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Biomedical subjects

P S Herman

Publications and source records attributed to P S Herman.

At least 19 recordsLinked to original sources

Dermal fibroblasts genetically engineered to release nerve growth factor.

Current surgical strategies for repair of critical nerves involves the transfer of normal donor nerve from an uninjured body location. One possible alternative to autogenous tissue replacement is the development of engineered constructs to replace those elements necessary for axonal proliferation. Delivery of growth factors is one strategy to enhance synthetic nerve constructs. Thus, this study focused on the delivery of nerve growth factor (NGF) by genetic engineering to begin approaching the microenvironment dictated, in part, by Schwann's cells. Rat dermal fibroblasts (DFBs) were modified genetically to release rat NGF. The reporter gene LacZ was used to assess the optimum nonviral transfection method commercially available before NGF transfection. FuGENE6 provided the optimum transfection efficiency (24% maximum, 20.1 +/- 1.9% 5-day average) as measured by beta-galactosidase catalytic activity. NGF release from transfected DFBs was assessed over a 3-day period. Compared with control (no transfection) DFBs and DFBs transfected with vector alone, DFBs transfected with an expression vector encoding rat beta-NGF demonstrated significantly (p < 0.05) higher levels of NGF, with a 3-day maximum of 111 pg NGF per milliliter. When normalized to cell number, NGF-transfected DFBs released 1.2 pg NGF per milliliter/10(3) cells. The NGF-transfected DFBs demonstrated a maximal NGF release rate at day 1 (1.2 ng NGF/10(6) cells per day), followed by a markedly lower, sustained release rate at days 2 and 3 (0.44 ng NGF/10(6) cells per day and 0.48 ng NGF/10(6) cells per day respectively). The release rate curves for control and vector-transfected DFBs also exhibited a maximal NGF release rate at day 1, but were followed by a decreasing release rate, potentially representing in vitro degradation of NGF present in fetal bovine serum. Although not first with the development of growth factor delivery through fibroblasts, these findings suggest that rat DFBs can be modified genetically to act like Schwann's cells to deliver NGF.

Animals↗

The evaluation of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) in cutaneous lesions of Kaposi's sarcoma: a study of formalin-fixed paraffin-embedded tissue.

The etiologic role of human herpesvirus 8 (HHV8) in Kaposi's sarcoma (KS) remains controversial. This polymerase chain reaction (PCR)-based study was undertaken to evaluate the relationship of HHV8 in KS from our geographical region and to determine its utility in formalin-fixed, paraffin-embedded biopsy specimens. Forty-two biopsy specimens were studied, including nine AIDS-associated cases and four from classic KS. Of the 39 patients included, 21 were HIV+ and 18 had no clinical evidence of HIV infection. Only a single (internal) primer pair was used in the PCR. All PCR products were tested with an HHV8 specific probe by dot blot analysis. Seven of the nine AIDS KS specimens were positive for HHV8 on electrophoresis, and all nine were positive after dot blot. Two of four specimens from classic KS were positive for HHV8 on the gel electrophoresis, and three of four were positive on blot confirmation. Non-KS specimens from 15 HIV+ patients yielded one positive venous hemangioma from a man with HHV8-positive KS at another site. Specimens from HIV-unrelated controls with a variety of diagnoses were negative by PCR with blot. The predominant negativity for HHV8 in non-KS lesions suggests that HHV8 is not widespread in our patients. These results demonstrate yet another series linking KS with HHV8 and show that paraffin-embedded biopsy specimens are satisfactory for this technique.

Adolescent↗

Relative stabilities of nitrenium ions derived from polycyclic aromatic amines. Relationship to mutagenicity.

The relative energetics of arylamine N-hydroxylation and N-O heterolysis (ArNH2----ArNHOH----ArNH+) for condensed systems of two, three and four rings were calculated using semiempirical AM1 molecular orbital theory. The overall thermodynamics of N-hydroxylation were almost insensitive to the structure of the amine while differences in the energetics of nitrenium ion formation varied from 0 to 35 kcal mol-1. Limited correlations between the latter and the experimental TA98 and TA100 mutagenicities of the amines are presented.

Amines↗

Colonic hamartomas in tuberous sclerosis.

Twelve patients, 5 from the same family, diagnosed consecutively to suffer from tuberous sclerosis were investigated for gastrointestinal polyps. Six patients had no clinical neurologic involvement. Nine had colonic polyps: in 5 patients, these were hamartomas, in 3 patients adenomatous polyps, and the ninth patient had hamartomas and adenomatous and villoglandular polyps. Hamartomatous polyps were identical to those found in the Peutz-Jeghers syndrome. However, in 1 patient they included neural structures and in another there were angiomatous and adipous structures in addition to colitis cystica profunda. Two patients with hamartomatous polyps had normal intelligence and no clinical neurologic symptoms. The evaluation of one kindred revealed the association of hamartomatous polyps of the colon with forme fruste of tuberous sclerosis in different members, but none had the typical disease. Tuberous sclerosis should thus be considered in the differential diagnosis of hamartomatous colonic polyps. Conversely, colonic endoscopy may be a useful adjunctive test in the diagnosis of tuberous sclerosis, particularly in the incomplete varieties of disease.

Adolescent↗

Punctuate porokeratotic keratoderma.

Two unrelated patients had numerous palmoplantar "music box spine" keratotic plugs and pits of 11 and 13 years' duration. Histologic examination revealed a compact column of parakeratosis resembling that of a cornoid lamella of porokeratotic conditions. Ultrastructurally in clinically affected skin, the stratum corneum contained numerous variable-sized pyknotic nuclei, and cells in the stratum granulosum contained fewer keratohyalin granules. The ultrastructural findings differed from those of porokeratosis of Mibelli and disseminated superficial actinic porokeratosis. The proper nosologic designation should be punctuate porokeratotic keratoderma.

Aged↗

Hair casts.

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Hair↗

Peripilar casts.

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Adult↗

Ichthyosis.

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Genes↗