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Biomedical subjects

M L Berman

Publications and source records attributed to M L Berman.

At least 127 records · Page 7Linked to original sources
PubMed1984

Photoradiation therapy of gynecologic malignancies.

Four patients with gynecologic tumors recurrent either to the vagina or skin were treated with photoradiation therapy. A cytotoxic effect on the tumor was achieved by injecting hematoporphyrin derivative intravenously followed by exposing the treatment area to light of 630 nm from an argon-ion pumped-dye laser 72 hr later. Of seven tumor sites which were treated, one was completely destroyed, two were diminished in volume by more than 30%, and no response was seen in four. Toxicity was limited to one episode of facial edema and first-degree burn after prolonged exposure to bright artificial light. Phototherapy might be a useful treatment of some gynecologic tumors which recur after standard attempts at control of disease.

Aged↗
PubMed1984

Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study).

Ninety-eight of 621 evaluable patients (16%) with cervical cancer enrolled into Gynecologic Oncology Group protocols were found to have periaortic lymph node metastases at staging laparotomy or at exploration for definitive operative management. As expected there was a progressive increase in the prevalence of periaortic metastases including 5% of 150 patients with Stage IB, 16% of 222 patients with Stage II, and 25% of 135 patients with Stage III. Periaortic lymph node metastases in the absence of pelvic lymph node metastases was an infrequent occurrence in patients so evaluated. The median survival of patients with periaortic metastases was 15.2 months with a survival probability of 25% at 3 years. The median duration of survival following recurrence was only 5 months. Recurrences were divided approximately equally between the pelvis and distant sites.

Adenocarcinoma↗
PubMed1984

Immediate vaginal reconstruction following resection for malignancy using the gluteal thigh flap.

Immediate flap closure of perineal defects following extirpative procedures for gynecologic malignancies is highly desirable. Advantages include more rapid healing, reduced infection rate, decreased nutritional demands, early rehabilitation, greater safety in radiated fields, and more functional results. The posterior thigh flap, deriving its blood supply from the inferior gluteal artery, was used in 7 patients (9 flaps) with excellent results. The flap has proven reliable and quite feasible at the time of resection. While most partial pelvic or vaginal defects can be reconstructed with a single flap, bilateral flaps are recommended for more extensive defects. The major postoperative problem has been discomfort while sitting and paresthesias along the distribution of the posterior cutaneous nerve. To avoid these problems, the flap should be rotated distal to the ischium and, in subtotal reconstruction, the nerve excluded.

Adult↗
PubMed1984

The subrenal capsule tumor implant assay as a predictor of clinical response to chemotherapy: 3 years of experience.

The clinical response to chemotherapy of a series of female patients with advanced pelvic malignancies was compared to the response of their tumors to the same agents in the murine subrenal capsule implant assay. A total of 194 different patients were studied in 242 different assays; 89.3% of the assays were evaluable. There were 83 prospective assays (assays performed before the patient received the chemotherapy) of 66 different patients for which clinical correlations were available. In these assays the sensitivity (frequency of positive test results in responding patients) was 85.0%, the specificity (frequency of negative test results in nonresponding patients) was 57.1%, and the efficiency (percentage correctly classified) was 63.9%. There were 100 retrospective assays (assays performed after the patient had been treated with the chemotherapy) of 69 different patients for which clinical correlations were available. In these assays the sensitivity was 66.7%, the specificity 70.7%, and the efficiency 70.0%. Thirty-one of the patients had both prospective and retrospective assays. There were 59 patients for whom the clinical response to chemotherapy could not be determined. It is believed that the clinical utility of the SRC assay has been validated by the good prospective sensitivity of the assay.

Animals↗
PubMed1984

Paradoxical effects of perturbation of intracellular levels of glutathione on halothane-induced hepatotoxicity in hyperthyroid rats.

Exposure of hyperthyroid rats to halothane results in a centrilobular necrosis of the liver and an 11-fold increase in serum glutamate-pyruvate transaminase (SGPT) levels. These effects are not seen in euthyroid animals. Paradoxically, administration of diethylmaleate to hyperthyroid rats significantly decreased the levels of hepatic glutathione and blocked the halothane-induced hepatic necrosis as well as decreased the elevation of SGPT. In contrast, pretreatment of animals with N-acetylcysteine, an intracellular sulfhydryl repletor , significantly increased the severity of the halothane-induced hepatic necrosis and increased the elevation of SGPT. Similarly, cysteamine, another intracellular sulfhydryl repletor , also exacerbated halothane-induced liver injury. Halothane-induced hepatotoxicity is at least in part apparently regulated by cellular glutathione levels. Paradoxically, glutathione seems to be involved in the bioactivation rather than the detoxification of halothane.

Acetylcysteine↗
PubMed1984

Cloning vectors that yield high levels of single-stranded DNA for rapid DNA sequencing.

We have constructed chimeric plasmid vectors with the origin and intergenic region from M13 phage cloned into the PvuII ( pZ145 ) and AhaIII ( pZ150 , pZ152 ) sites of pBR322. In the absence of M13 phage, these plasmids replicate like any other ColE1-derived plasmid and confer both ampicillin and tetracycline resistance (Amp, Tet). Upon infection with M13 phage, the viral origin present on the plasmids permits phage-directed plasmid replication and results in high yields of single-stranded (ss) plasmid DNA in M13-like particles. This ssDNA, which represents only one of the plasmid strands, is useful as a substrate for rapid DNA sequence determination by the dideoxy sequencing method described by Sanger et al. (1977). Since these plasmids contain an intact pBR322, the intergenic region can be transferred onto most pBR322 derivatives to yield ss plasmid DNA without affecting the recipient plasmid for further studies. We also constructed a deletion derivative of pZ145 , plasmid pZ146 , that does not exhibit interference with the growth of the M13 helper, although this plasmid is encapsidated into phage particles. This result confirms the theory that the intergenic region consists of two domains: one domain being a segment involved in phage morphogenesis and the other being a region of functional origin which interferes with M13 replication.

Base Sequence↗
PubMed1984

Mutagenesis and mutation transfer induced by ultraviolet light in plasmid-cloned DNA.

We describe here simple techniques for increasing the frequency of UV-induced mutations in a DNA fragment cloned in plasmid pBR322. Irradiation of both the host and the plasmid DNA before transformation is necessary to produce new mutations in the plasmid DNA, presumably because the UV-damaged pBR322 replicon cannot efficiently induce the error-prone repair pathway of Escherichia coli. In contrast, UV irradiation of the plasmid DNA alone before transformation primarily causes the transfer of preexisting mutations from the host chromosome to homologous DNA present in the plasmid. The only other kind of mutants obtained were large deletions of the plasmid DNA. Two chromosomal mutations from the host galK gene and one from the lacZ gene have been transferred to the plasmid by UV irradiation of the plasmid DNA alone. The technique can thus be of general use.

Bacterial Proteins↗
PubMed1984

Selection of lac gene fusions in vivo: ompR-lacZ fusions that define a functional domain of the ompR gene product.

We describe a simple method for selecting Escherichia coli mutants that carry gene fusions between a cloned gene and lacZ. We test this technique with the ompR gene, which codes for a positive regulatory factor in porin synthesis. A number of OmpR-LacZ hybrid proteins are examined, and several unusual phenotypes associated with these protein fusions are described. Evidence is presented to support the two-domain model for ompR proposed previously (Hall and Silhavy, J. Mol. Biol. 151:1-15). In addition, one of the ompR-lacZ fusions exhibits a dominant OmpR- phenotype. The utility of isolating a series of lacZ gene fusions to any target gene is discussed.

Bacterial Outer Membrane Proteins↗
PubMed1984

A murine model of squamous intraepithelial neoplasia.

Focal areas of intraepithelial neoplasia were induced in the skin of mice by 1 intraperitoneal injection of urethane followed by twice weekly topical applications of 12-0-tetra-decanoyl phorbol-13-acetate (TPA). Microscopic lesions with histologic characteristics of intraepithelial neoplasia were seen in all animals after 11 weeks of TPA application. Fluorescence microscopy verified the increased DNA content of these lesions. This easily produced animal model of premalignant disease might be valuable in the preclinical testing of topically applied antineoplastic agents.

Administration, Topical↗
PubMed1983

Characterization of hyperthyroidism enhancement of halothane-induced hepatotoxicity.

Administration of anesthetic doses of halothane to hyperthyroid male rats results in the development of hepatic necrosis. The severity of the hepatic lesion was dependent on the dose of triiodothyronine (T3) and the length of time it was administered. Pretreatment of rats with iodinated metabolites of thyroxin which do not induce hyperthyroidism did not result in any signs of hepatotoxicity after halothane exposure. The administration of halothane to hyperthyroid female rats or mice of either sex did not result in the development of any overt hepatotoxicity. Likewise, hyperthyroidism did not enhance the hepatotoxicity of another hepatotoxin bromobenzene. The in vitro enzymatic activities associated with cytochrome P-450-dependent metabolism and glutathione S-transferase conjugation activity were markedly altered in hyperthyroid rats. Cytochrome P-450 levels, aminopyrine N-demethylase activity, glutathione levels and glutathione S-transferase activity were all significantly lower in hyperthyroid rats. However, other enzyme activities were stimulated by T3 pretreatment; aniline hydroxylase activity was increased by 45% and cytochrome c reductase activity was increased by 54% in hyperthyroid rats. Glutathione levels were also reduced significantly in hyperthyroid male rats. Maximal changes in both the cytochrome P-450 system and in the glutathione detoxification system were required before halothane demonstrated its hepatotoxic effects. Thus, a new balance between cytochrome P-450-dependent bioactivation and glutathione conjugation of halothane may be necessary for the exaggerated hepatotoxicity of halothane seen in hyperthyroid male rats.

Alanine Transaminase↗
PubMed1983

RNA polymerase interactions with the upstream region of the E. coli tyrT promoter.

The rate of in vivo transcription from the E. coli tRNA and rRNA promoters depends on both cellular growth rate and aminoacid availability. To investigate the molecular mechanisms involved we determined the extent of interaction of RNA polymerase with the promoter of the tyrT stable RNA gene. We show that the enzyme can protect from DNAase I digestion a region of at least 85 bp of the wild-type tyrT promoter and only approximately 62 bp of the lacUV5 mRNA promoter, the protected region extending on the antisense strand to approximately 65 and 42 bp respectively upstream of the transcription startpoint. A mutant tyrT promoter, tyrTp27, is protected more extensively, RNA polymerase interactions extending to at least approximately -130. We propose that these upstream interactions of RNA polymerase perform two functions; activating initiation by polymerase bound at the primary binding site and increasing the concentration of polymerase in the vicinity of the tyrT promoter, thus allowing a high rate of maximal expression and enabling the promoter to be regulated over a wide range of activity.

Base Sequence↗
PubMed1983

Open reading frame expression vectors: a general method for antigen production in Escherichia coli using protein fusions to beta-galactosidase.

We have developed an Escherichia coli plasmid vector for the identification and expression of foreign DNA segments that are open reading frames (ORFs). The 5' end of ompF, an E. coli gene encoding an abundant outer membrane protein, is used to provide a strong, regulated promoter, translation initiation site, and signal sequence for export from the cytoplasm. This sequence is coupled to the lacZ gene of E. coli so that expression of beta-galactosidase requires ompF transcription and translation signals. However, this hybrid gene is LacZ- because lacZ is out of frame with respect to ompF. Restriction enzyme recognition sites are located between ompF and lacZ to allow convenient insertion of DNA fragments. If an insert is an ORF of the correct length, ompF and lacZ become realigned in frame, resulting in a LacZ+ gene that produces a tribrid protein with the translation product of the insert sandwiched between OmpF and beta-galactosidase. The LacZ+ phenotype thus identifies clones containing an expressed ORF. To demonstrate the vector's utility we inserted a fragment from the herpes virus thymidine kinase gene and used the resulting tribrid protein to raise antibodies that precipitate thymidine kinase from herpes virus-infected cells. We also inserted a fragment from the E. coli lexA gene to produce a tribrid protein that is precipitated by antiserum raised with LexA protein. Thus, tribrid fusion proteins can be used to produce or detect antibodies and also to identify the product of a cloned gene.

Antigens, Bacterial↗
PubMed1983

Isoflurane and enflurane-induced hepatic necrosis in triiodothyronine-pretreated rats.

Exposure of triiodothyronine (T3)-pretreated rats to 1.3% isoflurane, 1.8% enflurane, or 1% halothane in 21% oxygen (air) for two hours resulted in hepatic centrilobular necrosis. The incidence of the liver lesion was 28, 24, and 92% after exposure to isoflurane, enflurane, and halothane, respectively. Histopathologic grading indicated that the necrosis was more severe after halothane than after isoflurane or enflurane anesthesia. No lesion was observed in livers prepared from non-anesthetized T3-pretreated rats or in livers prepared from rats which were pretreated with the vehicle for T3 and then anesthetized with either isoflurane, enflurane, or halothane. Hepatic necrosis was not observed in vehicle-treated rats exposed to isoflurane in 12% oxygen or in vehicle-treated rats that were deprived of food for 12 hours prior to exposure to isoflurane under hypoxic conditions. Food restriction to maintain the body weight gain of vehicle-treated rats similar to that of T3-treated rats did not result in hepatotoxicity after exposure to halothane in 21% oxygen. Liver necrosis did not occur in pentobarbital anesthetized (40 mg/kg, intraperitoneally) T3-pretreated rats. These results indicate that isoflurane and enflurane, like halothane, can induce hepatic centrilobular necrosis in T3-pretreated rats. The mechanism for liver toxicity of these volatile anesthetic agents in this model remains to be determined.

Animals↗