Necrotizing lymphadenitis (NEL) has been reported to be a reactive process described under differing terminology by Fujimoto et al. (1972), Kikuchi (1972), Wakasa et al. (1973) and other Japanese pathologists. Recently, this type of lymphadenitis has also been reported in America and Europe. In Japan, NEL is observed more frequently in the northern area, however, no characteristic seasonal occurrence has been noted. The disease affects young females more than males, particularly from the third and fourth decades onwards. Common cold-like symptoms, lymphadenopathy of the cervical region and leukopenia are characteristic clinical findings in the early stages. Morphological features of the involved lymph nodes include the presence of numerous immunoblasts, histiocytes and macrophages, the latter with phagocytized nuclear debris derived from degenerated lymphocytes. However, granulocytes are generally absent. Tubular inclusions are observed ultrastructurally. Immunohistochemical studies of peripheral blood using monoclonal antibodies have revealed that the helper/suppressor (Leu 3a/2a) ratio increases gradually with the clinical course because of a decrease in Leu 2a + cells. The pathogenesis of NEL is uncertain, but it has been speculated that there is cytolytic infection of lymphocytes by a virus or other organism, accompanied by secondary blastic transformation of suppressor T-lymphocytes.

Diagnosis, Differential↗

PubMedDate not supplied

MKC-242, a novel 5-HT1A receptor agonist, facilitates cortical acetylcholine release by a mechanism different from that of 8-OH-DPAT in awake rats.

We have previously reported that 5-¿3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy¿-1,3-be nzodioxole (MKC-242), a potent and selective serotonin (5-HT)1A receptor agonist, exerts anxiolytic- and antidepressant-like effects in animal models and that the antidepressant-like effect may be mediated by postsynaptic 5-HT1A receptors. The present study, using a microdialysis technique, was undertaken to characterize in vivo the effect of MKC-242 on cholinergic neurons. Subcutaneous injection of MKC-242 (0.5-1.0 mg/kg), like the typical 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), increased extracellular acetylcholine (ACh) levels in the rat cerebral cortex. The increase in ACh release by MKC-242 was also observed in the hippocampus. The effect of MKC-242 on cortical ACh release was attenuated by pretreatment with the 5-HT1A receptor antagonists (10 mg/kg, s.c.) propranolol and N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. The increase in cortical ACh release by MKC-242 was blocked by lesion of serotonergic neurons with 5,7-dihydroxytryptamine, whereas that by 8-OH-DPAT was not. Lesion of noradrenergic neurons with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine did not affect the MKC-242-induced increase in ACh release. These results suggest that systemic injection of MKC-242 facilitates in vivo ACh release via an activation of somadendritic 5-HT1A autoreceptors, and that MKC-242 and 8-OH-DPAT affect cholinergic neurons in the rat cerebral cortex via different mechanisms.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Scopadulciol, an inhibitor of gastric H+, K(+)-ATPase from Scoparia dulcis, and its structure-activity relationships.

A new tetracyclic diterpenoid, scopadulciol [3], together with 6-methoxybenzoxazolinone, glutinol, and acacetin, was isolated from the 70% EtOH extract of Scoparia dulcis collected in Taiwan. Its structure was elucidated to be 6 beta-benzoyl-12-methyl-13-oxo-9(12)a,9(12)b-dihomo-18-podocarpanol on the basis of spectral data. It mildly inhibited hog gastric H+, K(+)-ATPase. Examination of the inhibitory activities of derivatives of scopadulcic acid B [2], including 3, revealed that methylation of the carboxyl group and introduction of an acetyl group or oxime at C-13 or C-18 markedly enhanced the inhibitory activity, while debenzoylation reduced the activity. Among the 30 compounds tested, compound 12, a methyl ester of scopadulcic acid B [2], showed the most potent activity.

Abietanes↗

PubMedDate not supplied

Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of hormone-like glycoproteins that regulate haematopoietic cell proliferation and differentiation, and G-CSF almost exclusively stimulates the colony formation of granulocytes from committed precursor cells in semi-solid agar culture. Recently, Nomura et al. have established a human squamous carcinoma cell line (designated CHU-2) from a human oral cavity tumour which produces large quantities of CSF constitutively, and the CSF produced by CHU-2 cells has been purified to homogeneity from the conditioned medium. We have now determined the partial amino-acid sequence of the purified G-CSF protein, and by using oligonucleotides as probes, have isolated several clones containing G-CSF complementary DNA from the cDNA library prepared with messenger RNA from CHU-2 cells. The complete nucleotide sequences of two of these cDNAs were determined and the expression of the cDNA in monkey COS cells gave rise to a protein showing authentic G-CSF activity. Furthermore, Southern hybridization analysis of DNA from normal leukocytes and CHU-2 cells suggests that the human genome contains only one gene for G-CSF and that some rearrangement has occurred within one of the alleles of the G-CSF gene in CHU-2 cells.

Amino Acid Sequence↗

PubMedDate not supplied

Establishment of Leydig cell line, TTE1, from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene.

A Leydig cell line, TTE1, has been established from transgenic mice harboring a temperature-sensitive simian virus 40 (tsSV40) large T-antigen gene. The cells grew at a permissive temperature (33 degrees C), but growth was markedly prevented at a nonpermissive temperature (39 degrees C). T-antigen was expressed in the nuclei at 33 degrees C but disappeared at 39 degrees C, indicating that the cells show a temperature-sensitive growth phenotype reflected by the tsSV40 large T-antigen. TTE1 cells did not show any colony-forming activity in soft agar and form tumors in subcutaneous tissue in nude mice, indicating that the cells were not transformed. Alkaline phosphatase and 3beta-hydroxysteroid dehydrogenase (HSD) activities or expression of cytokeratin and vimentin were observed. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TTE1 cells expressed mRNAs encoding 17beta-HSD types 1 and 3, and inhibin-alpha. The cells with unique characteristics, therefore, should serve useful model study the function of Leydig cell.

17-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Effect of interferon-alpha in patients with chronic myelogenous leukemia in the accelerated phase: cytogenetic and molecular studies.

Human interferon-alpha (IFN-alpha) has been shown to be effective in the treatment of Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in the benign stable phase. The present study indicates that IFN-alpha may have a suppressive effect on Ph1-positive clones not only in the early stable phase but also in the accelerated phase with additional chromosomal abnormalities in some patients. In this study, in addition to 5 benign-phase patients, 3 patients with CML in the accelerated phase who had additional chromosomal abnormalities were treated with IFN-alpha. The presence of the Ph1-positive clone was estimated by chromosomal analysis and by Southern analysis at the DNA level using a 3' breakpoint cluster region (bcr) probe. Hematological remission and the suppression of proliferation of Ph1-positive clone to various extents were achieved by IFN-alpha treatment in 2 benign-phase patients and 3 patients with additional chromosomal abnormalities. Interestingly, in one of the latter three patients, Ph1-positive clones with or without additional chromosomal abnormalities were completely suppressed judging from chromosomal analysis and from the disappearance of bcr gene rearrangements.

Adult↗

PubMedDate not supplied

Abscess-forming granulomatous lymphadenitis: histological typing of suppurative granulomas and clinicopathological findings with special reference to cat scratch disease.

In order to clarify the histological and immunohistochemical characteristics of suppurative granuloma in abscess-forming granulomatous lymphadenitis (AGL), and the relation between AGL and cat scratch disease (CSD), 36 cases of AGL were studied. The combined results showed that there were two types of suppurative granulomas. The suppurative granulomas histologically revealed small lymphocytes of predominantly T cell phenotype distributed among the epithelioid histiocytes bordering central necrotic areas in the suppurative granulomas. These suppurative granulomas could be further subdivided into two groups, mainly those with and without the intermingling of large transformed cells of B-cell phenotypes: Type B granuloma with large transformed B cells and Type A without large transformed B cells. Both types of granulomas were observed in a varying degree in most cases. According to the predominant type of granulomas, 36 patients with AGL were further classified into two groups: Group I of Type A dominance and Group II of Type B dominance. Warthin-Starry (WS) silver stain positive bacteria, which are said to be a causative agent of CSD, were present in about 50% of both groups. No Brown-Hopps' Gram-positive bacteria, fungus, toxoplasma, Chlamydia or Bacillus Calmette-Guérin antigen were found in any case. Clinically, there was no significant difference between these two groups. On the other hand, the detection of WS-positive bacteria seemed to have some relationship with the duration of disease and the history of exposure to cats, and 70% of AGL cases occurred in autumn without a single concurrent epidemic.

Adolescent↗

PubMedDate not supplied

Morphological characterization of spindle cell tumors induced in transgenic Tg.AC mouse skin.

Transgenic Tg.AC mice carry a v-Ha-ras coding region flanked by a zeta-globin promoter and an SV40 polyadenylation signal sequence. These mice respond to carcinogens by developing epidermal papillomas. In some cases, malignancies develop at the sites of these papillomas. Various patterns of squamous cell differentiation were observed in these malignancies. One malignancy that developed at the site of the papillomas was composed of bundles of spindle cells. This lesion is difficult to distinguish from fibrosarcomas by light microscopy. We characterized 16 of these malignancies (tentatively classified as spindle cell tumors) to determine if they were of epithelial or mesenchymal origin. Papillomas were induced in Tg.AC mice by full thickness wounding, 12-O-tetradecanoyl-13-phorbol acetate treatment, or ultraviolet radiation. With time, some papillomas became broad-based, downwardly invading lesions. These lesions were examined by light microscopy with immunohistochemical analysis for cytokeratins and by electron microscopy. Immunohistochemical examination with a polyclonal anti-cytokeratin antibody demonstrated various degrees of keratin staining in all tumors examined. Attenuated desmosomes were also observed in these lesions by electron microscopy. These results indicate an epithelial origin for these malignancies; therefore, they should be classified as spindle cell carcinomas.

Animals↗

PubMedDate not supplied

Differential diagnosis between organic and inorganic mercury poisoning in human cases--the pathologic point of view.

Differences in pathology were found between acute and chronic exposure to methylmercury, mercury vapor, and inorganic mercury. Characteristic pathologic changes produced by organic mercury in the brain have previously been described in patients with Minamata disease. The brains of patients who presented with acute onset of symptoms and died within 2-mo showed loss of neurons with reactive proliferation of glial cells, microcavitation, vascular congestion, petechial hemorrhage, and edema in the cerebral cortices, predominantly in the calcarine, pre- and postcentral, and transverse temporal cortices and in the cerebellar cortex. The neuropathologic changes in the patients with acute onset of symptoms who survived for a long period (>10 yr) were also included neuronal loss with reactive proliferation of glial cells in similar anatomic locations. The neuropathologic changes in patients with inorganic mercury poisoning are quite different. Autopsies performed on 3 individuals with fatal cases of acute inorganic mercury poisoning who were exposed to mercury vapor for about 2 wk revealed diffuse organized pneumonia, renal cortical necrosis, disseminated intravascular coagulopathy, and infarctions in the brain and kidneys. In 2 other patients who worked in mercury mines for about 10 yr and who suffered from chronic inorganic poisoning, no specific lesions were demonstrated in the brain. However, the assay and the histochemistry of mercury revealed that inorganic mercury was present in the brain in all 3 groups irrespective of the brain lesions and the duration of clinical signs.

Adult↗

PubMedDate not supplied

A new concept for interpretation of first-order release from albumin microspheres.

A release mechanism from a microsphere that consisted of a water-swellable polymer and a uniformly dispersed, relatively small number of very slightly soluble large-core particles was considered. When the microsphere is dipped in release media the polymer swells instantly, and every core particle dissolves in the release media in the space between the core particles and the swollen polymer to make a saturated solution. It is assumed that Fickian diffusion of dissolved core substance between all spaces filled with saturated solution and outer sink occurs independent of each other, and release from one entire microsphere is the sum of diffusion from all spaces in the microsphere. Then, derived theoretical release kinetics is found to be first-order, and the derived first-order release rate constant is expressed as a function of the following parameters: radius of core particle, radius of the microsphere, solubility of core substance to media solution, density of the core particle, and permeability constant of core substance in swollen polymer. When rate constants were measured from release tests, varying each parameter, the relation between constants and each parameter follows the function. The permeability constant, which was calculated applying the function on measured rate constants and other known parameters, was in good agreement with the permeability constant measured from permeation study of planar membrane prepared in similar conditions to when preparing microspheres. These results are thought to show the validity of the mechanism and function proposed.

Carbazilquinone↗