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Biomedical subjects

J Frankel

Publications and source records attributed to J Frankel.

At least 19 recordsLinked to original sources
PubMed1992

Genes and structural patterns in ciliates: Vance Tartar and the "cellular architects".

The one form of cytoplasmic inheritance that has not been assimilated into the Central Dogma is the inheritance of surface structural patterns, a phenomenon most clearly expressed in ciliates. Vance Tartar, although he worked with a genetically undomesticated organism (Stentor coeruleus), provided early evidence for the crucial role of clonally propagated features of the cell cortex. He showed that the capacity for development of cortical organelle systems is associated with a particular relational feature, the "locus of stripe contrast" (LSC), and that clonally inherited cortical variants (homopolar doublets) could be created at will by microsurgical operations that duplicated the LSC. Tartar also hoped to demonstrate the existence of what David Nanney called "cellular architects" by provoking stentors to carry out entirely novel types of morphogenetic performances. He eventually acknowledged failure, although the bizarre juxtapositions by which he attempted to elicit such novel performances did bring about specific and illuminating defects in cortical development. Subsequent analyses of similar defects in other ciliates revealed not the unitary "pattern factor" postulated by Tartar, but rather a hierarchy of distinct patterning mechanisms. Nonetheless, by pursuing an embryological approach toward morphogenesis in a highly regulative ciliate, Tartar uncovered relational aspects of pattern-determination; this, in my view, delineates the major problem that we must solve to gain understanding of intracellular patterning.

Animals↗
PubMed1992

Phase I trial of postoperative 5-FU, radiation therapy, and high dose leucovorin for resectable rectal cancer.

Following surgery for Stages T3-4N0-2M0 primary and recurrent resectable rectal cancer limited to the pelvis, 25 patients have been entered on a Phase I trial of pelvic radiation therapy (RT) [5040 cGy] and 12 cycles of postoperative 5-FU and high dose Leucovorin (LV) chemotherapy. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were: combined-RT/chemotherapy = 200 mg/m2 and post-RT chemotherapy = 325 mg/m2. The median F/U was 25 months (range: 13-36). Two maximum tolerated doses (MTD's) have been determined, one for combined-RT/chemotherapy and one for post-RT chemotherapy. The MTD for combined-RT/chemotherapy was 250 mg/m2; therefore, the recommended dose of 5-FU is 200 mg/m2. The MTD for post-RT chemotherapy was 375 mg/m2; therefore, the recommended dose of 5-FU is 325 mg/m2. The dose limiting toxicities were diarrhea, tenesmus, frequent bowel movements, dysuria, and myelosuppression. For the nine patients who received 5-FU at the recommended dose level the median low counts were WBC 3.5 (2.2-4.0), HGB 10.3 (9.0-12.3), and PLT (x 1000) 167 (133-280), and the incidence of any grade greater than or equal to 3 toxicity was 22% diarrhea, 17% tenesmus, and 22% frequent bowel movements. The recommended dose of combined-RT/chemotherapy as used in this protocol was relatively well tolerated. However, optimal doses of 5-FU cannot be delivered until the fourth postoperative month. Therefore, despite the encouraging results reported with high dose LV in patients with advanced disease, we do not recommend that high dose LV be used with combined RT and 5-FU in the treatment regimen as presently designed.

Adenocarcinoma↗
PubMed1992

Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy.

PURPOSE: To determine if fluorouracil (5-FU) plus high-dose leucovorin (LV) enhances local response in patients receiving preoperative radiation therapy (RT) for adenocarcinoma of the rectum, we compared the degree of downstaging in patients receiving preoperative RT with or without chemotherapy. PATIENTS AND METHODS: For this comparison, three groups of patients who were treated with identical doses and techniques of preoperative pelvic RT (total dose of 5,040 cGy) were examined. Group 1 included 20 patients with unresectable disease who received combined RT and LV/5-FU. Group 2 included 11 patients with unresectable disease who received preoperative RT. Group 3 included 21 patients with invasive, resectable, primary disease who received preoperative RT. RESULTS: Patients with unresectable disease who received LV/5-FU had a higher rate of pathologic complete response (20% v 0%) and a lower incidence of positive nodes (30% v 64%) compared with those who did not receive chemotherapy. Even when the most favorable group of patients was included (group 3), patients who received LV/5-FU still had a higher complete response rate (20% v 6%) and a lower incidence of positive nodes (30% v 53%) compared with those who received RT without LV/5-FU. Of those patients with initially unresectable disease, the resectability rate was higher in those who received LV/5-FU compared with those who did not receive LV/5-FU (90% v 64%). Patients who received LV/5-FU experienced slightly more grade 1 to 2 fatigue, stomatitis, nausea, and grade 3 diarrhea, tenesmus, and dysuria. CONCLUSIONS: Despite the fact that patients who received chemotherapy (group 1) had more advanced disease compared with those with resectable disease (group 3), the addition of LV/5-FU increased the resectability and downstaging rates. The ultimate impact of a complete response as well as a decrease in the incidence of pelvic nodes on local control and survival remains to be determined. However, given the enhancement of down-staging in patients with unresectable rectal cancer, we are encouraged by the combined modality approach.

Adenocarcinoma↗
PubMed1992

Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach.

PURPOSE: We compared the combined radiation therapy (RT) plus chemotherapy segments of two separate parallel phase I trials to determine if combined pelvic RT, fluorouracil (5-FU), and high-dose leucovorin (LV) had less acute toxicity when delivered preoperatively versus postoperatively in patients with rectal cancer. PATIENTS AND METHODS: Patients with unresectable disease received preoperative RT plus LV and 5-FU followed by surgery and postoperative LV and 5-FU. Patients with resectable disease received identical doses, techniques, and schedules of RT and LV and 5-FU except all therapy was delivered postoperatively. On day 1, patients received LV and 5-FU times one cycle. RT began on day 8. A second cycle of LV and 5-FU was given concurrently with the fourth week of RT. RESULTS: Although more patients (75% v 32%; P = .02) received the higher dose level of 5-FU (250 mg/m2), significantly fewer experienced acute grade 3 to 4 toxicity with preoperative versus postoperative therapy (13% v 48%; P = .045). There was no grade 3 to 4 myelosuppression in either group. The two grade 3 toxicities in the preoperative group were gastrointestinal. The grade 3 toxicities in the postoperative group included seven gastrointestinal and two genitourinary; four patients had a grade 4 toxicity. CONCLUSION: Given the high incidence of grade 3 to 4 toxicity also reported in the postoperative combined modality adjuvant randomized trials, future adjuvant trials should explore the preoperative approach.

Adult↗
PubMed1991

Conjugal blocks in Tetrahymena pattern mutants and their cytoplasmic rescue. II. janus A.

A conjugal block phenotype is described for the Tetrahymena pattern mutant, janA. janA exhibits a characteristic "janus" phenotype in which cells develop with a global mirror-image duplication of the ventral pattern of cortical organelles. janA cells are competent to form mating pairs, but later become irreversibly fused as heteropolar doublets. The few pairs that successfully dissociate fail to undergo postconjugal oral replacement and perish. The janA conjugal block is 100% penetrant, is under prezygotic macronuclear control, and is lethal. Here we characterize this conjugal block genetically and cytologically and demonstrate that it can be rescued by a transferable, wild-type product. New insights into late conjugal events, especially the replacement of the oral apparatus, are reported for wild-type cells as well.

Animals↗
PubMed1979

Patients without communities: whose responsibility?

The authors conducted a study at an urban state hospital to determine if a patient's place of residence--within or outside the hospital's service district--was reflected in the admission rates or the quality of care received. No differences between in-district and out-of-district patients could be found on any parameter studied. The authors believe the results support the unique role of the state hospital as a facility that accepts its mandate as a referral of last resort.

Attitude of Health Personnel↗
PubMed1979

A controlled comparison of continuous intraarterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices.

Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.

Adult↗
PubMed1979

Double wedge resection for severe involutional ectropion.

Although the individual elements of our technique are well known to ophthalmic plastic surgeons and ophthalmologists, their combination into one procedure for use in severe cases of involutional (senile) ectropion has not been described. Some authors have advocated performing a two-stage procedure for a severe medial ectropion. We have met considerable success in our one-stage procedure and advocate its adoption.

Aged↗
PubMed1979

A mutant of Tetrahymena thermophila with a partial mirror-image duplication of cell surface pattern. I. Analysis of the phenotype.

Cells of a mutant clone, CU-127, of Tetrahymena thermophila (formerly T. pyriformis, syngen 1) manifest three anatomical abnormalities. First, the stable number of ciliary meridians is 21-25, above the usual number (17-21) in this species. Second, up to 30% of the cells have two oral apparatuses (OAs), one normal and the other abnormal. Third, more than one-half of the cells possess two distinct sets of contractile vacuole pores (CVPs). In some living cells two contractile vacuoles are seen. These abnormalities have persisted unchanged during more than 500 generations of vegetative propagation, and are similarly expressed in subclones. The normal and abnormal OAs are topographically segregated, with normal OAs developing along the "primary oral axis" and abnormal OAs developing along a "secondary oral axis" that is situated 170 degrees of the cell circumference to the cell's right of the primary oral axis. CVPs always appear within this 170 degree arc and never within the complementary 190 degrees arc to the left of the primary oral axis. A unique feature of the CU-127 clone is the commonly expressed mirror image reversal of the structural pattern of OAs that develop along the secondary oral axis. The primordia of such OAs initially appear (as usual) to the cell's left of a ciliary meridian, but as membranelles develop the frequently come to be oriented in a mirror image of the normal pattern, and an undulating membrane sometimes develops on the wrong (left) side of the oral primordium. When two sets of CVPs are formed, their average positions are roughly equidistant with respect to the two oral axes, with the two sets located 50-60 degrees to the right and left respectively of the primary and secondary oral axis. Such cells are thus bilaterally symmetrical about a plane defined by the central longitudinal axis and the halfway point between the two CVP sets (see Fig. 25). This plane bisects the cell into a normal and a "reversed" half-cell. However, only oral asymmetry and large-scale CVP positioning are subject to such reversal; all ciliary meridians remain of normal asymmetry and all CVPs are situated on the left side of CVP meridians. The fact that major aspects of large-scale cellular organization can be reversed while the "fine-positioning" associated with the ciliary meridians remains normal indicates that the two aspects of cell organization are distinct.

Animals↗
PubMed1979

A mutant of Tetrahymena thermophila with a partial mirror-image duplication of cell surface pattern. II. Nature of genic control.

The CU-127 clone of Tetrahymena thermophila, which manifests an unusually high number of ciliary rows plus a second set of abnormal oral structures and of contractile vacuole pores with partial mirror-image reversal of asymmetry (Jerka-Dziadosz & Frankel, 1979), has been subjected to breeding analysis. The progeny ratios obtained in various crosses indicate that the abnormalities of cell-surface asymmetry are brought to expression as a result of the action of a recessive allele at a single gene locus, here named janus. When previously normal cells were made homozygous for the jan allele, the cortical pattern characteristic of the CU-127 clone came rapidly to expression, often without associated change in number of ciliary meridians. Conversely, when cells previously expressing jan re-acquired the wild-type (jan+) allele, they returned to the normal pattern of a single normal oral structure and a single normally located set of contractile vacuole pores while still retaining the high ciliary meridian number characteristic of the original CU-127 clone. The capacity for manifestation of the unique asymmetry pattern depends solely on homozygous expression of the janus allele, whereas the stable number of ciliary meridians in janus clones and the degree of expression of secondary OAs is modulated by other factors, probably at least in part genic. These results, taken together with those of the preceding paper, indicate that the janus allele promotes the propagation and/or expression of a condition of reversed asymmetry in a precisely located cell region, and further indicates that the propagation and expression of this condition are largely independent of the number and asymmetry of ciliary meridians.

Alleles↗
PubMed1977

180 degrees rotation of ciliary rows and its morphogenetic implications in Tetrahymena pyriformis.

With quasi-surgical techniques, longitudinal somatic ciliary rows in Tetrahymena pyriformis have been rotated 180 degrees. New structures formed in the rotated ciliary rows during growth and reproduction are disposed 180 degrees opposite to their normal positions or orientations, confirming the earlier findings of Beisson and Sonneborn on Paramecium. However, during cell fission the rotated ciliary rows exhibit abnormality in orientation along the fission zone; the configuration of these rows near the anterior end of the posterior product of fission is consequently affected. Rotated ciliary rows have been employed as a tool in the analysis of morphogenetic problems: (a) The contractile vacuole pore is normally located on the left side of a ciliary row; but it is on the right of inverted rows. Hence, the morphogenetic properties of the two sides of the ciliary row associated with the contractile vacuole pore are different and this difference is the sole determinative factor as to the side of the ciliary row on which the contractile vacuole pore is located. (b) The process that generates the rotated ciliary rows frequently also brings about the implantation of an extra band of longitudinal microtubules at a specific site on the cell surface. This extra structure is inheritable, which opens up opportunities for the study of microtubular assembly in vivo.

Cell Division↗
PubMed1977

Inter-strain variability of structural proteins in Tetrahymena.

The high molecular weight proteins found in isolated pellicles of Tetrahymena have been compared in several individual strains within the genus using SDS polyacrylamide gel electrophoresis. Three variants of the beta-protein of epiplasm (MW 174,000; 155,000; 145,00) and 2 of the C-protein (MW 140,000; 122,000) were found among the strains examined. No variation was observed in the major kinetodesmal fiber protein (MW 250,000). The variation found between strains in the proteins of a structure which is (as far as we know) the same in all strains indicates a disjunction between evolutionary change at the 2 levels of organization. The taxonomic implications of the observed variation in structural proteins in Tetrahymena are discussed.

Animals↗
PubMed1977

Sex differences in parent-infant interaction during free play, departure, and separation.

20 18-month-olds were observed with their mothers and 20 with their fathers in laboratory free-play, departure, and separation situations. Parent and infant behaviors were allowed to vary naturally. Although there were no parent sex or infant sex differences in infants' free-play behavior, there were parent sex X infant sex differences in parental free-play behaviors. Parents talked to, sat on the floor more with, and tended to share play more with same-sexed than opposite-sexed infants, and the patterning of free-play behaviors was different for mothers and fathers. During departure, fathers talked to the infants more than mothers. Infants were more distressed in the absence of same-sexed than opposite-sexed parents. There were infant sex X parent sex differences in the relationships between separation distress and parental free-play and departure behaviors. The implications of these findings for understanding differential roles of mothers and fathers, the development of sex differences, and the determinants of separation distress are discussed.

Father-Child Relations↗
PubMed1977

Is adolescent rebellion universal?

Forty volunteer subjects were interviewed in an attempt to determine if indications of adolescent rebellion would be found across the range of disciplinary styles. An analysis of the taped interviews did not support the expectations. Twenty-five percent of the sample manifested high rebelliousness and none of these subjects came from low-control homes. Seveny-five percent of the sample showed little or no rebelliousness at all. Low rebelliousness was evently distributed across the spectrum of disciplinary styles. The twenty per-cent incidence of permissive homes was higher than other research indicated it might be. Authoritarian parents in this sample appeared to be less restricting than would have been expected. A wider range of adolescent behavior was accepted and fewer issues provoked conflict and rebellion as the parents appeared to be responding to a changing society.

Adolescent↗
PubMed1976

Causal relations among cell cycle processes in Tetrahymena pyriformis. An analysis employing temperature-sensitive mutants.

Utilization of temperature-sensitive mutants of Tetrahymena pyriformis affected in cell division or developmental pathway selection has permitted elucidation of causal dependencies interrelating micronuclear and macronuclear replication and division, oral development, and cytokinesis. In those mutants in which cell division is specifically blocked at restrictive temperatures, micronuclear division proceeds with somewhat accelerated periodicity but maintains normal coupling to predivision oral development. Macronuclear division is almost totally suppressed in an early acting mutant (mola) that prevents formation of the fission zone, and is variably affected in other mutants (such as mo3) that allow the fission zone to form but arrest constriction. However, macronuclear DNA synthesis can proceed for about four cycles in the nondividing mutant cells. A second class of mutants (psm) undergoes a switch of developmental pathway such that cells fail to enter division but instead repeatedly carry out an unusual type of oral replacement while growing in nutrient medium at the restrictive temperature. Under these circumstances no nuclei divide, yet macronuclear DNA accumulation continues. These results suggest that (a) macronuclear division is stringently affected by restriction of cell division, (b) micronuclear division and replication can continue in cells that are undergoing the type of oral development that is characteristic of division cycles, and (c) macronuclear DNA synthesis can continue in growing cells regardless of their developmental status. The observed relationships among events are consistent with the further suggestion that the cell cycle in this organism may consist of separate clusters of events. with a varying degree of coupling among clusters. A minimal model of the Tetrahymena cell cycle that takes these phenomena into account is suggested.

Animals↗