fertilization. Two (Vx 5 and Vx 8)of seven mAbs against murine spermatozoa inhibited IVF in micebut did not block mouse HZA. These findings suggest that antispermantibodies block fertilization at specific stages. Some of themmay inhibit sperm capacitation and thus prevent all processesof fertilization that follow. Some other antibodies may notaffect capacitation and sperm binding to zona pellucida butinhibit the acrosome reaction, followed by the blocking of spermpenetration through zona pellucida and ooplasm.     

Focal hyperplasia of intracytoplasmic filaments in the canine parathyroid gland treated with nalidixic acid

Focal hyperplasia of intracytoplasmic filaments of 100A in diameter was observed within chief cells of the parathyroid gland in dogs treated with nalidixic acid. The structure, as a rule, was located in the neighborhood of the nucleus and no other cell organelles were detected within it. Its size had a wide spectrum from a small part of the cytoplasm to as large as half a cell. Golgi apparatus and rough endoplasmic reticulum in the involved cells had a tendency to atrophy. These cells occasionally contained less secretory granules. Lipid droplets are diffusely increased. The pathogenesis and significance of the present intracytoplasmic filaments remain to be determined. However, as lipid deposition, atrophy of Golgi apparatus, poorly developed rough endoplasmic reticulum occur in a hypofunctional or degenerative state, it might be possible that filamentous hyperplasia is closely associated with that state.     

In vitro activity of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine against newly isolated clinical varicella-zoster viras strains

The highly potent and selective anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] was found to inhibit in vitro the replication of a number of clinical varicella-zoster virus strains within the concentration range of 0.63—5.7 ng/ml. With a mean 50 % inhibitory concentration of 1.8 ng/ml and selectivity index of 29000, (S)-HPMPA is one of the most potent and most selective varicella-zoster virus inhibitors discovered to date.     

Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

Ability of polymorphonuclear leukocytes to generate active oxygen species in children with bronchial asthma. Use of chemiluminescence probes with a Cypridina luciferin analog and luminol.

Airway inflammation with polymorphonuclear leukocytes (PMN) may play an important role in bronchial hyperresponsiveness (BHR). PMN generate superoxide anion (O2-) and other oxygen radicals that can damage lung tissue. We investigated the ability of peripheral PMN of children with bronchial asthma and control subjects to generate O2- and other active oxygen species using a 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one, a highly sensitive and specific chemiluminescence (CL) probe for O2-, and luminol-dependent CL. The ability of PMN of subjects with asthma to generate O2- and other active oxygen species was significantly greater than that of PMN of control subjects when stimulated with opsonized zymosan (OZ), phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine. Furthermore, in the same asthmatic children, the generation of O2- and other active oxygen species was significantly higher with attacks than without attacks when PMN were stimulated with OZ. We also demonstrated that O2- generation correlated with the degree of BHR to inhaled histamine. These results suggest that PMN of asthmatic children, especially those with attacks, generate more active oxygen species than that of control subjects and that airway inflammation caused by O2- may be closely related to BHR in subjects with bronchial asthma.     

Weight reduction of thymus and depletion of lymphocytes of T-dependent areas in peripheral lymphoid tissues of mice infected with Francisella tularensis.

When BALB/c mice (young and adult animals of both sexes) were infected intraperitoneally with 10(3) viable cells of Francisella tularensis (10(2) 50% lethal dose), all mice in these groups died on day 4. Reductions in thymus weights and in numbers of thymic cortex lymphocytes were observed in all the groups, but the decline was not so severe in the young females. Increases of plasma corticosterone in the adult males began 1 day after infection, but in the young females, the levels did not increase until day 3, the same days on which the respective thymus weights began to decline. Depletion of the thymus weights in the infected mice was prevented by adrenalectomy. The lymphocytes of the thymus (T)-dependent areas in peripheral lymphoid tissues in all groups were destroyed. By using an electron microscope, we found a large quantity of F. tularensis within the macrophages in the T-dependent areas but not in the thymus. The destruction of lymphocytes in the T-dependent areas was not prevented by adrenalectomy. Therefore, it was concluded that the weight reduction of the thymus is due to the stress of the F. tularensis infection. However, we think other mechanisms are responsible for the depression of lymphocytes in the T-dependent areas of peripheral lymphoid tissues.     

Studies of dialysates from Dermatophagoides farinae: partial purification and haptenic properties of dialysates from Dermatophagoides farinae.

Dialysates from Dermatophagoides farinae were partially purified. Fractionation on HPLC and anion exchange chromatography revealed that the dialysates consisted of 5 major fractions of glycoprotein whose apparent molecular sizes were 5.1, 4.1, 3.2, and less than 1.35 kD on HPLC. The apparent molecular size of two fractions was 5.3 and 2.9 kD on SDS-PAGE. They were basic glycoproteins which had a pI ranging from 7.46 to 8.71 on PAG-IEF. These fractions were allergenic in the RAST and ELISA inhibition tests but not in the skin prick test (SPT). Our results suggest that the dialysates from D. farinae have haptenic properties. The dialysates from D. farinae (low molecular weight) and its 5 fractions bound noncovalently to human serum albumin (HSA) at the free tyrosine residues of HSA. They proved to bind noncovalently to serum proteins and collagens. Once they bound to proteins, the conjugates became allergenic not only in the RAST and ELISA inhibition test but also in the SPT. Our results provide evidence that the dialysates from D. farinae have haptenic properties.