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Biomedical subjects

K J Friedman

Publications and source records attributed to K J Friedman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Detection of alpha 1-antitrypsin Z and S mutations by polymerase chain reaction-mediated site-directed mutagenesis.

alpha 1-Antitrypsin (A1AT) deficiency is a relatively common autosomal recessive disease, resulting most often from a single base pair (1 bp) substitution called the Z mutation. Previous genetic tests for carriers and affected patients have relied on quantitative binding of radioactive probes to an amplified gene product, because the mutation does not occur within a restriction enzyme site. Using polymerase chain reaction (PCR)-mediated site-directed mutagenesis, one can introduce a base substitution near the mutation site, such that an inexpensive restriction enzyme (Taq I) can be used to differentiate normal subjects, carriers, and affected patients. We have applied this method to the detection of the Z mutation and the S mutation, which in heterozygotes with a Z allele may lead to the development of symptoms similar to those in ZZ homozygous subjects.

Base Sequence↗
PubMed1991

Detecting multiple cystic fibrosis mutations by polymerase chain reaction-mediated site-directed mutagenesis.

The polymerase chain reaction (PCR) has been applied in a novel manner to detect the multiple mutations causing cystic fibrosis (CF). PCR-mediated site-directed mutagenesis (PSM) has been applied to create allele-specific restriction enzyme cutting sites for three of the more common mutations. Two other mutations after cutting sites on their own. We discuss the implications for the expedient detection of five different CF-causing mutations.

Base Sequence↗
PubMed1990

Cutaneous papillary squamous cell carcinoma. A report of two cases.

Several histologic patterns of squamous cell carcinomas (SCC) have been described, including classical, adenoid, verrucous, and clear cell. We report 2 cases of an unusual purely exophytic papillary growth pattern. Both tumors occurred on sun-exposed skin of elderly patients and exhibited rapid growth. The tumors were red-tan and fungating, raising the clinical differential diagnoses of pyogenic granuloma, SCC, metastatic carcinoma or amelanotic melanoma. Histologically there was a prominent papillary growth pattern with several layers of notably atypical squamous epithelium overlying a fibro-vascular core in both cases. Mitoses were frequent. The tumors lacked deep invasion, although focal invasion of the stalk was present. These tumors were histologically distinct from verrucous carcinoma, verrucous Bowen's disease, and previously described adnexal carcinomas. The lack of deep invasion and the absence of local recurrence or metastatic disease after 18 months follow-up suggest that this histologic variant is a low-grade malignancy, although study of more cases and longer follow-up will be necessary to accurately assess the biology of this papillary variant of SCC. We believe that this growth pattern has not yet been described and a pure papillary form must be included as one of the histological subtypes of cutaneous SCC.

Aged↗
PubMed1990

Molecular probe protocol for determining carrier status in Duchenne and Becker muscular dystrophies.

By use of cDNA probes, molecular deletions were identified in 66.6% of 42 patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD). Owing to this high deletion rate, a new strategy for detecting DMD/BMD carriers is feasible in which the polymerase chain reaction is used as an initial screen for detecting the deletions occurring in specific deletion-prone exons. Because the deletions do not occur randomly, specific cDNA probes are utilized first with Southern blot analysis. Identification of a deletion permits direct analysis for DMD carrier status and removes the inherent limitations of the conventional restriction fragment length polymorphism technique. Carrier status is determined by scanning the autoradiographs with a densitometric spectrophotometer or by detection of a junction fragment.

Bacterial Proteins↗
PubMed1990

A model for molecular screening of newborns: simultaneous detection of Duchenne/Becker muscular dystrophies and cystic fibrosis.

Gene mutations responsible for the majority of Duchenne/Becker muscular dystrophy (DMD/BMD) and cystic fibrosis (CF) chromosomes have been identified. We describe a DNA-based strategy, rather than the traditional biochemical assays, for screening newborns. DNA sequences spanning the CF mutation and several DMD/BMD deletion-prone exons are amplified simultaneously via a multiplex polymerase chain reaction. The gel is visually inspected for DMD/BMD deletions and then blotted and hybridized with allele-specific oligonucleotides to determine the presence or absence of the CF mutation. We determined that blood spots provide sufficient DNA for the molecular analysis, so the procedure can be used in screening programs of newborns.

Base Sequence↗
PubMed1990

Determination of carrier status in Duchenne and Becker muscular dystrophies by quantitative polymerase chain reaction and allele-specific oligonucleotides.

Detection of carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), in the deletion cases, involves calculating gene dosage from Southern blots. We show that the analysis of dosage can also be made from the polymerase chain reaction (PCR) with use of allele-specific oligonucleotides (ASOs). The deletion-prone exons are amplified, transferred to a membrane, and hybridized with ASOs complementary to the exons; the autoradiographic bands are then quantified with a densitometer. After determining the quantitative conditions of the amplification reaction, we were able to identify deletions in a DMD/BMD carrier female. The determination of carrier status via PCR removes several of the technical limitations of Southern analysis and is also cost- and labor-effective.

Alleles↗
PubMed1989

Low-grade primary cutaneous adenosquamous (mucoepidermoid) carcinoma. Report of a case and review of the literature.

A case of histologically low-grade primary cutaneous adenosquamous carcinoma is reported. Dermal invasion was limited to the superficial dermis. This pattern contrasts sharply with the deeply infiltrating pattern of previously reported examples of cutaneous adenosquamous carcinoma. Less aggressive biologic behavior is expected from this histologically low-grade variant when compared to the high potential for recurrence and metastasis of previously reported cutaneous adenosquamous carcinoma. Immunohistochemical studies support an eccrine origin for this tumor.

Adenocarcinoma↗
PubMed1989

Therapy of chronic graft-v-host disease in a rat model.

Chronic graft-v-host disease (GVHD) is the most frequent late complication of allogeneic bone marrow (BM) transplant. To test different treatments, we used a rat model of chronic GVHD which clinically, histologically, and immunologically resembles the disease occurring after human marrow transplant. The following treatments were administered: azathioprine 50 mg/kg/day plus prednisone 1 mg/kg/every other day; Cyclosporine (CsA) 30 mg/kg/day; CsA 30 mg/kg/day plus prednisone 1 mg/kg/every other day; thalidomide 50 mg/kg/day; thalidomide 10 mg/kg/day; CsA 10 mg/kg/day; and thalidomide 10 mg/kg/day plus CsA 10 mg/kg/day. All drugs were administered by gavage. Half of the animals (six of 12) treated with azathioprine plus prednisone every other day responded to treatment. The majority of animals (seven of 12) treated with CsA died early. The addition of prednisone every other day did not improve survival. The surviving animals treated with CsA (with or without prednisone) responded to treatment. Half of the animals treated with each of the above regimens had recurrent or progressive disease after therapy was discontinued. Thalidomide treatment was successful in the majority of animals (16 of 18). The addition of low-dose CsA to low-dose thalidomide resulted in a faster rate of response (12.1 +/- 1.8 v 28.2 +/- 1.6 days). We conclude that both thalidomide and thalidomide plus CsA appear promising in this model as treatment for chronic GVHD.

Animals↗
PubMed1988

Cutaneous squamous cell carcinoma with mucinous metaplasia.

A case of superficially invasive well-differentiated cutaneous squamous cell carcinoma containing numerous mucin-producing cells both within the epidermal and dermal components is reported. Histological, histochemical and immunohistochemical overlap exists between these cells and those of extramammary Paget's disease. The presence of mucinous metaplasia within this tumor supports an intraepidermal origin for extramammary Paget's disease.

Biopsy↗
PubMed1988

Acute follicular graft-vs-host reaction. A distinct clinicopathologic presentation.

Human graft-vs-host disease (GVHD) is a life-threatening complication that may occur following allogeneic bone marrow transplantation. In acute GVHD, skin involvement is frequent, and the skin is often the initial organ involved. The rash typically is a blanchable, erythematous macular eruption. We present the first report of follicular cutaneous GVHD. Three patients developed follicular papules simulating bacterial or fungal folliculitis as a major clinical expression of cutaneous involvement in acute GVHD following allogeneic bone marrow transplantation. In each case, histopathologic examination demonstrated features of acute graft-vs-host reaction involving hair follicles. This suggests that follicular epithelium may be an early target in acute GVHD.

Adolescent↗
PubMed1987

Histologic characteristics of vulvar nevocellular nevi.

Reports in the literature stress the premalignant potential of vulvar melanocytic lesions and the unusual histologic features associated with some vulvar nevi in premenopausal women. We examined biopsies of 85 pigmented vulvar lesions taken from women 13 to 73 years of age. There were 59 nevocellular nevi, 16 lentigines, 4 melanomas, and 6 miscellaneous lesions. The nevocellular nevi were compared to a control series of 200 nevi from the torsos of women 20 to 60 years old. Three vulvar nevi were considered to be unusual, but not dysplastic. These histologically unusual nevi occurred in women 20 to 30 years old. The lesions exhibited notable enlargement of junctional melanocytic nests with variability in the size, shape and position of the nests. Similar changes were not observed in the control group. There was a significant association (p less than 0.05) between the occurrence of these unusual lesions and their presentation on the vulva; however, these lesions showed no predilection for any particular site on the vulva. There was no evidence of an increased incidence of vulvar dysplastic nevi when compared with the control series.

Adolescent↗
PubMed1987

Superficial epithelioma with sebaceous differentiation.

Five cases of superficial epithelioma with sebaceous differentiation (SESD) are reported. They occurred as solitary papules on the face of 5 patients, aged 57 to 72. The tumor is characterized by a superficial platelike proliferation of basaloid to squamoid cells with broad attachments to the overlying epidermis. Clusters of mature sebaceous cells are present within the tumors. None of the tumors have recurred or spread following simple excision. SESD is a non-aggressive tumor of uncertain histogenesis with a tendency toward sebaceous differentiation.

Aged↗
PubMed1987

Cutaneous pathology following etoposide therapy.

Etoposide (VP-16) is a semisynthetic podophyllotoxin derivative that is active against a number of solid and hematologic malignancies. Previously reported cutaneous complications include Stevens-Johnson syndrome and radiation recall. We report 4 cases of cutaneous eruptions with distinctive histopathologic changes following etoposide therapy. Diffuse erythematous macules and papules developed 5-9 days after initiation of etoposide therapy and resolved spontaneously within 3 weeks. Histologic examination revealed epidermal maturation disturbances with scattered markedly enlarged individual keratinocytes. These cells had pale cytoplasms and fragmented, haphazardly dispersed nuclear chromatin in a starburst pattern ("starburst cells"). Many keratinocytes showed notable nuclear enlargement with multiple prominent nucleoli. In addition, numerous dyskeratotic cells and basilar mitotic figures in metaphase were present. Some of these changes have been described in condylomata acuminata treated with topical applications of podophyllin, a compound structurally related to etoposide. Starburst cells have not been reported in cutaneous eruptions produced by other chemotherapeutic agents. These cells may represent abnormal mitotic arrest secondary to podophyllin and its related compounds.

Adult↗
PubMed1987

Letterer-Siwe disease in an adult.

Letterer-Siwe disease, a proliferative disorder of Langerhans' cells, usually affects children during the first year of life. A 67-year-old woman is described here whose initial manifestation was a characteristic skin eruption. The clinical, pathologic, and ultrastructural features of Letterer-Siwe disease are reviewed and their role in diagnosis discussed.

Aged↗