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Biomedical subjects

R Makuch

Publications and source records attributed to R Makuch.

11 recordsLinked to original sources
PubMed1992

Lys-373 of actin is involved in binding to caldesmon.

Limited proteolysis of actin with trypsin removes its two or three C-terminal amino acid residues [Proc. Natl. Acad. Sci. USA 81 (1984) 3680-3684]. Carboxypeptidase B-treatment of G- and F-actin previously digested with trypsin revealed that in the first case preferential release of three and in the second two C-terminal amino acid residues takes place. Tryptic removal of three but not two C-terminal amino acid residues of actin causes weakening of its interaction with caldesmon and lowering of the caldesmon-induced inhibitory effect on actomyosin ATPase activity. Therefore, it is concluded that the third amino acid residue from the C terminus of actin, Lys-373, is important for the interaction with caldesmon.

Actins↗
PubMed1992

The importance of C-terminal amino acid residues of actin to the inhibition of actomyosin ATPase activity by caldesmon and troponin I.

Proteolytic elimination of three C-terminal amino acid residues from actin weakens its interaction with caldesmon and troponin I and, in consequence, lowers the inhibitory effects of both proteins on actomyosin ATPase activity. These results prove the importance of C-terminal extremity of actin to the overall interaction of this protein with caldesmon and troponin I.

Actins↗
PubMed1992

A model-based prediction for transvaginal ultrasonographic identification of early intrauterine pregnancy.

OBJECTIVE: Our objective was to develop a mathematic model for the prediction of transvaginal ultrasonographic identification of intrauterine gestation as a function of human chorionic gonadotropin titer or gestational age. STUDY DESIGN: In this prospective, descriptive study normal intrauterine pregnancies of 31 patients from the Yale in vitro fertilization and embryo transfer program and infertility clinic were studied. Logistic regression analysis was used to develop a probability curve of transvaginal ultrasonographic detection of intrauterine pregnancy as a function of human chorionic gonadotropin titer or gestational age with a 5 MHz vaginal transducer. RESULTS: A model-based prediction was constructed. It revealed that nearly all intrauterine sacs should be identified by a human chorionic gonadotropin titer of 3000 mIU/ml (first international reference preparation) or by a gestational age of 37 days on the basis of the 5 MHz vaginal transducer. CONCLUSIONS: A model-based prediction for transvaginal ultrasonographic identification of early intrauterine pregnancy is presented that can be readily adapted by individual institutions using their own ultrasonographic equipment and human chorionic gonadotropin assay.

Chorionic Gonadotropin↗
PubMed1979

Thymosin fraction V and intensive combination chemotherapy. Prolonging the survival of patients with small-cell lung cancer.

Patients with small-cell bronchogenic carcinoma who received intensive remission-induction chemotherapy randomly received either thymosin fraction V, 60 mg/sq m or 20 mg/sq m twice weekly, or no thymosin treatment during the initial six weeks of chemotherapy. Chemotherapy was then continued for two years. Thymosin administration did not increase the complete response rate. Patients receiving thymosin, 60 mg/sq m, had significantly prolonged survival times relative to the other treatment groups. This benefit was due to prolonged relapse-free survival in complete responders to treatment. The mechanism by which thymosin increased survival duration is unclear but may relate to restoration of immune deficits due to disease or treatment.

Antineoplastic Agents↗
PubMed1979

Recommendations for the analysis of the effect of treatment on the development of second malignancies.

Use of the person-years method for evaluating the association between treatment of a primary cancer and subsequent development of a second malignancy is reviewed. For this type of analysis, the risk of developing a second malignancy is implicitly assumed to remain constant during each patient's follow-up period; this assumption is shown to be inappropriate. When the oncogenic potential of two or more treatments is compared, results are biased unfavorably against the use of intensive treatments that prolong life. Misinterpretation of the oncogenic potential of such treatment regimens can therefore occur, and two alternative statistical techniques are proposed, each for use in a commonly encountered experimental situation. These fairly classic methods of survival analysis are recommended to ascertain the relationship between treatment and development of a second cancer.

Antineoplastic Agents↗
PubMed1979

Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma.

Sixty-one protocol-eligible patients with small cell bronchogenic carcinoma received cyclic alternating combination chemotherapy with two or three non-cross-resistant drug combinations. No chest or prophylactic brain radiation therapy was used. Twenty-eight months after starting treatment, disease-free survival was 23% for patients achieving a complete response (CR) and 13% overall. Initial treatment consisted of high-dose cyclophosphamide, methotrexate, and CCNU (CMC) for 6 weeks. Patients then received vincristine, adriamycin, and procarbazine (VAP) for 6 weeks. The addition of VAP increased the CR rate from 42% to 74% in limited-disease patients and from 24% to 36% in extensive-disease patients. Half of the patients were randomized to a third combination of VO-16-213 and ifosfamide. These patients were cycled at 6-week intervals through the three drug regimens while the remaining patients were cycled between CMC and VAP. The addition of VP-16-213 and ifosfamide did not increase the CR rate or prolong survival. Only complete responders survived beyond 24 months. Sequential use of non-cross-resistant drug combinations represents one method for increasing the CR rate.

Antineoplastic Agents↗
PubMed1978

Thymosin in cancer patients: in vitro effects and correlations with clinical response to thymosin immunotherapy.

Studies on the effect of thymosin on T-cell levels in vitro among normal persons and cancer patients show that, in general, T-cell levels increase after incubation with thymosin in populations with low initial T-cell levels while the levels decrease in populations with high initial T-cell levels. In patients with small cell carcinoma of the lung receiving intensive chemotherapy also randomized to receive thymosin at a dose of 60 mg/m2, thymosin at a dose of 20 mg/m2, or placebo twice weekly, increased survival occurred in patients receiving the thymosin dose of 60 mg/m2. The increase in survival was greatest in patients with low pretreatment T-cell and alpha2HS-glycoprotein levels. These observations suggest that the cancer patients most likely to benefit therapeutically from adjuvant treatment with thymosin are those with relatively low initial T-cell levels and other parameters of cellular immunity.

Carcinoma, Small Cell↗
PubMed1978

Sample size requirements for evaluating a conservative therapy.

Determination of an adequate sample size for a clinical trial has traditionally involved the specification of type I (false positive) and type II (false negative) error rates, and a difference that one wishes to detect. Because newer therapy has generally been more invasive or more toxic, it is conventional for the type I error to be 0.05 in order that new therapy not be accepted as superior unless its advantages are definitively established. Recently, many new trials have been directed toward showing that a more conservative treatment is equivalent in efficacy to a standard intensive therapy. In this paper, we provide formulas which prescribe the sample size necessary to meet certain criteria specified by the investigator for this alternative type of clinical trial. In addition, the percent increase in total sample size is described when more patients are allocated to one treatment than the other.

Biometry↗
PubMedDate not supplied

cis-Dichlorodiammineplatinum(II) for the treatment of advanced ovarian cancer.

cis-Dichlorodiammineplatinum(II) (cis-platinum) was used in the treatment of 25 patients with advanced ovarian adenocarcinoma refractory to alkylating agents. Seven of 24 evaluable patients (29%) responded to cis-platinum (one complete response and six partial responses). Life-table analysis of survival indicates that patients responding to therapy survive longer than those who fail to respond (9 months versus 3.2 months) (P = 0.014). In previously treated patients given 70 mg/m2 iv with forced diuresis, there was substantial nausea and vomiting (100%), hematologic toxicity (67%), and renal toxicity (34%). A review of the single-agent activity of cis-platinum in other ovarian cancer studies indicates an overall response rate of 25% (40 of 161 patients). At least nine combination chemotherapy studies utilizing cis-platinum are in progress, and preliminary information from several of these is encouraging and suggests that cis-platinum-containing combinations may have a major role in the treatment of ovarian adenocarcinoma.

Adenocarcinoma↗