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A To

Publications and source records attributed to A To.

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The beta3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered in the mouse hypopigmentation mutant pearl, a model for Hermansky-Pudlak syndrome and night blindness.

Lysosomes, melanosomes and platelet-dense granules are abnormal in the mouse hypopigmentation mutant pearl. The beta3A subunit of the AP-3 adaptor complex, which likely regulates protein trafficking in the trans - Golgi network/endosomal compartments, was identified as a candidate for the pearl gene by a positional/candidate cloning approach. Mutations, including a large internal tandem duplication and a deletion, were identified in two respective pearl alleles and are predicted to abrogate function of the beta3A protein. Significantly lowered expression of altered beta3A transcripts occurred in kidney of both mutant alleles. The several distinct pearl phenotypes suggest novel functions for the AP-3 complex in mammals. These experiments also suggest mutations in AP-3 subunits as a basis for unique forms of human Hermansky-Pudlak syndrome and congenital night blindness, for which the pearl mouse is an appropriate animal model.

Adaptor Protein Complex beta Subunits↗

Neurochemical changes in the rat brain after intraventricular administration of tryptamine-4,5-dione.

Tryptamine-4,5-dione (4,5-DKT) a neurotoxic derivative of serotonin (5-HT), was injected into the lateral ventricle of the rat in order to evaluate its biochemical effects. The levels of 8 substances in the hippocampus, striatum and prefrontal cortex were examined 3, 7 and 14 days after treatment with 4,5-DKT. 5-Hydroxytryptamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased in all three regions by days 7 and 14, respectively. Tryptamine-4,5-dione had no significant effect on dopaminergic or adrenergic systems or on the levels of L-tryptophan and L-tyrosine, in any of the three areas of brain examined. Reduced activity of tryptophan hydroxylase in the cortex was observed 14 days after administration of 4,5-DKT. However, administration of 4,5-DKT did not alter the binding of [3H]paroxetine, a specific antagonist of the uptake of 5-HT, to nerve terminals. These results indicate that 4,5-DKT produced depletion of 5-HT without eliminating serotoninergic nerve terminals.

Animals↗

Monitoring the course of cervical carcinoma with the squamous cell carcinoma serum radioimmunoassay.

Serum samples were collected from 611 gynecologic patients for measurement of squamous cell carcinoma antigen levels using the Abbott Laboratories squamous cell carcinoma antigen radioimmunoassay kit. Sixteen of 83 patients (19.3%) with cervical dysplasia and 72 of 135 (53.3%) with primary or recurrent cervical carcinoma had levels above 2.4 ng/mL. In contrast, only seven of 373 women (1.9%) without genital tract squamous cell intraepithelial neoplasia or carcinoma had squamous cell carcinoma antigen levels above 2.4 ng/mL. Fifty-six patients with cervical cancer were followed for correlation of squamous cell carcinoma antigen levels to disease course, and 20 had persistent or recurrent disease after therapy; rising squamous cell carcinoma antigen levels predicted disease in 15 of these 20 patients with recurrence (13 of 15 with elevated pre-treatment levels and two of five with normal pre-treatment levels). Rising squamous cell carcinoma antigen levels preceded the clinical detection of disease in ten patients by a mean of 4.6 months (range 2-7.5 months); in the remaining five, squamous cell carcinoma antigen levels were elevated only when disease recurrence was documented. Although measurement of squamous cell carcinoma antigen levels is not a sensitive screening method for cervical cancer (sensitivity 53.3%), the test has good specificity (94.3%); the majority of patients with false-positive elevations had other genital tract squamous cell neoplasias. The squamous cell carcinoma antigen assay may be a useful aid for monitoring the disease course of cervical carcinoma.

Antigens, Neoplasm↗

CA125 as a serum marker for poor prognosis in ovarian malignancies.

In cancer of the ovary, a tumor marker is much needed to assist the conventional methods for monitoring the disease course. All published reports of the CA125 serum immunoassay to date have indicated that rising or falling CA125 levels correlated with disease progression or regression in patients with ovarian malignancies. Our experience with CA125 at the University of Alabama at Birmingham shows that rising CA125 levels are highly suggestive of progressive disease. However, the significance of our findings with CA125 is that, contrary to other reports, falling CA125 levels are not a reliable indicator for regressive disease. Thus, falling CA125 levels are not clinically useful whereas rising CA125 levels may be interpreted as indicative of poor tumor response to therapy, and of the presence of persistent or recurrent disease either prior to second-look laparotomy or during post-treatment follow-up.

Antigens, Neoplasm↗

A rabbit model of focal herpes simplex encephalitis.

Results from studies designed to create a model of focal encephalitis caused by herpes simplex virus (HSV) are reported. Anesthetized rabbits underwent exposure and inoculation of the olfactory bulb with three different doses of a wild-type HSV. Lethal infection resulted in 69% of the animals, without evidence for a dose-response relationship. Necropsy specimens obtained on or before day 10 after inoculation routinely yielded HSV in culture. In 76% of the animals with positive cultures for virus, these cultures originated exclusively or primarily from the pyriform (or temporal) cortex and frontal lobes. Virus could not be cultured from animals killed more than two weeks after inoculation. Histological examination of brains obtained three or more days after inoculation demonstrated evidence of viral infection, with more severe involvement of temporal cortex than of the surrounding brain in 80%. Immunohistochemical demonstration of viral antigens persisted for up to three weeks after inoculation.

Animals↗

Comparison of prevalence of human papillomavirus antigen in biopsies from women with cervical intraepithelial neoplasia.

Human papillomavirus antigen was found in 39 (16%) of 253 colposcopic biopsies from a group of women at high risk for cervical cancer who had been examined in the early 1970s. Immunohistochemical evidence of papillomavirus infection was found in 20 (30%) of 67 cervical intraepithelial neoplasia lesions infected with wart virus from these patients. When these results were compared with results of a similar study carried out in the early 1980s there was no significant difference in the prevalence of human papillomavirus antigen in cervical intraepithelial neoplasia lesions infected with wart virus from women who had been examined over a decade apart.

Adolescent↗

Epithelial Membrane Antigen. Its use in the cytodiagnosis of malignancy in serous effusions.

The cytological distinction between reactive mesothelial and malignant cells frequently causes problems for the diagnostic cytologist. In order to determine whether an immunocytochemical method might help resolve these difficult cases, we have stained smears from 309 serous effusions from 246 patients for the Epithelial Membrane Antigen (EMA). The EMA staining was classified as strong, weak or negative. Carcinoma cells (as diagnosed by conventional cytology) stained strongly for EMA in 63 of the 116 positive smears (54%). Five out of 15 (33%) of cytologically suspicious smears from patients with known carcinomas gave a strong EMA stain. Of particular interest were three effusions in which malignant cells were not identified in conventionally stained smears and in which a small number of EMA positive cells were identified. The EMA positive cells were subsequently restained by the Papanicolaou method and identified as malignant on retrospective morphological examination.

Antigens, Surface↗

Chromosomal abnormalities in ascitic fluid from patients with alcoholic cirrhosis.

Cytology and cytogenetics were used to study ascitic fluid obtained from five patients with alcoholic cirrhosis. Cytological examination showed that all fluids contained numerous mesothelial cells and some leucocytes. Cytogenetic analysis showed abnormal karyotypes in cultured cells from all five patients and in uncultured cells from three. A consistent abnormality was the presence of spreads with over 70 chromosomes. Clones of abnormal cells, with marker chromosomes, pseudodiploidy, or aneuploidy, in an effusion are characteristic of malignancy; the abnormal karyotypes fulfilled these criteria. This finding of abnormal karyotypes indicates that transformation of the mesothelium can occur in vivo, and such a reaction may be a reflection of the mutagenic effect of alcohol.

Aged↗

Use of antisera to epithelial membrane antigen for the cytodiagnosis of malignancy in serous effusions.

A new human antigen, designated epithelial membrane antigen (EMA), has recently been described on surface membranes of a wide variety of normal epithelium but not on connective tissue cells. The antigen is only weakly expressed on normal or reactive mesothelium. Increased expression of the antigen has been observed in most neoplasms of epithelial origin and in malignant mesothelioma. We have investigated the possibility of using this difference in the expression of the antigen to distinguish between mesothelial cells and malignant cells in cytological smears of serous effusions. This distinction cannot always be made on morphological grounds alone and problems of differential diagnosis are encountered in about 15% of all specimens of serous effusions sent for cytological examination. Using antisera to EMA we have applied an indirect immunoalkaline phosphatase technique to alcohol-fixed smears prepared from serous effusions and have found that intense staining of the antigen is confined to effusions from patients in whom there is either clinical or cytological evidence of malignancy. The technique proved to be especially useful in cytologically equivocal cases, where there were problems of differential diagnosis.

Antigens, Surface↗

Chromosome studies on cells cultured from serous effusions. Use in routine cytologic practice.

Cytogenetic analysis was used to supplement the cytologic diagnosis of malignancy in serous effusions. Current methods of analysis involve immediate preparation, but our study showed that prior culture of the cells is a more practical approach to the use of chromosome analysis in the routine cytology laboratory. This method permits the retrospective selection of specimens for chromosome analysis from patients in whom there is a strong clinical suspicion of malignant disease but who have negative or equivocal cytology reports. The preparative technique and the recognition of structural and numerical chromosome anomalies can be readily learned by the cytotechnologist and incorporated into the routine cytology laboratory.

Aneuploidy↗