Search PubMed⌕ Search

Biomedical subjects

J L Klein

Publications and source records attributed to J L Klein.

At least 127 records · Page 7Linked to original sources

Multimodality treatment of patients with advanced ovarian carcinoma.

A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally resected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastatic and 6 with Stage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or without intraperitoneal antiserum and multiagent chemotherapy; their cumulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.

Adenocarcinoma, Mucinous↗

Phase I-II study of isotopic immunoglobulin therapy for primary liver cancer.

A phase I-II study of isotopic immunoglobulin therapy was performed in 18 patients with primary liver cancer; 14 were evaluable for toxicity. The patients received a dose of 37-157 millicuries of 131I-labeled antibody. The dose-limiting factor appears to be hematologic toxicity, especially thrombocytopenia. An objective antitumor effect was seen in six of nine patients who were evaluable for response. Present results suggest that further clinical studies with isotopic immunoglobulin are indicated.

Adenoma, Bile Duct↗

Ip immunotherapy and chemotherapy in advanced epithelial ovarian cancer.

Nine patients with advanced epithelial ovarian cancer, classified as either stage III with macrometastatic residual disease or stage IV, received combination chemotherapy in conjunction with ip rabbit-derived human ovarian antitumor serum (HOATS). The HOATS regimen consisted of the ip instillation of 100 ml of ovarian antitumor serum on Days 1 and 3 of the first chemotherapy cycle. Side effects attributable to HOATS were low-grade fever in three patients and diffuse skin rash in two. The 1-year cumulative survival was 87%, with a clinical response rate of 80%. No significant toxic reactions to HOATS have been observed. Continuation of the present study seems justified.

Adenocarcinoma↗

The integration of new therapies and radiation in the management of ovarian cancer.

New biologic information has led to a therapeutic program in Stage III ovarian cancer that considers the whole peritoneal cavity the tumor-bearing region and that uses intraperitoneal administration of ovarian cancer antiserum, intraperitoneal P-32, delayed split abdominal irradiation, and chemotherapy. The survival for those patients completing irradiation was 85%. Forty-nine patients with advanced (Stage III, IV, or recurrent) ovarian cancer have been treated with combinations of the present agents. Twenty-two patients have received intraperitoneal ovarian cancer antiserum without significant toxicity. Extensive staging has been a requirement for initial evaluation and includes maximal surgical resection, omentectomy, TAH and BSO, nodal biopsies, and peritoneal cytology. Nineteen patients had 5-mm nodules or less residual disease and were treated with colloidal P-32, abdominal irradiation, and chemotherapy; five of these patients received intraperitoneal antiserum before cytotoxic therapy. The four-year cumulative survival is 84%, and the disease-free survival 43%. A randomized prospective study is now examining the value of antiserum therapy. New experimental data from our laboratory indicate 1) the value of 2/3 biomarkers (alpha globulin and free secretory protein) in following patients for remission of disease and 2) the probability of the development of more effective antiserum with high specific titer. Studies of the radiosensitivity of ovarian cancer indicate the tumor was not different from other solid tumors. Our studies indicate the role of radiation therapy as a cytoreductive agent should be integrated in multimodality therapy and that the immune system offers new possibilities in amplifying therapeutic results.

Alpha-Globulins↗

Antiferritin IgG antibody for isotopic cancer therapy.

Radiolabeled antiferritin IgG will target ferritin-bearing tumors such as hepatoma, lung cancer, and neuroblastoma. In hepatoma 4 of 5 patients have had clinical remission of malignancy following intravenous doses up to 150 mCi of radiolabeled antiferritin IgG. The dosimetry of radiolabeled 131I-antiferritin reveals a 3-day effective half-life, low dose rate isotopic implant of tumors 5 rad/h, 2,000-3,000 rad to the tumor, and a tumor half-life of 7.7 days. The possibilities of this new cancer agent are discussed in regard to isotopes, greater antibody specificity, and methods of evaluation.

Adolescent↗

Use of isotopic immunoglobulin in therapy.

Antibodies raised in heterologous species against tumor-associated antigens such as ferritin and carcinoembryonic antigen may be utilized in diagnostic scanning and in cancer therapy. The radiolabeled (131I) antibodies have a mean effective half-life of 3 days. The tumor-bearing regions retain activity which was associated with objective evidence of remission in primary hepatic cancers. Major organ toxicity was not apparent in eight of nine patients treated with radioactive antibody. Objective evidence of clinical remission was documented by computer-assisted axial tomography scan remission in sequential studies that determine residual tumor in the same planar cuts. Future possible improvements in radioimmunoglobulin are discussed in light of the clinical findings.

Carcinoembryonic Antigen↗

Electron transport in the cni-1 mutant of Neurospora crassa.

1. Mitochondria from the nuclear mutant cni-1 have no optically detectable cytochrome aa3 in early log phase growth. These mitochondria have a high level of respiration that is not inhibited by cyanide but is inhibited by salicylhydroxamic acid. They also show a substantial amount of cyanide-sensitive respiration. 2. As cultures of mutant cni-1 age, flux through the hydroxamate-sensitive pathway decreases markedly while flux through the cytochrome chain remains constant. 3. Growth studies with mutant cni-1 indicate that the cytochrome chain in this mutant is more important in supporting growth than the hydroxamate-sensitive pathway. 4. Measurements of the steady-state level of reduction of cytochrome c in mutant cni-1 indicate that the rate-limiting step in the cytochrome chain is at the position occupied by cytochrome oxidase. 5. Electron spin resonance studies with cni-1 mitochondria show normal cytochrome oxidase signals in the g approximately 6 region although there is little or no optically detectable cytochrome aa3.

Cyanides↗

Quantitation of secretory protein levels by radioimmunoassay.

A radioimmunoassay was designed for the detection of secretory protein, a component of secretory immunoglobulin A, in human serum. The assay uses free secretory protein isolated from human colostrum, and antisera raised in rabbits to the purified antigen. The mean level of secretory protein in the control group was 2.34 +/- 0.41 microgram/ml (mean +/- S.E.M.). The level in cord blood was slightly lower (0.74 +/- 0.26 microgram/ml), while the level in patients with ovarian carcinoma was significantly increased (12.67 +/- 1.43 microgram/ml). Pregnant women have increasing secretory protein levels with increasing length of gestation (5.86 +/- 2.02, 11.55 +/- 1.30 and 17.00 +/- 1.16 microgram/ml for the first, second and third trimesters, respectively.

Adult↗

Quantitation of secretory component levels in cyst fluids, ascitic fluids, and sera from ovarian adenocarcinoma patients.

A secretory component (SC) was detected by radioimmunoassay in the cyst fluids, ascitic fluids, and sera from patients with ovarian adenocarcinomas. Serous cyst fluids and ascitic fluids showed lower levels (expressed as means +/- SE) of SC (1.37 +/- 0.37 and 1.24 +/- 0.24 microgram/ml, respectively) than mucinous cyst fluids (181.50 +/- 50.40 microgram/ml). SC levels in the sera of all patients with ovarian adenocarcinoma were high (12.67 +/- 1.43 microgram/ml) when compared to SC levels in the sera of normal individuals (2.34 +/- 0.41 microgram/ml). Sera from patients with ovarian cancers diagnosed as serous, mucinous, papillary, and poorly differentiated adenocarcinomas showed SC levels of 9.93 +/- 1.68, 22.44 +/- 3.24, 7.35 +/- 1.13, and 10.10 +/- 1.58 microgram/ml, respectively.

Adenocarcinoma↗

Immunologic studies on the cystic effusions of ovarian epithelial neoplasms.

Cystic effusions from 12 epithelial tumors of the ovary and pooled normal ovarian tissue were studied by immunodiffusion for the presence of immunoglobulins G (IgG), M (IgM), and A (IgA) and free secretory component (FSC). In pooled normal ovarian tissue, IgG was the only immunoglobulin detected. In the neoplastic samples studied, IgG was detected in each of the 12 samples (100%), IgM was found in 10 of the 12 samples (83%), and IgA was detected in 11 of the 12 samples (92%). There was no discernible correlation between the immunoglobulins detected and the composition of the effusions or the pathologic classification of the tumors. FSC was detected in all mucinous samples studied, malignant as well as benign. This substance was not detected in any of the nonmucinous samples or in pooled normal ovarian tissue. The data suggest a correlation between the presence of FSC and the mucinous composition of the tumor effusion. Possible use of FSC assays in the study of mucinous tumors of the ovary is discussed.

Adolescent↗

Regulation of mitochondrial membrane assembly in Neurospora crassa. Transient expression of a respiratory mutant phenotype.

Cultures of mutant cni-1, a chromosomal mutant of Neurospora crassa, undergo a marked change in respiratory properties as the age of the culture increases. Early log phase cultures have a high level of respiration that is insensitive to inhibition by cyanide or antimycin A. Late log and stationary phase cultures have reduced rates of respiration. A high percentage of this respiration is inhibited by cyanide. Mitochondria from early log phase cni-1 have an excess of cytochrome c and little or no detectable cytochrome aa3. Mitochondria from late log and stationary phase cultures have levels of c-, b-, and a-type cytochromes that are not significantly different in concentration from those found in wild type cells. The cytochrome aa3 content and the cytochrome oxidase activity of cni-1 mitochondria increase 5- to 10-fold as the age of the culture increases. Mitochondria from early log phase cells of cni-1 synthesize only polypeptides of apparent molecular weights 7,000 to 10,000 and donot synthesize any of the mitochondrial components of cytochrome oxidase. Mitochondria from late log and stationary phase cells synthesize the normal complement of mitochondrial translation products including the mitochondrial components of cytochrome oxidase. The assembly of cytochrome oxidase is likely due to the availability of the mitochondrially synthesized components of the enzyme. The regulation of mitochondrial translation in the cni-1 mutant is independent of the nutrient content of the growth medium and is due to the accumulation or depletion of some component within the cell.

Cell Division↗