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Biomedical subjects

M Rogers

Publications and source records attributed to M Rogers.

At least 199 records · Page 11Linked to original sources

An enzyme-assessed microplate-assay for neutrophil adherence. I. IgA-induced adherence of human PMNs.

The binding of PMNs to extracellular matrix and cells is crucial to PMN host defense. Adherence mechanisms and the many families of molecules involved are major areas of study. We present here details of an enzyme-assessed microtiter plate assay for neutrophil adherence. This assay uses low numbers of cells (50,000/well) and permits analysis of several hundred wells in a short period of time, by using an ELISA reader. With this assay we observed 5- to 10-fold increases in the number of adherent human PMNs in response to nanogram amounts of LPS or as little as 5.0 micrograms/ml of aggregated IgA. Although fluoride blocked the LPS-induced adherence response, IgA-induced cell binding was largely unaffected.

Cell Adhesion↗

Acquisition of protease resistance by prion proteins in scrapie-infected cells does not require asparagine-linked glycosylation.

The scrapie and cellular isoforms of the prion protein (PrPSc and PrPC) differ strikingly in a number of their biochemical and metabolic properties. The structural features underlying these differences are unknown, but they are thought to result from a posttranslational process. Both PrP isoforms contain complex type oligosaccharides, raising the possibility that differences in the asparagine-linked glycosylation account for the properties that distinguish PrPC and PrPSc. ScN2a and ScHaB cells in culture produce several PrP molecules with relative molecular masses of 26-35 kDa and proteinase K-resistant cores of 19-29 kDa. When the cells were treated with tunicamycin, this heterogeneity was eliminated and a single PrP species of 26 kDa was observed. Several hours after its synthesis, a fraction of this protein became insoluble in detergents and acquired a proteinase K-resistant core, thus displaying two of the biochemical hallmarks of PrPSc. Synthesis in the presence of tunicamycin restricted the proteinase K-resistant cores of PrP to a single species of 19 kDa. No proteinase K-resistant PrP was found in uninfected cells. Expression of a mutated PrP gene lacking both asparagine-linked glycosylation sites in ScN2a cells resulted in the synthesis of 19-kDa proteinase K-resistant PrP molecules. We conclude that asparagine-linked glycosylation is not essential for the synthesis of proteinase K-resistant PrP and that structural differences unrelated to asparagine-linked oligosaccharides must exist between PrPC and PrPSc. Whether unglycosylated PrPSc molecules are associated with scrapie prion infectivity remains to be established.

Amino Acid Sequence↗

Intracellular accumulation of the cellular prion protein after mutagenesis of its Asn-linked glycosylation sites.

The cellular isoform of the prion protein (PrPC) is a sialoglycoprotein bound almost exclusively on the external surface of the plasma membrane by a glycosyl phosphatidylinositol anchor. The deduced amino acid sequence of Syrian hamster PrPC identifies two potential sites for the addition of Asn-linked carbohydrates at amino acids 181-183 (Asn-Ile-Thr) and 197-199 (Asn-Phe-Thr). We have altered these sites by replacing the threonine residues with alanine and expressed the mutant proteins transiently in CV1 cells utilizing a mutagenesis vector with the T7 promoter located upstream from the PrP gene. The T7 RNA polymerase was supplied by infection with a recombinant vaccinia virus. The 3 mutant proteins (PrPAla183, PrPAla199 and PrPAla183/199) have a reduced relative molecular weight compared to wild-type (wt) PrP. Deglycosylation as well as synthesis in the presence of tunicamycin reduced the relative molecular weight of all the PrP species to that of the double mutant PrPAla183/199. Our results indicate that both single-site mutant prion proteins are glycosylated at non-mutated sites and they suggest that both potential sites for Asn-linked glycosylation are utilized in wt PrPC. Immunofluorescence studies demonstrate that while wt PrPC localizes to the cell surface, all the mutant PrP molecules accumulate intracellularly. The site of accumulation of PrPAla183 is probably prior to the mid-Golgi stack since this protein does not acquire resistance to endoglycosidase H. Whether the intracellular locations of the mutant PrPC species are the same as those identified for the scrapie isoform of the prion protein (PrPSc) remains to be established.

Amino Acid Sequence↗

A randomized trial of combination therapy with intralesional interferon alpha 2b and podophyllin versus podophyllin alone for the therapy of anogenital warts.

To determine the value of combining interferon with standard local therapy in the treatment of human papillomavirus infection, 97 patients with anogenital warts were randomized to a short course of either interferon plus podophyllin or podophyllin alone. Interferon alpha 2b (1.5 x 10(6) IU) was injected intralesionally and podophyllin resin applied topically to each of three warts once weekly for 3 weeks. Maximal responses occurred within 2 weeks of therapy, and overall there was complete clearance of treated warts in 67% of interferon and podophyllin versus 42% of podophyllin recipients (P less than .05, chi 2). Clearance rates were greater in women, patients with warts of less than or equal to 12 months' duration, and HIV-seronegative patients. Of patients with complete clearance, 67% of interferon and podophyllin and 65% of podophyllin recipients experienced recurrences. Thus, in short treatment courses of anogenital warts, intralesional interferon enhanced the effect of topical podophyllin, and trials of combination therapy using more intensive or prolonged regimens of interferon are warranted.

Administration, Topical↗

Additional evidence for lack of transmission of HIV infection by close interpersonal (casual) contact.

To further study the possibility of transmission of HIV infection by close personal but non-sexual, non-parenteral contact we have continued to enroll and evaluate household contacts of adult patients with AIDS. Two hundred and six household contacts of 90 patients with AIDS were evaluated with detailed interviews, physical examinations, and detection of HIV antibodies and p24 antigen from 1984 to 1987; 118 of these contacts were re-evaluated 6-12 months after cessation of household contact or death of the patient. The median duration of household contact from 18 months prior to symptoms in the AIDS patients to last contact was 23 months (range 3-101 months). The median time elapsed from first contact during this period to the last evaluation was 38 months (range 13-66 months). No household contact had signs or symptoms suggesting HIV infection. All 206 were negative for serum antibodies to HIV and HIV p24 antigen, despite extensive sharing of household facilities and items and personal interactions with AIDS patients. This study continues to show that household members without other risks remain at minimal to no risk for HIV transmission (95% confidence interval, 0-1.44) despite prolonged and substantial close non-sexual contact with AIDS patients, and after re-evaluation at a median of 10.9 months after initial evaluation.

Acquired Immunodeficiency Syndrome↗

Giant centrifugal miliaria profunda.

A 4-month-old developed rapidly enlarging, white plaques up to several centimeters in diameter in areas where occlusive tape had been applied, almost all on the sites of venous or arterial punctures. Microscopy demonstrated the features of miliaria profunda, with sweat duct occlusion and evidence of extravasation of sweat into the dermis. This clinical entity has not been described previously, and we suggest the name giant centrifugal miliaria profunda.

Humans↗

Cushing's ulcer as a consequence of adrenocorticotropic hormone administration for infantile spasms.

Adrenocorticotropic hormone (ACTH) is the treatment of choice for infantile spasms despite its multiple side effects. This case represents a previously unreported side effect, peptic ulceration, occurring during ACTH treatment of infantile spasms. Two pathophysiologic mechanisms are proposed and examined. A direct effect of ACTH on the duodenum is considered but deemed unlikely. Alternatively, the combination of the patient's communicating hydrocephalus and ACTH's central effects is proposed to have led to increased intracranial pressure and a Cushing's ulcer. The need for pretreatment neuroimaging and H2-receptor antagonist use during ACTH therapy in all cases, along with gastrin level measurements in selected cases, is recommended.

Adrenocorticotropic Hormone↗

Risk factors for human immunodeficiency virus infection in intravenous drug users.

To identify risk factors for human immunodeficiency virus (HIV) infection in intravenous drug users, we undertook a study of the seroprevalence of HIV antibody in 452 persons enrolled in a methadone-treatment program in the Bronx, New York. The seroprevalence of HIV was 39.4 percent overall, 49.1 percent in blacks, 41.8 percent in Hispanics, and 17.2 percent in non-Hispanic whites (P less than 0.001 for all comparisons). The presence of HIV antibody was associated with the number of injections per month (P less than 0.001), the percentage of injections with used needles (P less than 0.001), the average number of injections with cocaine per month (P less than 0.001), and the percentage of injections with needles that were shared with strangers or acquaintances (P less than 0.001), a practice that was more common among blacks and Hispanics than among whites. The number of heterosexual sex partners who used intravenous drugs was associated with HIV infection in women (P less than 0.004) and was the only risk factor found for users who had not injected drugs after 1982 (P less than 0.05). The presence of HIV antibody was independently associated with being black or Hispanic (adjusted odds ratio, 4.56; 95 percent confidence interval, 2.65 to 8.14), a more recent year of the last injection of drugs (adjusted odds ratio, 1.24; 95 percent confidence interval, 1.13 to 1.35), the percentage of injections of drugs that took place in "shooting galleries" (adjusted odds ratio, 1.49; 95 percent confidence interval, 1.19 to 1.88), having sex partners who used intravenous drugs (adjusted odds ratio 1.24; 95 percent confidence interval, 1.06 to 1.45), and low income (adjusted odds ratio, 1.55; 95 percent confidence interval, 1.10 to 2.17). We conclude that differences in both the social setting of drug use and behavior related to injection carry different risks for infection with HIV and may explain, in part, the higher seroprevalence of HIV among blacks and Hispanics. In addition, we found that heterosexual activity was an independent risk factor for drug users.

Acquired Immunodeficiency Syndrome↗

Stimulatory role of transforming growth factors in multistage skin carcinogenesis: possible explanation for the tumor-inducing effect of wounding in initiated NMRI mouse skin.

Mechanical wounding provides a convertogenic ("stage I tumor-promoting") stimulus in initiated NMRI mouse skin, indicating that this stage of carcinogenesis can be entirely controlled by endogenous factors. A search for such factors led to the finding that both platelet-derived Epstein-Barr-virus-inducing factor (EIF), alias human TGF beta 1 and porcine TGF beta, exhibited--upon intracutaneous injection--convertogenic efficacy in initiated NMRI-mouse skin in vivo provided that their injection was combined with a single topical application of the non-convertogenic tumor promoter 12-O-retinolyphorbol-13-acetate (RPA). Since TGF beta inhibits epidermal cell proliferation, the RPA treatment is thought to provide a mitogenic stimulus required for conversion. The RPA treatment can be replaced by intracutaneous injection of transforming growth factor alpha (TGF alpha). These results indicate that the stage of conversion consists of two components, one of which is related to mitogenesis (RPA or TGF alpha), the other to a still unknown activity exhibited by TGF beta-like factors. Thus, endogenous factors with the quality of "wound hormones" may be involved in multistage skin carcinogenesis. This finding could explain the convertogenic effect of skin wounding.

Animals↗

Anogenital warts in childhood.

Fifteen children with anogenital warts are presented. Twelve cases were referred for assessment of sexual abuse which was established in six cases, strongly suspected in one, and excluded in three. In two, the source was unclear. Papillomavirus typing was carried out by HPV DNA dot and Southern blot hybridization using mixed HPV 6/11, 16/18, and 2/3 DNA probes on 15 specimens from 12 of the children. Seven biopsy specimens were positive for HPV 6 or 11 and one hybridized with both HPV 6/11 and 16/18 mixed sets of probes. Two specimens were positive for HPV 2, and a further two hybridized with both HPV 18 and 2. Three wart specimens could not be typed with the available genital or skin probes. The viruses causing genital tract papillomata are the same for children and adults. The identification of HPV 16/18 raises the concern of potential oncogenicity and stresses the need for long-term assessment. The diagnosis of sexual abuse was made on history rather than examination, as only two cases showed additional physical signs of sexual abuse. It is advocated that the presence of anogenital warts alone be sufficient grounds to pursue the possibility of sexual abuse. Nonsexual transmission, although possible, is far less likely.

Adolescent↗

Epidermal nevi and the epidermal nevus syndrome. A review of 131 cases.

One hundred thirty-one patients with epidermal nevi are reviewed. The commonest site of involvement was the head and neck, and 13% of patients had widespread lesions. Ages of onset ranged from birth to 14 years. A spread beyond the original distribution was noted in 37% of patients. Many clinical patterns occurred, including eight cases of inflammatory linear verrucous epidermal nevus. A variety of other cutaneous abnormalities were found. Biopsies were performed in 41 cases. Three patients developed secondary tumors. One hundred nineteen of the patients were assessed for the presence of abnormalities in other organ systems. One or more abnormalities were demonstrated in 33% of patients, and in 5%, five or more abnormalities were detected. This study indicates that patients with epidermal nevi are at significant risk of having other abnormalities and warrant detailed initial assessment and close follow-up.

Age Factors↗

Parapharyngeal mass presenting with sleep apnoea.

A 60-year-old man presented with a history of progressive sleep disturbance due to an intraoral parapharyngeal salivary gland tumour. The sleep study performed post-operatively showed rapid resolution of nocturnal hypoxic episodes. This appears to be the first recorded case of a parapharyngeal mass causing sleep apnoea and we review the current literature on obstructive sleep apnoea.

Humans↗

Giant parapox infection in a two year old child.

We report the case of a two year old boy who developed a large tumour on his face. The lesion resembled a pyogenic granuloma clinically and histologically. Viral studies indicated a parapox infection and a bovine source was supported on epidemiological grounds. The lesion was removed by shave excision and the area healed without significant scarring.

Animals↗

Harlequin baby treated with etretinate.

A child born with the harlequin fetus abnormality survived and showed a surprising degree of spontaneous improvement in the first six weeks of life. At this age etretinate was instituted, producing considerable further resolution. The child is now over 2 years old.

Etretinate↗

Juvenile hyaline fibromatosis: an expanded clinicopathologic spectrum.

A female infant had the typical cutaneous and soft tissue lesions of juvenile hyaline fibromatosis with the characteristic histologic and ultrastructural features of the disease. Her clinical course and autopsy findings strongly resembled those of infantile systemic hyalinosis, suggesting that the two conditions may be parts of a spectrum.

Age Factors↗